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263 Cards in this Set

  • Front
  • Back
Heart failure is usually the result of?
Systolic Dysfxn
- a product of IHD
- HTN
With an increased work load cardiac myocytes are subject to hypertrophy but not...
HYPERPLASIA
- cardiac myocytes are unable to divide
Left-sided heart failure has what ill-effects in which organ systems?
Lungs - congestion and edema --> dyspnea; presence of heart-failure cells
Kidneys - decreased perfusion --> Na, H2O retention
Brain - Hypoxic encephalopathy
Right-sided heart failure has what ill-effects in which organ systems?
Liver - congestive hepatomegaly
Spleen - congestive splenomegaly
Kidneys - marked congestion and fluid retention
Brain - hypoxic encephalopathy
Pleural and pericardial spaces - effusions
Subcutaneous tissues - peripheral edema and anasarca
Is there death of cardiac muscle with angina pectoris?
NO
What is the leading cause of death in the US and other industrialized nations?
IHD
Pathogenesis of IHD is highly assoc w/ coronary atherosclerosis and has what 2 clinical manifestations?
1) Progressive narrowing of lumen = chronic fixed obstruction
2) Acute plaque disruption w/ thrombosis = sudden obstruction
Sx's of chronic obstruction are the result of narrowing of the lumen. What are the normal degrees of lumen narrowing and what is their symptomatic correlate?
Narrowing >75% --> symptomatic ischemia w/ exercise
Narrowing >90% --> symptoms at rest
vulnerable plaques (those that are more likely to undergo an acute plaque change)
have increased foam cells, lipid, and a thin fibrous cap
Fissures occur
at the jxn of the fibrous cap and the adjacent normal arterial wall and where there is highest mechanical stress and thinnest portion of fibrous cap
Which plaques are most likely to undergo acute change leading to coronary occlusion?
() 66% of ruptured plaques had <50% stenosis before rupture
() 85% of ruptured plaques had <70% stenosis before rupture
What are the 3 types of Angina Pectoris and what is the overlying cause?
() Stable or typical angina
() Prinzmetal or variant angina
() Unstable or crescendo angina
- Angina pectoris is known for paroxysmal and recurrent attacks of chest pain caused by transient myocardial ischemia. There is NO CELL DEATH
Stable angina
aka typical angina
- is the most common
- aggravated by exercise, relieved by rest
- treated w/ vasodilators (nitroglycerin)
Prinzmetal angina
aka variant angina
- uncommon
- chest pain occurs at rest and is unrelated to physical activity or BP
- treated w/ vasodilators
Unstable angina
aka crescendo angina
- chest pain w/ progressive, increasing frequency
- precipitated w/ progressively less effort and often occurs at rest
- PRODROME OF SUBSEQUENT ACUTE MI = preinfarction angina
Risk factors for atherosclerosis:
Males
HTN
smoking
DM
hyperlipidemia
genetics
When is it impossible to determine a lesions age?
when it is healed
Transmural infarction
- *more common
- ischemic necrosis involves full/nearly full thickness of ventricular wall
- limited to distribution of one coronary artery
Subendocardial infarction
- ischemic necrosis limited to inner 1/3 of ventricular wall
- may extend beyond perfusion territory of a single coronary artery
- usually the least well perfused area
Pathogenesis of MI:
() coronary artery occlusion
() myocardial response
() infarct modification
() reperfusion
At what point does the damage from cardiac ischemia become irreversible?
only 20-40 minutes after ischemia onset necrosis begins
When is it most critical to administer reperfusion?
by hours 3-4
Complications resulting from MI:
() Contractile Dysfxn (60%)
() Arrhythmias (90%)
() Myocardial rupture
() Ventricular Aneurysm
() Mural Thrombus (30%)
() Pericarditis
Sudden cardiac death is an unexpected occurrance that may arise early after sx onset and may even be the 1st clinical manifestation of IHD. What is it's mechanism of death?
Lethal arrhythmia
- ventricular fibrillation, asystole
- irritability of ischemic myocardium
Cardiomyopathy
- heart disease resulting from a primary abnormality in the myocardium w/ an underlying genetic defect in cardiac energy metabolism or structural/contractile proteins
- most are idiopathic
Types:
- dilated cardiomyopathy (most common)
- hypertrophic cardiomyopathy
- restrictive cardiomyopathy
What serves as one of the most common causes of sudden unexplained death in young athletes?
hypertrophic cardiomyopathy
Endomyocardial fibrosis
- affects children and young adults in Africa
- characterized by fibrosis of the ventricular endocardium and subendocardium
- etiology unknown
Loeffler endomyocarditis
- endomyocardial fibrosis
- eosinophilic leukemia
- poor prognosis
Endocardial fibroelastosis
- focal or diffuse fibroelastic thickening of the mural left ventricular endocardium
- first 2yrs of life
- accompanied by some form of congenital anomaly
What is the most common cause of myocarditis in the US?
viral infections
Cardiac sx's with hyperthyroidism/hypothyroidism:
Hyperthyroidism = tachycardia, palpitations, cardiomegaly, and supraventricular arrhythmias

