Block Iv

Front 1

What is the distribution of cholinergic neurons?

Back 1

Motor neurons to skeletal muscle; Parasympathetic pre- and postganglionic neurons; ; Sympathetic preganglionic neurons; Sympathetic postganglionic neurons to sweat glands and skeletal vesselsh

Front 2

Which receptors mediate the actions of NE and Epi, and how do they differ?

Back 2

α-adrenoceptors: α1=postjunctional/smooth muscle, α2=prejunctional/nerve terminals;
β-adrenoceptors: β1=heart, β2=smooth muscle, β3=lipocytes

Front 3

How are receptor subtypes classified?

Back 3

Based on relative affinities for agonist and antagonist drugs

Front 4

What are nonadrenergic noncholinergic (NANC) mediators and what are some examples of them?

Back 4

Substances released from nerve endings that act as neurotransmitters, co-transmitters, or neuromodulators – Examples: ATP, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), NO; all are released from motor or sensory nerves, except NO which is nitrergic

Front 5

What is the distribution of nitrergic neurons?

Back 5

Sympathetic and parasympathetic postganglionic neurons

Front 6

What is the distribution of dopaminergic neurons?

Back 6

Sympathetic postganglionic neurons to renal vasculature smooth muscle

Front 7

What is the distribution of noradrenergic (aka adrenergic) neurons?

Back 7

Most sympathetic postganglionic neurons

Front 8

What neurotransmitters are associated with the sympathetic and parasympathetic nervous systems respectively?

Back 8

Sympathetic: preganglionic=ACh, postganglionic=NE, adrenal medulla=ACh
Parasympathetic: : preganglionic=ACh, postganglionic=ACh

Front 9

How does myelination differ between pre- and postganglionic nerves of the ANS?

Back 9

Preganglionic nerves are myelinated whereas the postganglionic nerves are not

Front 10

What happens at the varicosities of neurons?

Back 10

Release of neurotransmitters

Front 11

What do NO activate?

Back 11

Not a receptor, but rather activates guanylate cyclase (GTP --> cGMP)

Front 12

What are the sympathetic and parasympathetic effects on the iris/pupil?

Back 12

Sympathetic: mydriasis (dilation); Parasympathetic: miosis (constriction)

Front 13

Are the vascular endothelium and ventricular myocardium innervated by parasympathetic nerves?

Back 13

No, but muscarinic receptors are present and the cells will respond when muscarinic agonists are administered

Front 14

What describes the parasympathetic innervation of blood vessels?

Back 14

Cholinergic innervation restricted to facial region (blush), uro-genital organs, GI mucosa, tongue and pharynx

Front 15

What describes the sympathetic innervation of blood vessels?

Back 15

Nearly all vascular beds receive noradrenergic innervation via the sympathetic nervous system – the exception is that skeletal muscle receives cholinergic innervation from the SNS which causes dilation of the blood vessels

Front 16

What is the effect of sympathetic fibers on the heart?

Back 16

Affect rate, conduction velocity, and contractility by innervating every aspect of the heart

Front 17

What is the effect of parasympathetic fibers on the heart?

Back 17

Affect rate and conduction velocity by innervating the SA node, AV node, and atria – they do not have an appreciable effect on the His-Purkinje system and ventricular myocardium!

Front 18

What are the subtypes of dopamine receptors and how do they differ?

Back 18

D1-4: renal vasculature; D2: prejunctional; D5: brain

Front 19

What two subtypes of cholinoceptors exist?

Back 19

Muscarinic: M1-5 (smooth muscle, heart, glands, endothelium); Nicotinic: Nn (parasympathetic and sympathetic ganglia – i.e. autonomic) and Nm (skeletal muscle end-plate – i.e. somatic)

Front 20

Which part of the autonomic nervous system controls gluconeogenesis and glycogenolysis?

Back 20

Sympathetic

Front 21

Which physical effects are produced by both the sympathetic and parasympathetic nervous systems?

Back 21

Secretion at the salivary glands; Contraction of the uterus

Front 22

Which drugs reduce the synthesis and storage of NE and by what mechanism?

Back 22

α-methyltyrosine: competes with tyrosine for tyrosine hydroxylase (used for pheochromocytoma);
α-methyldopa: taken up by the vesicle and is converted to α-methylnorepinephrine (=false transmitter used for the treatment of hypertension due to its effects on α2-receptors)

Front 23

What effect can glucocorticoids have on noradrenergic nerve endings?

Back 23

They can inhibit uptake 2 and potentiate Epi

Front 24

What is the effect of Bretylium and Guanethidine?

Back 24

They inhibit NE release (can cause some initial NE release) – used for arrhythmias

Front 25

What drugs can block the postsynaptic NE receptors?

Back 25

α- and β-adrenoceptor antagonists

Front 26

What is the mechanism of action of Tyramine and what cautions should be provided with this drug?

Back 26

It is an indirect-acting stimulator of NE release (it does so by getting into the vesicle and causing NE release) – Tyramine is found in many food stuffs (e.g. cheese, beer, red wine) and is normally degraded by MAO; however for people on MAO-inhibitors, consuming these foods can lead to high enough Tyramine levels to have an effect on the vesicles and cause NE release

Front 27

What is the mechanism of action of Reserpine?

Back 27

It inhibits the active transporter on the vesicle membrane that pumps dopamine in, and it inhibits the pumping of NE back into the storage vesicle as it is being recycled (i.e. there is a partial depletion of NE from the storage vesicle); toxicities of Reserpine prevent its widespread use

Front 28

What is the mechanism of action of cocaine?

Back 28

It blocks uptake 1, thus prolonging the presence of NE in the synaptic cleft

Front 29

What is the terminal product of metabolism by COMT and MAO of DA?

Back 29

Homovanillic acid (HVA)

Front 30

What factors in CHF cause diastolic dysfunction?

Back 30

Massive left ventricular hypertrophy; Myocardial fibrosis; Deposition of amyloid; Constrictive pericarditis

Front 31

What is cor pulmonale?

Back 31

Chronic severe pulmonary hypertension resulting in right-sided heart failure; can be caused by disease of the lungs or by left-sided heart failure

Front 32

What usually causes right-sided heart failure and what changes are seen in the heart?

Back 32

Usually caused by left-sided heart failure; Presents with right ventricular dilation and hypertrophy

Front 33

What signs/symptoms are associated with left-sided heart failure?

Back 33

Pulmonary congestion/edema; Alveoli with hemosiderin-laden macrophages; Prerenal azotemia; Hypoxic encephalopathy

Front 34

What are causes of left-sided heart failure?

Back 34

Ischemic heart disease; HTN; Aortic/mitral valvular disease; Non-ischemic myocardial disease

Front 35

How does the size of a heart correlate with disease?

Back 35

350-600 grams: pulmonary HTN, ischemic heart disease; 400-800 grams: systemic HTH, aortic stenosis, mitral regurgitation, dilated cardiomyopathy; 600-1000 grams: aortic regurgitation, hypertrophic cardiomyopathy

Front 36

What is the difference between forward and backward failure with CHF?

Back 36

Forward: diminished CO; Backward: damning back of blood in the venous system

Front 37

What events follow cardiac dysfunction?

Back 37

Increased cardiac output --> dilation of the ventricles --> left-ventricular hypertrophy --> heart failure

Front 38

What is true according to the Frank-Starling mechanism?

Back 38

Increasing preload (i.e. through dilation) will increase contractility

Front 39

What is congestive heart failure preceded by?

Back 39

Cardiac hypertrophy (in an attempt to maintain arterial pressure and perfusion of vital organs) – myocytes can hypertrophy, but they cannot increase in numbers

Front 40

gWhat are the three variants of angina?

Back 40

Stable: comes on with exertion; Prinzmetal: episodic, comes on at rest, due to coronary artery spasm, elevated ST segment on EKG; Unstable: occurs at rest, prolonged duration of chest pain, induced by disruption of atherosclerotic plaque with superimposed thrombosis, pre-infarction angina

Front 41

What microscopic changes are seen after MI?

Back 41

4-12 hours: coagulation necrosis (wavy fibers); 2-3 days: acute inflammation; 2-4 weeks: vascularized granulation tissue (fibrosis)

Front 42

What macroscopic changes are seen after MI?

Back 42

<12 hours: nothing; 12-24 hours: red-blue hue; 7-10 days: soft yellow-tan area; 10 days-2 weeks: hyperemic zone of granulation tissues

Front 43

What parts of the heart are associated with the left anterior descending, right, and left circumflex coronary arteries, respectively?

Back 43

Left anterior descending: anterior left ventricle, apex, anterior interventricular septum; Right: posterior left ventricle, posterior interventricular septum; Left circumflex: lateral left ventricle

Front 44

What change is seen in the heart, 2 months or more after an MI?

Back 44

Dense collagenous scar

Front 45

What is the prominent mechanism of cell death associated with MI?

Back 45

Coagulative necrosis (visible within 12-24 hours after MI)

Front 46

Besides plaques, what are some other causes of MI?

Back 46

Vasospasm, emboli, vegetative endocarditis, vasculitis, hematologic abnormalities, amyloid deposition

Front 47

What signs/symptoms are associated with right-sided heart failure?

Back 47

Congestive hepatomegaly; Passive congestion; Centrilobular necrosis; Cardiac sclerosis; Congestive splenomegaly; Ascites; Congested kidneys; Hypoxic encephalopathy; Pleural effusions; Subcutaneous edema

Front 48

What are examples of acute coronary syndromes?

Back 48

Acute MI; Unstable angina; Sudden cardiac death

Front 49

At what point does an obstructive lesion prevent sufficient myocardial oxygen demand?

Back 49

When it causes >75% obstruction; >90% stenosis will lead to inadequate blood flow at rest (unstable angina)

Front 50

What clinical signs are associated with MI?

Back 50

Rapid, weak pulse; Diaphoresis; Dyspnea; New Q waves on EKG – silent MI is common in diabetics and elderly

Front 51

What complications are associated with MI?

Back 51

Rupture of the ventricular wall (2-3 days post-MI) --> cardiac tamponade; Arrhythmias (most common cause of death post-MI)

Front 52

Which enzymes involved in the metabolism of tyrosine to epi are found in the cytoplasm?

Back 52

Tyrosine hydroxylase, Dopa decarboxylase, Phenylethanolamine-N-methyltransferase (adrenal);
Dopamine-β-hydroxylase is found inside the storage vesicle

Front 53

What is the terminal product of metabolism by COMT and MAO of NE and Epi?

Back 53

Vanillylmandelic acid (VMA)

Front 54

What characterizes the MAO enzymes?

Back 54

They are not very specific and will metabolize many types of amines by removing the amine from the α-carbon, which abolishes agonist activity; They are located inside mitochondria and are mostly found in noradrenergic nerve ending and in the liver (most important site); there are two isoforms

Front 55

What type of compound is metabolized by COMT and where does this mainly happen?

Back 55

Catechols (phenolic rings with 2 adjacent hydroxyls) – the most important site of COMT metabolism is in the liver; degradation by COMT reduces potency ~100 fold

Front 56

By what mechanisms is NE removed after its release?

Back 56

Taken up by effector cells (facilitated diffusion/uptake 2) and degraded by MAO or COMT;
Taken up by nerve terminal (active transport/uptake 1), moved to vesicles or degraded by MAO; Diffusion from synaptic cleft (if it diffuses to the liver, it can be degraded by MAO and COMT)

Front 57

What are the catecholamines?

Back 57

DA, NE, Epi

Front 58

What molecule has an effect on Tyrosine Hydroxylase?

Back 58

NE negatively inhibits this enzyme

Front 59

What is the difference between autoreceptors and heteroreceptors found on varicosities?

Back 59

Regarding the noradrenergic neuron, α2-autoreceptors will reduce subsequent NE release in response to NE, whereas heteroreceptors will modulate the release of NE in response to other neurotransmitters (e.g. ACh from adjacent neurons)

Front 60

What important enzyme associated with the degradation of neurotransmitters is found inside the mitochondria?

Back 60

Monoamine oxidase: involved in the breakdown of 5-HT, NE, Epi, DA

Front 61

What enzymes are responsible for the metabolism of tyrosine into epinephrine?

Back 61

Tyrosine --> (via tyrosine hydroxylase) Dopa --> (via dopa decarboxylase) Dopamine --> (via dopamine-β-hydroxylase) Norepinephrine --> (via phenylethanolamine-N-methyltransferase) Epinephrine (only in adrenal glands)

Front 62

What is the terminal product of metabolism by COMT and MAO of DA?

Back 62

Homovanillic acid (HVA)

Front 63

What clinical signs are associated with aortic stenosis?

Back 63

Heaped up calcified masses within the aortic cusps; Left ventricular hypertrophy – poor prognosis if angina, CHF, or syncope are present

Front 64

What causes rheumatic heart disease?

Back 64

Antibodies against M protein of Streptococci which cross-react with glycoprotein antigens in the heart

Front 65

What causes mitral valve prolapse?

Back 65

Enlarged, myxomatous, floppy mitral valve leaflets that balloon back into the left atrium during systole, causing a midsystolic click; often found in young females (incidental finding), and associated with Marfan syndrome

Front 66

In what patients is mitral annular calcification seen and what problems are associated with these deposits?

Back 66

Females > 60; can lead to mitral regurgitation, stenosis, and arrhythmias

Front 67

What are causes of mitral regurgitation?

Back 67

Abnormalities of leaflets and commissures (e.g. infective endocarditis, mitral valve prolapse);
Abnormalities of tensor apparatus (e.g. rupture of papillary muscle, rupture of chordae tendineae);
Abnormalities of left ventricular cavity/annulus (e.g. left ventricular enlargement, calcification of mitral ring)

Front 68

What is the major cause of mitral stenosis?

Back 68

Rheumatic heart disease

Front 69

What problems arise in a patient with a congenitally bicuspid aortic valve?

Back 69

Not symptomatic at birth, but they are predisposed to degenerative calcifications (on midline raphe of larger cusp)

Front 70

What sign is usually responsible for bringing systemic hypertensive heart disease to the attention of medical personnel?

Back 70

Atrial fibrillation

Front 71

What are the most common causes of death in patients with hypertensive heart disease?

Back 71

CHF, sudden cardiac death, renal disease stroke

Front 72

What is the most common valvular abnormality and what is it often caused by?

Back 72

Aortic stenosis; caused by post-inflammatory scarring

Front 73

What age range does rheumatic fever usually present in?

Back 73

5-15 years; it is very uncommon these days

Front 74

What clinical findings are associated with infective endocarditis?

Back 74

Fever, murmur, petechiae, splinter hemorrhages, Janeway lesions (lesions on palms/soles), Osler nodules (nodules in pulp of digits), Roth spots (retinal hemorrhages)

Front 75

What valves are most commonly affected by infective endocarditis?

Back 75

Aortic/mitral valve; Right heart valves in IV drug abuse

Front 76

What organisms are mostly responsible for infective endocarditis?

Back 76

Streptococcus viridans > Staphylococcus aureus (most common bug with IV drug abuse)

Front 77

What factors contribute to the development of infective endocarditis?

Back 77

Neutropenia, immunodeficiency, alcohol abuse, IV drug abuse (!), DM

Front 78

What are the two forms of infective endocarditis and how do they differ?

Back 78

Acute: highly virulent organism affecting previously normal valve, patient will have rapidly developing fever with rigor/malaise/weakness, death occurs in 50% of patients within days-weeks;
Subacute: low virulence organism affecting an abnormal/injured valve, patient will have less valvular destruction and will present with low-grade fever/weight loss/flu-like symptoms, disease has protracted course causing lower mortality rates

Front 79

What causes infective endocarditis?

Back 79

Microbial colonization of heart valves resulting in friable, infected vegetations, frequently causing valve damage

Front 80

What part of the heart is mostly affected by rheumatic heart disease?

Back 80

Valves

Front 81

What is the morphology associated with rheumatic heart disease?

Back 81

Aschoff bodies: foci of fibrinoid necrosis surrounded by leukocytes found in the pericardium, myocardium (mainly), and endocardium; Bread and butter pericarditis; Fibrinoid necrosis of cusps; Vegetations along lines of closure; MacCallum plaques: subendocardial collections of Aschoff nodules

Front 82

What are the Jones criteria for rheumatic heart disease?

Back 82

2 of 5 major manifestations: migratory polyarthritis of large joints, carditis (any layer), subcutaneous nodules, erythema marginatum (macular skin lesions in bathing suit distribution), Sydenham chorea (rapid, involuntary, purposeless movements);
2 minor manifestations: fever, arthralgia, increased blood levels of acute phase reactants

Front 83

What complications are associated with artificial valves?

Back 83

Thromboembolic complications, infective endocarditis, structural deterioration, hemolysis, obstruction, exuberant healing

Front 84

What is the problem with arrhythmogenic right ventricular cardiomyopathy?

Back 84

Right-sided failure and rhythm disturbances leading to ventricular tachycardia and sudden death; Right ventricular wall is thinned, with profound fatty infiltration (defect on chromosome 14)

Front 85

What are the subtypes of restrictive cardiomyopathy?

Back 85

Endomyocardial fibrosis: African children, ventricular subendocardial fibrosis, etiology unknown;
Loeffler endocarditis: occurs in temperate zones, endomyocardial fibrosis, eosinophilic leukemia;
Endocardial fibroelastosis: focal/diffuse fibroelastic thickening of the endocardium, most common in children younger than 2, often accompanied by congenital cardiac anomalies

Front 86

What are possible causes of restrictive cardiomyopathy?

Back 86

Idiopathic, radiation fibrosis, amyloidosis, sarcoidosis, tumors, inborn-errors of metabolism

Front 87

What are possible causes of hypertrophic cardiomyopathy?

Back 87

Genetic mutations in genes that encode sarcomeric proteins (e.g. β-myosin heavy chain, troponin T, α-tropomyosin, myosin-binding protein C)

Front 88

What are possible causes of dilated cardiomyopathy?

Back 88

Idiopathic, alcohol, peripartum, genetics (e.g. dystrophin), doxorubicin

Front 89

What are the three different types of cardiomyopathy and how do they differ?

Back 89

Dilated: most common, dilation of all chambers, impairment of contractility, death in <5 years;
Hypertrophic: myocardial hypertrophy, thickening of interventricular septum, “banana-like configuration”, impairment of compliance = poor diastolic relaxation, variable clinical features;
Restrictive: impairment of compliance = impaired diastolic filling = reduced CO

Front 90

What causes nonbacterial thrombotic endocarditis?

Back 90

Deposition of small masses of fibrin/platelets/blood components on valve leaflets; seen in patients with cancer (adenocarcinoma) and sepsis who have developed hypercoagulable states (e.g. DIC) – nonbacterial thrombotic endocarditis is also known as marantic endocarditis

Front 91

What is Libman-Sacks disease associated with?

Back 91

SLE – sterile vegetations mainly affecting the AV valves

Front 92

What causes carcinoid heart disease and what does it affect?

Back 92

Carcinoid tumors produce serotonin and other bioactive products which cause cardiac lesions, mainly affecting the tricuspid and pulmonary valves

Front 93

What are common causes of pericarditis?

Back 93

It is usually secondary to disorders involving the heart or adjacent mediastinal structures (e.g. MI, surgery, trauma, radiation, tumors, infections)

Front 94

Which form of acute pericarditis is commonly associated with tuberculosis or mycotic infection?

Back 94

Caseous pericarditis: caseation within the pericardial sac; leads to constrictive pericarditis

Front 95

What characterizes hemorrhagic pericarditis?

Back 95

An exudate of blood mixed with a fibrinous/suppurative effusion; follows cardiac surgery, tuberculosis, or malignancy

Front 96

Which form of acute pericarditis is mostly associated with infection and what characterizes it?

Back 96

Purulent/suppurative pericarditis: infection can reach pericardium via direct extension, seeding from blood, lymphatic extension, or during cardiotomy; associated with a creamy pus over red, granular coated serosal surfaces – can lead to constrictive pericarditis

Front 97

What is the most common clinical form of acute pericarditis and what characterizes it?

Back 97

Fibrinous/serofibrinous pericarditis: associated with a pericardial friction rub; often seen with MI (Dressler’s syndrome), but can also be due to any of the etiologies for serous pericarditis

Front 98

What diseases are associated with acute serous pericarditis (slow accumulation of exudate)?

Back 98

Rheumatic fever, SLE, scleroderma, tumors, uremia

Front 99

When are pericardial effusions problematic?

Back 99

When there is a rapid accumulation of fluid (can cause fatal cardiac tamponade)

Front 100

What is myocarditis and what is the most common cause in the US?

Back 100

Inflammatory process that injures cardiac myocytes – most common US cause is viral infections (mainly coxsackievirus A and B)

Front 101

What clinical signs are associated with myocarditis?

Back 101

Heart failure, arrhythmias, systolic murmur, sudden death – can mimic acute MI

Front 102

What other causes are associated with myocarditis?

Back 102

Infectious: Trypanosoma cruzi (Chagas disease in South America), parasitic disease (Toxoplasma gondii), bacterial disease (diphtheria, Lyme disease) – common in immunodeficient patients;
Noninfectious: rheumatic fever, SLE, drug allergies (doxorubicin/Adriamycin, lithium, cocaine), catecholamines, amyloidosis (seen with congo red dye), iron overload (due to hereditary hemochromatosis, hemosiderosis)

Front 103

What is the most common primary tumor of the heart in adults?

Back 103

Myxoma: neoplastic lesion that occurs most commonly in the left atrium in the region of the fossa ovale; histologically they are composed of stellate/globular myxoma cells, endothelial cells, smooth muscle cells, and undifferentiated cells – can be identified by ECG, 10% is familial; can be seen in a Carney complex

Front 104

What complications are associated with heart transplants?

