P1- Pharmacodynamics Ii Exam 2 (Cubeddu)

Front 1

higher the preload the greater the what?

Back 1

amount of oxygen used by the heart muscles
(myocardial oxygen consumption)

Front 2

drugs that lower BP leads to sympathetic _______ and parasympathetic ________ via the baroreceptor reflex

Back 2

sympathetic stimulation

parasympathetic inhibition

Front 3

insensitive baroreceptor mechanisms ________ the BP-lowering actrion of drugs

Back 3

enhance

Front 4

major adrenergic receptors involved in BP control

Back 4

alpha1
alpha2
beta1

Front 5

_________ are the major determinant of peripheral resistance?

Back 5

arterioles

Front 6

protease in the juxtaglomerular cells of the afferent arterioles in the kidney

Back 6

Renin

major determinant of the rate of AII production

Front 7

Women on birthcontrol pills tend to have an increase in BP due to what?

Back 7

increased synthesis of angiotensinogen

Front 8

enzyme located mainly in the endothelial cells of the vasculature; converts AI to AII

Back 8

ACE

aka

Kininase II

Front 9

Factors that stimulate the production and release of renin

Back 9

beta-adrenergic stimulation (SNS activation)
decreased renal perfusion (intrarenal baroreceptor mechanisms)
decreased sodium intake
prostaglandins

Front 10

besides the renin-ACE system, AII can also be produced how?

Back 10

chymase
cathepsin
chymostain-sensitive AII-generating system
tissue plasminogen activator
tonin

therefore, inhibition of ACE may not completely suppress AII production

Front 11

what happens to renin levels when the effects of AII are inhibited with an AII-AT1 receptor antagonist?

Back 11

renin levels increase

Front 12

AII effects besides vasoconstriction

Back 12

a. ↑ aldosterone synthesis (↑ Na and H2O conservation)
b. ↑ Na, HCO3 reabsorption
c. ↑ SNS activity
d. ↑Ne and Endothelin-1 release
e. ↑ Thirst and vasopressin release
f. ↓ Renin release (negative feedback)
g. ↑ Filtration allowing protein in urine
h. contracts more selectively efferent than afferent arterioles
i. ↑ angiogenesis
j. plays a role in ovaries and testes (required for normal fetal growth)

Front 13

mineralocorticoid produced by the adrenal cortex

sodium retaining-potassium, hydrogen, and magnesium ion-loosing hormone

Back 13

Aldosterone

-increases number of active sodium channels in the luminal side of cells
- increases number of membrane bound Na-K ATPase on the basolateral side
-also has important effects on collagen formation and favors clotting

Front 14

AII retains sodium through what 3 methods?

Back 14

1. increase in aldosterone
2. increases sodium reabsorption on the proximal tubule
3. increases SNS activity

Front 15

when renal perfusion pressure drops (low BP) the reabsorption of sodium is increased at the _________

Back 15

proximal tubules

Front 16

high _____ levels induce salt sensitivity

Back 16

Angiotensin II (AII)

Front 17

powerful vasoconstrictor peptide (21 aa) formed in and released from the endothelium

Back 17

Endothelins

Front 18

What increases the release of Endothelins?

Back 18

1. AII
2. Hypoxia
3. Stress

Front 19

______Receptor→ high affinity for ET-1 in vascular muscle causing vasoconstriction
______ Receptor→ same affinity for ET-1 and ET-3 in vascular endothelium leading to NO and prostanoid release

Back 19

ETA Receptor→ high affinity for ET-1 in vascular muscle causing vasoconstriction
ETB Receptor→ same affinity for ET-1 and ET-3 in vascular endothelium leading to NO and prostanoid release

Front 20

ETA Receptor Blockers (ERA)

Back 20

ETA Receptor Blockers (ERA)
Bosaltan
Darusentan

Front 21

Vascular smooth muscle has more or less depolarized resting potential than the skeletal and heart muscle?