Hypothyroidism = decreased CO, SV, HR, hearty may be flabby, enlarged, dilated
Stenosis
Failure of a valve to open completely impeding forward flow of blood
- primary chronic valvular abnormality
Insufficiency (regurgitation)
Failure of a valve to close completely, allowing reversed blood flow
- primary intrinsic disease, secondary to damage to supporting structures, acute or chronic process
The most common valve abnormality?
Calcific Aortic Stenosis
Mitral valve prolapse comes in 2 forms:
Structure (primary)
- 20% of cases
- autosomal dominant CT disease
- may be assoc w/ Marfan's, Ehlers-Danlos, other CT disease

Functional (Secondary)
- 80% cases
- referred to as 'mitral valve prolapse syndrome'
- commonly disappears w/ pregnancy or aging
- may be assoc w/ arrhythmias, atypical chest pain, and postural syncope
HACEK group for infective endocarditis:
H - Haemophilus
A - Actinobacillus
C - Cardiobacterium
E - Eikenella
K - Kingella
These are often seen in acute rheumatic fever:
Aschoff bodies - focal inflammatory lesions characterized by eosinophilic collagen surrounded by T cells and Anitschkow cells

Anitschkow cells - plump macrophages w/ abundant cytoplasm and chromatin in a central wavy "ribbon" - aka caterpillar cells
Associated w/ SLE?
Libman-Sacks Endocarditis
Angiotensinogen
- constitutively synthesized and released by the liver into the plasma
- levels increased by:
corticosteroids
estrogens (and estrogen containing contraceptives)
pregnancy
angiotensin II
Renin
- RLS in formation of angiotensin II
- released from the kidney juxtaglomerular cells by a variety of stimuli
() decreased stretch/decreased BP/decreased renal perfusion sensed by the afferent arteriole
() decreased reabsorption of Na (prostaglandins fxn as messenger)
() sympathetic activation at beta1 adrenoceptor
()
Angiotensin Converting Enzyme (ACE)
- on lumenal surface of vascular endothelial cells (esp in lung)
- also breaks down bradykinin
Angiotensin (1-7)
- formed as a branch from anigotensin I if ACE is inhibitied
- has opposite effects of angiotensin II
AT_2
- the lesser of the angiotensin II receptors
- highly expressed in the fetus
- may have antiproliferative, proapoptotic, vasodilatory, and antihypertensive effects
AT_1
- mediates most actions of angiotensin II
- Gq --> PLC --> IP3 + DAG
- MAP Kinase, tyr kinase, JAK/STAT --> gene expression, cell growth, mitogenic effects
What are the 4 ways to decrease the activity of ATII?
1) inhibit the release of renin via beta blockers
2) inhibit the activity of renin
3) inhibit the formation of ATII by ACE
4) block the AT_1 receptors for ATII
Function of diuretics:
increase urine flow rate and Na excretion (natriuresis)
Crush syndrome
- occurs when myoglobin released from damaged muscles causes damage to the renal tubules
- help by increasing urine flow and maintaining a dilute urine
These diuretics are indicated in use for acute renal failure, as well as for cerebral and ocular edema (surgery)
osmotic diuretics
- glycerin
- mannitol
- urea (IV)
These diuretics are indicated in use for glaucoma and acute mountain sickness. They also cause urinary alkalinization.
carbonic anhydrase inhibitors
- acetazolamide
- dichlorphenamide
- methazolamide
- dorzolamide
- brinzolamide
When you want profound diuresis or in the case of acute pulmonary edema, CHF, ARF, or hyperkalemia, what diuretic would you use?
loop ('high ceiling') diuretics
- furosemide
- bumetanide
- torsemide
- ethacrynic acid (toxicities)

