Vasodilators etc Flashcards
Long-term outpatient therapy of severe or resistant hypertension
Hydralazine
Hypertensive emergencies
nitroprusside
Hypertensive emergencies; angina
Nitrates
- Long-term outpatient therapy of hypertension
- hypertensive emergencies
- angina
Verapamil
diltiazem
nifedipine
amlodopine
Reduction of calcium influx
Hyperpolarization of smooth muscle membrane through opening of potassium channels
Minoxidil
Diazoxide
Long-term outpatient therapy of severe or resistant hypertension
Minoxidil
-Hyperpolarization of smooth muscle membrane through opening of potassium channels
Hypertensive emergencies (and not a NO releaser)
Diazoxide
-Hyperpolarization of smooth muscle membrane through opening of potassium channels
Hypertensive emergencies, and not a NO releaser, potassium channel opener, or a calcium influx inhibitor
Fenoldopam: Activation of dopamine receptors
excessive hypotension, dizziness, headache, peripheral edema, flushing, tachycardia, rash, and gingival hyperplasia have been reported
Dihydropyridines
Dizziness, headache, peripheral edema, AV block, bradycardia, heart failure, lupus-like rash, pulmonary edema, coughing, and wheezing are possible
diltiazem
Dizziness, headache, peripheral edema, constipation, AV block, bradycardia, heart failure, pulmonary edema, coughing, and wheezing are possible
verapamil, non-DHP
slow heart rate, can slow atrioventricular conduction, can cause heart block, and are contraindicated in patients also taking a beta-blocker
Non-DHPs (verapamil > diltiazem)
does not decrease AV conduction and therefore can be used more safely than non-DHPs in the presence of AV conduction abnormalities
Nifedipine
may increase digoxin blood levels through a pharmacokinetic interaction
verapamil
Additive with other vasodilators
DHPs
Additive with other cardiac depressants and hypotensive drugs
non-DHPs
Long-term outpatient therapy of hypertension; hypertensive emergencies; angina
CALCIUM CHANNEL BLOCKERS
prototype DHPs, MOA
Amlodipine and nefidipine
MOA: Blocks L-type calcium channels in vasculature > cardiac channels
Prototype non-DHP drugs, MOA
Non-Dihydropyridines
(1) Prototypes: Verapamil, Diltiazem
(2) MOA: Nonselective block of vascular and cardiac L-type calcium channels
- cause vasodilation–> decreases peripheral resistance
- arterioles are more sensitive than veins
- orthostatic hypotension is not usually a problem
- relaxation of arteriolar smooth muscle leads to decreased afterload and decreased O2 demand by the heart
Ca channel blockers (CCBs)
CCBs: block channels in smooth muscle at much lower concentrations
non-DHPs: this is significant because while they have more cardiac effects, their cardiac effects are negligible at effective therapeutic concentrations
(t1/2) of 35-50 hours
amlodipine: the other CCBs typically 2-12 hrs
Excessive hypotension–> stroke & MI
Hypotensive effects worse in
- patients with renal failure (due to reduced protein binding
- patients pretreated with β-blockers to prevent reflex tachycardia
K+ channel opener: Diazoxide
in which patients should K channel opener diazoxide be administered in smaller doses than other patient populations?
- renal failure patients (reduced protein binding)
- patients pre-tx with beta blockers for reflux tachycardia
- hyperglycemic patients, especially if they have renal insufficiency
in which patients should diazoxide be avoided?
patients with ischemic heart disease due to propensity for angina,
ischemia, and cardiac failure
contrast dizoxide to other diuretics
diazoxide causes sodium and water retention; this is rarely a problem due to the typical short duration of use
Common: headache, sweating, hypertrichosis (abnormal hair growth)
Minoxidil
use is associated with
- reflex sympathetic stimulation
- sodium + fluid retention –> tachycardia, palpitations, angina, and edema
minoxidil
must be used in combination with a beta blocker and loop diuretic to avoid AEs
minoxidil must be used in combination with a β-blocker and loop diuretic in order to avoid these effects
Long-term outpatient therapy of severe hypertension and in topical formulations used to stimulate hair growth
minoxidil
Administered by continuous IV infusion due to rapid metabolism and short half-life (10 min)
fendolapam
Tachycardia, headache, and flushing
fendolapam
Should be avoided in patients with glaucoma due to increases in intraocular pressure
D1 receptor agonist fendolapam
Hypertensive emergencies, peri- and postoperative hypertension
fendolapam
Stimulates release of nitric oxide from endothelium resulting in increased cGMP levels
Hydralazine
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
- pharmacodynamics of hydralazine
- pharmacokinetics of diazoxide
- pharmacokinetics of minoxidil
- pharmoacokinetics of fendolapam
- pharmacokinetics of hydralazine
- pharmocodynamics of nitroprusside
- pharmacokinetics of nitroprusside
- pharmacodynamics of organic nitrates
- pharmacodynamics of organic nitrates
- pharmacodynamics of organic nitrates
headache, nausea, anorexia, palpitations, sweating, and flushing
hydralazine
In patients with ischemic heart disease, reflex tachycardia and sympathetic stimulation may provoke angina or ischemic arrhythmias
hydralazine
peripheral neuropathy, drug fever
rare outcome of hydralazine use
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
hydralazine
First-line therapy for hypertension in pregnancy, with methyldopa
hydralazine
Parenteral formulation is useful in hypertensive emergencies.
hydralazine
results in increased cGMP levels
MOA nitroprusside
Powerful dilation of arterial and venous vessels, reduces peripheral vascular resistance and venous return
nitroprusside
- Excessive hypotension…..Cyanide and thiocyanate are released during metabolism; this is typically not problematic because it is used only briefly
- metabolic acidosis, arrhythmias, excessive hypotension, and death can occur if infusions are administered for several days
1 = nitroprusside
2 = nitroprusside (as well)
Hypertensive emergencies; acute decompensated heart failure
nitroprusside
Release of nitric oxide via enzymatic metabolism
organic nitrates
Common: orthostatic hypotension, syncope, throbbing headache
organic nitrates
Contraindicated if intracranial pressure is elevated
organic nitrates
Synergistic hypotension with phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil)
organic nitrates
Hypertensive emergencies, angina, heart failure
organic nitrates
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
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
1 = CCB, DHPs
2 = CCB, Non-DHPs
- 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
- 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
1 = diazoxide
2 = minoxidil
- cyanide poisoning (metabolic acidosis, arrhythmias, excessive hypotension, and death) can occur if infusions are administered for several days
- orthostatic hypotension, syncope, throbbing headache, contraindicated if intracranial pressure is elevated, increased generation of oxygen free radicals
- nitroprusside
- nitroglycerin (prototype organic nitrates)
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.
organic nitrates
- sublingual route of administration is typically used to avoid first-pass
- Oral, transdermal, and buccal preparations are available when longer duration of action is needed