Back 21

Vascular smooth muscle has a more depolarized resting potential than the skeletal and heart muscle?

Vascular= -30
Heart Muscle=-70

Important because CCB bind with greater affinity to channels that are inactive/more depolarized

CCB have better affect on Vascular smooth muscle

Skeletal Muscle relies little on Calcium entry

Front 22

How do Na/K blockers lower BP?

Back 22

inhibiting Na/K ATPase causes an increase in intracelullar Na

Na/Ca2+ exchanger is then activated allowing Ca2+ in and Na+ out

increase in external Ca2+ is what contracts smooth muscle, SA, and AV nodes= increasing HR and constricting vessels

Front 23

vasodilator produced by the vascular endothelium

Back 23

Nitric Oxide

Front 24

Release of NO stimulated by?

Back 24

a. Hypoxia
b. Increased Blood flow
c. Bradykinin
d. Histamine
e. Serotonin
f. Arachidonic acid
g. ADP/ATP
h. Substance P
i. Ach
j. Thrombin

Front 25

NO is formed from?

Back 25

l-arginine in the prescence of eNOS (endothelial NO synthase)

Front 26

How does Sildenafil (Viagra) work?

Back 26

Sildenafil blocks Phosphodiesterase activity which allows for cGMP not to be destroyed= vasodilation= erection

Front 27

arteriolar and venodilator that increases production of cGMP, but can only be given thru IV. Once reacting with hemoglobin it turns into cyanomethemoglobin and cyanide ion and metabolized to thiocyanate; decomposes in light

Back 27

Sodium Nitroprusside

Used for hypertensive emergencies and congestive heart failure

Front 28

endothelium independent vasodilators that donate NO to tissues

Back 28

Organic Nitrates

(Nitroglicerine, isosorbide dinitrate)

Endothelium independent vasodilators

Front 29

does not induce smooth muscle relaxation via NO- endothelium independent mechanism; PGE2 and PGI2 activate adenylate cyclase increasing intracellular cAMP.

Back 29

Prostaglandin

Front 30

what does PGI2 do?

what does Thromboxane do?

Whast does Prostaglandin F2 alpha do?

Back 30

PGI2→ inhibits platelet aggregation
Thromboxane→ favors platelet aggregation
Prostaglandin F2 alpha → vasoconstrictor

Front 31

peptides with vasodilator action that lower BP by inducing vasodilation and getting rid of water and sodium, inhibit aldosterone secretion and decrease renin secretion

Back 31

Atrial Natriuretic Factors

ANP, BNP, CNP, DNP

Front 32

ANF vs NO

Back 32

ANF- act by activating membrane-bound guanylate cyclase

NO- diffuse through membrane and acts on cytoplasmic enzyme

Front 33

What are phosphodiesterases?

Back 33

enzymes that degrade cAMP and cGMP

Front 34

Affect of cAMP on:

Skeletal Muscle

Heart

Back 34

Skeletal Muscle- relaxation

Heart- contraction

Front 35

What is dyspnea?

Back 35

Shortness of breath

Front 36

What is nocturia?

Back 36

high volume of urination at night

Front 37

Ranges for:

Normal
Pre-Hypertensive
Hypertensive

Back 37

Normal: <120/<80
Pre-Hypertensive: 120-139/ 80-89
Hypertensive: >140/ >90

Front 38

Metabilic syndrome

Back 38

Obesity, hyperlipidemia, elevated glucose, hyperinsulinemia, and hypertension

Front 39

more than 11 million americans have both _________ and _________

Back 39

hypertension and diabetes mellitus

Front 40

major goal of treatment is to?