note - not very effective in damaged kidneys b/c need tubular secretion
First line diuretics
thiazides
- chlorothiazide, hydrochlorothiazide
- chlorthalidone
- indapamide
- metolazone
These diuretics are used in combination with loop or thiazide diuretics to maintain plasma K+ and also are indicated as an aerosol for CF
ENaC inhibitors
- triamterene
- amiloride
These (diuretics?) are used in combination with loop or thiazide diuretics to maintain plasma K+ and may be indicated with hyperaldosteronism and edema from hepatic cirrhosis
mineralocorticoid antagonists
- spirinolactone (not very selective)
- eplerenone (selective aldosterone receptor antagonist)
These diuretics are used to cause aquaresis, especially with the indication of hyponatremia
antidiuretic hormone antagonists
A normal EF is usually about?
66%
While a low EF is unwanted, what is worse?
The bodies compensatory response to the low EF - this is due to enzymes, inflammatory mediators, and other components trying to remodel the tissue
Why is dyspnea an associated sx of heart failure?
heart failure causes an increase in pulmonary capillary pressure and may even result in pulmonary edema. at this point the airways are harder to open due to the build up of fluid
CHF is...
a progressive syndrome
These drugs make the heart pump more, an effect that worsens HF
beta agonists
PDEIs
Cardiac Glycosides like digoxin are special in that they...
make the heart rate slow down w/out dropping the bp or make the heart get weaker
Digitalization
the administration of short boli of digoxin in order to avoid toxicities
Does digoxin improve survival?
NO
but some vasodilators do as well as ACEI's
What are the only diuretics (really hormone regulators) that are found to increase survival in HF?
Aldoant's (sprinolactone, eplerenone)
- improves survival w/out affecting bpm
What is the difference btw the tx for acute vs chronic heart failure?
Acute - systolic and diastolic dysfxn treated the same
Chronic - systolic and diastolic dysfxn treated differently
What are the compensatory responses to HF and how are they triggered?
() activation of SNS - triggered by decreased carotid sinus baroreceptor stimulation
() activation of RAAS - triggered by decreased renal blood flow which in turn causes decreased stimulation at the renal vascular receptors and disinhibition of renin production
Increased sympathetic activity in response to HF causes:
() increased vasoconstriction
() increased HR
() stimulation of RAS
() cardiac remodeling (hypertrophy, fibrosis)
Activation of RAS in response to HF causes:
() increased vasoconstriction
() increased aldosterone production (Na /H2O retention)
() increased sympathetic activity
() increased thirst
() cardiac remodeling (due to both ATII and aldosterone)
(+) ionotropic drugs...

[Cardiac Glycosides (digoxin), PDEI's, beta agonists]
increase the strength of contraction but can also cause cardiac arrhythmias
These drugs decrease cardiac work (no ionotropic effect) by counteracting the compensatory responses
ACEI's, ARB's, beta-blockers, and other vasodilators
coronary blood flow (CBF) of the left coronary is maximal during...
diastole
What are the factors that passively affect CBF?
() the arterial-venous pressure gradient
() the duration of diastole (HR)
() LVEDP (changing vessel architecture as ventricle distends)
Autoregulation is an intrinsic process by which the coronary bed maintains a constant CBF in the presence of changing perfusion pressures. What mediates this?
() pO2 - a decreased tissue pO2 causes coronary arteriolar vasodilation
() Adenosine - coronary vasodilator released from ATP during increased cardiac work
() Nitric oxide - released during increased O2 demand by the heart
Determinants of myocardial O2 consumption (MVO2)
() Wall tension (LVEDP)
() Myocardial contractility
() HR
- the last 2 being controlled by sympathetic activity, like in exercise and exersion
This type of angina is not exertional, but rather the product of coronary artery vasospasm and occurs at rest
Prinzmetal or variant angina
- not due to an increase in O2 demand
The benefits from nitric oxide are not direct, but are due to...
the production of cGMP --> decreases IC Ca --> vessel relaxation
What are the mechanisms used in treating stable angina?
(1) Preload reduction - dilation of venous vessels (increases capacitance) which decreases LVEDP. This decreases myocardial O2 demand.
(2) coronary artery dilation, increasing O2 supply
(3) afterload reduction
Blockade of Ca entry in the myocardium results in:
() reduced automaticity
() slowed conduction
() reduced myocardial contractility
Blockade of Ca entry in vascular smooth muscle results in:
() inhibition of vascular smooth muscle contraction
() relaxation of vasospastic smooth muscle
What 2 energy-dependent, active transport processes help to maintain a low cytosolic Ca?
() active extrusion across the plasma membrane by:
- Na/Ca exchanger
- Ca ATPase
() active uptake into intracellular organelles like mito and ER (passive)

