Vasodilators Flashcards
Drugs for Congestive Heart Failure
Diruetics, Beta-blockers, Vasoactive Drugs, Drugs affecting RAAS (renin agiotensin-aldosteron system)
Drugs for Hypertension
Diuretics, Adrenergic inhibitors, Calcium channel blockers, Direct Vasodilators, RAAS blockers
Direct Acting Vasodilators
Hydralazine
Minoxidil
Sodium Nitroprusside
Fenoldopam
Hydralazine
Class: Direct acting vasodilator
Mechanism: potent and direct arteriolar dilator; unknown mechanism
Uses: Hypertension, Heart failure (hypertensive patients with increasing creatine and want to avoid ACEi or ARB in acute); also used in combination with venodilator isosorbide dinitrate
Side Effects: reflex tachycardia (baroreceptpr mediated), use with caution if patient has CAD could precipitate myocardial ischemia; palpitations (secondary to reflex tachycardia), flushing, lupus like syndrome (esp. for slow acetylators), nausea, anorexia
Misc: Extensive first pass hepatic metabolism (50% of patient slow acetylators, rest fast). Short half life (2-4hrs) but binds avidly to vascular tissue so effect persits up to 12 hrs. More benefit in african americans
Minoxidil
Class: Direct acting vasodilator
Mechanism: arteriolar vasodilator, increase in potassium channel permeability leading to smooth muscle hyperpolarization and relaxation
Uses: severe intractable hypertension, also used for alopecia
Side Effects: reflex tachycardia, edema/fluid and Na retension (secondary to decreased renal perfusion), hypertrichosis (excessive hair growth); pericardial effusion is rare
Misc: metabolized by hepatic glucuronidation , short half-life but long effects due to avid binding to vasculature
Sodium Nitroprusside
Class: Direct Vasodilators
Mechanisms: acts on both arterioles and veins; NO decreases arterial resistance and increases venous capacitance
Uses: hypertensive emergency (often with beta-blocker),
Side Effects: caused by thiocynate accumulation (blurred vision, tinnitus, disorientation, and/or nausea), higher risk of toxicity if renal impairment
Misc: given continous IV (very potent and rapid action, within 30 sec affect felt peak in 2 mins and wanes quickly after discontinuation
- increased intracellular cGMP, which inhibits calcium entry into the cell, and decreases intracellular calcium concentrations (click here for details)
- activates K+ channels, which leads to hyperpolarization and relaxation
- stimulates a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to smooth muscle relaxation.
Fenoldopam
Class: Direct Acting Vasodilators
Mechanism: rapid and potent arteriolar vasodilator; peripheral dopamine 1 receptor agonist; activation results in increase of intracellular cAMP (via Gs) in smooth muscle resulting in vasodilation
Uses: Severe hypertension
Side Effects: increased intraocular pressure (slows down aqueous humor drainage so avoid use in patients with glaucoma); headache, dizziness, tachycardia
Misc: continuous IV infusion; maintains or enhances renal perfusion unlike other IV hypertensives, faciliates natriuresis via activation of renal tubular D1 receptors, acheieve 50% max efffec within 15 min, steady state 30-60 min, metabolized by liver excreted by kidneys
[Organic Nitrates]
Nitroglycerin
Class: Vasodilators (organic Nitrates)
Agents: Nitroglycerin
Mechanism: stimulates guanylate cyclase (via NO), leading to increase in cGMP that promotes smooth muscle relaxation. For angina pectoris, giving nitrates reduces preload (venodilation). Reducing preload decreases the radius of the left ventricular thereby reducing wall stress . Reduced wall stress decreases the oxygen demand of the heart allowing it to match its supply which relieves symptoms. Also useful to coronary artery spasm (prinzmetal variant agina) by dilating coronary arteries.
At low conc. promotes greater venous dilation than arterioles (arterial diation to some exent in coronary arteries, facial vessle and meningeal aerteries hence flushing and headach as side effects. At high does get arteriolr dilation (side effects of reflex tachycardia and hypotension)
Uses: Ischemic Heart Disease (angina pectoris, acute coronary syndromes), Congestive Heart Failure (with hydralazine)
Acute: (sublingual nitroglycern tablets or sprays)
Chronic managment of coronary artery disease (CAD): long acting nitrates such as isorbide dinitrate or mononitrate, transdermal or IV nitroglycerin. Dose regiments need to allow drug free interval or will develope tolerance.
Side effects: flushing, headache, reflex tachycardia, hypotension
[Natriuretic Peptide]
Nesiritide
Mechanism: human recombinant BNP
Uses: refractory Heart failure (IV given to hospitalized patients)
Sildenafil
Class: Phosphodiesterase-5 inhibitor
Mechanism: Inhibiting phosphodiesterase-5 prevents breakdown of cGMP in pulmonary vasculature (and corpus cavernosum vessels)
Uses: pulmonary hypertension, erectile dysnfunction (viagra)
Side affects: DO NOT USE WITH NITRATES leads to severe hypotension
Mechanism: impede influx of Ca2+ through membrane channels in cardiac and smooth muscle cells
Non-Dihydrppyridine
Verapamil and Diltiazem
Vasodilatiry and negative iontropic effect by suppressing AV node conduction
Uses: superventricular arrythmias, hypertension, ischemic heart disease
Side effects: hypotension & bradycardia (both), av node block & constipation (verapamil), peripheral edema (diltiazem)
(edema because arterioles more dilated than venous tso venous pressure increases)
Dihydropyridine (DIPINE)
Uses: (hypertension and ischemic heart disease)
Side effects: hypotension, headache, flushing, peripheral edema
NAF
Nefedipine
Amlodipine
Felodipine
INN (isradipine, nicardipine, nisoldipine)
Angiotensin Converting Enzyme (ACE) Inhibitors
Agents: **CLERT **captopril, lisinopril, enalapril, ramipril, trandolapril
Mechanism: in heart failure, ACE inhibitors reduce afterload, preload, decrease adrenegergic tone, increase renal blood flow and reverse remodeling
Uses: hypertension (especially diabetic hypertension because slows progression of renal disease (diabetic nephropathy )), **heart failure **, post-MI (myocardial infarction_)_
Side Effects: hypotension, hyperkalemia (esp. if used together with with potassium sparingf diuretics), renal insufficiency (esp. in bilateral renal artery stenosis since patients rely on high glomerule rsistance to maintain pressure), **cough **(ACEI increase levels of bradykinin. Angioedema, contraindicated during pregnancy because of fetal injury
Angiotensin II Type 1 (AT1) Receptor Antagonists
aka
ARBs (Angiotensin Receptor Blockers)
Class: ARBs
Agents: candesartan, valsartan (heart failure), losartan (hypertension slow progrssion of kidney disease in diabetics),
Mechanism: do not affect serum brandykinin levels as ACE inhibitors
Uses: hypertension (and slow progrssion of kidney disease in diabetics), heart failure
Side effects: same as ACE except no cough
Misc: unlike ACEi which are primarily renally secreted, ARBs secreted in bile
