Vasodilators etc

Question 1

Long-term outpatient therapy of severe or resistant hypertension

Answer 1

Hydralazine

Question 2

Hypertensive emergencies

Answer 2

nitroprusside

Question 3

Hypertensive emergencies; angina

Answer 3

Nitrates

Question 4

1. Long-term outpatient therapy of hypertension
2. hypertensive emergencies
3. angina

Answer 4

Verapamil

diltiazem

nifedipine

amlodopine

Reduction of calcium influx

Question 6

Hyperpolarization of smooth muscle membrane through opening of potassium channels

Answer 6

Minoxidil

Diazoxide

Question 7

Long-term outpatient therapy of severe or resistant hypertension

Answer 7

Minoxidil

-Hyperpolarization of smooth muscle membrane through opening of potassium channels

Question 8

Hypertensive emergencies (and not a NO releaser)

Answer 8

Diazoxide

-Hyperpolarization of smooth muscle membrane through opening of potassium channels

Question 9

Hypertensive emergencies, and not a NO releaser, potassium channel opener, or a calcium influx inhibitor

Answer 9

Fenoldopam: Activation of dopamine receptors

Question 10

excessive hypotension, dizziness, headache, peripheral edema, flushing, tachycardia, rash, and gingival hyperplasia have been reported

Answer 10

Dihydropyridines

Question 11

Dizziness, headache, peripheral edema, AV block, bradycardia, heart failure, lupus-like rash, pulmonary edema, coughing, and wheezing are possible

Answer 11

diltiazem

Question 12

Dizziness, headache, peripheral edema, constipation, AV block, bradycardia, heart failure, pulmonary edema, coughing, and wheezing are possible

Answer 12

verapamil, non-DHP

Question 13

slow heart rate, can slow atrioventricular conduction, can cause heart block, and are contraindicated in patients also taking a beta-blocker

Answer 13

Non-DHPs (verapamil > diltiazem)

Question 14

does not decrease AV conduction and therefore can be used more safely than non-DHPs in the presence of AV conduction abnormalities

Answer 14

Nifedipine

Question 15

may increase digoxin blood levels through a pharmacokinetic interaction

Answer 15

verapamil

Question 16

Additive with other vasodilators

Answer 16

DHPs

Question 17

Additive with other cardiac depressants and hypotensive drugs

Answer 17

non-DHPs

Question 18

Long-term outpatient therapy of hypertension; hypertensive emergencies; angina

Answer 18

CALCIUM CHANNEL BLOCKERS

Question 19

prototype DHPs, MOA

Answer 19

Amlodipine and nefidipine

MOA: Blocks L-type calcium channels in vasculature > cardiac channels

Question 20

Prototype non-DHP drugs, MOA

Answer 20

Non-Dihydropyridines

(1) Prototypes: Verapamil, Diltiazem
(2) MOA: Nonselective block of vascular and cardiac L-type calcium channels

Question 21

1. cause vasodilation–> decreases peripheral resistance
2. arterioles are more sensitive than veins
3. orthostatic hypotension is not usually a problem
4. relaxation of arteriolar smooth muscle leads to decreased afterload and decreased O2 demand by the heart

Answer 21

Ca channel blockers (CCBs)

Question 22

CCBs: block channels in smooth muscle at much lower concentrations

Answer 22

non-DHPs: this is significant because while they have more cardiac effects, their cardiac effects are negligible at effective therapeutic concentrations

Question 23

(t1/2) of 35-50 hours

Answer 23

amlodipine: the other CCBs typically 2-12 hrs

Question 24

Excessive hypotension–> stroke & MI

Hypotensive effects worse in

1. patients with renal failure (due to reduced protein binding
2. patients pretreated with β-blockers to prevent reflex tachycardia

Answer 24

K+ channel opener: Diazoxide

Question 25

in which patients should K channel opener diazoxide be administered in smaller doses than other patient populations?

Answer 25

1. renal failure patients (reduced protein binding) 2. patients pre-tx with beta blockers for reflux tachycardia 3. hyperglycemic patients, especially if they have renal insufficiency

Question 26

in which patients should diazoxide be avoided?

Answer 26

patients with ischemic heart disease due to propensity for angina, ischemia, and cardiac failure

Question 27

contrast dizoxide to other diuretics

Answer 27

diazoxide causes sodium and water retention; this is rarely a problem due to the typical short duration of use

Question 28

Common: headache, sweating, hypertrichosis (abnormal hair growth)

Answer 28

Minoxidil

Question 29

use **_is associated_** with 1. reflex sympathetic stimulation 2. sodium + fluid retention --\> tachycardia, palpitations, angina, and edema

Answer 29

minoxidil

Question 30

must be used in combination with a beta blocker and loop diuretic to avoid AEs

Answer 30

**_minoxidil_** must be used in combination with a β-blocker and loop diuretic in order to avoid these effects

Question 31

Long-term outpatient therapy of severe hypertension and in topical formulations used to stimulate hair growth

Answer 31

minoxidil

Question 32

Administered by continuous IV infusion due to rapid metabolism and short half-life (10 min)

Answer 32

fendolapam

Question 33

Tachycardia, headache, and flushing

Answer 33

fendolapam

Question 34

Should be avoided in patients with glaucoma due to increases in intraocular pressure

Answer 34

D1 receptor agonist fendolapam

Question 35

Hypertensive emergencies, **peri- and postoperative hypertension**

Answer 35

fendolapam

Question 36

Stimulates release of nitric oxide from endothelium resulting in increased cGMP levels