*to increase cytosolic Ca, these processes are merely reversed
*cardiac m uses both while skeletal m just uses SR
What are some of the effects of Ca entry across the plasma membrane?
() depolarization to generate APs (pacemaker)
() excitation-contraction coupling
() secretion at nerve terminals
The 3 conformations or "states" of Ca channels:
() open - occurs with depolarization
() resting closed - like a gate, seen at resting membrane potential
() inactivated closed - hard to get open, occurs with sustained depolarization, have to revert back to resting closed via repolarization
These calcium channel blockers only bind to slow L-type Ca channels in the open state (when activated) - a factor that accounts for their use-dependent block
phenylalkylamines (verapamil)
benzothiazepines (diltiazem)
These calcium channel blockers only bind to slow L-type Ca channels in the inactivated closed state
dihydropyridines (-dipines)
Use-dependent block by Ca Channel Blockers can prevent...
an increase in the rate of APs - such as during arrhythmia
What makes the vascular smooth muscle more susceptible to dihydropyridines?
vascular smooth muscle is vastly depolarized = more Ca channels in the inactivated closed state
While direct cardiac effects (decreased contractility, decreased HR, decreased AV conduction) are limited to non-DHP CCBs, some indirect increases in these values is seen with DHP CCBs, why?
DHP CCBs specifically cause peripheral and coronary artery vasodilation, but in doing so activate sympathetic stimulation of the heart.
*this effect can be blocked by beta blockers
Slowing conduction through the AV node and isolating/protecting the ventricular rhythm can be accomplished using these drugs
verapamil or diltiazem
Isolated systolic hypertension (ISH) is more common in what pt population and is effectively treated with...
in the elderly and is treated w/ a DHP CCB
This CCB has selectivity for the cerebral vasculature
nimodipine
This CCB beneficially dilates the efferent renal arterioles
lercanidipine
The action of ACh in the synaptic cleft is terminated by...
hydrolysis via membrane bound AChE
*this is apposed to NTs like serotonin, epi and NE, whose actions can be terminated by reuptake as well as enzymatic degradation
Botulinum Toxin
- produced by the anaerobic bacterium c. botulinum
- chews up proteins involved in the fusion of ACh vesicles w/ the presynaptic membrane
- used cosmetically to paralyze muscles or to prevent muscle spasms
What are some main differences btw the cholinoceptors (Nicotinic vs Muscarinic)
Nicotinic cholinoceptor - receptor is an ion channel that binds 2 ACh, excitation is rapid and utilizes entry of Na
Muscarinic cholinoceptor - receptor is an integral G protein that binds 1 ACh, activation through either Gq or Gi is slow and fxns using Ca and K respectively
Persistent binding of ACh (or other agonists) to nicotinic cholinoceptors causes...
rapid desensitization and closure of the channel
Curare blocks
muscle nicotinic cholinoceptors (N_m)
Hexamethonium blocks
nerve nicotinic cholinoceptors (N_n)
Odd # muscarinic cholinoceptors (M1, M3, M5)
act through Gq to cause hydrolysis of PLC --> IP3 + DAG --> increased Ca + PKC, respectively
Even # muscarinic cholinoceptors (M2, M4)
act through Gi to inhibit adenylyl cyclase and through G(beta, gamma) to activate K channels in the heart --> hyperpolarization (decreased excitability)
Cholinergic agonists (muscarinic) can aid in decreasing the ocular pressure seen in glaucoma, how?
Cholinergic agonists (muscarinic) that act on the pupillary sphincter and ciliary muscles create a slight opening in the meshwork, allowing for fluid drainage.
When do congenital heart diseases arise?
during gestational wks 3-8
What are the 2 most prevalent congenital heart diseases associated with Downs Syndrome (trisomy 21)?
1) AV septal defect
2) Ventricular septal defect
What are the top 2 most common congenital cardiac malformations?
1) Ventricular septal defect
2) Atrial septal defect
What chromosome may be affected in outflow tract disorders?
chr. 22
- errors in this chromosome may account for failed neural crest cell migration into the heart
- also see chr. 22 errors w/ anomalies of the 4th branchial arch and the 3rd and 4th pharyngeal pouches (DiGeorge syndrome, parathyroid hypoplasia)
What physiological factor causes the closure of the foramen ovale?
increased venous return from the lungs which raises the pressure in the left atrium --> closing of the foramen ovale
Flow =
Pressure/Resistance
What changes occur in the systemic circuit at birth?
() vascular resistance increases
() loss of low-resistance placental circuit
What changes occur in the pulmonary circuit at birth?
() blood flow increases
() decreased vascular resistance
- aided by expansion of lungs
- elevated oxygen tension
() pulmonary arterial tone
- responds to hypoxia, hypercapnia, acidosis by vasoconstricting
What are the left-to-right shunts?
() ASD
() VSD
() PDA
() AV SD
Don't confuse this with an ASD, they do not allow blood flow
patent foramen ovale
- present in 1/3 of normal ppl
What are the ASDs and which is most common?
() Primum ASD - adjacent to AV valve
() Secundum ASD* - deficient or fenestrated oval fossa, the most common ASD
() Sinus venosus defects - near the entrance of the SVC
What is the most common cardiac anomaly?
VSD
Most VSDs involve
the membranous septum
A 'machinery-like' murmur may signify?