Back 104

Graft arteriosclerosis (progressive, diffuse intimal proliferation of the coronary arteries causing downstream myocardial ischemia = major limitation to long-term success); Infection; Malignancies (lymphoma related to EBV)

Front 105

What are the most common reasons for heart transplants?

Back 105

Dilated cardiomyopathy and ischemic heart disease

Front 106

What tumors frequently metastasize to the heart?

Back 106

Lung, breast, melanoma, leukemia, lymphoma

Front 107

What is the most frequent primary cardiac tumor in children?

Back 107

Rhabdomyoma: may cause valvular or outflow tract obstruction; they are hamartomas and may be associated with tuberous sclerosis; grossly they are grey-white ventricular wall masses; microscopically they are composed of “spider cells”: polygonal cells with glycogen-laden vacuoles

Front 108

What are papillary fibroelastomas and where are they usually found?

Back 108

Hair-like projections on the endothelial surface (resemble Lambl excrescences); usually found on right-sided valves in children and left-sided valves in adults

Front 109

What is a lipoma and where in the heart are they most commonly found?

Back 109

Excessive fat accumulation; more commonly seen in the left ventricle, right atrium, septum

Front 110

What are the two forms of chronic/healed pericarditis and what characterizes each?

Back 110

Adhesive mediastinopericarditis: pericardial sac is obliterated and the parietal layer is tethered to mediastinal tissue, leading to a strain on cardiac function; may follow suppurative/caseous pericarditis, cardiac surgery, irradiation to the mediastinum;
Constrictive pericarditis: heart is encased in dense fibrous/fibrocalcific sac, limiting diastolic expansion, restricting cardiac output; resembles a restrictive cardiomyopathy

Front 111

What characterized rheumatic heart disease?

Back 111

The most common finding is fibrinous pericarditis; there may be rheumatoid granulomatous nodules in the myocardium, endocardium, valves, and the root of the aorta

Front 112

In a normal heart, which horizontal lead would show the largest depolarization?

Back 112

Either V4 or V5

Front 113

How does a right bundle branch block (RBBB) show up on EKG?

Back 113

Widened QRS (>0.12 sec); rsR’ pattern in V1 (double peak)

Front 114

What defines a third degree heart block?

Back 114

No relation between atrial and ventricular activity (requires pacemaker)

Front 115

What defines a second degree heart block, Mobitz Type II?

Back 115

QRS wave dropped without PR interval lengthening (extreme bradycardia, requires pacemaker)

Front 116

What defines a second degree heart block, Mobitz Type I (Wenckebach)?

Back 116

PR interval lengthening until a QRS wave is dropped (causes mild bradycardia)

Front 117

What defines a first degree AV block?

Back 117

PR interval > 0.2 seconds; is not associated with any complications except in patients who are taking beta-blockers or calcium-channel blockers (since they can worsen the AV block)

Front 118

What must be present to call something a sinus rhythm?

Back 118

Upright p-wave in lead II (except in dextrocardia) that is related to the QRS complex

Front 119

Why do both depolarization and repolarization of the heart show up as positive deflections on EKG?

Back 119

Depolarization is a “positive deflection” flowing towards the electrode, whereas repolarization is a “negative deflection” flowing away from the electrode (two negatives make a positive)

Front 120

What are the various waves seen on EKG associated with?

Back 120

P wave: depolarization of the atria; QRS complex: ventricular depolarization; T wave: ventricular repolarization

Front 121

In a normal heart, which vertical lead would show the largest depolarization?

Back 121

Lead II, since it is oriented in the same direction as that of normal depolarization

Front 122

What is the difference in atrial fibrillation and atrial flutter?

Back 122

Atrial fibrillation: rapid, irregular P waves originating from many sites on the atrium;
Atrial flutter: fewer sites that generate P waves are present, leading to a more organized, “saw-tooth” appearance on EKG

Front 123

Where is the indeterminate axis?

Back 123

Between 180° and 270°

Front 124

What are causes of right axis deviation (axis between 90° and 180°)?

Back 124

Right ventricular hypertrophy, significant myocardial infarction, dextrocardia, posterior hemiblock

Front 125

What are causes of left axis deviation (axis between 0 and -90°)?

Back 125

Left ventricular hypertrophy, anterior hemiblock

Front 126

What is meant by a rhythm described as bigeminy?

Back 126

Alternating supraventricular/ventricular rhythms

Front 127

What does a junctional rhythm look like on EKG?

Back 127

Narrow QRS, no obvious atrial activity (check lead II), rate around 60 bpm (since the rhythm originates from the AV node)

Front 128

What is the defect with a wandering pacemaker?

Back 128

The site of the controlling pacemaker shifts from beat to beat, leading to changes in the P wave (switches from upright to inverted, and back)

Front 129

How does a left bundle branch block (LBBB) show up on EKG?

Back 129

Widened QRS (>0.12 sec); Completely upright QRS in V6 and I

Front 130

What is seen on EKG with atrial fibrillation?

Back 130

Rapid and irregular rhythm

Front 131

What clinical implications are associated with atrial fibrillation/flutter?

Back 131

Rapid ventricular response (= decreased filling, decreased output, increased oxygen demand);
Loss of atrial contraction (aka atrial “kick” = decreased ventricular filling, decreased output);
Risk of embolic events from stagnant atria

Front 132

Which leads are used to find atrial abnormalities and what is considered abnormal?

Back 132

Lead II and V1/V2; Abnormal: wide, tall, double-peaked or biphasic P waves

Front 133

What are the lateral leads?

Back 133

AVL/I/V5/V6

Front 134

What are the septal and anterior leads, respectively?

Back 134

Septal: V1/V2; Anterior: V2/V3/V4

Front 135

Which leads are associated with the bottom of the heart?

Back 135

III/AVF/II

Front 136

What are the characteristics of ischemia, injury, and infarction on EKG, respectively?

Back 136

Ischemia: T wave inversion; Injury: ST segment elevation; Infarction: larger Q waves

Front 137

What is an indication of right ventricular hypertrophy on EKG?

Back 137

Tall R in V1 (where you would expect a deep S)

Front 138

What is the calculation for left ventricular hypertrophy?

Back 138

Height of S in V1 + Height of R in V5/V6 (whichever is larger) > 35mm (patient has to be over 35 years of age)

Front 139

What does a net positive deflection in lead I indicate?

Back 139

Patient is either WNL or has a LAD; a net negative deflection would indicated RAD or indeterminate axis

Front 140

How is the actual axis determined once the correct quadrant has been identified?

Back 140

Find the isoelectric point and move 90° into the correct quadrant

Front 141

What would a net positive deflection in AVF indicate?

Back 141

Patient is either WNL or has a RAD; a net negative deflection would indicate LAD or indeterminate axis

Front 142

What are the posterior leads?

Back 142

V1/V2 – looking for ST depression and a tall R

Front 143

What does ST depression in V1/V2 without any other abnormalities mean?

Back 143

Subendocardial infarction

Front 144

What is the blood supply associated with each of the leads?

Back 144

Inferior (III/AVF/II): right coronary or LAD; Septal (V1/V2): LAD; Anterior (V2/V3/V4): LAD; Lateral (AVL/I/V5/V6): circumflex; Posterior (V1/V2): right coronary

Front 145

How do agonistic effects differ between NE, Epi, and Isoproterenol (Iso) on the β-receptor and what are the β-receptor subtypes?

Back 145

Iso > Epi ≥ NE; consist of β1 (Epi = NE), β2 (Epi > NE), β3-subtypes (Iso = NE > Epi)

Front 146

What are the effects of catecholamines on other cardiac cells?

Back 146

Shorten the effective refractory period (i.e. channel inactivation) and shorten action potential duration: lead to arrhythmias; Increase [Ca2+]i leading to an increase in contractility

Front 147

What are the effects of catecholamines on pacemaker and latent pacemaker cells of the heart?

Back 147

Increase phase 4 depolarization (more rapid succession of APs = increased HR); Increase phase 0 depolarization (increased conduction velocity)

Front 148

What adrenoceptor is involved mainly in metabolic effects?

Back 148

β2

Front 149

What location in the body has β3 receptors?

Back 149

Fat cells, stimulation causes activation of glycolysis

Front 150

What are the actions of the catecholamines on cardiac muscle and smooth muscle, respectively?

Back 150

Cardiac muscle (β1): excitation, causing an increase in contractility, HR, and conduction velocity; Smooth muscle: vasoconstriction of arterioles/pre-capillary sphincters/veins (via α1 and α2), vasodilation of skeletal/visceral beds (β2), pupillary dilation (α1), airway smooth muscle relaxation (β2), renin release (stimulation: β1, inhibition: α2), transmitter release inhibition (α2)

Front 151

Besides stimulating Dopamine receptors, what other receptor does DA have an effect on?

Back 151

β1-receptors

Front 152

What are the sympathomimetic amines and how do they function?

Back 152

DA, NE, Epi; their action mimics the effects of stimulating the sympathetic nervous system

Front 153

How do agonistic effects differ between NE, Epi, and Isoproterenol (Iso) on the α-receptor and what are the α-receptor subtypes?

Back 153

Epi ≥ NE >> Iso; consist of α1-receptors (A, B, D) and α2-receptors (A, B, C)

Front 154

What kinds of receptors are adrenoceptors and why is that important?

Back 154

G-protein coupled receptors: are able to detect very small differences between similar molecules

Front 155

What receptor is important in renal vascular beds (as well as coronary/cerebral)?

Back 155

D1 receptor: DA causes dilation

Front 156

What are the effects of Phenylephrine on diastolic/systolic BP and HR?

Back 156

Phenylephrine: causes vasoconstriction via α-receptors which increases diastolic and systolic pressures equally, which causes a decrease in HR due to the baroreceptor reflex (it has no direct effect on the heart)

Front 157

What is the α- and β-specificity of the agonists Phenylephrine, NE, Iso, and Epi?

Back 157

Phenylephrine: α1
NE: α1, α2, β1
Iso: β1, β2
Epi: α1, α2, β1, β2

Front 158

Where are stretch receptors located and what happens when BP increases?

Back 158

Carotid sinus and aortic arch; Increased BP stretches the receptors, which increases firing of afferents to the CNS

Front 159

What effect does the sympathetic nervous system have on blood pressure?

Back 159

Heart: increased HR and increased force of contraction (--> increased SV) will increase CO which leads to an increase in BP; Arterioles: increases vasoconstriction --> increased TPR --> increased BP; Veins: increased vasoconstriction --> increased venous return --> increased SV --> increased CO --> increased BP

Front 160

What effect does the parasympathetic nervous system have on blood pressure?

Back 160

It decreases HR (via the vagus nerve), which decreases CO, which leads to a decrease in BP; blood pressure is not affected by parasympathetic effects on the arterioles/veins (face, larynx, etc.)

Front 161

What factors affect mean arterial blood pressure?

Back 161

BP = CO x TPR; CO is dependent on HR and stroke volume, TPR is dependent on arteriolar radius and blood viscosity (not of much importance)

Front 162

Which value gives an indication of total peripheral resistance?

Back 162

Diastolic blood pressure

Front 163

What two toxicities of catecholamines can lead to arrhythmias?

Back 163

Activation of latent (ectopic) pacemakers; Shortened effective refractory period (ERP)

Front 164

What is the difference in adrenoceptors present on the vascular beds in skin, splanchnic, and skeletal systems?

Back 164

Skin: α1, α2 (Epi/NE cause constriction, Iso has no effect); Splanchnic: α1, α2, some β2 (Epi/NE cause constriction, Iso causes weak dilation); Skeletal: α1, α2, β2 (Epi/Iso cause dilation via β2, NE causes constriction since it has little effect on β2 receptors)

Front 165

What are the effects of NE on diastolic/systolic BP and HR?

Back 165

NE: diastolic pressure increases but systolic pressure increases more (since it also increases cardiac contractility via β-receptors), HR goes down due to baroreceptor reflex (despite increases in contractility)

Front 166

Which G-protein is activated by α2 agonists and what are the effects of this activation?

Back 166

Gi-protein: activation of Gi causes inhibition of adenylate cyclase whereas activation of the β- and γ-subunits of Gi-protein cause opening of K+ channels and closure of Ca2+ channels (thus leading to decreased neurotransmitter release in adrenergic neurons)

Front 167

Which G-protein is activated by α1 agonists and what are the effects of this activation?

Back 167

Gq-protein: directly activates MAP/PI-3 kinase, open calcium channels, and causes activation of phospholipase C which leads to hydrolysis of PIP2 forming DAG (activation of protein kinase C) and IP3 (raises intracellular calcium)

Front 168

Which G-protein is activated by β1/β2 agonists and what are the effects of this activation?

Back 168

Gs-protein: directly opens calcium channels (in cardiac muscle) and activates adenylate cyclase (which leads to a number of down-stream events such as the production of glucose)

Front 169

What is responsible for the fact that the diastolic pressure in response to Epi drops below the baseline level after its initial increase?

Back 169

As the concentration of Epi falls (i.e. as it is being metabolized), the preponderant effect of Epi is on the β-receptors, leading to a more significant drop in diastolic pressure (due to skeletal muscle vasodilation)

Front 170

What are the effects of Epi on diastolic/systolic BP and HR?

Back 170

Epi: causes a small increase in diastolic pressure (due to α-receptors) and a greater increase in systolic pressure (due to α- and β-receptors); although these pressures are increased, the baroreceptor reflex is countered by Epi’s potent effect on β-receptors of the heart which lead to increases in contractility and HR – Epi effects on diastolic pressure are dose-dependent

Front 171

What are the effects of Isoproterenol on diastolic/systolic BP and HR?

Back 171

Iso: causes a decrease in diastolic and systolic pressures (diastolic drop > systolic drop) due to skeletal muscle vasodilation combined with increases in contractility – HR is increased due to the baroreceptor reflex and direct cardiac stimulation

Front 172

What is required chemically for direct action of a compound on adrenoceptors?

Back 172

At least 2 OH groups among positions 3, 4, and the β-carbon – Dopamine is the exception

Front 173

What kinds of compounds can displace and release NE from storage vesicles?

Back 173

α-CH3 compounds (phenylisopropylamines)

Front 174

What is required for metabolism by MAO?

Back 174

NH2 group; no substitutions are allowed on the α-carbon, nor are substitutions of more than 2 carbons on the NH2

Front 175

What is required for metabolism by COMT?

Back 175

Both 3’ and 4’ OH groups – amphetamine and ephedrine are not substrates

Front 176

What substitution confers isomerism?

Back 176

β-carbon substitutions; most agonists are more potent as l-isomers; β-carbon substitutions may be required for storage of catecholamines (DA is the exception)

Front 177

What happens when adding bulk to the amino terminal of adrenoceptor agonists?

Back 177

2 or more carbon atoms will confer β-specificity – Phenylephrine somewhat violates that principle

Front 178

What does loss of the 4’ OH group confer?

Back 178

α-selectivity; whereas the presence of a 4’ OH group increases β-selectivity – the presence of a 5’ OH group specifically increases β2-selectivity

Front 179

What is the adrenoceptor specificity of Albuterol and Terbutaline?

Back 179

High affinity for β2 receptors (moderate β1)

Front 180

What is the adrenoceptor specificity of Dobutamine?

Back 180

High affinity for β1 receptors (moderate α1)

Front 181

What is the adrenoceptor specificity of Clonidine and α-Methyl NE?

Back 181

High affinity for α2 receptors (moderate α1)

Front 182

What is the mechanism of action of Botulinum toxin?

Back 182

It is a protease that is taken up into the presynaptic terminal of cholinergic neurons and interferes with the docking of ACh vesicles required for their release – only need one copy of the protease per nerve terminal to completely block ACh release

Front 183

Which cholinergic receptors are found on the adrenal glands and sweat glands, respectively?

Back 183

Adrenal glands: NN; Sweat glands: M3

Front 184

Which muscarinic receptors are found on postganglionic autonomic targets and what is their purpose?

Back 184

M1, M3: cause slow modulatory excitation of the response to NN activation

Front 185

How can the muscarinic receptors be divided up and what actions are associated with each class?

Back 185

Odd-numbered receptors (M1, M3, M5): activate Gq-protein leading to activation of calcium-dependent processes (e.g. contraction of smooth muscle, secretion); Even-numbered receptors (M2, M4): activate Gi-protein leading to activation of adenylate cyclase (which leads to a decrease of cAMP) and opening of K+ channels (e.g. hyperpolarization of heart SA/AV nodes)

Front 186

What are the two types of nicotinic receptors and what is their pharmacologic difference?

Back 186

NN: located on nerves, can be blocked by hexamethonium; NM: located on muscle, can be blocked by curare

Front 187

What describes the nicotinic receptors?

Back 187

Na+ channel that opens in response to the binding of two ACh molecules – continuous binding of ACh will cause a rapid desensitization, leading to closure of the channel

Front 188

What is a common clinical application of Botulinum toxin?

Back 188

Botox, used to fight wrinkles and muscle spasms

Front 189

How is ACh synthesized?

Back 189

By choline acetyltransferase (CAT) which combines acetyl CoA (synthesized in mitochondria) and choline (obtained by uptake from the extracellular space or by release from phophatidylcholine, a membrane phospholipid)

Front 190

What is the only way that the action of ACh is terminated in the synaptic cleft?

Back 190

By its degradation through acetylcholinesterase (AChE) bound to synaptic membranes – ACh can diffuse from the synaptic cleft and be degraded by plasma cholinesterases as well

Front 191

What happens after ACh is degraded by AChE?

Back 191

Choline is taken back up into the nerve terminal and is recycled

Front 192

Which cholinergic receptor type is involved in memory?

Back 192

Muscarinic receptors – whereas the NN receptor is involved in addiction to nicotine via pre-synaptic modulation

Front 193

What characterizes the function of Methacholine?

Back 193

It is ACh with an added methyl group; this causes it to be degraded slowly and be specific for muscarinic receptors only – the only clinical use it has is in diagnosing asthma; the drug is inhaled and if the person has had a break in the bronchial lining (i.e. due to developing asthma) they will have a strong response to the Methacholine and have trouble breathing

Front 194

Why is therapeutic ACh not very helpful?

Back 194

It is rapidly degraded by AChE and it is not specific for either nicotinic or muscarinic receptors – however, it can be useful for dilation of the eye

Front 195

What is the key difference between direct- and indirect-acting cholinomimetic drugs?

Back 195

Direct: ACh agonists; Indirect: AChE inhibitors

Front 196

What differentiates the cardiac effects of a muscarinic agonist in low and high dose?

Back 196

Low dose: tachycardia due to the response to dilation of vasculature; High dose: bradycardia due to the decreased rate of impulse generation and conduction in the SA/AV nodes

Front 197

What do presynaptic nicotinic/muscarinic receptors lead to?

Back 197

A decrease in the release of ACh

Front 198

Which cholinergic receptor type is found on the vascular endothelium and what is the associated effect?

Back 198

M3: leads to the release of NO with subsequent vascular smooth muscle release

Front 199

What does activation of muscarinic receptors lead to on the iris and the lens?

Back 199

Iris: contraction of pupillary sphincter muscle (miosis); Lens: contraction of ciliary muscle (accommodation to near vision)

Front 200

Which muscarinic receptor type is responsible for the calcium-dependent smooth muscle contraction and secretory gland secretion?

Back 200

M3

Front 201

Which muscarinic receptor type is responsible for the hyperpolarizing effects on the SA/AV nodes and the atria?

Back 201

M2

Front 202

How does Cevimeline function?

Back 202

As a M1, M3 agonist it can cause secretion from salivary glands and be used to treat xerostomia

Front 203

What are the reversible inhibitors of AChE used in the treatment of Alzheimer’s disease?

Back 203

Tacrine (no longer used), Donepezil, Galantamine, Rivastigmine – although they significantly improve the symptoms of early Alzheimer’s patients, they do not alter the course of the disease

Front 204

What are characteristics of irreversible AChE inhibitors and what drugs belong to this classification?

Back 204

Low molecular weight, lipid-soluble compounds that readily enter the CNS; they bind to the esteratic site on AChE with covalent attachment of a phosphate group to the enzyme’s active site; Examples: DFP (Isoflurophate), Echothiophate (only one used clinically), Parathion (insecticide, common with poisoning on the farm), Soman (nerve gas), Sarin (nerve gas) – treatment is possible with Pralidoxime (2-PAM), but must be done quickly before “aging” of the inhibited AChE occurs

Front 205

By what mechanism do the Carbamate inhibitors function and what is specific about each?

Back 205

These compound contain a carbamyl ester linkage that is hydrolyzed by AChE; after this hydrolysis, AChE will be carbamoylated and will not be able to hydrolyze ACh; this effect lasts 3-4 hours – Physostigmine: can enter CNS; Pyridostigmine/Neostigmine: cannot enter CNS; Carbaryl: pesticide

Front 206

What are the competitive antagonists of AChE and how are they used clinically?

Back 206

Edrophonium: used to help diagnose Myasthenia Gravis (patients will regain muscle strength upon administration, very short-term effect); Ambenonium: longer effect, used in the treatment of Myasthenia Gravis – both drugs do not contain an ester linkage and are not hydrolyzed

Front 207

By what mechanism does AChE cause the breakdown of ACh?

Back 207

AChE is a serine esterase; its anionic site attracts the positively-charged quarternary ammonium group of ACh and its esteratic site binds the acetyl portion causing hydrolysis by nucleophilic attack; After degrading ACh, AChE is acetylated, but rapid hydrolysis causes release of the acetyl group, regenerating the free enzyme

Front 208

What are the naturally-occurring cholinomimetics and what characterizes each?