Back 40

prevent target-organ damange and to reduce the rate of adverse cardiovascular events

Front 41

Normal BP
Pre
Stage 1
Stage 2

Back 41

Normal BP: <120/80
Prehypertension: 120-139/ 80-89
Stage 1Hypertension: 140-159/ 90-99
Stage 2 Hypertension: >160/100

Front 42

causes for secondary hypertension

Back 42

renal disease
renovascular disease
drug-induced hypertension
pheochromocytoma
endocrine tumors

Front 43

• First-line drug for uncomplicated essential hypertension

Back 43

Diuretics and beta-blockers

Front 44

ACEI are drugs of choice for patients with what conditions?

Back 44

diabetes mellitus
diabetic nephropathy
myocardial infarction
chronic kidney disease
increase risk for coronary artery disease

Front 45

• Drug used for post MI/Ischemic heart disease

Back 45

Beta-blockers

Front 46

• Drugs used for indication for secondary prevention of strokes

Back 46

Diuretics and ACEI

Front 47

Elderly and AA are more sensitive to what type of antihypertensive drugs?

Back 47

Diuretics

NOT ACEI, AII-ATi (ARB), renin inhibitors, beta-blockers

Front 48

Caucasians respond well to?

Back 48

Beta-blockers

Front 49

People with high salt diets are less sensitive to what type of HT drug?

Back 49

ACEI
ARB
Beta-Blockers

Front 50

who experiences excessive drop in BP with antihypertensives?

Back 50

Elderly with poor compensatory mechanisms

and

patients with low circulating volume

Front 51

AA and Asians have more complications (cough and angioedema) with what class of HT drugs

Back 51

ACEI

Front 52

What is the initial treatment for AA?

Back 52

Thiazide diuretics and/or Calcium Channel blockers

Front 53

What should be prescribed for a black or white diabetic with proteinuria?

Back 53

ACEI

low dose of diuretic may be added if initial treatment does not make significant results

Front 54

Post-M/I patients should be on __________ regardless of his/her race

Back 54

Beta-blocker

Front 55

compare alpha 1 antagonists and a selective arterioloar dilator

Back 55

alpha 1 antagonist- decrease both afterload and preload

selective arteriolar dilator- just decreases afterload

both lower BP, but alpha antagonist require less myocardial consumption

Front 56

non-selective beta-blockers inhibit?

Back 56

chronotropic
inotropic
vasodilator
bronchodilator
uterine-relaxing responses

to beta-adrenergic stimulation

Front 57

ISA vs Non-ISA beta blockers

Back 57

ISA= partial agonist
(not indicated for HR reduction, or in patients with angina pectoris)

Non-ISA= full antagonist

Front 58

Non-selective beta-blocker with ISA

Selective beta-Blocker wiht ISA

Back 58

Non-selective beta-blocker with ISA- Pindolol and Penbutolol

Selective beta-Blocker with ISA- Acebutolol and Celiprolol

Front 59

drug of choice for people with peripheral vascular disease?

Back 59

Calcium Channel blockers

Front 60

Beta blocker prefered for patients with Asthma or Chronic obstructive pulmonary disease (COPD)

Back 60

Acebutolol

b/c beta-1 antagonist and beta-2 agonist

Front 61

Beta blockers cover up signs of hypoglycemia except for what?

Back 61

sweating

tachycardia, palpitations, tremor, hunger are all covered up by beta blockers

Front 62

in general, drugs with vasodilator activity do or do not improve insulin resistance

Back 62

do not change or improve insuline resistance

Front 63

epinephrine acting on beta-2 receptors is known to lower _______ by increasing its uptake into the skeletal muscle

Back 63

serum potassium

Front 64

Non-selective beta-blocker agents inhibit _____________ ___________

Back 64

Epinephrine-induced hypokalemia

Front 65

Name the Beta blockers eliminated by:

Liver

Kidney

Back 65

Eliminated by Liver→ propranolol, metoprolol, acebutolol
Eliminated by Kidney→ atenolol, nadolol (longest half-life)

Front 66

commonly used intravenously by hypertensive crisis

Back 66

Labetalol

Front 67

Beta blocker with antioxidant activity

also has been shown to reduce mortality by 60% in CHF patients receiving standard treatment with ACEI, diuretics, and digitalis