PDA
- may be assoc w/ immaturity, hypoxemia
- tx w/ indomethacin
- sometimes patency is keeping pt alive, need to keep patent w/ PGE
What are the 2 types of AV SD?
() Partial - primum ASD cleft anterior mitral leaflet --> mitral insufficiency
() Complete - combined AV SD and common AV valve, all 4 chambers freely communicate, 1/3 of pts have Downs Syndrome
What are the right-to-left shunts?
() Tetralogy of Fallot
() Transposition of the Great Arteries
() Truncus Arteriosus
() Tricuspid Atresia
() Total Anomalous Pulmonary Venous Connection
What 4 characteristics make up the Tetralogy of Fallot, the most common cyanotic congenital heart disease?
() VSD
() Obstruction of right ventricular outflow tract (usually due to narrowed infundibulum, sometimes subpulmonary stenosis)
() Aorta that overrides the VSD
() Right ventricular hypertrophy - boot-shaped heart
What causes Transposition of the Great Arteries?
abnormal formation of the truncal and aortopulmonary septae
What causes Truncus Arteriosus?
failure of septation of the truncus into the aorta and pulmonary artery
What are the obstructive abnormalities assoc w/ the heart?
() Coarctation of the aorty
() Pulmonary stenosis and atresia
() Aortic stenosis and atresia
Aside from a systolic murmur, "notching" of the ribs on an X-ray from enlarged intercostal arteries and lower body cyanosis may be present with this obstructive abnormality
Coarctation of the Aorta
Lengthening the action potential (ex. by inhibiting K+ efflux for repolarization) has what effect on an EKG?
increases the QT interval
Why is the initial depolarization at the pacemakers (SA, AV) slow?
b/c there is NO Na current @ the SA and AV nodes (just in the ventricular myocyte and like cells)
What is the 'funny' current?
The 'funny' current is an inward current that produces slow depolarization until the threshold is reached. At this point voltage-dep Ca channels are activated and depolarization takes place.
The 'funny' current is increased by sympathetic stimulation via beta1 receptors and decreased by parasympathetic stimulation of M2 receptors.
Automaticity
- refers to the spontaneous depolarization that takes place at the SA>AV>PF
- rhythmic depolarization is attributable to 'funny' current, which is regulated by cAMP
- sympathetic beta1 stimulation (increases cAMP)
- parasympathetic M2 stimulation (decreases cAMP)
Responsiveness
Rate of depolarization of Vm during Phase 0
What are Wolff-Parkinson-White pathways?
Wolff-Parkinson-White pathways are anatomical defects resulting in an accessory electrical pathway
Which, hypo or hyperkalemia, is pro-arrhythmic?
BOTH
Sick sinus syndrome
a disorder of automaticity with alternating periods of bradycardia and tachycardia that are unaffected by high doses of atropine (not a simple ACh problem)
Ectopic pacemakers
a disorder of automaticity where impulses are initiated at locations other than the SA node
What are the strategies for decreasing automaticity?
() increasing maximum diastolic Vm (adenosine, increased vagal tone)
() decreasing phase 4 slope (beta blockers, increased vagal tone)
() increasing threshold potential (Na or Ca channel blockers)
() increasing refractory period (K channel blockers)
What are the types of reentrant signals ?
() Anatomically defined - loops of electrical activity that follows accessory pathways (Wolff-Parkinson-White)
() Functionally defined - loops of electrical activity created by uni-directional block of conduction and slowed conduction
What are the strategies for decreasing reentrant activity?
() decrease conduction velocity (Na or Ca channel blockers) ideally converting the partial block into a bidirectional complete block
() increase the refractory pd (K channel blockers) so that reentrant excitation enters an area of refractory
Early afterdepolarization (EAD)
- is a spontaneous depolarization that occurs during the latter part of the repolarization
- become more frequent when QT interval is lengthened (blocked K channels)
- may cause torsades de pointes
Delayed afterdepolarization (DAD)
- is a spontaneous depolarization that occurs after an AP is complete, probably due to an overload of IC Ca and activation of the electrogenic Na/Ca exchanger
- may be an adverse effect of digoxin
What are the strategies for decreasing triggered signals?
() increase threshold potential (Na channel blockers)
() decrease the cytosolic Ca (CCBs, beta blockers)
Do we need to stop an atrial arrhythmia to prevent it from affecting the ventricular rhythm?
No, it is best to aim at changing the rate in order to protect the ventricular rhythm rather than changing the rhythm to correct the arrhythmia.
Do so by decreasing AV conduction (CCBs, beta blockers, adenosine in a pinch, increasing vagal tone)
What is the most common arrhythmia?
Atrial fibrillation
- is caused by MANY reentrant circuits
- may produce a thrombus and embolism
What arrhythmia is the lethal product of many small reentrant circuits?
Ventricular fibrillaion
Are post ganglionic nerves myelinated?
NO
What is the rank order of potency refer to?
Tissues possess certain types and densities of receptors, allowing them to exhibit different sensitivities to nerve products
Alkyloids
a substance taken from nature and used pharmacologically
Purinoceptors
mediate the actions of ATP
Nitric oxide is special in that..
it is not stored in granules and doesn't act through a receptor