Back 208

Muscarine: selective agonist of muscarinic receptors, found in certain mushrooms;
Pilocarpine: selective agonist of muscarinic receptors, useful for the treatment of open-angle glaucoma (can trigger immense sweating when taken systemically);
Nicotine; selective agonist of nicotinic receptors, found in tobacco

Front 209

What characterizes the function of Carbachol?

Back 209

Substitutes a methyl group on ACh by an amino group; Not degraded by AChE; Not specific for either nicotinic or muscarinic receptors – its only clinical use is in treating open-angle glaucoma

Front 210

Why should direct-acting cholinomimetic drugs not be allowed to enter systemic circulation?

Back 210

They will act on the vascular endothelium and cause a dangerous drop in blood pressure

Front 211

What characterizes the function of Bethanechol?

Back 211

Combines both modifications seen in Methacholine and Carbachol, thus causing it to not be degraded by AChE yet be specific for muscarinic receptors – clinical uses include treatment of post-operative abdominal distention, promote gastric motility, promote voiding of bladder

Front 212

Why are AChE inhibitors sometimes preferred over a drug like Bethanechol?

Back 212

They do not have the effect of systemic activation of muscarinic receptors on the vascular endothelium

Front 213

Which muscarinic antagonist is used to treat some of the symptoms of Parkinson’s disease?

Back 213

Benztropine

Front 214

Which muscarinic antagonist is used to prevent motion sickness?

Back 214

Scopolamine (must be used prophylactically)

Front 215

What are synthetic muscarinic antagonists and what are they used for?

Back 215

Ipratropium, Tiotropium: quarternary ammonium salts used as inhalants for the treatment of COPD (same effects as atropine but without inhibition of mucociliary clearance);
Homatropine, Cyclopentolate, Tropicamide: shorter-acting production of mydriasis/cycloplegia;
Darifenacin, Solifenacin: selective M3 receptor antagonist used for the treatment of incontinence

Front 216

What effects do Atropine and Scopolamine have, other than CNS effects?

Back 216

Eye: mydriasis, cycloplegia (paralyzes accommodation), increases intraocular pressure;
Heart: tachycardia (with strong vagal tone – i.e. young people), blocks vasodilation/hypotension; GI: block of salivary secretion, block of gastric acid secretion (high dose), inhibition of peristalsis; Respiratory tract: bronchodilation, inhibits secretions and mucociliary clearance;
Urinary tract: urinary retention; Skin: inhibits sweating

Front 217

What are the Belladonna Alkaloids and how do they function?

Back 217

Atropine, Scopolamine; they are competitive antagonists of muscarinic receptors; Scopolamine enter the CNS more readily and produces CNS depression (low dose) or CNS excitation (high dose); Atropine can have a very long duration of effect (~1 week)

Front 218

What can be used in the treatment of AChE inhibitor poisoning?

Back 218

Atropine: block muscarinic receptors; Respiratory support; 2-PAM: for reactivation of phosphorylated AChE (2-PAM does not enter the CNS)

Front 219

What are the three classes of effects of AChE inhibitors?

Back 219

Muscarinic stimulation of organs; Stimulation/block of ganglionic/neuromuscular transmission; Stimulation/block of cholinoceptors in the CNS

Front 220

What is the most dangerous effect of AChE inhibitors?

Back 220

Paralysis of the diaphragm

Front 221

What are therapeutic uses of AChE inhibitors?

Back 221

Atony of the GI tract and urinary bladder; Glaucoma; Myasthenia Gravis; Termination of the effects of competitive neuromuscular blocking agents; Atropine poisoning; Alzheimer’s disease

Front 222

What are contraindications and toxicities associated with muscarinic antagonists?

Back 222

Contraindications: narrow-angle glaucoma; Toxicities: can aggravate cognitive problems in the elderly, and increase the risk of hyperthermia (unable to sweat)

Front 223

What are the two classes of Neuromuscular Junction (NMJ) blocking drugs?

Back 223

Non-depolarizing antagonists: d-Tubocurare, Pancuronium, Vecuronium, Atracurium; they competitively block the binding of ACh to the NM receptor, causing weakness/paralysis –
Depolarizing antagonists: Succinylcholine (2x ACh); causes persistent stimulation of NM receptors, leading to muscular fasciculations followed by weakness/paralysis

Front 224

What therapeutic uses are associated with NMJ blocking drugs and what are some associated adverse effects?

Back 224

Relax skeletal muscle and reduce the dose of anesthesia required; Relax skeletal muscle in orthopedic procedures; Facilitate intubation – Adverse effects: prolonged apnea, electrolyte imbalance due to excessive release of K+ (depolarizing antagonists only)

Front 225

What is the difference between Phenylephrine and Oxymetazoline in treating nasal congestion?

Back 225

Phenylephrine treats nasal congestion by working on the nasal veins (α1-selective), whereas Oxymetazoline works on the nasal arterioles (α2-selective)

Front 226

What is unique about Amphetamine and what is it used for?

Back 226

It is more potent in its dextro-form; used for appetite suppression, but has a high abuse potential

Front 227

What is the isomer of Ephedrine and what is it used for?

Back 227

Pseudoephedrine; used for nasal congestion (has less CNS activity and less β activity than Ephedrine)

Front 228

Besides its indirect effects, what direct effects are seen with Ephedrine and what is it used for clinically?

Back 228

Ephedrine has α and β activity; it is used for postural hypotension

Front 229

What are the main uses of indirectly-acting sympathomimetics?

Back 229

Alerting, sleep deferring; Narcolepsy; Appetite suppression; ADHD – since these drugs release NE, they can increase HR and BP (also, tolerance may develop)

Front 230

What is Ritodrine given for?

Back 230

It is β2-selective and is given IV as a uterine relaxant in premature labor

Front 231

What is the key difference from Terbutaline and Albuterol?

Back 231

β2-selectivity in Terbutaline is due to a 5’ OH group whereas β2-selectivity in Albuterol is due to a 4’ OH group

Front 232

What is the adrenoceptor specificity of Methoxamine and what is it used for?

Back 232

α1-selective; used for hypotensive emergencies

Front 233

How do the different isomers of Dobutamine differ in effect and what is a racemic mixture used for?

Back 233

+ isomer: β1-agonist, α1-antagonist
- isomer: α1-agonist; racemic mixture: α1 effects cancel out and β1 effect remains, used as a + inotropic drug in end-stage CHF

Front 234

How does Clonidine cause its antihypertensive effects?

Back 234

As a α1-selective agonists in the CNS; also has some peripheral effects which lower HNT, but they are not as significant as the central effects

Front 235

What adverse effect occurred with Phenylpropanolamine?

Back 235

Hemorrhagic stroke (taken off the market)

Front 236

What is Phenoxybenzamine’s main site of action and what other actions does it have?

Back 236

Main site: α-receptors (α1 > α2); Other actions: inhibits ACh, 5-HT, Histamine receptors, and blocks uptake I and II

Front 237

What commonality in name do α1-specific antagonists have and what can happen with these drugs when given in high doses?

Back 237

“-osin” as in Prazosin; At high doses they can cause cyclic nucleotide PDE inhibition which causes vasodilation, leading to orthostatic hypotension

Front 238

What is the key difference between Prazosin and Phentolamine/Phenoxybenzamine?

Back 238

Prazosin is α1-specific and will therefore not cause the release of NE associated with α2 antagonists

Front 239

How does Phentolamine differ from Phenoxybenzamine?

Back 239

It is equilibrium competitive and has equal affinity for α1 and α2; other actions include inhibition of 5-HT and histamine receptors, release of histamine (causes GI disturbances), it has some α efficacy and cholinomimetic activity; It’s hemodynamic effects are the same as Phenoxybenzamine except Phentolamine has a greater effect on NE release

Front 240

What are the indications for Phenoxybenzamine?

Back 240

Pheochromocytoma, Peripheral vascular disease (Raynaud’s)

Front 241

What adverse reactions are seen with Phenoxybenzamine?

Back 241

Orthostatic hypotension, tachycardia (due to baroreceptor reflex/α2 antagonism), miosis, nasal stuffiness, inhibited ejaculation

Front 242

What hemodynamic effects are seen with Phenoxybenzamine?

Back 242

Decrease in TPR/BP; Venodilation; Orthostatic hypotension; Cardiac stimulation: increased HR/contractility (baroreceptor reflex), increase in NE release (due to α2 antagonism)

Front 243

What is the α-receptor antagonist selectivity of Phentolamine, Phenoxybenzamine, Prazosin, and Yohimbine?

Back 243

Phentolamine: α1, α2; Phenoxybenzamine: α1, α2; Prazosin: α1; Yohimbine: α2

Front 244

What kind of antagonism is associated with Phenoxybenzamine and does this mean for its duration of action?

Back 244

Nonequilibrium competitive (i.e. irreversible covalent bond formation with receptors); has a long duration of action (days)

Front 245

What is Yohimbine used for?

Back 245

Impotence, although not much since there are better drugs available

Front 246

What are the indications of α1-specific antagonists?

Back 246

Mild to moderate hypertension; BPH

Front 247

What are the ergot alkaloids and what is their use in medicine?

Back 247

An old class of drugs with complex pharmacology (function as α-adrenoceptor antagonists); Ergotamine and Dihydroergotamine are used for the treatment of migraine (due to their interaction with 5-HT and DA receptors); Ergonovine is used in post-partum hemorrhage (due to its vasoconstrictive effects)

Front 248

What happens when Epi is given after a person has taken Phentolamine?

Back 248

It functions solely as a β-receptor agonist (like Isoproterenol) since the Phentolamine has block both α-receptors

Front 249

What is special about Tamsulosin (Flomax)?

Back 249

It is specific for the α1A-receptors which are clustered on the urinary bladder base and prostate smooth muscle, leading to a smaller incidence of vascular side effects

Front 250

What is the β-adrenoceptor selectivity for Propranolol, Metoprolol, Butoxamine, and Labetalol?

Back 250

Propranolol: β1, β2; Metoprolol: β1; Butoxamine: β2; :Labetalol: α1, β1

Front 251

What characterizes Pindolol?

Back 251

Some membrane-stabilizing activity; Slight agonist activity (may produce smaller fall in HR/BP)

Front 252

How does Nadolol compare to Propranolol?

Back 252

It is longer-acting; It has no membrane-stabilizing activity; like, Propranolol it does not have any agonist activity

Front 253

In what patient population is Propranolol contraindicated?

Back 253

Patients with asthma (since it is an antagonist of β2)

Front 254

How does Propranolol function as an anti-arrhythmatic?

Back 254

It is a membrane stabilizer and blocks β-receptors – also used as an anti-hypertensive agent and to decrease contractility

Front 255

Besides blocking β-receptors, what other actions may be seen with beta-adrenoceptor antagonists?

Back 255

Stimulate β-receptors as partial agonists, exhibit partial agonism, elicit NO release from endothelium (decrease BP), as antioxidants, block Ca2+ channels, block α-receptors

Front 256

What is the clinical use of Labetalol?

Back 256

It is used as an anti-hypertensive; the α1-blocker component causes vasodilation and thus a reduction in BP; the β1-blocker subsequently prevents the heart from becoming tachycardic in response to the baroreceptor reflex (i.e. there is a drop in BP without an increase in HR) – Labetalol has a slight β2 agonist activity

Front 257

What direct effects on the heart are seen with β1-antagonists?

Back 257

Slowed AV-conduction; Decreased phase 4 depolarization; Decreased contractility (due to antagonist or inverse agonist activity); Decreased SV, Increased residual volume; Decreased velocity of contraction; Decreased CO; Decreased oxygen consumption

Front 258

What is particular about the use of Esmolol (β1-selective antagonist)?

Back 258

It is fast acting and has a short duration of action, making it useful for the minute-minute control of hypertension

Front 259

How does Metoprolol function?

Back 259

It is a selective β1-antagonists that has no agonist activity, but has very strong inverse agonist activity

Front 260

What is Metoprolol used for?

Back 260

CHF, HTN, myocardial ischemia

Front 261

What additional effect of Carvedilol functions as an important pharmacological effect?

Back 261

It’s antioxidant activity

Front 262

What is the β:α selectivity of Carvedilol?

Back 262

10:1 – it has the same effect as Labetalol but is much more efficient; used for the treatment of CHF; (Carvedilol is a weak inverse agonist)

Front 263

What is the function of Timolol (non-selective β-adrenoceptor antagonist)?

Back 263

Reduction of anterior-chamber pressure in glaucoma (has no membrane-stabilizing activity or agonist effect)

Front 264

What is the difference between the SR- and RR-isomers of Labetalol?

Back 264

SR isomer: α1-blocker; RR isomer: β1-, β2-blocker – β:α = 1.5:1

Front 265

What peripheral cardiovascular effects are seen with β1-antagonists?

Back 265

Decreased BP (due to decreased CO); Decreased Renin release --> decreased Angiotensin II in blood; Decreased GFR --> Na+ retention and edema – (there is also a decrease in lipolysis)

Front 266

What side effects are associated with β-adrenoceptor antagonists?

Back 266

Rebound ischemia (long-term use increases the number of β-receptors, so sudden discontinuation can lead to this problem); Tiredness; Vivid dreams; Insomnia; Hallucinations; Exercise intolerance

Front 267

What contraindications are associated with β-adrenoceptor antagonists?

Back 267

CHF (severe); Asthma; AV-node conduction disturbances; Hypoglycemia

Front 268

What are other uses associated with β-adrenoceptor antagonists?

Back 268

CHF (mild); Hyperthyroidism; Performance anxiety

Front 269

What are the primary uses of β-adrenoceptor antagonists?

Back 269

Myocardial ischemia; MI; Supra-ventricular arrhythmias; HTN (CNS, ↓ Renin, ↓ CO); Glaucoma

Front 270

What are the effects of β2-antagonists?

Back 270

Vasoconstriction in skeletal beds; Bronchoconstriction; Decreased glycogenolysis; Decreased recognition of hypoglycemia; Decreased Insulin release

Front 271

What characterizes the synthesis pathway of Epinephrine?

Back 271

Tyrosine --> Dopa --> DA --> NE --> Epi

Front 272

What characterizes the mesolimbic pathway?

Back 272

Connect ventral tegmental area and limbic regions; Control affect, emotion, cognition; Excess activity causes schizophrenia; Stimulation is associated with award and addiction; Insufficient activity is seen with ADHD and depression

Front 273

What characterizes the nigrostriatal pathway?

Back 273

Project from substantia nigra to neostriatum; Involved in control of posture/voluntary movement; Loss occurs in Parkinson’s disease

Front 274

What are the isoforms of MAO?

Back 274

MAO-A: found in liver and catecholamine brain regions;
MAO-B: found in 5-HT brain regions and in the periphery (more selective for DA)

Front 275

What are the substrates of MAO and where is it found?

Back 275

Many types of amines – found in liver, and in mitochondria of nerve terminals/post-synaptic cells

Front 276

What are the substrates of COMT and where is it found?

Back 276

DA, NE, Epi, Levodopa – found in postsynaptic neurons and glia, as well as in the liver

Front 277

How is the activity of catecholamines terminated?

Back 277

Reuptake, breakdown by COMT, breakdown by MAO

Front 278

What is the difference between metabotropic and ionotropic receptors?

Back 278

Metabotropic: GPCR, slow response; Ionotropic: Ion channel receptor, fast response

Front 279

What characterizes Acetylcholine (ACh)?

Back 279

Project from ventral forebrain to cerebral cortex and hippocampus; Role in cognitive function and memory: loss in Alzheimer’s, Huntington’s; Role in control of movement: loss of DA neurons that inhibit ACh release in striatum (Parkinson’s), excess activates M1 receptors causing tremor

Front 280

What are the receptor subtypes for ACh in the CNS?

Back 280

M1, M3: metabotropic, excitatory; M2, M4: metabotropic, inhibitory; Nicotinic: ionotropic (cation channel), excitatory

Front 281

In what diseased states is impaired function of NE seen?

Back 281

ADHD, depressive disorders, anxiety disorders

Front 282

What characterizes GABA?

Back 282

Found throughout the brain and brainstem, major inhibitory neurotransmitter in the CNS

Front 283

What are the Histamine receptor subtypes in the CNS?

Back 283

H1: on neurons/blood vessels/glia, excitatory, sedation from antihistamines due to H1 antagonism;
H2: function unknown

Front 284

What characterizes Histamine?

Back 284

Project from hypothalamus to many brain areas; Involved in arousal, body temperature, vascular dynamics – maintain awake state

Front 285

What receptor subtypes are associated with 5-HT?

Back 285

5-HT1A: on somatodendritic autoreceptors, decreases neuronal firing, altered by SSRIs/anxiolytics;
5-HT1D: pre-synaptic, decreases 5-HT release, altered by antimigraine drugs (↓ pain perception);
5-HT1-7: post-synaptic; 5-HT2A: excitatory post-synaptic, excess activity in schizophrenia;
5-HT3: ionotropic, cation channel, postsynaptic excitatory, chemoreceptor trigger zone (n/v)

Front 286

What characterizes Serotonin (5-HT)?

Back 286

Project from dorsal raphe nucleus to amygdala, hippocampus, cerebral cortex; Associated with mood, fear/anxiety, emotional memory; Excess activity seen with schizophrenia; Impaired function seen with depressive and anxiety disorders – other projections to the spinal cord are involved in inhibition of physiological sexual responses; 5-HT receptors on the vagus and chemoreceptor trigger zone stimulate nausea/vomiting

Front 287

What are the receptor subtypes of NE in the CNS?

Back 287

α1: metabotropic, excitatory postsynaptic receptors; α2: metabotropic, presynaptic autoreceptors (decrease Ca2+ influx), inhibitory postsynaptic receptors; β: metabotropic, postsynaptic excitatory

Front 288

What characterizes the tuberoinfundibular pathway?

Back 288

DA inhibits prolactin secretion

Front 289

What distinguishes the D1/D1-like receptors from the D2/D2-like receptors?

Back 289

D1/D1-like receptors: GPCR, stimulate activity of adenylate cyclase, found post-synaptically;
D2/D2-like receptors: GPCR, inhibits activity of adenylate cyclase, found post-synaptically, as well as pre-synaptically and as somatodendritic autoreceptors (i.e. on the neuron cell body)

Front 290

What characterizes NE?

Back 290

Cell bodies located in locus ceruleus, project to cerebral cortex/thalamus/hypothalamus/ cerebellum/spinal cord; Released in response to external stimuli, arousal/attention, learning, memory, mood

Front 291

What characterizes Glycine?

Back 291

Released by interneurons, mainly in the spinal cord and brainstem; Inhibitory, involved in pain transmission/respiration/motor coordination – there are multiple subtypes with multiple subunits; ionotropic subtype binding causes hyperpolarization; Strychnine (a convulsant) is an antagonist

Front 292

What are the receptor subtypes of Endocannabinoids in the CNS?

Back 292

CB1: metabotropic, inhibitory, marijuana effects – CB1 antagonists are used for obesity and smoking cessation

Front 293

What characterizes the Endocannabinoids?

Back 293

Anandamide and others; Found throughout the CNS and body; Regulate mood/appetite/pain sensation/smooth muscle tone in GI/immune function

Front 294

What are the receptor subtypes of Opioid peptides in the CNS?

Back 294

Mu: narcotic analgesia (most); causes respiratory depression; Kappa: narcotic analgesia (some), dysphoria, less respiratory depression; Delta; Epsilon – all are metabotropic, inhibitory

Front 295

What characterizes the Opioid peptides?

Back 295

Enkephalins, β-endorphin, dynorphin, endomorphins; Found throughout the CNS; Opioids decrease pain perception/respiration/consciousness level; Opioid cause euphoria

Front 296

What are the receptor subtypes of Glutamate in the CNS?

Back 296

Group I: excitatory; Group II/III: inhibitory; associated with schizophrenia, pain, post-trauma cytotoxicity – Ionotropic glutamate receptors: Excitatory (increase Ca conductance, prolonged stimulation causes excitotoxicity), receptors named for agonists (NMDA, AMPA, Kainate)

Front 297

What characterizes Glutamate?

Back 297

Found in interneurons and relay neurons throughout the CNS; It is the principle fast excitatory neurotransmitter in the CNS; Excitotoxicity with prolonged high concentrations causing neuron death

Front 298

What are the GABA receptor subtypes in the CNS?

Back 298

GABAA: postsynaptic, Cl- channel, hyperpolarization, drug binding modulates activity, subunit composition determines pharmacology, deficit in anxiety disorders

Front 299

What innervation is responsible for the release of NO in erection?

Back 299

PNS activation via ACh causing NO release from the endothelium;
NANC activation (PNS) causing direct release of NO

Front 300

What other drugs are used to treat ED?

Back 300

An injection of PGE2 into the corpus cavernosum

Front 301

How does Yohimbine treat ED?

Back 301

It blocks the prejunctional α2-adrenoceptors causing an increase NE release which will increase penile blood flow – however, Yohimbine may also increase BP and HR and it is less effective than the PDE inhibitors

Front 302

How does Vardenafil differ from Sildenafil and Tadalafil?

Back 302

Vardenafil is more specific for PDE5 than for PDE6; it also has the fastest onset

Front 303

Where is PDE6 found and why is this important to drugs treating ED?

Back 303

Found in the retina – most of the ED drugs are not specific for PDE5, but rather act on both forms; their action on PDE6 can cause abnormal color perception

Front 304

What enzyme causes degradation of cGMP?

Back 304

Phosphodiesterase 5 (PDE5); converts cGMP to GMP – this is the enzyme that ED drugs inhibit

Front 305

What does the release of NO lead to?