Back 67

Carvedilol

Front 68

ETA Receptor Blockers

Back 68

Bosaltan
Darusentan

Front 69

Na-Ca2+ Channel Blocker

Back 69

Digoxin

Front 70

Type V Phosphodiesterase Inhibitor

Back 70

Sildenafil
(destroys Phosphodiesterases which break down cGMP= more cGMP= venodilation=erection)

Front 71

NO Synthase Inhibitor

Back 71

Dexamethasone
(prevents production of NO)

Front 72

Organic Nitrates

Back 72

Nitroglicerine
Isosorbide dinitrate
(Donates NO to tissue)

Front 73

Selective α1-Blockers

Back 73

• Prazosin
• Doxazosin
• Terazosin
• Tamsulosin (uroselective)

Front 74

Selective α2-Blockers

Back 74

• Yohimbine

Front 75

Non-Selective α-Blockers

Back 75

• Phentolamine
• Phenoxybenzamine

Front 76

Selective β1-Blockers

Back 76

(↓broncho and arteriolar vasoconstriction)
• Atenolol
• Metoprolol
• Acebutolol (ISA)/ (beta2 agonist)
• Betaxolol
• Bisoprolol
• Celiprolol (ISA)
• Nebivolol (↑NO)

Front 77

Non-Selective β-Blockers

Which ones are ISA and alpha blockers?

Back 77

• Propanolol
• Nadolol
• Pindolol (ISA)
• Penbutolol (ISA)
• Levobunolol
• Timolol
• Carteolol
• Carvedilol (alpha blocker)
• Labetalol (alpha blocker)

Front 78

α2 and imidazoline receptor agonists

Back 78

• Clonidine
• Alpha-methyldopa
• Guanfacine
• Guanabenz
• Tizanidin
• Monoxidine

Front 79

Indicated for: hypertensive urgencies and emergencies; fourth-line agent b/c of side effects

Back 79

alpha 2 and imidazoline receptor agonists

Front 80

management of opiate detoxification, alcohol, and cigarette withdrawal, for menopausal hot flashes, ulcerative colitis and for spasticity of the skeletal muscle present in multiple sclerosis and following spinal cord trauma

Back 80

Clonidine

Front 81

management of increased muscle tone associated with spasticity; acts on presynaptic alpha2 receptors located on the ach-containing nerve terminal of motor neurons innervating the skeletal muscle. Activation of these receptors inhibits ach release producing muscle relaxation (decreased muscle tone)

Back 81

Tizanidine (zanaflex)

Front 82

alpha 2 adrenergic agent used for chronic treatment of open angle glaucoma and ocular hypertension; reduces production and increases outflow of aqueous humor; preoperative oral administration of alpha 2 agonists reduces dose requirements for anesthetic and analgesic drugs, decreases preoperative anxiety and induces sedation

Back 82

Brimonidine (alphagan)

Front 83

developed specifically for preoperative anxiety and sedation

Back 83

Dexmedetomidine and azepexole

Front 84

Side effects of alpha 2 and imidazoline receptor agonists

Back 84

drowsiness, sleepiness, tiredness, dry mouth , constipation; rebound hypertension and withdrawal symptoms if not discontinued gradually;
Alpha-methyldopa→ hemolytic anemia, liver (cholestatic hepatitis) and hematological (neutropenia) disorders

Front 85

Interactions/ Contraindications of alpha 2 and imidazoline receptor agonists

Back 85

don't use with constipating drug- loperamide, opioids, anticholinergics, antidepressants, verapamil; don't use with tricyclic-antidepressants because they may block the BP lowering effects of clonidine

Front 86

activates both α2 and imidazoline receptors located in rostral-ventral medulla

Back 86

Clonidine

Front 87

must be converted to its active metabolites (alpha-methyl-NE and alpha-methyl-epinephrine) to exert its antihypertensive effect by activating alpha-2 receptors