NO--> Guanylate Cyclase --> cGMP --> activation of K channels, inhibition of Ca channels --> decreased IC Ca --> vasodilation
The catecholamines:
NE, Epi, DA
What is the end product of the breakdown of Epi and NE?
Vanillylmandellic Acid (VMA)
What is the breakdown product of DA?
Homovanillic Acid (HVA)
alpha-methyl tyrosine
- taken up via AA transporter but is not a substrate for tyrosine hydroxylase (competes for enzyme) --> decreased NE
- used for pheochromocytoma (adrenal tumor)
methyl dopa
- enters varicosity and substitutes for DOPA --> methyl-NE (false NT)
- alpha2 selective agonist (anti-HTN effect in brain)
cocaine
blocks NET, decreasing NE recycling --> potentiation on effector cell
reserpine
- inhibits VMAT for BOTH DA and NE --> decreased NE in granules
- used as an anti-HTN due to NE tonic vasoconstrictive control of blood vessels
tyramine
- an example of a dietary amine
- an independent-acting sympathomimetic that causes the release of NE
- normally broken down by MAO, so if inhibited by MAOI then there may be an increase in sympathetic stimulation
Bretylium, guanethidine
considered a local anesthetic for noradrenergic neurons --> inhibits NE release
What is done by the sympathetic nervous system in increasing the pacemaker's production of HR?
() an increase in the slope of the 'funny' current
() an increase in the slope of depolarization via open Ca channels
What is the reason for the possible pro-arrhythmic effect of sympathomimetics?
They shorten the effective refractory period (ERP) and AP duration (APD) which leads to an increase in conduction velocity, a factor that may cause arrhythmias.
What serves as an index for diastolic pressure?
TPR
An increase in systolic pressure more than diastolic pressure signifies
an increase in contractility
- pulse width also changes w/ increases contractility (must affect beta1 receptors)
As far as vascular affects go, what agent causes widespread vasoconstriction in all areas but the skin, due to the absence of beta receptor effect?
isoproterenol (beta1, beta2 selective agonist)
Loss of 4'OH -->
alpha selectivity
Presence of 4'OH -->
beta selectivity
Presence of 5'OH -->
beta2 selectivity
Larger amino substitutions -->
favors beta selectivity
Adrenoceptor agonist direct action requires
() at least 2 OH's among positions 3,4 and beta carbon
() beta carbon substitutions (exception is dopamine)
Requirements for substrates of COMT
both 3-OH and 4-OH
Requirements for substrates of MAO
() NH2 - substitutions w/ more than 2C's prevents metabolism
() No substitution allowed on the alpha carbon
Direct vs Indirect acting agonists
() conferred by chemical structure
() Direct acting agonists stimulate the receptor while Indirect acting agonists stimulate the cell to release NE --> receptor stimulation
What type of movement is possible into the CNS?
transcellular
What 3 criteria are NTs identified by?
() Localization
() Release
() Synaptic mimicry
Metabotropic receptors
() G-protein coupled
() slow response
Ionotropic receptors
() Ion channel is part of receptor
() fast response
MAO-B has a preference for?
DA
What are the core symptoms of ADHD?
inattention, hyperactivity, and impulsivity
- it also must be excessive, pervasive, long-term, and not due to something else
Phasic NT release
transient high levels from bursts of APs
Tonic NT release
constant, low levels from basal neuronal activity
Inattention is associate with
a loss of ACh
- nicotinic stimulation enhances attention
What are the 2 major NTs in the prefrontal cortex?
NE and DA
Compelling indications for HTN
Heart Failure, post-MI, high CAD, diabetes, chronic kidney disease, recurrent stroke
M3 cholinergic stimulation causes vasodilation, an effect that seems contradictory given Gq's capacity to increase Ca. How is this so?
The VSM probably has very few M3 cholinoreceptors following that pathway. Instead, the vascular endothelium have M3 cholinoreceptors that release NO upon stimulation --> vasodilation.
Low dose stimulation vs High dose stimulation of muscarinic receptors
() Low dose stimulation - vasodilation via M3/NO may cause reflex tachycardia (sympathetic stimulation)
() High dose stimulation - hyperpolarization of the heart bia increased K/M2 may lead to bradycardia
What are the 2 active centers of AChE?
() an anionic site that attracts (+) charged quaternary ammonium group of ACh
() an esteratic site where the ester linkage is hydrolyzed via nucleophilic attack
SLUDGE BBB acronym for cholinergic toxicity (may be caused by too high concentration of AChE inhibitors)
S - salivation
L - lacrimation
U - urination
D - Defectation
G - GI sx's
E - emesis