Back 305

NO reacts with guanylate cyclase and GTP to for cGMP; cGMP then causes muscle relaxation

Front 306

What are the effects of post-synaptic D1 stimulation?

Back 306

Moderate stimulation: suppresses noise; Excess stimulation: suppresses signals and noise;
Inadequate stimulation: causes excessive phasic DA release which suppresses signal and noise

Front 307

What side effects are associated Amphetamines?

Back 307

Nervousness/insomnia (very common, don’t give close to bedtime), anorexia (very common), abdominal pain, HA, emotional lability, dullness/fatigue, lack of spontaneity in social situations, dry mouth

Front 308

What is the mechanism of action of the Amphetamines?

Back 308

Reverse the direction of the nerve terminal reuptake transporter, causing NE/DA release;
Minor mechanism: inhibit NE/DA reuptake and MAO – overall effect: increased synaptic NE/DA

Front 309

What characterizes the Amphetamines used in the treatment of ADHD?

Back 309

Amphetamine mixed salts: amphetamine + dextroamphetamine; Dextroamphetamine: less commonly prescribed; Lisdexamfetamine: prodrug (lysine + dextroamphetamine), designed to decrease risk of overdose and abuse

Front 310

What CNS alterations occur in ADHD regarding NE?

Back 310

Polymorphisms in α2A result in a lower affinity for NE; this leads to a decreased enhancement of the signal – only true for a minority of ADHD cases

Front 311

What CNS alterations occur in ADHD regarding DA?

Back 311

Deficit in prefrontal cortex function due to a decrease in the tonic DA pool; this leads to less stimulation of autoreceptors, excess release of DA in response to stimuli, excess stimulation of post-synaptic D1 receptors (signal/noise suppressed), attention drifts/all stimuli demand attention

Front 312

What are the effects of pre-synaptic α2A stimulation?

Back 312

Moderate stimulation: enhances signal; Excess stimulation: impairs prefrontal cortex;
Inadequate stimulation: causes excessive phasic NE release which impairs prefrontal cortex

Front 313

What are the symptoms of ADHD?

Back 313

Inattention, hyperactivity, impulsivity – must be excessive, pervasive, long-term, and not due to something else

Front 314

What happens when DA/NE bind to the axon terminal autoreceptors (D2/α2)?

Back 314

They cause a decrease in the amount of DA/NE released by each AP – tonic levels of DA/NE present in synapses control the amount of impulse-associated DA/NE release (i.e. phasic levels)

Front 315

What are the major neurotransmitters in the prefrontal cortex?

Back 315

NE/DA: involved in regulation and inhibition of behavior, attention, impulse control – act on postsynaptic D1 and α2A receptors

Front 316

What absolute contraindications are associated with Amphetamines?

Back 316

Eating disorders, substance abuse, advanced cardiovascular disease, moderate/severe HTN, structural heart defects, hyperthyroidism, glaucoma, breastfeeding, abrupt discontinuation

Front 317

What characterizes Atomoxetine?

Back 317

Selective NE reuptake inhibitor, low affinity for DA/5-HT transporters; onset of action is 1week; Non-stimulant, used specifically for ADHD; no abuse potential, not a controlled substance –
less potent than other ADHD drugs

Front 318

What absolute contraindications are associated with Methylphenidate?

Back 318

Severe anxiety/psychosis, substance abuse, glaucoma, breastfeeding

Front 319

What adverse effects are associated with Methylphenidate?

Back 319

Mental effects: nervousness, insomnia, dullness, fatigue, emotional lability worsening of tics; growth inhibition, psychological dependence (less physical dependence than Amphetamines)

Front 320

What is the mechanism of action of Methylphenidate?

Back 320

Blocks DA reuptake in CNS – no effect on NE (thus less peripheral/cardiovascular effects)

Front 321

What characterizes Methylphenidate?

Back 321

Adverse effects primarily seen are more mental and less peripheral/cardiovascular; Methylphenidate has a shorter duration of action than mixed Amphetamines

Front 322

What drug interactions are associated with Amphetamines?

Back 322

Sympathomimetics and drugs that increase synaptic NE levels (e.g. MAOIs) cause additive CNS and cardiovascular stimulation; Lithium and antipsychotics antagonize Amphetamine’s actions

Front 323

What are less common side effects of Amphetamines?

Back 323

Worsening of tic disorders, increased BP, growth inhibition (rebound if drug is discontinued in adolescence), sudden unexplained death (caution in those with structural heart defects, patients should be screened before starting stimulants), dependence (physiological/psychological), abrupt discontinuation causes withdrawal symptoms

Front 324

What are the effects of toxic doses of Amphetamines?

Back 324

Cardiac arrhythmias, heart block, circulatory collapse, rhabdomyolysis, seizures, coma, death – toxic effects in children occur over a wider dose range

Front 325

What are signs of a supra-therapeutic dose of Amphetamines?

Back 325

Supra-normalization, anxiety, psychosis, blurred vision, dilated pupils, sweating, flushing, pallor, hyperthermia, labile vital signs, purposeless movement, tremor

Front 326

What are the absolute contraindications of Atomoxetine?

Back 326

Glaucoma, jaundice

Front 327

What are some general principles of ADHD therapy?

Back 327

Therapy is highly individualized; Continually monitor effectiveness of drug therapy (feedback from home/school); Periodically discontinue drugs to check for remission; Efficacy of drugs is increased by psychological therapies

Front 328

What characterizes the use of Modafinil in ADHD?

Back 328

Stimulant for narcolepsy – significant adverse effects

Front 329

What characterizes the use of Clonidine in ADHD?

Back 329

Agonist of α2 autoreceptors – normally used as antihypertensive; has significant adverse effects, rarely used

Front 330

What characterizes the use of TCAs in ADHD?

Back 330

Onset of action is weeks; Beneficial for anxiety/depression; Doesn’t worsen tics; Unexplained cardiac deaths in children; Fatal in overdose

Front 331

What are the second-line/off-label drugs used in ADHD?

Back 331

TCAs and other antidepressants (Bupropion/Buspirone), Clonidine, Modafinil

Front 332

What drug interactions are associated with Atomoxetine?

Back 332

MAOIs: cardiovascular stimulation; CYP interactions

Front 333

What adverse effects are associated with Atomoxetine?

Back 333

In children: GI upset, increased suicidal thoughts/behaviors; In adults: insomnia, anticholinergic effects, GI upset, sexual effects

Front 334

What is the purpose of the juxtaglomerular apparatus?

Back 334

By sensing Na+ levels and blood pressure, the juxtaglomerular apparatus can adjust flow through the release of renin and vasoconstriction of the afferent arteriole

Front 335

What are the carbonic anhydrase inhibitors?

Back 335

Acetazolamide, Dichlorphenamide, Methazolamide; they work in the proximal tubule by inhibiting carbonic anhydrase

Front 336

What toxicities/adverse effects are associated with osmotic diuretics?

Back 336

Heart failure, pulmonary congestion; Urea: impaired liver function; Mannitol/urea: cranial bleeding (can cause reoccurrence of hemorrhage due to increased extracellular volume)

Front 337

What are the uses of osmotic diuretics?

Back 337

Treatment of acute renal failure (can convert oliguric renal failure into polyuric renal failure); Prophylaxis of acute renal failure (e.g. with radiocontrast or crush syndrome); Cerebral/ocular edema (due to surgery or head trauma)

Front 338

What are the effects of osmotic diuretics?

Back 338

Pull fluid into the extracellular space (at the expense of intracellular fluid); Increase excretion of electrolytes; Increase renal blood flow – they increase Na+ excretion to about 5%

Front 339

What is the mechanism of action of the osmotic diuretics?

Back 339

They have an osmotic effect in the proximal tubule (i.e. they keep fluid in the tubule), which leads to a washout of NaCl and urea in the loop of Henle

Front 340

What are the osmotic diuretics?

Back 340

Glycerin: can be given orally, but gets metabolized; Mannitol: most common, given IV, not metabolized); Urea: given IV

Front 341

What is the function of diuretics?

Back 341

Increase urine flow rate and Na+ excretion

Front 342

What happens in distal portions of the nephron with increased Na+ levels?

Back 342

It can be involved in Na+ ↔ K+ and Na+ ↔ H+ exchange

Front 343

Where in the nephron is Na+ reabsorbed?

Back 343

65% in the proximal tubule (some by Na+ ↔ H+), and 25% in the ascending limb of the loop of Henle (thick portion especially)

Front 344

What toxicities are associated with carbonic anhydrase inhibitors?

Back 344

Metabolic acidosis; Stone (due to increased phosphate excretion); Potassium wasting; Contraindicated in hepatic cirrhosis (due to decreased NH4+ excretion); Hypersensitivity reactions (since they are sulfonamide drugs) – they are self-limiting since they will no longer work when HCO3- is depleted

Front 345

What toxicities/adverse effects are associated with loop diuretics?

Back 345

Depletion of Na+, loss of ECF volume, circulatory collapse; Hypokalemia, hypomagnesemia, hypocalcemia (can be used in patients with hypercalcemia when given in conjunction with saline); Hyperuricemia (since they compete with the organic anion transporter); Ototoxicity (Ethacrynic acid and Furosemide to a lesser degree); Increase LDL/triglycerides, decrease HDL, hyperglycemia (precipitates diabetes) – latter effects are less severe than with thiazide diuretics

Front 346

What pharmacokinetics are associated with loop diuretics?

Back 346

Highly protein bound; Tubular secretion (in PCT); Short half-life

Front 347

What are the uses of loop diuretics?

Back 347

Acute pulmonary edema; CHF (venous capacitance); Acute renal failure (not effective if renal failure is due to damage to the proximal convoluted tubule); HTN

Front 348

What is the effect of loop diuretics?

Back 348

Increased excretion of Na+, K+, H+, Ca2+, Mg2+, Cl-;Furosemide will also increase excretion of HCO3- and H2PO4- (due to its carbonic anhydrase inhibitor activity) and increase RBF;
~25% FENa (which is why they are called high-ceiling diuretics)

Front 349

What is the mechanism of action of the loop diuretics?

Back 349

They inhibit the Na+-K+-2Cl- symporter in the thick ascending limb; they require transport by an organic anion transporter in the proximal convoluted tubule to get access to the tubular lumen

Front 350

What are the loop/high-ceiling diuretics?

Back 350

Furosemide (Lasix), Bumetanide, Torsemide, Ethacrynic acid

Front 351

What does inhibition of carbonic anhydrase result in?

Back 351

In the lumen: inhibits conversion of H2CO3 to CO2 + H2O, which prevents their reabsorption into the proximal tubule cell; In the proximal tubule cell: inhibits conversion of CO2 + H2O to H2CO (and subsequently to HCO3- + H+), which prevents HCO3- from being symported with Na+ into the blood and prevents Na+ in the lumen from being antiported into the proximal tubule cell by H+

Front 352

What are the uses for carbonic anhydrase inhibitors?

Back 352

Glaucoma; Acute mountain sickness (prophylaxis/treatment) by decreasing CSF formation and CSF pH (causes increased ventilation); Treatment of alkalosis from increased H+ excretion (due to other diuretics); Cause urinary alkalinization

Front 353

What is the effect of carbonic anhydrase inhibitors?

Back 353

Increased excretion of HCO3-, Na+, K+, H2PO4-; ~5% FENa

Front 354

What are the uses of thiazide diuretics?

Back 354

Edema, HTN

Front 355

What toxicities/adverse effects are associated with ENaC inhibitors?

Back 355

Hyperkalemia (especially with ACE inhibitors, NSAIDs, β-blockers), GI disturbances; Triamterene: impaired glucose tolerance, musculoskeletal effects; Amiloride: headaches

Front 356

What are the uses of ENaC inhibitors?

Back 356

In combination with a loop/thiazide diuretic to maintain plasma K+; Treatment of HTN due to ENaC polymorphism (which makes it constitutively active); Amiloride can be used as an aerosol for the treatment of cystic fibrosis (makes mucus thinner)

Front 357

What are the effects of ENaC inhibitors?

Back 357

Increased excretion of Na+, Cl-; Decreased excretion of K+, H+, Ca2+, Mg2+; ~2% FENa

Front 358

What are the ENaC inhibitors and what is their mechanism of action?

Back 358

Triamterene, Amiloride – MOA: inhibit epithelial Na+ channel in the late distal tubule and early collecting duct (prevents activation of K+ secretion)

Front 359

What are the two types of potassium-sparing diuretics?

Back 359

ENaC inhibitors; Mineralocorticoid antagonists

Front 360

What toxicities/adverse effects are associated with thiazide diuretics?

Back 360

Hyperuricemia (with chronic use --> gout); Hypokalemic metabolic alkalosis; Hyponatremia; Increased LDL/total cholesterol/triglycerides; Decreased insulin secretion (impaired glucose tolerance); Erectile dysfunction; Hypersensitivity reactions (rare)

Front 361

What are the thiazides and thiazide-like diuretics?

Back 361

Chlorothiazide/Hydrochlorothiazide (HCTZ), Chlorthalidone, Indapamide, Metolazone

Front 362

What are the effects of thiazide diuretics?

Back 362

Increased excretion of Na+, K+, H+, HCO3-, Cl-, H2PO4-; There is a decrease in Ca2+ excretion with long-term effects (can be used in women with osteoporosis); ~5% FENa; Has no effect on the juxtaglomerular apparatus (and thus no effect on renal blood flow)

Front 363

What is the mechanism of action of the thiazides?

Back 363

Inhibit Na+-Cl- symporter in the distal convoluted tubule; they require transport by an organic anion transporter in the proximal convoluted tubule to get access to the tubular lumen

Front 364

What are the mineralocorticoid antagonists and how do they differ?

Back 364

Spironolactone: not very selective; Eplerenone: selective aldosterone receptor antagonist

Front 365

What are the toxicities associated with the mineralocorticoid antagonists?

Back 365

Hyperkalemia; Spironolactone: gynecomastia, impotence, decreased libido, hirsutism, diarrhea, gastritis, gastric bleeding, peptic ulcers (contraindication); Eplerenone: GI effects, interaction with CYP3A4 inhibitors (since it is metabolized by 3A4)

Front 366

What are the uses of mineralocorticoid antagonists?

Back 366

In combination with a loop/thiazide diuretic to maintain plasma K+; Hyperaldosteronism (1°/2°); Edema from hepatic cirrhosis

Front 367

What are the effects of the mineralocorticoid antagonists?

Back 367

Increased excretion of Na+, Cl-; Decreased excretion of K+, H+, Ca2+, Mg2+; ~2% FENa (overall effect depends on how much aldosterone is normally active in the nephron)

Front 368

What is the mechanism of action of the mineralocorticoid antagonists?

Back 368

Antagonists for aldosterone receptor in the late distal tubule and early collecting duct

Front 369

What enzyme converts angiotensin I to angiotensin II and where is it mainly found?

Back 369

Angiotensin converting enzyme (ACE): present on lumenal surface of vascular endothelial cells, particularly in the lungs

Front 370

How does sympathetic stimulation affect renin release?

Back 370

It stimulates renin release by activating β1 receptors

Front 371

By what mechanism does NaCl reabsorption across the macula densa affect renin release?

Back 371

Decreased reabsorption of Na+ will cause the release of renin using prostaglandins as a messenger; Increased reabsorption of Na+ will inhibit renin release using adenosine as a messenger

Front 372

What can be a complication of atherosclerosis of the renal artery?

Back 372

It can decrease blood flow to the glomeruli, thus activating the renin-angiotensin system which will work to elevate a normal blood pressure

Front 373

Where is renin released and what is the baroreceptor stimulus responsible for its release?

Back 373

By the juxtaglomerular cells in response to the baroreceptor function of the afferent arteriole: decreased stretch leads to increased renin release, and vice versa

Front 374

When the conversion of angiotensin I to angiotensin II is prevented by an ACE inhibitor, what compounds are generated instead?

Back 374

Angiotensin (1-7) and angiotensin IV (they have opposite effects to that of angiotensin II)

Front 375

What is the half-life of angiotensin II?

Back 375

Very short (~1 min.) – it is degraded by aminopeptidase and angiotensinase to peptide fragments

Front 376

What characterizes the synthesis of angiotensinogen?
It is constitutively synthesized

Back 376

by liver, leading to its abundance in plasma

Front 377

What substances can increase angiotensinogen levels?

Back 377

Corticosteroids, estrogen, pregnancy, estrogen-containing contraceptive, angiotensin II

Front 378

What is the rate-limiting step in the formation of angiotensin II?

Back 378

The conversion of angiotensinogen to angiotensin I by renin (released from the kidney)

Front 379

What are the rapid responses of angiotensin II that involves increases in blood pressure?

Back 379

Direct vasoconstriction of peripheral vasculature (very potent); Enhanced peripheral noradrenergic transmission; Increased CNS sympathetic tone (increases baroreceptor set-point); Increased release of catecholamines from the adrenal medulla

Front 380

What are the effects associated with kinins?

Back 380

Vasodilation (leads to increased blood flow and reduced effects of the renin-angiotensin system); Increased sodium excretion, diuresis; Powerful algesic; Mimic inflammation, produce edema, wheal and flare; Play a role in inflammatory disease (IBD, arthritis, asthma) – they have a very short half-life and thus very localized effects

Front 381

What characterizes the kinin receptors?

Back 381

They are GPCRs; B1: limited distribution, upregulated in inflammation; B2: activated by bradykinin and kallidin, mediates the majority of effects in the absence of inflammation, stimulation leads to production of NO and prostacyclin

Front 382

What factors increase the activation of kallikreins and thus the production of kinins?

Back 382

Factors that oppose renin release: increased ECF volume, BP, Na+ retention, mineralocorticoids, and angiotensin II

Front 383

What are the precursors to kallidin and bradykinin and how are they degraded?

Back 383

Kallidin is produced from LMW kininogen by tissue kallikrein, whereas bradykinin is produced from HMW kininogen by plasma kallikrein; both are degraded by Kininases I&II, which are ACEs

Front 384

What effects of angiotensin II are due to its mitogenic actions?

Back 384

Hypertrophy of vascular and cardiac cells, thickening of walls, cardiac fibrosis, increased preload/afterload

Front 385

What are the slow responses of angiotensin II that involves increases in blood pressure?

Back 385

Increases Na+ reabsorption in proximal tubule (direct effect); Increased release of aldosterone; Altered renal hemodynamics: direct renal vasoconstriction (especially on the efferent arteriole, thus maintaining glomerular pressure), enhanced noradrenergic neurotransmission in kidney, increased renal sympathetic tone

Front 386

What is meant by the short loop feedback of the renin-angiotensin system?

Back 386

Angiotensin II produced in response to renin release, will work to lower the secretion of renin

Front 387

What characterizes the angiotensin receptors?

Back 387

They are GPCRs; AT1: mediates most actions of angiotensin II, high affinity for the antagonist Losartan, Gq-receptor (PLC/IP3/DAG), stimulates gene expression/cell growth/mitogenic effect;
AT2: role poorly defined, opposite effects to AT1, highly expressed in fetus

Front 388

Drugs with what action will cause the release of renin?

Back 388

Drugs that decrease blood volume/blood pressure, and drugs that cause β1 stimulation

Front 389

What are some common ACE inhibitors?

Back 389

Captopril: active form with an active metabolite; Alopril: ester pro-drug which is converted to Enalaprilat, the active metabolite; Lisinopril: active form is excreted

Front 390

What side effects/adverse reactions are associated with drugs that inhibit the renin-angiotensin system?

Back 390

Severe hypotension in patients who are hypovolemic, salt-depleted, or have CHF;
Hyperkalemia in patients with impaired renal function; Acute renal failure in patients with bilateral renal artery stenosis; Cough, angioedema (due to increased kinins with ACE inhibitors); Fetopathic after first trimester of pregnancy

Front 391

What therapeutic applications are associated with the drugs that inhibit the renin-angiotensin system?

Back 391

HTN: do not trigger reflex tachycardia, can be effective even with low renin;
CHF: improved hemodynamics/left ventricular systolic function, slows hypertrophy/remodeling;
MI: prevent excessive remodeling of cardiac tissue, begin immediately after an infarction;
Slowing of diabetic nephropathy: ↓ arterial BP; ↓ afferent arteriolar resistance; ↓ intraglomerular pressure

Front 392

What effects do ACE inhibitors, AT1 receptor antagonist, and Aliskiren have in common?

Back 392

They decrease PVR/BP, increase renal blood flow, and decrease secretion of aldosterone

Front 393

How do the effects of Aliskiren differ from those of an ACE inhibitor?

Back 393

It does not increase angiotensin (1-7), does not increase renin activity, and does not increase kinins

Front 394

How do the effects of an AT1 receptor antagonist differ from those of an ACE inhibitor?

Back 394

They do not increase angiotensin (1-7), do not increase kinins, and do not decrease stimulation of AT2 receptors

Front 395

What are some common competitive AT1 receptor antagonists?

Back 395

Losartan, Irbesartan, Valsartan

Front 396

What happens to bradykinin levels when a patient is given an ACE inhibitor?

Back 396

It will be increased, thus causing more vasodilation and a lowering of blood pressure; however, it will also act as an irritant which may cause cough

Front 397

By what four ways can the activity of angiotensin II (AT-II) be inhibited?

Back 397

Inhibit the release of renin (β-blockers); Inhibit the activity of renin (Aliskiren);
Inhibit the formation of AT-II by ACE inhibitors; Block the AT1 receptors for AT-II

Front 398

Which calcium channel type is affected by the calcium-entry antagonists?