Back 87

Alpha-methyldopa

Front 88

Sympathetic Nerve Terminal Drugs

Back 88

• Reserpine
• Guanethidine
• Guanadrel

Front 89

lowers BP effectively; only used as last resort for patients with severe, uncontrolled hypertension

Back 89

Guanethidine/ Guanadrel

Front 90

affects storage system for catecholamines and serotonin; reduces amount of NE available for release resulting in decreased stimulation of alpha and beta receptors; enters CNS

Back 90

Reserpine

Front 91

inhibit NE release from postganglionic sympathetic terminals; both are quaternary amines so do NOT reach CNS

Back 91

Guanethidine & Guanadrel

Front 92

Side Effects of Reserpine and Guanethidine/ Guanadrel

Back 92

Reserpine→ tertiary amine so it reaches CNS reducing both peripheral and brain monoamine levels (less NE, EPI, Dopamine, and Serotonin); depression, tiredness, and drowsiness
Guanethidine/ Guanadrel→ dizziness, orthostatic hypotension, retrograde ejaculation, nasal obstruction, fluid retention (Thiazides help reduce incidence of fluid retention and edema)

Front 93

contraindications with sympathetic nerve terminal drugs (Reserpine, Guanethidine, Guanadrel)

Back 93

don't use with patients with history of depression or if suicidal or breast cancer and/or GI ulcers; don't use with patients with nasal obstruction, orthostatic hypotension, and ejaculatory problems

Front 94

Dopamine 1-receptor agonist

Back 94

• Fenoldopam

Front 95

management of severe hypertension (up to 48 hours) rapid effects; maximum effects develop within 20-30 minutes

Back 95

Dopamine 1-receptor agonist:
• Fenoldopam

Front 96

lowers diastolic BP and increases renal perfusion by activating Dopamine-1 receptors; vasodilator; given parenterally to vasodilate peripheral arteries decreasing TPR and acts as diuretic; increases sodium chloride and water excretion); increases renal blood flow

Back 96

Dopamine 1-receptor agonist:
• Fenoldopam

Front 97

Side effecs of Dopamine 1-receptor agonist:
• Fenoldopam

Back 97

headache, flushing, dizziness, tachycardia; not degraded by light

Front 98

contraindications for Dopamine 1-receptor agonist:
• Fenoldopam

Back 98

Patients with glaucoma because it decreases drainage of aqueous humor

Front 99

Thiazides/ thiazide-like

Back 99

• Hydrochlorothiazide (16hr)
• Bendroflumethiazide
• Chlorothiazide
• Polythiazide
• Chlorthalidone (24hr)
• Indapamide
• Xipamide
• Metolazone (okay with renal failure)

Front 100

inhibits reabsorption of NaCl on the cortical portion of thick ascending limb of Henle

Back 100

Thiazides/ thiazide-like

Front 101

Loop diuretics

Back 101

• Furosemide (12hr)
• Bumetanide
• Torsemide
• Piritanide
• Ethacrinic acid

Front 102

reduce NaCl reabsorption in the thick ascending limb of Henle by inhibiting the Na-K-2Cl symport

Back 102

Loop Diuretics

Front 103

used when hypertension is associated with edematous states (sodium retention, CHF) or when renal dysfunction is present; synergistic diuretic interaction between thiazides and loop diuretics

Back 103

Loop Diuretics

Front 104

Potassium-Sparing diuretics

Back 104

• Triamterene
• Amiloride
• Spironolactone
• Eplerenone

Front 105

inhibitors of the renal epithelial sodium channels block sodium channels present in the luminal membrane of principal cells in the late distal tubule and collecting ducts

Back 105

Triamterene and Amiloride

Front 106

aldosterone antagonists reduce aldosterone mediated increased synthesis, distribution and activation of sodium channels and of membrane bound sodium-potassium ATPase of principal cells in the late distal and collecting ducts. Reduces number of sodium channels or blocks the channels inhibiting sodium reabsorption