B - bronchorrhea
B - Bronchospasm (possible diaphragm paralysis)
B - bradycardia
How do you treat cholinergic toxicity?
administer atropine (competitive muscarinic antagonist) and give respiratory support (due to possible diaphragm paralysis from nicotinic desensitization)
Irreversible AChE inhibitors are dangerous substances used as insecticides and nerve gases. What would you use in attempts to reverse their effects?
Need rapid administration of pralidoxamine (2 PAM) otherwise have to wait until new enzyme is synthesized.
What are the therapeutic uses of AChE inhibitors?
() atony of GI tract and urinary bladder
() glaucoma
() competitive NM blocking agents
() atropine poisoning
() Alzheimer's disease
Anti-cholinergic poisoning
blind as a bat, mad as a hatter, red as a beet, hot as hell, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone

*tachycardia is earliest and most reliable sx alongwith decreased bowel sounds
What happens to parasympathetic vagal tone with age?
parasympathetic vagal tone decreases with age, leading to a faster normal HR
What 3 sites are under a predominantly sympathetic tone?
() arterioles
() venules
() sweat glands
MethylCholine
- M selectivity
- tests bronchial reactivity
Carbachol
- primary tx for open-angle glaucoma
- synthetic choline ester
Bethanechol
- M selectivity
- tx for post-operative abdominal distention
- increases GI motility
Tx for xerostomia (dry mouth)
cevimeline, an M1/M3 agonist
Varenicline
- partial N agonist
- decreased w/drawal sx's
- decreased nicotinic reward
- nasty side effects
Naturally occurring ACh agonists
() muscarine - M agonist, toxin
() pilocarpine - M agonist, 4-8hr duration, Tx open angle glaucoma
() Nicotine - N agonist, toxin
Competitive AChE Antagonists (Indirect acting)
() Edrophonium - Dx for myasthenia gravis
() Ambenonium - Tx for myasthenia gravis
Carbamate AChE Inhibitors (Indirect acting) - inhibit AChE for 3-4hrs
() Physostigmine - enters CNS
() Pyridostigmine
() Neostigmine
() Carbaryl - insecticide used for suicide
Irrev. AChE Inhibitors (Indirect acting) - extremely lethal, absorbed in the skin and can enter CNS
DFP and Echothiophate
Parathion - most common poisoning on farms
Soman and Sarin - nerve gases
Rev. Inhibitors - Alzheimer's and Dementias - only Tx Sx's
Tacrine - off market b/c of pathologies
Donepezil - brain AChE
Galantamine - tertiary alkyloid
Rivastigmine - carbamate
Belladonna Alkyloids (muscarinic antagonists) - CI with narrow-angle glaucoma
() Atropine - long duration
() Scopolamine - Tx to prevent motion sickness, greater CNS penetration
NMJ blocking drugs (nicotinic antagonists)
- non depol antagonists
- competitive block of ACh-Nm interaction (rev. by increasing ACh)
- rapid weakness --> flaccid paralysis
D-tubocurare
Pancuronium
Vecuronium
Atracuronium
SuccinylCholine
- overstimulates Nm receptors
- rapid onset, short duration
- possible hyperkalemia w/ severe burns
Inhaled Tx for COPD/Asthma w/out inhibition of mucociliary clearance (muscarinic antagonist)
Ipratropium
Tiotropium
Synthetic Muscarinic Antagonists used for mydriasis and cycloplegia
Homatropine
Cyclopentolate
Tropicamide

- short acting
These synthetic muscarinic antagonists are used at Tx for neurogenic bladder problems
Darifenacin - M3 selective
Solifenacin - M3 selective
Oxybutynin
Tolterodine
A synthetic muscarinic antagonist used to Tx Parkinson's
Benztropine
Renin inhibitor
Aliskiren
ACEIs
Captopril
Enalopril
Lisinopril
ARBs
Losartan
Irbesartan
Valsartan
DHPs
- bind to inactivated-closed state
end in -dipine
Nifedipine
Felodipine
Isradipine
Lercanidipine - dilates renal efferent arterioles
Nicardipine
Amlodipine
Nimodipine - selective for cerebral vasculature
Nisoldipine
Non-DHPs
Verapamil and Diltiazem
- bind to open state
Osmotic Diuretics
- Tx ARF, cerebral/ocular edema
Glycerin - PO
Mannitol - IV
Urea - IV
Carbonic Anhydrase Inhibitors
- Tx glaucoma, Acute Mountain sickness
- block Na/H antiporter
Dichlorphenamide
Acetazolamide
Brinzolamide
Dorzolamide
Methazolamide
Loop Diuretics
- PG dependent
- block Na/K/Cl symporter
Ethacrynic Acid - ototoxicity
Furosemide
Torsemide - longest half-life
Bumetanide
Thiazides
- block Na/Cl symporter
Chlorothiazide, hydrochlorothiazide
Chlorthalidone
Indapamide
Metolazone
Mineralocorticoid Antagonists - aldoants
- K sparing
Spirinolactone - not very selective
Eplerenone - selective aldoant
ENaC inhibitors
- K sparing
- block Na/K,H antiporter
Triamterene
Amiloride
ADH antagonists
Convaptan - CYP3A4 inhibitor (CI)
Tolvaptan - specific
Amphetamine salts
- reverse reuptake of BOTH DA and NE
Dextroamphetamine
Lisdexamphetamine
Methylphenidate
blocks DA reuptake --> increased DA
Atomoxetine
a non-stimulant for ADHD that blocks NE reuptake --> increased NE
2nd line and Off-label Tx's for ADHD
Tricyclic Antidepressants
Clonidine
Buspropion, Busiprone
Modanifil
PDE5 Inhibitors - for Erectile Dysfxn
Sildenafil
Tadalafil*
Vardenafil* - fastest onset

*selective for PDE5 over PDE6 (retina)
Indirect acting sympathomimetics
- cause NE release (increasing bp and HR)
- can develop a tolerance
Tyramine
Ephedrine - long duration, nasty side effects
PseudoEphedrine - nasal congestion less CNS effects than Ephedrine
Amphetamine - high abuse potential, enters CNS
Phenylpropranolamine - taken off market (hemorrhagic stroke)
Carvediol
- for CHF, HTN
b1, b2 selectivity (some a1)
Labetolol
a1, b1, b2
Phentolamine (imidazolines)
a1 = a2 selectivity
Phenoxybenzamine (b-haloalkyamines)
a1 > a2
Prazosin (quinazolines)
a1 antagonist
Yohimbine
a2 antagonist
- 2nd line tx for ED
b1, b2 selective antagonists
Propanolol
Nadelol
Pindolol
Timolol
Carvediol~
Metaprolol
- for CHF, HTN
b1 antagonist
Acebutolol
- for HTN
b1 antagonist
Esmolol
- fast acting, short duration
b1 antagonist
Butoxamine
b2 antagonist
Isoproterenol
b1, b2 AGONIST
PE
- nasal congestion (venules)
- hypotensive emergency
a1 AGONIST
Methoxamine
- hypotensive emergency
a1 AGONIST
a2 selective AGONISTS
a-methyl NE
Oxymetazoline - long lasting, nasal congestion (arterioles)
Clonidine (central anti-HTN, ADHD)
b1 selective AGONISTS
Dopamine
Dobutamine