Back 398

Slow channels (L-type)

Front 399

What are the effects of the dihydropyridines?

Back 399

They cause prominent vasodilation (peripheral/coronary artery) which triggers sympathetic reflexes, which in turn cause increases in heart rate and contractility; they have no effect on AV conduction (β-blockers can prevent the cardiac effects without reducing vasodilatory effects)

Front 400

How does depolarization differ between vascular smooth muscle and cardiac muscle, and what does this mean for the action of dihydropyridines?

Back 400

Vascular smooth muscle is found to be in a chronic state of depolarization, which means that its calcium receptors will spend a much greater amount of time in the inactivated-closed state than cardiac muscle will; this means that dihydropyridines will have a much greater effect on vascular smooth muscle than on cardiac muscle

Front 401

Which antagonists bind to calcium channels in the inactivated-closed state?

Back 401

Dihydropyridines

Front 402

What happens to the fraction of calcium channels that are blocked by Verapamil/Diltiazem when heart rate increases?

Back 402

It will go up, since the calcium channels will be in their open state more frequently (i.e. use-dependent block: the higher the heart rate, the more effective the drug becomes at lowering it)

Front 403

Which antagonists bind to calcium channels in the open state?

Back 403

Verapamil, Diltiazem

Front 404

What three groups can the calcium-entry antagonists be divided up in?

Back 404

1-4 dihydropyridines (Nifedipine, -dipine); phenylalkylamines (Verapamil, D-600);
benzothiazepines (Diltiazem)

Front 405

In what three states can the calcium channel be found?

Back 405

Open; Resting-closed; Inactivated-closed

Front 406

What happens when calcium channels are depolarized?

Back 406

They fluctuate between open and resting-closed (thus allowing for the influx of calcium ions), until they assume the inactivated-closed state; at this point, they have to be hyperpolarized again before being able to go to the open state once more

Front 407

What calcium channel states are favored by hyperpolarization vs. depolarization?

Back 407

Hyperpolarization: resting-closed; Depolarization: open/inactivated-closed

Front 408

For what type of angina is Bepridil used and what side effect is associated with it?

Back 408

Angina that is refractory to other calcium antagonists; however, it can broaden the cardiac action potential (long QT) and be pro-arrhythmic

Front 409

What should be kept in mind when giving an elderly patient Verapamil/Diltiazem?

Back 409

Whether their AV conduction is already compromised or if β-blockers are in use (contraindication)

Front 410

What must be done with patients who recently had a heart attack and are now taking Nifedipine?

Back 410

They must be given a β-blocker as well to avoid the positive chronotropic/inotropic effects on the heart

Front 411

What are the main adverse effects seen with dihydropyridines and Verapamil, respectively?

Back 411

DHP: hypotension, HA, peripheral edema, tachycardia, gingival hyperplasia
Verapamil: hypotension, AV block, bradycardia, constipation, gingival hyperplasia

Front 412

Which of the calcium channel blockers is used in the treatment of Raynaud’s phenomenon?

Back 412

Dihydropyridines

Front 413

What common indication is seen with all three classes of calcium channel blockers?

Back 413

HTN: Nifedipine would be most useful for treating HTN alone, whereas Verapamil/Diltiazem are most useful in a patient with HTN and angina/arrhythmia)

Front 414

What type of arrhythmias are treated by Verapamil/Diltiazem?

Back 414

Supraventricular tachycardias (AV node reentry, atrial flutter/fibrillation) – the dihydropyridines have no use in treating arrhythmias

Front 415

What are the effects of Verapamil/Diltiazem?

Back 415

They increase vasodilation (peripheral/coronary artery), but their most prominent effects are in reducing heart contractility, rate, and AV conduction (Verapamil > Diltiazem)

Front 416

What calcium-entry antagonists are recommended for the treatment of variant/unstable angina?

Back 416

All three classes of calcium channel antagonists are effective

Front 417

What calcium-entry antagonists are recommended for the treatment of exertional angina?

Back 417

Verapamil/Diltiazem; can also give Nifedipine and a β-blocker as co-treatment

Front 418

What are some common indications for Heparin?

Back 418

Pre- and post-surgical management of DVT and pulmonary thrombosis as well as arterial and heart valve emboli; Venous stasis; Unstable angina and post-MI; DIC – Heparin does not break down clots, it just inhibits their formation

Front 419

How does the mechanism of action of LMWH differ from that of Heparin?

Back 419

LMWH has the pentasaccharide sequence that binds to ATIII, but not the 18 saccharide sequence found in Heparin that binds to thrombin --> this means that LMWH affects Xa without affecting thrombin – Fondaparinux only has the pentasaccharide sequence needed to bind ATIII

Front 420

How are Low Molecular Weight Heparins (LMWH) recognized?

Back 420

They end on –parin: Enoxaparin, Fondaparinux

Front 421

How does low-dose Heparin differ in effects from high-dose Heparin?

Back 421

Low-dose: prevents thrombin formation only; High-dose: prevents thrombin formation and inhibits the actions of already formed thrombin

Front 422

What contraindications are associated with Heparin and most other anticoagulant drugs?

Back 422

GI ulcerative lesions/occult bleeding, severe hypertension, recent eye/brain/spinal surgery, visceral carcinoma, threatened abortion; Anti-platelet drugs (caution required); Presence of thrombocytopenia (may result in serious bleeding)

Front 423

What is the Heparin “antidote” and how does it function?

Back 423

Protamine: basic (+) low molecular weight proteins that bind to negatively charged Heparin to neutralize its anticoagulant effects – does not affect Fondaparinux (LMWH)

Front 424

What toxicities are associated with Heparin?

Back 424

Primary: hemorrhage, thrombocytopenia, HIT; Secondary: hypersensitivity, fever, anaphylaxis

Front 425

What is the mechanism of action of unfractionated Heparin?

Back 425

It binds to Antithrombin III (ATIII) and accelerates the inactivation of factors IIa, IXa, Xa, and XIIa by ATIII

Front 426

What is the difference in IV vs. SC administration of Heparin?

Back 426

IV: immediate anticoagulation effect; SC: anticoagulation is delayed due to absorption

Front 427

What pharmacokinetics are associated with Heparin?

Back 427

Not bound to plasma proteins – Metabolism: initial, rapid zero-order mechanism (cellular uptake and depolymerization) followed by slower first-order renal clearance

Front 428

Which factor is affected the earliest by Warfarin?

Back 428

Factor VII, since it has the shortest half-life; With chronic doses, however, all of the Vitamin K dependent factors will be affected

Front 429

What are indications for antiplatelet drugs?

Back 429

Prosthetic heart valves; MI (prophylaxis and prevention of re-thrombosis); Combination therapy with anticoagulant and fibrinolytic drugs; Percutaneous transluminal angioplasty (PCTA or PCI) and stenting

Front 430

What class of anticoagulants is used in a patient with thrombocytopenia?

Back 430

Direct thrombin inhibitors: all end on –rudin (Lepirudin, Bivalirudin, Desirudin)

Front 431

What drug is an oral alternative to Warfarin?

Back 431

Rivaroxaban: small molecule, active site inhibitor of factor Xa

Front 432

How can Warfarin toxicity be countered?

Back 432

No “antidote” available; Can administer Vitamin K1 but takes hours to have an effect; In emergencies, FFP or concentrates containing functional factors can be administered

Front 433

What are the toxicities associated with Warfarin?

Back 433

Same as Heparin, but also contraindication in pregnancy

Front 434

What pharmacokinetics are associated with Warfarin?

Back 434

>95% bound to plasma proteins; Crosses the placenta; CYP450 metabolism

Front 435

How do the pharmacokinetics of LMWH differ from that of Heparin?

Back 435

Greater bioavailability; Longer lasting; 1st order pharmacokinetics only

Front 436

What is a key clinical difference between Warfarin and Heparin?

Back 436

Warfarin can be given PO, wheras Heparin is only given IV/SC

Front 437

What is the mechanism of action of Warfarin?

Back 437

Warfarin is a Vitamin K antagonist that inhibits an epoxide reductase reaction required to recycle Vitamin K --> this lack of recycling means that Vitamin K is unable to perform γ-carboxylation of glutamic acid residues on factors II, VI, IX, X, as well as Proteins C and S --> this lack of γ-carboxylation means that the factors are unable to complex with Ca2+ during coagulation

Front 438

What are the pharmacokinetics of Ticlopidine and Clopidogrel?

Back 438

Bind plasma proteins, metabolized by the liver; Onset of Ticlopidine is slow (days) whereas that of Clopidogrel is much faster

Front 439

What is the indication for Urokinase?

Back 439

Pulmonary embolism – Urokinase is not antigenic

Front 440

What characterizes Streptokinase?

Back 440

Not an enzyme; Forms a complex with plasminogen, exposing an active site that converts additional plasminogen into plasmin; Obtained from β-hemolytic streptococci, making it antigenic; Antigenic effects can be minimized by giving the drug as an intracoronary injection

Front 441

What are the indications of plasminogen activators?

Back 441

Ischemic stroke, arterial thrombosis, MI (early therapy is essential, must establish flow first), DVT, pulmonary embolism

Front 442

How do first, second, and third generation plasminogen activators differ?

Back 442

First: Streptokinase, Urokinase --> not fibrin-specific; Second: Alteplase (t-PA) --> causes less fibrinogenolysis; Third: Reteplase, Tenecteplase --> improved fibrin specificity and kinetics

Front 443

What is the difference between fibrinolysis and fibrinogenolysis?

Back 443

Fibrinolysis: breakdown of a fibrin clot by plasmin; Fibrinogenolysis: breakdown of clotting factors in the plasma by plasmin (prevented by α2-antiplasmin)

Front 444

What drugs function as GPIIb/IIIa inhibitors and how do they differ?

Back 444

Abciximab: monoclonal antibody that noncompetitively inhibits GPIIb/IIIa (indication: PCI);
Eptifibatide, Tirofiban: competitive inhibitors of GPIIb/IIIa (contain “fib” and “ban” portions)

Front 445

How does a baby Aspirin/day affect coagulation?

Back 445

It prevents TXA2 formation in platelets more than it prevents PGI2 formation in endothelial cells (since endothelial cells can synthesize COX de novo and platelets can’t), thus tipping the balance towards anticoagulation

Front 446

What are examples of ADP receptor inhibitors and how do they function?

Back 446

“clop” drugs: Ticlopidine, Clopidogrel (Plavix); They irreversibly inhibit platelet ADP receptors and thus inhibit ADP-induced exposure of platelet membrane GPIIb/IIIa and fibrinogen binding to activated platelets

Front 447

What are the indications for Ticlopidine and Clopidogrel and what are associated toxicities?

Back 447

Indications: prevention/treatment of thrombotic stroke, PCTA/PCI; Toxicities (more so with Ticlopidine): GI disturbances, potential life-threatening neutropenia, blood dyscrasias

Front 448

What characterizes Alteplase?

Back 448

Single chain peptide that is converted to a two-chain t-PA dimer upon exposure to fibrin; 30 min half-life (may require multiple administrations)

Front 449

What is the mechanism of action of Antifibrinolytic drugs (e.g. Aminocaproic acid, Tranexamic acid) and what are they used for?

Back 449

They block the lysine-binding interactions between plasminogen/plasmin and fibrin, thus inhibiting plasminogen activation and plasmin fibrinolysis – used for dental procedures in Hemophiliacs and to control bleeding during surgery

Front 450

How are Reteplase and Tenecteplase improvements over Alteplase?

Back 450

They contain only the domain necessary for binding to fibrin and the protease domain of t-PA; this allows for a more rapid onset and potent effect than is seen with Alteplase; However, they still have some fibrongenolytic properties

Front 451

How does Anistreplase function?

Back 451

It is a noncovalent complex of streptokinase and plasminogen which is catalytically inert but is deacetylated to give rise to active plasminogen; has a prolonged fibrinolytic effect, but is still antigenic

Front 452

What is the drug of choice for HTN in African-Americans?

Back 452

Thiazides (CCBs also work very well)

Front 453

What name is associated with the α-blockers and why are they α1-specific?

Back 453

-osin (e.g. Prazosin); they are α1-specific so that they don’t cause the increase in NE release associated with α2-blockers; since α-blockers cause vasodilation, they will have a reflex tachycardia and cause activation of the RAS – this is why they are usually prescribed along with a β-blocker and diuretics

Front 454

What are the key differences between pure β-blockers (BB) and those with ISA?

Back 454

Pure BB decrease CO by decreasing both HR and SV, and they inhibit RAS; pure BB cause a reflex increase in TPR (can lead to cold hands and extremities);
BB with ISA do not decrease CO (since inotropic activity is balanced by the partial agonist activity), but they do decrease TPR (due to β2 ISA); BB with ISA do not inhibit RAS;

Front 455

Which β-blockers have intrinsic sympathomimetic activity (ISA)?

Back 455

Pindolol, Penbutalol, Carteolol, Acebutolol – they have weak partial agonist activity

Front 456

What does activation of the SNS stimulate regarding control of BP?

Back 456

β1 activation in the heart; β1 activation in the kidney (activates RAS); α1 activation in the vasculature

Front 457

What two major systems are involved in the regulation of BP?

Back 457

SNS (short-term) and RAS (long-term)

Front 458

Which classes of drugs used in the treatment of HTN are K+ sparing?

Back 458

Aldosterone antagonists, ACE inhibitors/ARB, Triamterene/Amiloride

Front 459

What is the primary class of diuretics used in HTN?

Back 459

Thiazides (whereas loop diuretics are the primary class used in CHF)

Front 460

What is the long-term effect of thiazide diuretics?

Back 460

Plasma volume returns to normal, but TPR remains decreased

Front 461

Do diuretics cause a baroreceptor reflex?

Back 461

No, since their effects take days-weeks to take place (same goes for RAS inhibitors – they reset the baroreceptor reflex)

Front 462

What does Guanethidine lead to?

Back 462

Depletion of NE – mechanism not well understood

Front 463

What drugs are used for hypertensive emergencies?

Back 463

Sodium nitroprusside, Labetalol (IV bolus), Fenoldopam, Diazoxide, Nicardipine, Hydralazine

Front 464

What is the mechanism of action of Minoxidil?

Back 464

It is a K-channel opener, meaning it will cause hyperpolarization of the cell; therefore it will make cells much less likely to contract --> causes dilation of arteries

Front 465

What should hydralazine always be combined with?

Back 465

BB (to prevent reflex tachycardia) and a diuretic (to reverse edema caused by RAS activation) – the same is true for Minoxidil, although the effects are more severe (contraindicated in CHF)

Front 466

What are the two most important side effects of an ACE inhibitor?

Back 466

Cough, angioedema (these side effects are not as prominent with ARBs)

Front 467

Why is the combination of a thiazide diuretic with an ACE inhibitor so effective?

Back 467

The thiazide makes the HTN more renin dependent, which increases the efficacy of the ACE inhibitor; also, ACE inhibition preserves K, which offsets the K loss causes by the thiazide

Front 468

What contraindication is given for all drugs that inhibit the RAS?

Back 468

They should not be used in pregnancy (since AT-II is used in fetal development)

Front 469

Which drugs inhibit both α- and β-receptors?

Back 469

Carvedilol, Labetalol (they are not first-line therapy, due to orthostatic hypotension/bradycardia)

Front 470

Which drugs are centrally-acting inhibitors of the SNS that used to be popular for treating HTN, and how do they exert their effects?

Back 470

α-methyldopa (metabolized to α-methylNE in the brain) and Clonidine (direct-acting agonist) – they are α2-selective agonists that only work in the brain; in this fashion, they lower NE outflow to the heart, vasculature, and kidney (side effects, like sedation/drowsiness, has made them mostly obsolete)

Front 471

What is the mechanism of action of Reserpine?

Back 471

It blocks NE uptake into the storage vesicle, causing it to be degraded by MAO – knocks out the sympathetic nervous system

Front 472

What type of drug is Fenoldopam?

Back 472

Selective DA1 agonist; it dilates arterioles in renal, mesenteric, and cerebral vascular beds;
it increases RBF while lowering BP (useful for patient with renal insufficiency in hypertensive emergencies)

Front 473

What is the mechanism of action of Diazoxide?

Back 473

K-channel opener (like Minoxidil, but IV), so it dilates arterioles – reflex tachycardia is one of the major adverse effects (caution in ischemic heart disease)

Front 474

Considering the fact that CHF is a neurohormonal disorder, what classes of drugs would be beneficial for its treatment?

Back 474

ACE inhibitor/ARB (for AT-II), and a β-blocker (for NE) – also effective would be inotropic agents (to increase CO), arterial vasodilators (decrease afterload), venodilators (decrease preload), and diuretics (eliminate edema, decreases preload)

Front 475

What makes cardiac glycosides especially dangerous?

Back 475

They have a low therapeutic index; Side effects include AV block, arrhythmias, anorexia, nausea, vomiting, fatigue, visual disturbances

Front 476

What are the CNS effects of cardiac glycosides?

Back 476

They increase vagal tone which slows HR, and at high levels can cause an AV block (can be desired in atrial fibrillation)

Front 477

How do cardiac glycosides cause ectopic contractions?

Back 477

Excessive increases in intracellular calcium lead to Ca-induced-Ca release from SR, which lead to calcium-dependent after-depolarizations (= ectopic contractions)

Front 478

Why are the cardiac glycosides pro-arrhythmic?

Back 478

Because they inhibit the Na/K-ATPase, which causes extracellular potassium to increase;
this causes a partial membrane depolarization, which has a pro-arrhythmic effect

Front 479

What is the mechanism of action of the cardiac glycosides?

Back 479

They inhibit the Na/K-ATPase --> increases intracellular sodium --> decreases the driving force for the Na/Ca exchanger --> increases intracellular calcium --> increases inotropy

Front 480

What are the cardiac glycosides (inotropes) used in chronic CHF?

Back 480

Digitalis glycosides: Digoxin, Digitoxin, Ouabain

Front 481

How are inotropy, afterload (TPR), and preload (LVEDP) affected in CHF?

Back 481

Inotropy is decreased, whereas afterload and preload are increased

Front 482

What is meant by the statement that CHF is a neurohormonal disorder?

Back 482

A failing heart activates the renin-angiotensin system (AT-II/Aldosterone) and causes sympathetic nervous system activation: β1 (heart/renin), β2 (vasodilation), α1 (vasoconstriction)

Front 483

What is meant by the vicious cycle in CHF?

Back 483

Outer loop: left ventricular failure (e.g. due to ischemic heart disease) --> decrease in CO --> reflex increase in sympathetic nervous system activity --> vasoconstriction --> increase in BP --> increase in afterload --> worsens left ventricular failure;
Inner loop: ventricular failure --> decrease in CO --> activation of renin-angiotensin system --> fluid retention --> increase in preload --> worsens ventricular failure

Front 484

What do the cardiac glycosides and diuretics have in common, concerning the treatment of CHF?

Back 484

They do not reduce mortality, but they do improve the QOL for patients (reduce hospital visits)

Front 485

What are the adverse effects associated with Isosorbide Dinitrate?

Back 485

HA, dizziness, flushing, orthostatic hypotension, drug rash

Front 486

How does Isosorbide Dinitrate reduce the load on the heart?

Back 486

It causes venodilation which reduces preload, thus decreasing LVEDP – it also has less activation of the SNS than Hydralazine

Front 487

What are the adverse effects associated with Hydralazine?

Back 487

HA, flushing, nasal congestion, reflex tachycardia/palpitations (less common in CHF), fluid retention, myocardial ischemia/infarction (due to increased cardiac work); also Lupus syndrome at higher doses

Front 488

How does Hydralazine increase CO?

Back 488

It causes arterial vasodilation which decreases afterload, thus decreasing the impedance to LV ejection

Front 489

How do they aldosterone antagonists differ in their effects on CHF when compared to other diuretics?

Back 489

They do reduce mortality because they cause potassium retention (thus preventing hypokalemia!)

Front 490

Which diuretics are used in CHF?

Back 490

Loop diuretics (since they are the only ones powerful enough to decrease edema and pulmonary congestion

Front 491

What is the danger in giving a patient cardiac glycosides in combination with diuretics?

Back 491

Diuretics can cause hypokalemia which will worsen the pro-arrhythmic toxicity associated with cardiac glycosides (!)

Front 492

What are the notable differences between Digitoxin, Digoxin, and Ouabain?

Back 492

Digitoxin: longest half-life; Digoxin: intermediate half-life, most common;
Ouabain: shortest half-life, given IV

Front 493

What is the treatment for digitalis toxicity?

Back 493

Stop digitalis, control arrhythmias, give potassium, use anti-glycoside antibodies

Front 494

What are the ONLY β-blockers effective in the treatment of CHF?

Back 494

Carvedilol, Metoprolol (long-acting), Bisoprolol – there is not a class effect!

Front 495

Which of the sympathomimetic amines cause the greatest increase in RBF?

Back 495

DA (since it acts on DA1 receptors); Dobutamine will cause a slight increase (due to increase CO), and Isoproterenol can cause either increase or decrease depending on which receptor activity dominates (β2 vs. β1)

Front 496

How do the effects of DA, Dobutamine, and Isoproterenol differ in regards to BP and preload?

Back 496

DA: increase in BP/preload; Dobutamine: no change in BP/increase in preload;
Isoproterenol: decrease in BP/preload

Front 497

Which receptors are affected by DA, Dobutamine, and Isoproterenol, besides their common effects on β1?

Back 497

DA: α1, DA1; Dobutamine: β2, α1; Isoproterenol: β2

Front 498

What are the goals of therapy with cAMP elevators?

Back 498

Improve LV function, increase CO, improve circulatory status and tissue perfusion, decrease pulmonary congestion

Front 499

Which drugs are used in acute CHF?