Answer 36

Hydralazine

Question 37

1) dilation of arterioles, but not veins; reflex tachycardia 2) hyperpolarizes the smooth muscle membrane, reducing the probability of contraction; arteriolar dilator resulting in reduced systemic vascular resistance and mean arterial pressure 3) hyperpolarizes the smooth muscle membrane, reducing the probability of contraction. dilation of arterioles, but not veins; more efficacious than hydralazine 4) Administered by continuous IV infusion due to rapid metabolism and short half-life (10 min) 5) Metabolism occurs in part via acetylation, so bioavailability is variable among individuals dependent on rate of acetylation 6) Powerful dilation of arterial and venous vessels, reduces peripheral vascular resistance and venous return 7) Rapid metabolism results in rapid onset and short duration of effect; Should be administered by IV infusion with continuous monitoring of arterial blood pressure 8) Relaxes most types of smooth muscle (veins \> arteries); virtually no direct effect on cardiac or skeletal muscle 9) Increases venous capacitance; decrease ventricular preload; pulmonary vascular pressures and heart size are reduced. In the absence of heart failure, cardiac output is reduced. 10) Decreases platelet aggregation

Answer 37

1. pharmacodynamics of hydralazine 2. pharmacokinetics of diazoxide 3. pharmacokinetics of minoxidil 4. pharmoacokinetics of fendolapam 5. pharmacokinetics of hydralazine 6. pharmocodynamics of nitroprusside 7. pharmacokinetics of nitroprusside 8. pharmacodynamics of organic nitrates 9. pharmacodynamics of organic nitrates 10. pharmacodynamics of organic nitrates

Question 38

headache, nausea, anorexia, palpitations, sweating, and flushing

Answer 38

hydralazine

Question 39

In patients with ischemic heart disease, reflex tachycardia and sympathetic stimulation may provoke angina or ischemic arrhythmias

Answer 39

hydralazine

Question 40

peripheral neuropathy, drug fever

Answer 40

rare outcome of hydralazine use

Question 41

Long-term outpatient therapy of hypertension. Combination with nitrates is effective in heart failure and should be considered in patients, especially African-Americans, with both hypertension and heart failure

Answer 41

hydralazine

Question 42

First-line therapy for hypertension in pregnancy, with methyldopa

Answer 42

hydralazine

Question 43

Parenteral formulation is useful in hypertensive emergencies.

Answer 43

hydralazine

Question 44

results in increased cGMP levels

Answer 44

MOA nitroprusside

Question 46

Powerful dilation of arterial and venous vessels, reduces peripheral vascular resistance and venous return

Answer 46

nitroprusside

Question 47

1. Excessive hypotension.....Cyanide and thiocyanate are released during metabolism; this is typically not problematic because it is used only briefly 2. metabolic acidosis, arrhythmias, excessive hypotension, and death can occur if infusions are administered for several days

Answer 47

1 = nitroprusside 2 = nitroprusside (as well)

Question 48

Hypertensive emergencies; acute decompensated heart failure

Answer 48

nitroprusside

Question 49

Release of nitric oxide via enzymatic metabolism

Answer 49

organic nitrates

Question 50

Common: orthostatic hypotension, syncope, throbbing headache

Answer 50

organic nitrates

Question 51

Contraindicated if intracranial pressure is elevated

Answer 51

organic nitrates

Question 52

Synergistic hypotension with phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil)

Answer 52

organic nitrates

Question 53

Hypertensive emergencies, angina, heart failure

Answer 53

organic nitrates

Question 54

**1) excessive hypotension**, dizziness, headache, peripheral edema, flushing, **tachycardia**, rash, and **gingival hyperplasia** have been reported, potentially **increased risk of MI, stroke, or death** in patients receiving short term tx for HTN ## Footnote **2)** Dizziness, headache, peripheral edema, _constipation,_ **AV block**, **bradycardia**, heart failure, **lupus-like rash.** pulmonary edema, **coughing, and wheezing** are possible, can slow atrioventricular conduction, can cause heart block, and are **contraindicated in patients also taking a beta-blocker**

Answer 54

1 = CCB, DHPs 2 = CCB, Non-DHPs

Question 55

1. Hypotensive effects are greater in patients with renal failure (due to reduced protein binding) and in patients pretreated with β-blockers to prevent reflex tachycardia; smaller doses should be administered to these patients 2. associated with reflex sympathetic stimulation and sodium and fluid retention resulting in tachycardia, palpitations, angina, and edema; must be used in combination with a β-blocker and loop diuretic in order to avoid these effects

Answer 55

1 = diazoxide 2 = minoxidil

Question 56

1. cyanide poisoning (metabolic acidosis, arrhythmias, excessive hypotension, and death) can occur if infusions are administered for several days 2. orthostatic hypotension, syncope, throbbing headache, contraindicated if intracranial pressure is elevated, increased generation of oxygen free radicals

Answer 56

1. nitroprusside 2. nitroglycerin (prototype organic nitrates)

Question 57

Diminished availability of calcitonin gene-related peptide (CGRP). Compensatory responses contributing to the development of tolerance: tachycardia, increased cardiac contractility, retention of salt and water.

Answer 57

organic nitrates

Question 58

1. sublingual route of administration is typically used to avoid first-pass 2. Oral, transdermal, and buccal preparations are available when longer duration of action is needed