(+) inotropes
b2 selective AGONISTS
Albuterol - inhalation asthma
Terbutaline - inhalation asthma
Ritodrine (IV - uterine relaxant)
What are the Vit K dependent factors?
II, VII, IX, X, Protein C and S
Unfractionated Heparin
- binds to ATIII (through a pentasaccharide sequences) to accelerate it's inactivation of factors II, IX, X
- no effect on formed clots, only preventitive
- increases aPTTT (intrinsic pathway)
- reversed using protamine
- not to be given IM
What are the primary adverse effects of unfractionated heparin?
Hemorrhage - visible or occult
Thrombocytopenia - HIT
Protamine
A (+) charged compound that is capable of binding to and neutralizing heparin
LMW Heparin - parin drugs
- enoxaparin
- dalteparin
- tinzaparin
- fondaparinux (*protamine ineffective and is associated with less bleeding)
- just like unfractionated heparin, it binds to ATIII, but is factor Xa selective (can't bind to thrombin due to lack of 18 saccharide sequence)
- greater bioavailability and longer lasting than unfractionated heparin
Warfarin
- blocks Vit K epoxide reductase, meaning Vit K dependent factors lack gamma-carboxylation and can't complex w/ Ca
- orally effective (outpt)
- highly bound to plasma proteins (watch for other drugs that bind plasma proteins)
- interacts w/ aspirin (also binds plasma proteins)
- CI: preganncy, HIT
Rivaroxaban
- inhibits factor X
- an orally effective alternative to warfarin
Direct Thrombin Inhibitors
- no antidotes available
- not used during surgery
Lepirudin
Bivalirudin
Desirudin
Argatroban (synthetic arginine analog)
Antiplatelet Drugs
Aspirin
Dipyradimole
Platelet ADP receptors (P2Y12) inhibitors
- Ticlopidine
- Clopidogrel
- Prasugrel
GPIIb/IIIa inhibitors
- Abciximab
- Eptifibatide
- Tirofiban
Aspirin
- irrev inhibition of COX inhibits TXA2 on platelets (decreases adhesion/aggregation) but also PGI2 on endothelial cells (prevents platelet adhesion)
Fibrinolysis vs Fibrinogenolysis
Fibrinolyis - proteolysis/lysing of formed clot
Fibrinogenolysis - degradation of circulating coagulating factors --> lytic state and hemorrhage
(+) feedback during the platelet phase involves
TXA2 and ADP from the platelet
bpm =
300/# heavy lines

each heavy line = .2sec

tachycardia > 100
bradycardia < 60

300, 150, 100, 75, 60, 50
a wide QRS complex (> 3 little blocks = .12s) signifies
- a ventricular rhythm (electrical activity originating below the AV node)
- could be either a right or left bundle branch block
Rt = rsR' pattern in V1
Lt = completely upright QRS in V6 and Lead I
A sinus rhythm is one that originates in the SA node. What criteria from the EKG help you establish the presence of a sinus rhythm?
a P wave that is present and upright in lead II, while being related to a QRS complex
What criteria point to a 1st degree AV block?
a PR interval >.2s (one dark line)
What is the difference btw a Mobitz Type I and Type II 2nd degree AV block?
Mobitz Type I (Wenckebach) = lengthening PR interval then QRS dropped
Mobitz Type II = QRS dropped w/out lengthening, more of an emergency, need pacemaker
3rd Degree AV block
- No relation btw Atrial and ventricular activity
- very dangerous, need pacemaker ASAP
Junctional Non-sinus Rhythm
- will have a slower HR (40-60bpm)
- no obvious atrial activity
- result of atherosclerotic heart disease
- narrow QRS (supraventricular)
Bigeminy
alternating supraventricular/ventricular rhythms - very few implications
Ventricular Non-sinus Rhythm
- tachycardia/fibrillation
- wide QRS (pace 30-40bpm)
T wave inversion suggests
ischemia
ST segment elevation suggests
injury
Q waves suggest
infarction
Singh-Vaughan Williams Classification of antiarrhythmic drugs
I = Na channel block
Ia - medium affinity, Na and K channels (prolongs QRS and QT)
Ib - low affinity
Ic - high affinity (prolongs QRS)
II = b-adrenergic block (decreases automaticity and increases PR)
III = K channel block (increases QT)
IV = Ca channel block (decreases automaticity and increases PR)