Directly acting vasodilators Flashcards
what are the different types of vasodilators
calcium channel blockers (dihydropyridine and non-dihydropyridine), hydralazine, potassium channel agonists (minoxidil), nitrates
what is the GENERAL mechanism of all vasodilators
they act directly on vascular smooth muscle cells and reduce the magnitude of smooth muscle contraction—> reducing the myogenic tone of the cells, resulting in vasodilation
the major difference between DHP and nDHP is _____
nDHP’s also decrease heart rate
what are the dihydropyridines
amlodipine, felodipine, isradipine, nicardipine, cifedipine, nimodipine, clevidipine
what are the non-dihydropyridines
diltiazem, verapamil
diltiazem is a _____
benzothiazepine
verapamil is a ______
phenylalkylamine
calcium channel blockers bind to ______ calcium channels
voltage-sensitive, L-type
which subunit of the calcium channel do CCBs bind to
the alpha 1 subunit (part that forms the pore thru which calcium passes)
CCBs binding to the L-type calcium channel causes it to _____
stay in the closed inactivated conformation
what is the result of CCBs inactivating channels
less calcium can enter smooth muscle cells, which decreases contraction
contractions depend on ____
availability of calcium
CCBs relax the vascular smooth muscle of _______, which reduces ___
arteries and arterioles, TPR
the vascular smooth muscle of ____ is NOT significantly affected by CCBs
veins
CCBs are especially useful for patients with _____
LOW renin
clinical uses of CCB
use alone or in combo, effective in reducing BP, also useful in the treatment of coronary artery disease
why are CCBs useful in coronary artery disease
since they are able to relax coronary arteries and increase blood flow to the heart muscle. since they lower BP, they reduce the work that the heart must do to provide the energy to move blood through the blood vessels
when are CCBs a great alternative to BBs
for patients with asthma
which CCB should you NOT combine w/ a BB and why?
nDHP–> because they both lower heart rate
diltiazem and verapamil are also used to treat _____
arrhythmias
dihydropyridines do not have a major effect on ________, so they are not used as antiarrhythmics
AV node conduction
what is a side effect with CCBs
peripheral edema (ankles in particular)
how would CCBs cause peripheral edema
they relax the small arterioles leading into capillaries but not the veins leading out of the capillary bed–> which elevates the hydrostatic pressure within the capillary and favors leakage of fluid into interstitial space
which patients should not take CCBs
in heart failure patients, the decrease in contractility could depress cardiac function. in patients with cardiac disease that is associated with AV node conduction, they are a bad choice as they can further reduce AV node conduction
what is the mechanism of hydralazine
it enters vascular smooth muscle cells–> keeps Ca channels closed–> blocks release of Ca from sarcoplasmic reticulum–> reduces cytoplasmic Ca concentration–> reduces contraction
hydralazine has an affect on ____ smooth muscle which decreases ____
arterial; TPR
hydralazine has no effect on ____ smooth muscle
venous
what is an adverse effect of hydralazine
systemic lupus erythematosus-like syndrome (an antibody response causing rash and muscle pain)
what are the clinical uses of hydralazine in HTN
reserved for pts whose HTN is refractory to treatment with other agents
hydralazine can be combined with ______ to prevent sympathetic reflex activation
beta blockers
hydralazine can be combined with a _____ to prevent sodium retention
diuretic
hydralazine can be combined with ______ for heart failure
isosorbide dinitrate
what is the mechanism of minoxidil
potassium channel agonist–> K channel opens–> more negative membrane potential–> more voltage gated L-type calcium channels will be closed—> less Ca will enter the cells—> smooth muscle relaxed
minoxidil is a potent _____ vasodilator that decreases ____
arterial, TPR
minoxidil has no significant effect on ____ smooth muscle
venous
how does sympathetic reflex activation work against the vasodilators
baroreceptors detect the decrease in blood pressure and compensate
use of minoxidil in HTN
reserved for complicated patients
adverse effect of minoxidil
hypertrichosis (hair growth)–> rogaine
what are the nitrates
nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, sodium nitroprusside
use of sodium nitroprusside
hypertensive emergencies
use of nitroglycerin
coronary artery disease (chronic stable angina and acute MI)
use of isosorbide mononitrate & dinitrate
chronic stable angina
the metabolism of nitrates and sodium nitroprusside leads to intracellular production of _____ in vascular smooth muscle
nitric oxide
nitric oxide stimulates _____
guanylate cyclase
the increased production of ______ by guanylate cyclase causes cytoplasmic Ca to decrease
cyclic GMP
it has been hypothesized that impaired formation of _____ may be a cause of hypertension
nitric oxide
what are symptoms of sodium nitroprusside toxicity
metabolic acidosis, decreased oxygen saturation, bradycardia, confusion, convulsions
when does toxicity occur with sodium nitroprusside
high doses, long term administration, poor liver/kidney function
what is the mechanism of sodium nitroprusside toxicity
it is made up of ferric cyanide and nitric oxide–> cyanide is released into the bloodstream, then further metabolized by the liver to thiocyanate which is then slowly cleared by the kidneys