Back 499

cAMP elevators (inotropes): sympathomimetic amines (DA, Dobutamine, Isoproterenol) and phosphodiesterase III inhibitors (Milrinone, Amrinone); Short-acting vasodilators: Sodium nitroprusside, Nesiritide

Front 500

What adverse effects are associated with the use of β-blockers in CHF?

Back 500

May worsen CHF, especially acutely (must be carefully titrated on initiation of therapy); Bradycardia; Hypotension; Worsen asthma/COPD; Increase glucose (diabetogenic);
Increase VLDL/decrease HDL; Fatigue; Insomnia

Front 501

In which patients is a combination treatment of Hydralazine and Isosorbide Dinitrate indicated?

Back 501

African-Americans (due to reduced effectiveness of inhibitors of RAS and β-blockers)

Front 502

When a patient taking an ACE inhibitor complains of excessive coughing (due to excess bradykinin), what drug can be substituted?

Back 502

AT1 receptor antagonist

Front 503

What drugs are part of the standard therapy for CHF?

Back 503

Digoxin, diuretic, ACE inhibitor, β-blocker (certain kinds)

Front 504

Which sympathomimetic amine would be given to a patient with acute CHF who has low BP and low RBF?

Back 504

DA: increases BP/RBF – if the patient’s BP is normal but preload too high, Dobutamine would be the best choice; if the patient has high BP, Isoproterenol would be the drug of choice

Front 505

What are the adverse effects associated with Nesiritide?

Back 505

Hypotension, insomnia, dizziness, vomiting

Front 506

What is the mechanism of action of Nesiritide?

Back 506

As a recombinant form of BNP it increase cGMP and produces vasodilation (both arterial and venous); it has no direct inotropic effect but increase CO due to reduced LV impedance; may also produce a mild diuresis

Front 507

What are the adverse effects associated with Sodium nitroprusside?

Back 507

HA; n/v; Thiocyanate toxicity on longer infusions (!) which can lead to metabolic acidosis, confusion, coma, and death

Front 508

What is the mechanism of action of Sodium nitroprusside?

Back 508

It is metabolized to NO which is a potent vasodilator (both arterial and venous); vasodilation decreases LV impedance, and thus CO is increased – can also cause some reflex tachycardia, renin release and fluid retention (not severe)

Front 509

What are the adverse effects associated with PDE III inhibitors?

Back 509

Arrhythmias (also GI/hepatic effects and thrombocytopenia)

Front 510

What is the mechanism of action of phosphodiesterase III inhibitors in acute CHF?

Back 510

They inhibit PDE III’s degradation of cAMP (which was generated by the activation of β-receptors), thus prolonging the effect that cAMP has on the phosphorylation of calcium channels which increases calcium flow into the cell causing increased force of contraction

Front 511

Case #1: What drug would be useful in a patient with post-operative atrial fibrillation?

Back 511

Digitalis glycoside

Front 512

Case #6: What can be given to a patient with Class IV heart failure, who is on Digoxin, Captopril, Furosemide, Carvedilol, and Spironolactone?

Back 512

Any drug used for acute decompensation (i.e. β1-agonist, PDEIII inhibitors, short-acting vasodilators); patient needs a “tune-up”

Front 513

Case #5: What can be done for a patient who has an ACE inhibitor-induced cough?

Back 513

Replace the ACE inhibitor by an ARB

Front 514

Case #4: What can be given to a patient who is hemodynamically unstable, for CHF symptoms and survival improvement?

Back 514

Aldosterone antagonist: Spironolactone/Eplerenone

Front 515

Case #3: What can be given to a patient who is hemodynamically stable, for CHF symptom and survival improvement?

Back 515

β-blocker: Carvedilol

Front 516

Case #2: Why can a patient on Digoxin, who is also given Verapamil, develop toxicity?

Back 516

Anytime another drug is added to Digoxin, it can increase Digoxin levels; also, if the patient has diarrhea, a loss of potassium can exacerbate cardiac effects

Front 517

What are the stages of hypertension?

Back 517

Pre-hypertension: 120-139/80/89; Stage 1: 140-159/90-99; Stage 2: >160/100

Front 518

What is the common treatment for HTN without compelling indications?

Back 518

Thiazide diuretics (ACE inhibitors with combined treatment)

Front 519

What are some of the causes of secondary HTN?

Back 519

Primary renal disease, renovascular disease, oral contraceptive, pheochromocytoma, primary hyperaldosteronism, Cushing’s, coarctation of the aorta, sleep apnea

Front 520

What are the Sokolow and Lyon criteria for LVH?

Back 520

S on V1 + R on V5/6 > 35 mm

Front 521

What is the Keith, Wagener, Barker classification regarding hypertensive retinopathy?

Back 521

Group 1 (benign HTN): mild narrowing/sclerosis of retinal arterioles;
Group 2 (more marked hypertensive retinopathy): moderate/marked sclerosis of arterioles, exaggerated arterial light reflex, A-V crossing changes (nicking!);
Group 3 (mild angiospastic retinopathy): retinal edema, cotton-wool spots!/hemorrhages, sclerosis/spastic lesions of arterioles;
Group 4 (malignant HTN): group 3 with papilledema

Front 522

What factors are important in getting an accurate BP measurement?

Back 522

Patient should avoid exercise, eating, smoking, caffeine 60 min. before; They should sit quietly for 5 min; check both arms

Front 523

What treatment is suggested for patients with pre-hypertension?

Back 523

Lifestyle changes

Front 524

What are the criteria required for a diagnosis of hypertension?

Back 524

Systolic>140 OR Diastolic>90 on 2+ readings after the initial visit

Front 525

What are the desired systolic and diastolic pressures for patients with chronic kidney disease and in diabetics?

Back 525

Systolic<130; Diastolic<80

Front 526

What percent of hypertensive patients are properly controlled?

Back 526

One-third

Front 527

What are the organic nitrates used with angina?

Back 527

Nitroglycerin (most common); Amyl nitrite (inhalant, drug of abuse); Isosorbide mono/dinitrate (long-acting)

Front 528

What drug interactions are associated with organic nitrates?

Back 528

PDE5 inhibitors for impotence; leads to profound hypotension

Front 529

Which enzyme is responsible for the breakdown of organic nitrates?

Back 529

Hepatic glutathione organic nitrate reductase (which is why sublingual administration of nitroglycerin is effective – no first-pass effect)

Front 530

How does tolerance come about with organic nitrates?

Back 530

Through depletion of –SH groups (i.e. cysteine) and by down-regulation of aldehyde dehydrogenase (involved in metabolism of nitroglycerin to NO)

Front 531

What side effects are associated with organic nitrates?

Back 531

HA, postural hypotension, methemoglobinemia (Fe2+ --> Fe3+)

Front 532

By what three mechanisms do the effects of the organic nitrates take place?

Back 532

1° mech.: preload reduction by preferential dilation of venous capacitance vessels (↓ LVEDP);
2° mech.: large coronary artery dilation, causing a redistribution of blood to the ischemic zone;
3° mech.: afterload reduction due to arterial dilation, causing decreased vascular wall compression

Front 533

What is the mechanism of action of organic nitrates?

Back 533

They stimulate guanylate cyclase to produced cGMP which causes a decrease in intracellular calcium and thus vascular smooth muscle relaxation; organic nitrates can do this either through the formation of NO directly, or through NO binding with cysteine which causes formation of
S-nitrosothiols

Front 534

When is left coronary blood flow maximal?

Back 534

During diastole

Front 535

What substances cause vasodilation in coronary vessels as part of autoregulation?

Back 535

pO2, adenosine, NO

Front 536

What factors affect myocardial O2 consumption?

Back 536

Wall tension (LVEDP), myocardial contractility, HR

Front 537

Why should β-blockers not be used in Prinzmetal angina?

Back 537

Since they cause the unmasking of α-receptors, they can worsen vasospasms by causing vasoconstriction in affected vessels

Front 538

Why are calcium channel blockers effective in the treatment of variant angina?

Back 538

Because they inhibit coronary vasospasm and relax vasospastic vessels – the direct calcium channel blocker’s effects on the heart are not important

Front 539

What does a blockade of calcium channels lead to in the heart?

Back 539

SA-node: reduced HR, slowed conduction; Myocardial cell: reduced contractility

Front 540

How do the effects of slow calcium currents differ between myocardial cells and SA-nodal cells?

Back 540

In myocardial cells they are responsible for the plateau phase of the action potential, whereas in the SA-nodal cells they are responsible for the upstroke of the action potential

Front 541

What are the indications of calcium channel blockers in myocardial ischemia?

Back 541

Medium to long-range prophylaxis of variant angina and stable angina (in conjunction with nitrates and β-blockers)

Front 542

Why is the combination of organic nitrate and β-blocker therapy so effective?

Back 542

β-blockers offset the baroreceptor response caused by the nitrate-induced hypotension;
Nitrates offset the increase in LVEDP caused by β-blockers by decreasing venous return

Front 543

What can occur if a β-blocker is withdrawn suddenly?

Back 543

Rebound ischemia

Front 544

What is the indication of β-adrenoceptor antagonists in myocardial ischemia?

Back 544

Used for medium to long-range prophylaxis (not for acute attacks)

Front 545

By what mechanisms of action do β-blockers treat myocardial ischemia?

Back 545

By blocking β1-receptors they decrease HR/contractility which directly decreases oxygen demand and indirectly increases oxygen supply (increase diastolic perfusion/decrease wall compression);
By unmasking α-receptors in the normal zone, flow is shunted away from healthy vessels toward the ischemic zone, thus increasing its oxygen supply

Front 546

What β-blockers are approved for the treatment of myocardial ischemia?

Back 546

β1/β2-nonselective: Propranolol, Nadolol, Pindolol; β1-selective: Atenolol, Metoprolol

Front 547

What is the tissue selectivity of each of the classes of calcium channel blockers?

Back 547

Verapamil: AV node > myocardium > vascular smooth muscle, used for stable angina;
Diltiazem: vascular smooth muscle > myocardium; some effect on AV node, intermediate use;
Nifedipine: vascular smooth muscle > myocardium; no effect on AV node, used for variant angina

Front 548

What is the mechanism of action of Ranolazine?

Back 548

It blocks late Na+ channels, which in effect decreases intracellular Na+, and subsequently decreases intracellular Ca2+ via the Na/Ca exchanger (since extracellular Na+ is increased);
It is also a partial fatty acid oxidation inhibitor, meaning that it enhances glucose metabolism at the expense of lipid metabolism, which translates into more efficient oxygen consumption

Front 549

What is the indication for Ranolazine?

Back 549

Chronic angina in patients in whom other anti-angina drugs have not been effective

Front 550

What drug combinations are useful with calcium channel blockers?

Back 550

Verapamil & nitrates: nitrates offset congestion caused by Verapamil (by reducing pre/afterload);
Diltiazem & β-blockers: additive effects; Nifedipine & β-blockers: β-blockers offset the baroreceptor reflex caused by Nifedipine’s vasodilatory actions

Front 551

What maternal factors are associated with congenital heart disease?

Back 551

Rubella infection during 1st trimester; Drugs (thalidomide, alcohol, phenytoin, lithium, estrogenic steroids); Diabetes

Front 552

What is formed when the septum secundum grows down to join with the endocardial cushions?

Back 552

Foramen ovale (a small hole in the septum secundum allowing blood to flow through it and through the ostium secundum from the right atrium into the left)

Front 553

What does the septum primum join with as it extends downward and what is formed in the process?

Back 553

Septum primum joins with the endocardial cushions thus closing off the ostium primum; however, as this happens, a hole is formed in the septum primum (called the ostium secundum)

Front 554

What are congenital heart defects called that have a permanent right-to-left shunt?

Back 554

Cyanotic: tertralogy of Fallot, truncus arteriosus, tricuspid atresia, complete transposition of the great vessels, total anomalous pulmonary venous connection

Front 555

What are some examples of heart defects that are cyanose tardive?

Back 555

PDA, ASD, VSD, AVSD

Front 556

What are the congenital heart defects called that cause a reversal of flow later in life?

Back 556

Cyanose Tardive: an initial left-to-right shunt progressively increases pulmonary vascular resistance to such levels that right ventricular pressure exceeds that of the left ventricle, at which point the left-to-right shunt is reversed and becomes a right-to-left shunt (patient becomes cyanotic)

Front 557

What are congenital heart defects called that do not have abnormal communication between the two circulations?

Back 557

Acyanotic: coarctation of the aorta, right-sided aortic arch, Ebstein-malformation

Front 558

During what period of embryogenesis do congenital heart defects form?

Back 558

3-8 weeks

Front 559

What happens around the 5th week of gestation regarding the heart?

Back 559

Single chamber heart is divided by interatrial and interventricular septa; also, the formation of atrioventricular valves from endocardial cushions occur

Front 560

Deletion of what gene leads to failure of cardiac myocyte specification?

Back 560

Csx/Mkx2-5 (member of NK homeobox gene family); it is possible for cardiac myocytes to form even with the deletion, but this can lead to a host of other cardiac defects

Front 561

Where do sinus venosus ASDs occur and what other problem is seen with them?

Back 561

Near the entrance of the SVC or IVC; they can be accompanied by an anomalous connection of the right pulmonary veins to the SVC or right atrium

Front 562

What defect can lead to a AVSD?

Back 562

Failure of fusion of the superior and inferior endocardial cushions – leads to inadequate formation of the tricuspid and mitral valves

Front 563

What substance is used to keep a PDA open in infants with multiple congenital heart defects?

Back 563

Prostaglandin E1 (Alprostadil) – NSAIDs are used to close an isolated PDA (Indomethacin)

Front 564

What murmur is associated with a PDA?

Back 564

Harsh, “machine-like” murmur

Front 565

What results in a patient with a PDA?

Back 565

Oxygenated blood from the aorta flows into the deoxygenated blood of the pulmonary artery

Front 566

What is the most common congenital cardiac anomaly?

Back 566

VSD – almost all are associated with the membranous ventricular septum

Front 567

What structures form the interventricular septum?

Back 567

Upward growth of the muscular ventricular septum and downward growth of the membranous ventricular septum

Front 568

What clinical signs are associated with an ASD?

Back 568

Murmur; Volume hypertrophy of the right atrium/ventricle; Irreversible pulmonary hypertension (less common)

Front 569

What is the most common ASD?

Back 569

A defect of the ostium secundum leading to a deficient/fenestrated fossa ovalis

Front 570

In patients with what syndrome are AVSDs common?

Back 570

Down syndrome

Front 571

What other defects can be found in a patient with Tetralogy of Fallot?

Back 571

ASD, right aortic arch; also, the aorta becomes larger in diameter while the pulmonary arteries become smaller and thin-walled

Front 572

How can a patient with Tetralogy of Fallot still get blood to the lungs?

Back 572

Via a PDA or dilated bronchial arteries

Front 573

What clinical findings are associated with Tetralogy of Fallot?

Back 573

Boot-shaped heart (on x-ray); Physical development may be retarded; Cerebral tromboses; Bacterial endocarditis; Brain abscess

Front 574

What causes Tetralogy of Fallot?

Back 574

Anterosuperior displacement of the infundibular septum (leads to stenosis at or around the pulmonary valve)

Front 575

What is the Tetralogy of Fallot?

Back 575

Pulmonary stenosis (obstruction of the right ventricular outflow tract); Right ventricular hypertrophy; Overriding aorta; VSD

Front 576

What is the key clinical sign associated with right-to-left shunts?

Back 576

Cyanosis – “blue babies”

Front 577

What can cause a partial AVSD?

Back 577

Primum ASD (leads to mitral insufficiency)

Front 578

What are fully developed combined atrial and ventricular septal defects called?

Back 578

Persistent common AVSD

Front 579

In what congenital heart defect do all four heart chambers freely communicate?

Back 579

Complete AVSD

Front 580

What causes Truncus Arteriosus?

Back 580

Developmental failure of separation of the embryologic truncus arteriosus into the aorta and pulmonary artery

Front 581

What other heart defects are found with TAPVC?

Back 581

ASD/PFO; Volume/pressure hypertrophy of the right atrium/ventricle; Dilation of right atrium/ventricle/pulmonary trunk; Hypoplastic left atrium; (left ventricle is normal)

Front 582

What causes a Total Anomalous Pulmonary Venous Connection (TAPVC)?

Back 582

The common pulmonary vein fails to develop or becomes atretic; so, instead of pulmonary circulation flowing into the left atrium, they flow into the left innominate (brachiocephalic) vein or to the coronary sinus

Front 583

What other heart defects are found with Tricuspid Atresia?

Back 583

Hypoplasia of the right ventricle; ASD/patent foramen ovale (maintained by right-to-left shunt); VSD

Front 584

What causes Tricuspid Atresia?

Back 584

Unequal division of the AV canal during development; leads to complete occlusion of the tricuspid valve

Front 585

What clinical signs are associated with a Truncus Arteriosus?

Back 585

Systemic cyanosis; Irreversible pulmonary hypertension; CHF; Harsh holosystolic murmur; Widened pulse pressure; Bounding arterial pulses

Front 586

What other heart defect is associated with a Truncus Arteriosus?

Back 586

VSD

Front 587

What are “tet spells”?

Back 587

Acute hypoxia characterized by sudden cyanosis and syncope; patient will feel better in a squatting position since it will shunt more blood to the brain instead of the extremities

Front 588

What signs are associated with TGA?

Back 588

Prominent right ventricular hypertrophy; ASD (present in all patients); VSD and PDA are also common

Front 589

What causes Transposition of the Great Arteries (TGA)?

Back 589

Abnormal formation of truncal and aortopulmonary septa during development; causes the aorta to come off the right ventricle whereas the pulmonary artery comes off the left ventricle

Front 590

What causes an Ebstein Malformation?

Back 590

Downward displacement of an abnormal tricuspid valve into an underdeveloped right ventricle; there will be functional hypoplasia of the right ventricle, and tricuspid regurgitation or stenosis

Front 591

How does pulmonary stenosis usually present?

Back 591

As part of a complex anomaly (e.g. Tetralogy of Fallot)

Front 592

What clinical signs are associated with aortic coarctation without PDA?

Back 592

Enlarged intercostal/internal mammary arteries; Notching of the undersurfaces of ribs (on x-ray); Systolic murmur; Thrill; Cardiomegaly

Front 593

How does the presentation of aortic coarctation differ with and without a PDA?

Back 593

With PDA: presents early in life with cyanosis to lower half of the body (require immediate intervention); Without PDA: asymptomatic until adulthood, will have hypertension in upper extremities and weak pulses in lower extremities

Front 594

What differentiates between the infantile and adult forms associated with coarctation of the aorta?

Back 594

Infantile: tubular hypoplasia of the aortic arch; Adult: discrete ridge-like infolding of the aorta

Front 595

What genetic abnormality is associated with coarctation of the aorta?

Back 595

Turner syndrome

Front 596

What signs/symptoms are associated with an Ebstein malformation that can be potentially lethal?

Back 596

Attacks of supraventricular tachycardia; Wolfe-Parkinson-White syndrome (direct connection between SA node and ventricle, bypassing the modulatory actions of the AV node) – can lead to sudden death

Front 597

What causes Hypoplastic Left Heart syndrome?

Back 597

Severe underdevelopment of the left side of the heart, leading to hypoplasia of the left ventricle and ascending aorta, hypoplasia of the left-sided valves, and severe aortic valve stenosis/atresia;

Front 598

How does blood get into systemic circulation with Hypoplastic Left Heart syndrome?

Back 598

After flowing into the left atrium, a left-to-right shunt forces flow back into the right atrium; from here it goes into the right ventricle, out the pulmonary artery, and then through a PDA into systemic circulation

Front 599

How does an infant with Hypoplastic Left Heart syndrome present?

Back 599

They will initially appear well, but quickly become short of breath; most will die within the first month if they don’t receive surgical treatment

Front 600

What are the three types of aortic stenosis and how do they differ?

Back 600

Valvular: due to hypoplastic/dysplastic cusps or cusps abnormal in number, seen in Hypoplastic Left Heart syndrome; Subvalvular: due to a thickened ring/collar, dense endocardial stenosis;
Supravalvular: inherited form with ascending aorta wall thickening (due to defect in elastin gene)

Front 601

What is dextrocardia?

Back 601

Displacement of the heart to the right, which can be due to complete transposition of the right and left chambers; often associated with severe cardiovascular anomalies

Front 602

What causes Endocardial Fibroelastosis?

Back 602

Fibroelastic thickening of the endocardium in the left ventricle

Front 603

What clinical signs are associated with aortic stenosis?

Back 603

Prominent systolic murmur; Thrill; Pressure hypertrophy of left ventricle; Sudden death can occur with exertion

Front 604

What keeps electrical signals in the heart from traveling both ways through their gap junctions?

Back 604

Their inherent refractory period

Front 605

What does lengthening of the PR interval imply?

Back 605

Slowing of AV conduction

Front 606

What does a broadened QRS wave imply?

Back 606

Slowing of ventricular depolarization (ex. through drugs that inhibit the opening of voltage-gated sodium channels)

Front 607

What does lengthening of the QT interval imply?

Back 607

Lengthening of the ventricular action potential

Front 608

What are the three types of aortic stenosis and how do they differ?

Back 608

Valvular: due to hypoplastic/dysplastic cusps or cusps abnormal in number, seen in Hypoplastic Left Heart syndrome; Subvalvular: due to a thickened ring/collar, dense endocardial stenosis;
Supravalvular: inherited form with ascending aorta wall thickening (due to defect in elastin gene)

Front 609

What are the phases of the ventricular myocyte AP associated with?