Back 106

Spironolactone and Eplerenone

Front 107

Used in combination with other diuretics to avoid or reverse hypokalemia; reduces the loss of potassium, hydrogen ion, and magnesium induced by thiazides and loop diuretics; weaker diuretics than loop diuretics

Back 107

Potassium-Sparing diuretics

Front 108

alternative to thiazides in patients with low potassium, hyperuricemia, glucose intolerance and/or the presence of high aldosterone levels; used to treat hirsutism in females

Back 108

Spironolactone

Front 109

Which Diuretics is best for patients with renal failure (serum creatine greater than 2.5 mg/dl) but want to prevent hyperkalemia?

NSAIDS and steroids may increase the risk of hyperkalemia in which diuretics?

Back 109

Potassium-Sparing diuretics

Front 110

Which diuretic is good to use if patient has:

hypokalemia, ↑serum uric acid and gout, hyperglycemia, hyperlipidemia, ↑or↓ in Ca2+, sexual function, erectile dysfunction, decreased libido, delay in orgasm, ↓lithium clearance, and ↑serum lithium levels

Back 110

Potassium-Sparing diuretics

Front 111

interferes with testosterone synthesis and may increase conversion of testosterone to estradiol; endocrine abnormalities; gynecomastia

Back 111

Spironolactone

Front 112

may cause hyperkalemia; does not have endocrine side effects like Spironolactone

Back 112

Eplerenone

Front 113

Low salt intake ________ effects of diuretics; high salt diet _____ the potassium-loosing effect of diuretics

Back 113

Low salt intake enhances effects of diuretics; high salt diet accentuates the potassium-loosing effect of diuretics

Front 114

Hypokalemia is known to potentiate the effects of __________

Back 114

Hypokalemia is known to potentiate the effects of digoxin

Front 115

Hypokalemia should be avoided in patients with

Back 115

• hypertension
• diabetes
• ischemic heart disease
• arrhythmia
• CHF
• taking antiarrhythmic drugs
• taking digoxin
• taking beta-2 agonists

Front 116

Preferred in patients with renal impairment

Back 116

Loop Diuretics

Front 117

Not effective in patients with renal impairment

Back 117

Thiazide Diuretics

Front 118

thiazide-type diuretic that retains efficacy in renal failure; used with small doses with furosemide in hypertensives with renal disease

Back 118

Metolazone

Front 119

______ stimulation to the kidney induces the release of renin via stimulation of beta receptors?

Back 119

Sympathetic

Front 120

What does Aldosterone do?

Back 120

1. sodium retaining
2. K, H, and Mg loosing
3. collagen formation
4. favors clotting

AKA repair-promoting substance

Front 121

What induces salt sensitivity?

Back 121

High levels of AII

Front 122

Compare NE, AII, and Endothelins as vasocontrictors

Back 122

ET-1>>> AII>>NE

Front 123

ETA vs ETB receptors

Back 123

ETA→ vascular smooth muscle; vasoconstriction

ETB→vascular endothelium; release NO and prostanoids (vasodilation)

Front 124

What do CCB do to the ECG?

Back 124

prolongs the PR interval

Front 125

Name 4 ways to modulate intracellular Ca2+

Back 125

1. Voltage-dependent calcium channel (CCB)
2. Cell membrane Ca2+ pump
3. Na+/Ca2+ exchanger (Digoxin)
4. Sarcoplasmic Reticulum and Mitochondria (IP3)

Front 126

How does NO cause vasodilation?

Back 126

NO passes from the endothelium to the smooth muscle, where it stimulates cGMP production, which in turn leads to vasodilation

NO also reduces platelet adhesion and aggregation; inhibits adherence of platelets, WBC, and LDL-C to the endothelium

Front 127

What is the max daily intake of Salt?

What other supplement can you take to help lower your BP?

Back 127

Max Salt Intake= 6 grams/day

Increasing Potassium intake can lower BP