Back 609

Phase 0: opening of Na channels; Phase 1: opening of K channels; Phase 2: opening of Ca channels (plateau); Phase 3: inactivation of Ca channel/opening of K channels; Phase 4: myocytes are waiting for stimulus

Front 610

What are the phases of the SA/AV nodal cell AP associated with?

Back 610

Phase 0: opening of Ca channels; Phase 3: opening of K channels; Phase 4: If/“funny current”/Na-K leakage current

Front 611

What anatomical defect can cause arrhythmias?

Back 611

Wolff-Parkinson-White syndrome: accessory pathways

Front 612

What are early afterdepolarizations (EADs) and what can they lead to?

Back 612

A spontaneous depolarization that occurs during the latter part of the repolarization; caused by a lengthening of the QT interval (e.g. by blocking K channels) which delays the inactivation of Na/Ca channels – EADs can lead to torsades de pointes

Front 613

How do functionally defined reentrant signals cause tachyarrhythmias?

Back 613

A region of Purkinje fibers is damaged (e.g. due to MI) and does not allow the propagation of active Na APs through that region --> this means that the anterograde signal coming from the Purkinje fibers encounters resistance as it travels down to innervate the myocardium --> at the same time, signals that traveled down through non-impeded Purkinje fibers have already activated the myocardium and these signals now reach the opposite side of the damaged region --> the signal from the myocardium is much larger (since there is more tissue on that end) and is able to passively cross the damaged region in a retrograde manner to cause a functionally defined loop

Front 614

How do anatomically defined accessory pathways (e.g. with Wolff-Parkinson-White) cause tachyarrhythmia?

Back 614

The signal from the SA node travels through both the AV node and the accessory pathway --> in the AV node, conduction is slowed whereas in the accessory node it is not --> once the signal exists the AV node, the accessory node has already recovered from the AP and will now conduct the AV node signal in a retrograde fashion --> this sends the signal back up to the AV node and in effect creates a continuous loop of APs that is independent of the SA node which causes tachycardia

Front 615

What do ectopic pacemakers cause?

Back 615

Impulses initiated in locations other than the SA node

Front 616

What does Sick sinus syndrome cause?

Back 616

Alternating periods of bradycardia and tachycardia caused by a dysfunctional SA node

Front 617

What does hypokalemia cause?

Back 617

Broadening of the AP/QT interval

Front 618

What does responsiveness refer to?

Back 618

Rate of depolarization of Vm during phase 0

Front 619

What does conduction velocity depend on?

Back 619

Number of open channels per unit area

Front 620

What are two common types of mutations that cause arrhythmias?

Back 620

Gain of function: Na channels that don’t inactivate; Loss of function: K channels that don’t conduct

Front 621

What are strategies for decreasing arrhythmic activity, using drugs that decrease activity in reentrant circuits?

Back 621

Decrease conduction velocity: Na/Ca channel blockers (cause complete block in reentrant circuit);
Increase refractory period (in accessory pathways): K channel blockers

Front 622

What are the effects of Class III antiarrhythmic drugs?

Back 622

K channel blockade, leading to slowed repolarization (↑QT), ↑AP duration, and ↑refractoriness

Front 623

How do Class II antiarrhythmic drugs exert their effects and what are those effects?

Back 623

As β-blockers they decrease cAMP in the cell and in effect decrease Ca channel recruitment; this leads to an overall decrease in intracellular Ca; because of this mechanism, Class II drugs will ↓AV conduction (= ↑PR), ↓HR, ↓Ca overload, and ↓triggering by DAD

Front 624

What are the subdivisions of the Class I antiarrhythmic drugs and what characterizes each?

Back 624

Class IA: medium-affinity block of Na and K channels (class III effect), ↑QRS and ↑QT
Class IB: low-affinity block of Na channels, use-dependent, ↓QT
Class IC: high-affinity block of Na channels, ↑QRS, small effect on repolarization

Front 625

What are the main classes of the Singh-Vaughan Williams classification of antiarrhythmic drugs?

Back 625

Class I: Na channel blockers
Class II: β-blockers
Class III: K channel blockers
Class IV: Ca channel blockers

Front 626

What are strategies for decreasing arrhythmic activity, using drugs that functionally isolate the ventricular rhythm from atrial arrhythmias?

Back 626

Decrease AV conduction: CCBs, β-blockers, adenosine, and vagal stimulation

Front 627

What are strategies for decreasing arrhythmic activity, using drugs that decrease triggering (i.e. DADs)?

Back 627

Increase threshold potential: Na channel blockers; Decrease cytosolic Ca: CCBs and β-blockers

Front 628

What causes delayed afterdepolarization (DAD)?

Back 628

Ca overload causes excess activation of the Na/Ca exchanger which in turn generates a Na current that creates an AP; can occur with β-receptor stimulation and with digitalis glycosides

Front 629

What causes atrial flutter/fibrillation?

Back 629

Reentrant circuits in the right atrium

Front 630

What are strategies for decreasing arrhythmic activity, using drugs that decrease automaticity?

Back 630

Increase max. diastolic Vm (i.e. hyperpolarize membrane during diastole): adenosine and vagal stimulation (both hyperpolarize cells by opening K channels, although by different mechanisms);
Decrease phase 4 slope (If): β-blockers and vagal stimulation; Increase threshold potential: Na/Ca channel blockers; Increase refractory period: K channel blockers

Front 631

Which S-V W Classes are useful in treating atrial fibrillation and why?

Back 631

Class III: ↑refractoriness; Class IA/IC: slow conduction; Class II/IV/Digitalis/adenosine: ↓AV conduction – adenosine is added here since it is given IV (emergency situations)

Front 632

Which drug can cause an increase in DADs and why?

Back 632

Digitalis, since it increases intracellular Ca indirectly by blocking the Na/K-ATPase which decreases the effectiveness of the Na/Ca exchanger

Front 633

Which S-V W Classes are associated with toxicities leading to EADs/torsades de pointes and increased reentry, respectively?

Back 633

EADs/torsades de pointes: IA/III, since both cause K channel blockade which leads to ↑QT;
Increased reentry (proarrhythmia): IC, since it can slow conduction in less damaged regions, forming another reentry circuit

Front 634

Which treatments are useful for torsades de pointes and why?

Back 634

Remove QT-prolonging drug; If genetic: Mg (required for processing of K)

Front 635

Which S-V W Classes are useful in treating VT caused by DADs and why?

Back 635

Class II/IV: ↓intracellular Ca

Front 636

Which S-V W Classes are useful in treating ventricular tachycardia (VT) and why?

Back 636

Class IA/IB/IC: blocking of Na channels (slows conduction); Class III: ↑refractoriness

Front 637

Which S-V W Classes are useful in treating AV nodal reentry and why?

Back 637

Class II/IV/Digitalis/adenosine: ↓AV conduction; Class IC: high-affinity block of Na channels in the case of an accessory pathway

Front 638

What are the effects of Class IV antiarrhythmic drugs?

Back 638

Ca channel blockade, leading to decreased intracellular Ca; this will be effective in slow-response cells (SA/AV nodes), causing ↓responsiveness, ↓AV conduction (= ↑PR), ↓DAD, ↑refractoriness; can uncouple ventricular rhythm from atrial arrhythmia

Front 639

Which S-V W Classes are useful in treating nodal automaticities and why?

Back 639

Class II/IV: both cause a decrease in intracellular Ca and Ca influx (↓AV conduction)

Front 640

Which S-V W Classes are useful in treating atrial flutter and why?

Back 640

Class III: ↑refractoriness decreases reentrant circuits; Class II/IV/Digitalis: ↓AV conduction

Front 641

Which S-V W Classes are associated with toxicities leading to depression of LV function and why?

Back 641

Class II/IV: ↓intracellular Ca

Front 642

What is the usefulness of digitalis regarding arrhythmias?

Back 642

Its “vagotonic” actions promoting the release of ACh from vagal nerve terminals; (not its effects on phase 4 slope and automaticity) – digitalis does produce harmful DADs

Front 643

What is the usefulness of adenosine regarding arrhythmias?

Back 643

It has a very short half-life (<10 sec), so it can be given IV to inhibit AV nodal arrhythmias, and once the arrhythmia has been treated, the effects of the drug will cease within seconds

Front 644

Which drugs are mainly associated with a Class IV effect regarding the S-V W system?

Back 644

Verapamil/Diltiazem (suppress DADs, negative inotropy, hypotension)

Front 645

Which drugs are mainly associated with a Class III effect regarding the S-V W system?

Back 645

Sotalol (d isomer), Amiodarone (many effects, long half-life, little risk of torsades de pointes), Dofetilide/Ibutilide (very K channel specific, high risk of torsades de pointes)

Front 646

Which drugs are mainly associated with a Class II effect regarding the S-V W system?

Back 646

Propranolol, Esmolol (IV only), Sotalol (l isomer: class II/III, d isomer: class III; both ↑EADs)

Front 647

Which drugs are mainly associated with a Class I effect regarding the S-V W system?

Back 647

Class IA: Quinidine (many effects, high risk of torsades de pointes), Procainamide, Disopyramide;
Class IB: Lidocaine (rapid metabolistm, given IV, ↑mortality post-MI), Mexiletine (given PO);
Class IC: Flecainide (does not produce EADs), Propafenone (Propranolol deriv., Class II effects)

Front 648

Which S-V W Classes are associated with toxicities leading to sinus bradycardia and AV block, respectively?

Back 648

Sinus bradycardia: Class II/IV due to ↓AV conduction, Class III due to ↑refractoriness;
AV block: Class II/IV due to ↓AV conduction

Front 649

Which S-V W Classes are associated with toxicities leading to infranodal conduction block and why?

Back 649

Class IA/IB/IC: blocking of Na channels can lead to a block of ventricular signal propagation, which can be lethal

Front 650

Which S-V W Classes are associated with toxicities leading negative inotropism and why?

Back 650

Class IA/IB/IC: ↓rate of depolarization; Class IV: ↓Ca entry

Front 651

What adverse effects are associated with Amiodarone?

Back 651

Pulmonary fibrosis (can be fatal), phospholipidosis; increases Digoxin levels; thyroid/hepatic dysfunction; CNS disturbance; Photosensitive reactions

Front 652

What non-drug therapies have been successful in the treatment of arrhythmias?

Back 652

Radio-frequency catheter ablation; Implantable converter/defibrillator

Front 653

Which antiarrhythmic drugs are known to reduce mortality with chronic treatment?

Back 653

β-blockers and (maybe) Amiodarone

Front 654

What did the CAST clinical trial elicit?

Back 654

Class IC drugs (e.g. Flecainide) uncover latent reentrant circuits and can increase mortality

Front 655

What did the AFFIRM clinical trial elicit?

Back 655

Treatment of rate control in atrial fibrillation is more important than rhythm control

Front 656

What drugs should not be used in patients with Wolff-Parkinson-White syndrome with atrial fibrillation and why?

Back 656

Digitalis, Verapamil, Diltiazem – since blocking AV conduction in this case will shunt all of the electrical signals from the atrial fibrillation through the accessory pathway, thus significantly increasing the rate of ventricular contraction

Front 657

What adverse effects are associated with Digitalis?

Back 657

Hyperkalemia, GI disturbance

Front 658

What adverse effects are associated with Quinidine?

Back 658

Diarrhea, cinchonism (tinnitus, HA, nausea, dizziness), hypersensitivity reactions

Front 659

What adverse effects are associated with Procainamide, Disopyramide, Lidocaine/Mexiletine, and Propafenone?

Back 659

Procainamide: Lupus-like syndrome; Disopyramide: anti-muscarinic effects; Lidocaine/Mexiletine: neurologic effects; Propafenone: 2D6 metabolism

Front 660

What is the most important ADH receptor in maintaining fluid balance?

Back 660

V2 receptors in the collecting duct --> leads to aquaporin-2 expression --> increased water permeability

Front 661

Besides extrarenal and diuretic causes of hypovolemic hyponatremia, what other less common issues can be responsible?

Back 661

Salt-losing nephropathy (advanced kidney disease with renal Na/K wasting); Mineralocorticoid deficiency (urine sodium>20, high serum K); Osmotic diuresis (glucosuria, urea diuresis after obstruction relief); Cerebral salt wasting

Front 662

How can hypovolemic hyponatremia present with high urine sodium?

Back 662

If the patient is on diuretics (thiazides > loop diuretics), a loss of fluid volume can cause hypovolemic-stimulated ADH release which will conserve free water but not sodium

Front 663

How can hypovolemic hyponatremia be caused?

Back 663

High GI loss of water or third-spacing along with free water intake (i.e. patient is losing isotonic fluids and taking in hypotonic fluids) --> this leads to nonosmotic release of ADH --> causes the kidney to conserve water as well as sodium and chloride (i.e. patient will have low urine sodium)

Front 664

What causes pseudohyponatremia?

Back 664

Errors in the lab calculation of sodium levels; can be due to severe hypertriglyceridemia or paraproteinemias

Front 665

What is translocational hyponatremia?

Back 665

Hyponatremia due to substances that increase osmolality (e.g. glucose); not a true hyponatremia since it is caused by sodium compensation due to the increase of another osmole

Front 666

What causes hypo- and hypernatremia, respectively?

Back 666

Hyponatremia: defect in urine-diluting capacity coupled with excess water intake;
Hypernatremia: defect in urine-concentrating capacity coupled with inadequate water intake

Front 667

How is plasma osmolality calculated?

Back 667

2x[Na+] + glucose/18 + BUN/8 --> normal range is 275-290 mosm/kg

Front 668

What two stimuli have a role in ADH secretion?

Back 668

Osmotic stimuli: effective osmoles (since they enhance water movement out of the cell, decreasing cell volume); Nonosmotic stimuli: decreased effective circulating volume, nausea, postoperative pain, pregnancy

Front 669

What is the difference between effective and ineffective osmoles?

Back 669

Effective osmoles (hypertonic saline, mannitol) cannot cross the cell membrane whereas ineffective osmoles (urea, methanol, ethanol) can

Front 670

What are causes of euvolemic hyponatremia?

Back 670

Glucocorticoid deficiency: impaired water excretion, but normal sodium excretion;
Severe hypothyroidism: reduction in cardiac output is a nonosmotic stimulus for ADH release;
Drugs; SIADH: defect in osmoregulation leading to inappropriate ADH secretion

Front 671

What is the treatment associated with SIADH?

Back 671

Water restriction; saline can worsen hyponatremia (since the kidney is handling salt normally, but not water)

Front 672

What is the treatment associated with hypervolemic hyponatremia?

Back 672

Water removal via loop diuretics; no additional sodium given; patient’s water intake is restricted

Front 673

What is the treatment associated with hypovolemic hyponatremia?

Back 673

Normal saline (since this will correct the hypovolemia --> halts excessive ADH secretion --> normalizes sodium levels)

Front 674

What can be inferred if the urine osmolality of a patient is <100 mosm/L?

Back 674

They are not producing ADH (everything else being equal)

Front 675

What physical signs give a clue regarding the patient’s volume status?

Back 675

Mucus membranes, skin turgor; Edema; Orthostatic drop in blood pressure; Weight gain

Front 676

What are the clinical signs of SIADH?

Back 676

Low serum osmolality (<270); Inappropriate urine concentration (>100); Clinical euvolemia; Elevated urine sodium levels – must rule out other causes of euvolemic hyponatremia

Front 677

How is hypervolemic hyponatremia caused in a patient with CHF?

Back 677

Low CO --> reduced effective circulating volume --> nonosmotic ADH stimulation --> increased free water retention and sodium excretion; patients will have also have a strong thirst stimulation in response to their decreased CO

Front 678

How can nephrotic syndrome and advanced chronic kidney disease lead to hypervolemic hyponatremia?

Back 678

Nephrotic syndrome: either through a renal defect in sodium excretion or through protein loss which leads to lowered plasma oncotic pressure and intravascular volume depletion;
Advanced chronic kidney disease: can lead to an increase in sodium excretion to counteract the loss of nephrons

Front 679

How can liver disease lead to hypervolemic hyponatremia?

Back 679

There is vasodilation and AV fistulas which leads to a decrease in mean arterial BP and effective CO --> this is a nonosmotic stimulus for ADH secretion

Front 680

What formula can be used to determine the change in sodium after giving them 1L of saline?

Back 680

[ ([Na]fluid – [Na]serum)/(0.6 x weight + 1) ]; 0.6 is used for men/0.5 for women

Front 681

How can Diabetes Insipidus cause euvolemic hypernatremia?

Back 681

Since there is a defect in ADH action (central/secretion vs. nephrogenic/receptor), the patient will have polyuria; they compensate for this through polydipsia; however, if they cannot take in their excess amount of water (e.g. during a hospital stay) they will become hypernatremic

Front 682

What are causes of euvolemic hypernatremia?

Back 682

Lack of access to free water (young, elderly); Extrarenal causes (insensible losses: respiratory, dermal); Renal causes (hypodipsia, Diabetes Insipidus)

Front 683

What are causes of hypervolemic hypernatremia?

Back 683

Hypertonic solutions (3% saline, NaHCO3), salt tablets

Front 684

What are causes of hypovolemic hypernatremia?

Back 684

Loss of hypotonic water: kidney loss (osmotic/loop diuretics, postobstructive injury), extrarenal loss (burns, diarrhea, fistulas)

Front 685

What normally prevents people from becoming hypernatremic?

Back 685

Thirst – people do not typically become hypernatremic if they have access to water

Front 686

What is the major problem with overly rapid correction of hyponatremia?

Back 686

Since the brain cells have adapted to the hyponatremia, correcting it too rapidly may result in cerebral dehydration and demyelination --> central pontine myelinolysis --> paraparesis, quadriparesis, dysarthria, dysphagia, coma

Front 687

What is the maximum rate of correction for sodium levels and what is given to hyponatremic patients in an emergency setting?

Back 687

Max. rate: <12meq/L/day; Emergency: hypertonic saline (max. rate still applies)

Front 688

How is the amount of saline required to correct a patient’s hyponatremia determined?

Back 688

[Total body water x Na+ deficit/L] – can use 3% saline (513meq/L), normal saline (154meq/L), ½ saline (77meq/L) or D5W (0meq/L)

Front 689

How is chronic asymptomatic hyponatremia treated?

Back 689

Fluid restriction

Front 690

How is the diagnosis of Diabetes Insipidus made?

Back 690

Polyuria, polydipsia, urine osmolality<serum osmolality; By giving the patient dDAVP (synthetic vasopressin) and seeing if the kidney responds (central problem) or not (nephrogenic problem)

Front 691

What happens when the sodium levels are corrected too rapidly in hypernatremia?

Back 691

Rapid correction will lead to cerebral edema (seizures, neurological damage, death); correction rate should be 0.5meq/L/hour

Front 692

What is the treatment for hypernatremia?

Back 692

Apply same concepts as for hyponatremia (i.e. change in Na after 1L formula)

Front 693

What drugs are used for slowing ventricular rate?

Back 693

BB (Metoprolol), Diltiazem (and some Verapamil), Digoxin – a combination of a BB and Digoxin is most effective

Front 694

What drugs used for the maintenance of sinus rhythm are used in a patient with HTN and LVH?

Back 694

Amiodarone; or catheter ablation if treatment is unsuccessful

Front 695

What drugs used for the maintenance of sinus rhythm are first-line in a patient no heart disease?

Back 695

Flecainide, Propafenone, Sotalol; if those fail, Amiodarone, Dofetilide, or catheter ablation are useful – same drugs are also used in patients with hypertension, but with no substantial LVH

Front 696

What is the biggest danger in giving a patient Dofetilide?

Back 696

QT prolongation (since it has Class III effects) – however, Dofetilide is safer than other drugs in patients with CAD or heart failure; with CAD Sotalol/Amiodarone can also be used, and in heart failure Amiodarone is an option (not Sotalol due to its negative inotropic effects)

Front 697

Which drugs are used for rhythm control of A-fib?

Back 697

Dofetilide, Sotalol, Amiodarone, Propafenone, Flecainide; Ibutilide is for acute treatment only

Front 698

What is the danger of blocking AV conduction in a patient with WPW in A-fib?

Back 698

Signals traveling through the AV node go to the accessory pathway and cause a “road block”; by removing this mechanism, signals from the A-fib will be able to travel through the accessory pathway unobstructed, leading to a much greater ventricular rate

Front 699

What is required along with ablative therapy for A-fib?

Back 699

A pacemaker to take over the ventricular rhythm

Front 700

What antiarrhythmic drugs are used in emergency situations?

Back 700

Amiodarone (cardiac arrest with VT or V-fib), BB/Diltiazem (rate-control of A-fib),
Adenosine (termination of SVT: AV nodal or AP reentry)

Front 701

What is the therapeutic approach for A-fib?

Back 701

Slow ventricular rate (AV blocking drugs); Restoration of sinus rhythm (antiarrhythmic drug/DC shock); Anticoagulation (Heparin/Warfarin)

Front 702

What symptoms are associated with atrial fibrillation?

Back 702

Palpitations, dyspnea, fatigue, chest discomfort, lightheadedness, syncope – major risk with A-fib is thromboemboli in the left atrial appendage due to stagnating blood (consider anticoagulation)

Front 703

What drug might be considered in people with benign premature ventricular beats?

Back 703

BB (Propranolol), although therapy is not needed nor indicated

Front 704

Which antiarrhythmic drugs are associated with renal and hepatic elimination, respectively?

Back 704

Renal: Sotalol, Dofetilide, Digoxin; Hepatic: Propafenone, Amiodarone, Lidocaine

Front 705

What drug interactions are associated with Amiodarone, Dofetilide, and Propafenone?

Back 705

Amiodarone: increases Warfarin, Digoxin, Cyclosporine; Dofetilide: metabolized by CYP3A4 and P-glycoprotein transport; Propafenone: increases Digoxin, Warfarin, and increased by Cimetidine

Front 706

What treatment is effective in V-fib?

Back 706

Asynchronous shock; if not effective, include Epinephrine and subsequently Amiodarone

Front 707

Which drugs reduce the need for ICD shocks?

Back 707

Sotalol and Amiodarone

Front 708

What treatment is effective in sustained ventricular tachycardia in patient presenting with hypotension, angina, or heart failure?

Back 708

Direct current (DC) shock after sedation; if chronic: ICD

Front 709

What treatment is effective in non-sustained ventricular tachycardia?

Back 709

ICD (implantable cardioverter-defibrillator)

Front 710

What treatment choice is more effective in atrial flutter as compared to A-fib?

Back 710

Catheter ablation (since destroying one reentry loop is easier than taking out multiple entities)

Front 711

What is the main therapy for Paroxysmal Supraventricular Tachycardia?

Back 711

Adenosine (slows AV conduction) – avoid with asthma, dipyridamole (increases effect by blocking cell uptake), theophylline (reduced effect by blocking receptors)

Front 712

What is the calculation used for BMI?

Back 712

for kg/m2: Weight/(Height)2; for lb/in2: (Weight x 703)/(Height)2

Front 713

Where and when is Ghrelin produced?

Back 713

By the stomach when it is empty

Front 714

What type of drug is Rimonabant?

Back 714

Endogenous canabinoid

Front 715

What main side effect do appetite suppressants have in common and what is the exception?

Back 715

They are stimulants (HR, BP, insomnia) – the exception is Orlistat which is a lipase inhibitor; its main side effects are gastric problems (diarrhea, flatulence, bloating, etc.)

Front 716

What symptoms are often seen in conjunction with mitral stenosis?

Back 716

Atrial fibrillation (palpitations), thromboembolism (stroke), endocarditis, right heart failure, hoarseness (recurrent laryngeal nerve paralysis)

Front 717

What is factor determines the severity of symptoms of a patient with mitral regurgitation?

Back 717

LV function

Front 718

What is the difference between acute and chronic mitral regurgitation?

Back 718

Acute: inadequate compensation, causes an increase in LA pressure without dilation, which leads to pulmonary congestion/edema; Chronic: time for compensation to occur (increased LA size, LV dilation/eccentric hypertrophy, increased LVEF with normal SV) but eventually leads to progressive worsening LVEF/CO

Front 719

What is the pathophysiology of mitral regurgitation?

Back 719

LV volume overload --> portion of LVSV ejected into low pressure LA --> enlarged LA/LV (eccentric) --> increased SV/EDV

Front 720

What is the etiology for mitral regurgitation?

Back 720

Degenerative (prolapse, Marfan); Papillary muscle dysfunction; Dilated LV; Infective endocarditis; Mitral annular calcification; Rheumatic heart disease

Front 721

What physical findings are associated with mitral stenosis?

Back 721

Increased S1 (more prominent) due to high LA pressure; Opening snap prior to diastole (audible leaflet opening); Diastolic rumble (low pitch, occurs during diastole, severity is related to length of rumble but not intensity, best heard in L lateral decubitus position); L parasternal heave (with increased P2); Right heart failure

Front 722

What describes the latent period of mitral stenosis?

Back 722

It is very long (~20 years)

Front 723

What is the most common etiology for mitral stenosis?

Back 723

Younger people: rheumatic fever; Older people: calcific

Front 724

What symptoms are associated with mitral stenosis?

Back 724

Dyspnea (early: dyspnea of exertion, later: paroxysmal nocturnal dyspnea), fatigue, hemoptysis

Front 725

What symptoms are associated with aortic stenosis?

Back 725

Dyspnea (due to CHF); Angina (often with CAD); Syncope (with exertion)

Front 726

What is the natural history of aortic regurgitation?

Back 726

Depends on rapidity of onset; LV function preserved early --> gradual fall of EF seen (but EF fall may precede symptoms)

Front 727

What is the difference between acute and chronic aortic regurgitation?

Back 727

Acute: inadequate compensation, causes an increase in LV diastolic pressure and LA pressure without dilation, which leads to pulmonary congestion/edema; Chronic: time for compensation to occur (LV dilation/eccentric hypertrophy, increased LVEF/SV, widened pulse pressure), but eventually leads to progressive worsening of LVEF/CO

Front 728

What is the pathophysiology of aortic regurgitations?

Back 728

Regurgitation from aorta to LV during diastole --> volume overload of LV --> eccentric hypertrophy (increased LV/LA size, increased SV/EDV)

Front 729

What etiologies are associated with aortic regurgitation?

Back 729

Abnormalities of leaflets (bicuspid, endocarditis, rheumatic); Dilation of the aortic root (degenerative/ectasia, aortic dissection, Marfan)

Front 730

What physical findings are associated with aortic stenosis?

Back 730

Systolic ejection murmur; Decreased A2 (leaflet immobility); Delayed carotid upstroke (may go unnoticed in elderly due to carotid hardening); Carotid shudder/suprasternal notch thrill (seen with bicuspid aortic valve)

Front 731

What must be done when the patient with aortic stenosis becomes symptomatic?

Back 731

Immediate aortic valve replacement

Front 732

What physical findings are associated with mitral regurgitation?

Back 732

Holosystolic murmur (in MV area); Displaced PMI (point of maximal impulse);
L parasternal heave; MV prolapse (systolic click and late systolic murmur)

Front 733

What is the pathophysiology of aortic stenosis?

Back 733

Pressure overload of LV due to increased afterload  concentric hypertrophy --> LV to aorta pressure gradient; there will be normal chamber size (early on)

Front 734

What etiologies are associated with aortic stenosis?

Back 734

Calcific: senile/degenerative (>65); Congenital bicuspid valve (<65); Rheumatic disease (95% with MV involvement as well)

Front 735

What physical findings are associated with aortic regurgitation?

Back 735

Low blowing diastolic murmur; Widened pulse pressure (bounding pulses); Displaces PMI (if significant/chronic)

Front 736

What characterizes pulmonary regurgitation?

Back 736

Can be caused by pediatric congenital surgeries; also, secondary to pulmonary hypertension; Physical findings will be similar to AR (e.g. RV eccentric hypertrophy)

Front 737

What characterizes pulmonary stenosis?

Back 737

Usually congenital; gradient between PA and RV in systole; Physical findings can include a systolic ejection murmur that increases with inspiration

Front 738

What characterizes tricuspid regurgitation?

Back 738

Usually due to pulmonary hypertension or RV annulus dilation; symptoms will be similar to those of right heart failure; Physical findings will be similar to MR except sounds increase on inspiration; also, neck vein distention (with prominent v waves) and a pulsatile liver can be seen

Front 739

What characterizes tricuspid stenosis?

Back 739

Often associated with rheumatic disease; Physical finding similar to MS except sounds increase with inspiration (due to the increase in blood volume that occurs during inspiration); also, neck vein distention can be seen

Front 740

How is the quality of pain associated with angina pectoris described?

Back 740

Pain, pressure, burning, tightness

Front 741

What are the most common GI causes of chest pain?

Back 741

Esophageal reflux (GERD, rarely radiates) > Esophageal spasms (mimics angina) > Peptic ulcers > Biliary disease

Front 742

Besides the most common cause of angina pectoris (atherosclerosis), what other disease can cause these symptoms?

Back 742

Syndrome X (ischemia, normal arteries); Coronary spasm (epicardial arteries); Aortic valve disease (stenosis)

Front 743

What is the difference between stable and unstable angina?

Back 743

Stable: due to stable coronary artery plaques (i.e. reduced flow related to stenosis), presents on exertion, it is predictable, and its course unchanging; Unstable: presents at rest, nocturnally, or with minimal exertion, it is unpredictable, and its course changing

Front 744

What other discomfort is relieved by nitroglyerin?

Back 744

Esophageal spasm

Front 745

How long does it take for nitroglycerin to take effect?

Back 745

1-5 minutes (it’s not instant and will not last longer than 20 min) – must be sure to see whether the nitroglycerin is still good (i.e. it hasn’t been exposed to the environment for too long)

Front 746

What activities is the onset of angina associated with and how long does it normally last?

Back 746

Related to exertion, eating, emotion, coitus, cold exposure – usually lasts 30 sec. to minutes

Front 747

What are the key differences between superficial and visceral chest pain?

Back 747

Superficial: pain specific fibers, felt as “pain”, well localized, pain related to movement;
Visceral: autonomic fibers, felt as a vague sensation which may not be “pain”, poorly localized

Front 748

What is the definition of angina pectoris?

Back 748

A visceral quality discomfort anywhere between the nose and the umbilicus that comes on with exertion, emotion, or other activity that either increases HR, BP, inotropic state of the heart, or heart size or decreases oxygen supply; and that abates with rest, subsidence of emotion, or resolution of either the increases in the determinants of myocardial oxygen demand or decreases in oxygen supply

Front 749

What techniques should be done on physical exam for chest pain?

Back 749

Check for chest wall tenderness; Passive limb movement; Auscultate the chest

Front 750

What are some common pulmonary causes of

Back 750

chest pain?
Pneumonia (fever, sputum); Pulmonary embolus (dyspnea); Pneumothorax (absence of breath sounds); Pleurisy (URI)

Front 751

What are some miscellaneous causes of chest pain?

Back 751

Pericarditis (relieved by sitting up and leaning forward, pericardial friction rub, EKG changes); Aortic dissection (tearing quality pain with radiation into the back, abnormalities of pulses)

Front 752

What are some common musculoskeletal causes of chest pain?

Back 752

Costochondritis (most common, tender); Xiphodynia; Precordial catch (relief by chest splinting)

Front 753

What defines situational couple violence?

Back 753

Violence that arises out of conflicts that lead to arguments and then to violence (most common form in every day life)

Front 754

What questions should be avoided during the domestic violence interview?

Back 754

“What keeps you with someone like that”; “What did you do that caused him to hit you”; “How long are you going to put up with this”; Why don’t you just leave”; “Do you realize you are a battered woman” (avoid stigmatisms)

Front 755

What behavioral health effects are associated with domestic violence?

Back 755

Chronic pain syndromes, substance abuse, sleep disturbances, chronic fatigue, anxiety/panic disorders PTSD, hypervigilance, depression, suicidal ideation/attempts

Front 756

What adverse health effects are associated with domestic violence?

Back 756

Homicide, acute injury, chronic headaches, chronic abdominal pain, pelvic pain, recurrent STDs/UTIs, musculoskeletal complaints, eating disorders

Front 757

What is a key difference between the female and male victims of intimate terrorism?

Back 757

Women are more likely to be injured by the violence

Front 758

What is the prevalence of intimate terrorism (when looking at rape and/or physical assault)?

Back 758

In the past year: women 1.5%, men 0.9%; During lifetime: women 25%, men 7.6%

Front 759

What defines mutual violent control?

Back 759

Both partners are violent and controlling, while battling for control in a relationship (not sure this exists, very rare)

Front 760

What are the typologies of partner violence?

Back 760

Intimate terrorism, violent resistance, situational couple violence, mutual violent control

Front 761

What defines violent resistance?

Back 761

Violence used in resistance to an intimate terrorist (can be self-defensive, like payback)

Front 762

What defines intimate terrorism and what characterizes it?

Back 762

One partner uses violence along with emotional/psychological abuse to maintain control over the other; most commonly done by the male, more likely to escalate over time, most often seen by police/hospitals

Front 763

What is the role of the physician in patients with domestic violence?

Back 763

Communicate concern, offer information, provide medical treatment, review options (refer as necessary), initiate safety planning

Front 764

What is the role of the physician in patients with domestic violence?

Back 764

Communicate concern, offer information, provide medical treatment, review options (refer as necessary), initiate safety planning

Front 765

What does the mnemonic RADAR stand for?

Back 765

Remember to ask about domestic violence; Ask direct questions; Document findings;
Assess safety; Review options – also, know the local resources available to the patient

Front 766

What does the mnemonic RADAR stand for?

Back 766

Remember to ask about domestic violence; Ask direct questions; Document findings;
Assess safety; Review options – also, know the local resources available to the patient

Front 767

What are the rules regarding the reporting of domestic violence to law enforcement?

Back 767

Domestic violence is not a reportable condition (unless there is an attempt at lethal violence)
and should only be reported if the victim requests it

Front 768

What are the rules regarding the reporting of domestic violence to law enforcement?

Back 768

Domestic violence is not a reportable condition (unless there is an attempt at lethal violence)
and should only be reported if the victim requests it

Front 769

What should be included in the medical documentation of domestic violence cases?

Back 769

Written information recorded in quotations; Body charts and injury maps; Photographs –
Do not speculate, be vague, victimize the victim

Front 770

What should be included in the medical documentation of domestic violence cases?

Back 770

Written information recorded in quotations; Body charts and injury maps; Photographs –
Do not speculate, be vague, victimize the victim

Front 771

What information should be provided to the patient?

Back 771

IPV is common, IPV often escalates over time, IPV has adverse effects on children, there are resources in the community to help the patient

Front 772

What information should be provided to the patient?

Back 772

IPV is common, IPV often escalates over time, IPV has adverse effects on children, there are resources in the community to help the patient

Front 773

What are clues uncovered during the physical examination that may indicate domestic violence?

Back 773

Frontal injuries (from direct blow), perforated tympanic membrane (from slap), injuries in various stages of healing, explanation inconsistent with injury, delay in help-seeking

Front 774

What are clues uncovered during the physical examination that may indicate domestic violence?

Back 774

Frontal injuries (from direct blow), perforated tympanic membrane (from slap), injuries in various stages of healing, explanation inconsistent with injury, delay in help-seeking

Front 775

What are examples of atypical symptoms associated with MI?

Back 775

Abdominal pain, jaw pain, altered mental status (in elderly patients)

Front 776

What is the treatment for acute MI?

Back 776

If at a center where an interventional cardiologist can perform a PTCA, this would be the preferred method; however, if out in the field, give thrombolytics and then get the patient to a center where PTCA can be performed

Front 777

What is the purpose of GP IIb/IIIa inhibitors?

Back 777

Keep a vessel open after thrombolytic therapy

Front 778

What are indications for the use of thrombolytics?

Back 778

ST segment elevation greater than 0.1 mV in 2+ contiguous leads; New LBBB; Anterior ST depression consistent with posterior infarction

Front 779

What should always be done when giving a patient nitrates in the ED?

Back 779

Get an IV ready to push fluids in case they become hypotensive (since nitrates reduce preload)

Front 780

What are the indications for Heparin and LMWH regarding MI?

Back 780

Heparin for catheterization (since its effects can be stopped); LMWH in NSTEMI/unstable angina

Front 781

In the treatment of MI, what may be used as an alternative to aspirin?

Back 781

Clopidogrel

Front 782

What are the criteria associated with air medical transport?

Back 782

When the outcome of the patient is dependent on rapid transport or the patient requires the expertise of the flight team at the scene or en route (medical transport is activated by EMS personnel)

Front 783

How is chest pain of substernal origin described by patients?

Back 783

Often as a pressure sensation, but can be described as any kind of pain

Front 784

If an EKG does not clearly show ST segment elevation, what can be looked at for a more definitive diagnosis?

Back 784

Reciprocal ST segment depression (i.e. ST segment depression in the other areas of distribution)

Front 785

What is meant by the statement that traumatic death is tri-modal?

Back 785

Patients either die immediately, within 6 hours, or within 2-7 days

Front 786

What is the leading cause of adult disability in the US?

Back 786

Stroke (men are at higher risk)

Front 787

What should be given to a patient needing a massive transfusion?

Back 787

FFP/cryo

Front 788

What is meant by the secondary survey?

Back 788

Head-to-toe examination for injury (most important is the head)

Front 789

What does tachycardia/hypotension mean until proven otherwise?

Back 789

Blood loss

Front 790

What is meant by the ABCDEs of emergency medicine (primary survey)?

Back 790

A (airway): provide suppl. oxygen  non-definitive (jaw thrust, suction), definitive (intubate);
B (breathing): check rate, depth, work, sounds, symmetry, if inadequate, intubate;
C (circulation): BP, HR, perfusion, control bleeding (pressure dressing), IV access;
D (deficit/deformity): neurologic assessment (GCS: 3-15), major deformities (face, pelvis, back);
E (exposure/environment): take everything off patient for examination, keep patient warm!

Front 791

What is an essential approach when evaluating a trauma patient?

Back 791

Use a systematic approach so that nothing big is missed

Front 792

What other disease processes can cause ST segment elevation?

Back 792

Ventricular aneurysm (anterior ST elevation); Acute pericarditis (diffuse ST elevation)

Front 793

What is the first sign that changes in a trauma patient?

Back 793

Heart rate

Front 794

What are the three considerations to be looked at with a trauma patient?

Back 794

Mechanism, anatomy, physiology

Front 795

What is the purpose of a MERCI catheter?

Back 795

Physically remove a clot from the patient’s artery (funnel shaped, spiral wire, hooks onto clot)

Front 796

What is the purpose of a MERCI catheter?

Back 796

Physically remove a clot from the patient’s artery (funnel shaped, spiral wire, hooks onto clot)

Front 797

What are causes of left ventricular systolic dysfunction in CHF?

Back 797

Impaired contractility (MI, mitral/aortic regurgitation, dilated cardiomyopathy) and/or excessive afterload (aortic stenosis, uncontrolled HTN) – will see ESPVR shifted downward, SV down, ESV up, and EDV/LVEDP up

Front 798

What are causes of left ventricular systolic dysfunction in CHF?

Back 798

Impaired contractility (MI, mitral/aortic regurgitation, dilated cardiomyopathy) and/or excessive afterload (aortic stenosis, uncontrolled HTN) – will see ESPVR shifted downward, SV down, ESV up, and EDV/LVEDP up

Front 799

What increases SV?
Increased

Back 799

preload/contractility, decreased afterload

Front 800

What increases SV?
Increased

Back 800

preload/contractility, decreased afterload

Front 801

What does ESV depend on?

Back 801

Afterload, contractility

Front 802

What does ESV depend on?

Back 802

Afterload, contractility

Front 803

What does ejection fraction depend on?

Back 803

Preload, afterload, contractility

Front 804

What does ejection fraction depend on?

Back 804

Preload, afterload, contractility

Front 805

What is the Law of LaPlace and what does it relate to?

Back 805

[stress = (pressure x radius)/(2 x wall thickness)]; used to calculate afterload

Front 806

What are non-invasive measures of looking at left ventricular preload and right ventricular preload, respectively?

Back 806

Left-ventricular: echocardiogram, cardiac MRI; Right-ventricular: jugular venous pressure

Front 807

What is the Law of LaPlace and what does it relate to?

Back 807

[stress = (pressure x radius)/(2 x wall thickness)]; used to calculate afterload

Front 808

What will be affected in a patient with a stroke in the basilar artery (posterior circulation)?

Back 808

Vision, balance, consciousness, breathing, CN X-XII

Front 809

What are non-invasive measures of looking at left ventricular preload and right ventricular preload, respectively?

Back 809

Left-ventricular: echocardiogram, cardiac MRI; Right-ventricular: jugular venous pressure

Front 810

What are the 5 aspects of the NIH stroke scale?

Back 810

Wakefulness, Visual, Motor, Sensation, Language

Front 811

What will be affected in a patient with a stroke in the basilar artery (posterior circulation)?

Back 811

Vision, balance, consciousness, breathing, CN X-XII

Front 812

What is the time-frame for the use of IV tPA?

Back 812

Must be administered in the first 3 hours (tPA is associated with a 10x increase in hemorrhage)

Front 813

What are the 5 aspects of the NIH stroke scale?

Back 813

Wakefulness, Visual, Motor, Sensation, Language

Front 814

What is the time-frame for the use of IV tPA?

Back 814

Must be administered in the first 3 hours (tPA is associated with a 10x increase in hemorrhage)

Front 815

What is the hallmark of eccentric ventricular hypertrophy?

Back 815

Ventricular dilation (due to volume overload, new sarcomeres in series with old) – there is no chamber dilation in concentric ventricular hypertrophy (due to pressure overload, new sarcomeres in parallel with old)

Front 816

What physical findings are associated with RV CHF?

Back 816

Jugular venous distention (increase RA pressure), hepatomegaly, peripheral edema

Front 817

What physical findings are associated with LV CHF?

Back 817

Diaphoresis, tachycardia, tachypnea, crackles/wheezes, dullness over lung bases (effusion), abnormal cardiac impulse (cardiomegaly), S3 (S4) gallop (abnormal filling sound)

Front 818

What symptoms are associated with RV CHF?

Back 818

Peripheral edema (better in morning), weight gain, RUQ discomfort (swollen liver), anorexia/nausea (bowel edema)

Front 819

What symptoms are associated with LV CHF?

Back 819

Orthopnea (sleep with pillows), paroxysmal nocturnal dyspnea, nocturnal cough, fatigue, nocturia

Front 820

How does ethanol affect the heart?
It is a negative inotropic

Back 820

compound

Front 821

What are causes of left ventricular diastolic dysfunction in CHF?

Back 821

Impaired relaxation or increased stiffness (left ventricular hypertrophy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, transient myocardial ischemia) – will see lower part of PV loop shifted upwards, increased LVEDP but lower EDV

Front 822

What is the problem with mitral stenosis, regarding the PV loop?

Back 822

It lowers CO by reducing a to b time and volume (i.e. there is less LV filling time and thus less LV volume)