Antihypertensive Agents - PPT II - Exam 3

What are agents used for hypertension?

-diuretics

-angiotensin converting enzyme inhibitors

-angiotensin II receptor blockers/antagonists

-direct renin inhibitor

-sympatholytic drugs

-vasodilators

-calcium channel blockers

-dopamin agonist

What are the common agents used for hypertension?

-thiazide diuretics

-ACE-inhibitors

-ARBs

-calcium channel blockers

What are the angiotensin converting enzyme inhibitors?

-captorpil

-lisinopril

-enalapril

-ramipril

What are the active ACE inhibitors?

-catopril

-lisinopril

What ACE inhibitors are prodrugs?

-enalapril

-ramipril

What is the MOA of ACE inhibitors?

-inhibit formation of vasoconstrictor angiotensin II from angiotensin by blocking the ACE

-lowers BP by decrease in peripheral vascular resistance

-reduce breakdown of bradykinin

-vasodilation from reduced angiotensin-induced vasoconstriction

What are the therapeutic uses of ACE inhibitors?

-HTN

-heart failure

-diabetic nephropathy

What are the adverse effects of ACE inhibitors?

-dry and non-productive cough from increased bradykinin

-angioedema, hyperkalemia, renal failure

-contraindicated in pregnancy

What are the angiotensin II receptor blockers/antagonists?

-losartan

-valsartan

What are the two types of angiotensin II receptors?

AT1 and AT2

What is the role of AT1?

predominate in vascular smooth muscle and cause most of the known actions of agniotensin II

What is the MOA of angiotensin II receptor blockers?

selectively blocks angiotensin II to AT1 receptors and prevents vasoconstriction caused by angiotensin II, effects like ACE inhibitors but does not increase bradykinin

What are the therapeutic uses of ARBs?

-HTN

-heart failure

-chronic kidney disease with intolerance to ACE inhibitors

What are the adverse effects/contraindications of ARBs?

-hyperkalemia

-hypotension

-teratogenic effects

-contraindicated in pregnancy

What are the sympatholytic drugs?

-clonidine

-guanabenz

-guanfacine

-methyldopa

What are the characteristics of sympatholytic drugs?

centrally acting alpha 2 adrenergic receptor agonists

What is special about guanabenz and guanfacine?

they act directly

What is special about methyldopa?

a prodrug that is converted to alpha-methylnorepinephrine

How are sympatholytic drugs administered?

-orally

-clonidine as transdermal patch

What is the MOA of sympatholytic drugs?

-agonists that stimulate medullary alpha2 adrenergic receptors

-reduce peripheral sympathetic tone, resistance, plasma renin activity

-lower BP by decreasing vasoconstrictor tone and renin activity in kidney

What are the therapeutic uses of sympatholytic drugs?

-HTN in pregnancy

What are the specific therapeutic uses of clonidine?

-hypertensive urgency

-ADHD

-opioid withdrawl syndrome

What are the adverse effects of methyldopa?

-sedation

-dizziness

-headache

-SE diminishes with tolerance

-mild bradycardia

-lupus like syndrome

-mild edema

What are the adverse effects of clonidine?

-drowsiness, dizziness, and headache that goes away with tolerance

-mild edema

-xerostomia

-consitpation

-patch can cause itching, irritation, and redness

-sudden withdrawl may cause hypertensive crisis

What are the adverse effects of guanabenz and guanfacine?

-confusion

-depression

-antimuscarinic side effects

-headache

What are the direct renin inhibitor agents?

aliskiren

What is the MOA of direct renin inhibitors?

-inhibits enzyme activity of renin

-renin inhibitor that results in the inhibition of angiotensinogen to angiotensin II

-reduces angiotensin I, II and aldosterone

What are the therapeutic uses of direct renin inhibitors?

HTN

What are the adverse effects of direct renin inhibitors?

-cough (less common than ACEIs)

-angioedema

-mild GIT symptoms, including diarrhea

-contraindicated in pregnancy

What are the nonselective beta blockers?

-propanolol

-carteolol

-nadolol

-sotalol

-timolol

What are the cardioselective beta blockers?

-metoprolol

-atenolol

-betaxolol

What is the MOA of beta adrenergic receptor blockers?

lower BP by blocking beta receptors in the heart to reduce cardiac output, kidneys to reduce renin secretion, CNS to reduce sympathetic vasomotor tone

What is the MOA of beta blockers when combined with other antihypertensive drugs?

-reflex tachycardia caused by vasodilators

-increased renin secretion caused by thiazide or loop diuretics

What are the therapeutic uses of beta blockers?

-bradycardia

-reduced cardiac output, precipitation of heart failure

-bronchoconstriction

-inhibition of glycogenolysis

-mask symptoms of hypoglycemia

-fatigue

-vivid dreams

What are the contraindications/precautions of beta blockers?

-asthma

-COPD

-diabetes mellitus

-sinus bradycardia

-depression

-do not abruptly discontinue

What are the selective alpha 1 adrenergic receptor antagonists?

-prazosin

-terazosin

-doxazosin

What is the MOA of selective alpha 1 antagonists?

-alpha 1 receptor blockade reduced norepinephrine induced vasoconstriction to dilate both arteries and veins

-bp falls due to decreased peripheral vascular resistance

-less reflex tachycardia because alpha 2 receptors that inhibit norepinephrine release are unaffected

What are the therapeutic uses of selective alpha 1 receptor antagonists?

-HTN

-BPH

What are the adverse effects of selective alpha 1 receptor antagonists?

-orthostatic hypotension

-dizziness

-headache

-inhibition of ejaculation

What are the nonselective alpha adrenergic receptor antagonists?

-phentolamine

-phenoxynezamine

What are the characteristics of phentolamine?

irreversible and long-acting blocker

What are the characteristics of phenoxynezamine?

reversible and competitive

What is the MOA of nonselective alpha adrenergic receptor antagonists?

alpha-adrenergic blockade leads to decreased peripheral vascular resistance that decreases BP

What are the therapeutic uses of phenoxybenzamine?

pheochromocytoma to prevent catecholamine crisis

What are the therapeutic uses of phentolamine?

cocaine induced hypertension

What are the adverse effects of nonselective alpha adrenergic receptor antagonists?

-orthostatic hypotension

-reflex tachycardia

What are the mixed adrenergic receptor antagonist agents?

-labetalol

-carvedilol

What is the MOA of mixed adrenergic receptor antagonists?

lower BP by nonselective blockade of both alpha and beta adrenergic receptors

What are the therapeutic uses of mixed adrenergic receptor antagonists?

-hypertensive emergencies

-pheochromocytoma

What are the adverse effects of mixed adrenergic receptor antagonists?

-orthostatic hypotension

-bronchospasm

-hepatotoxicity

-fatigue

-dizziness

What are the arterial vasodilator agents?

-hydrazaline

-minoxidil

What is the arterial and venous vasodilator agent?

nitroprusside

What is the MOA of vasodilator agents?

lower BP by acting directly on vascular smooth muscles to cause relaxation and reduce peripheral vascular resistance

What is the MOA of hydralazine and minoxidil?

dilate arteries selectively without affecting venous smooth muscles and minoxidil may cause hyperpolarization of smooth muscle membrane through opening of K channels

What are hydrazaline and minodixil used for?

used in combination with other antihypertensives to treat moderate to severe HTN

What are the characteristics of sodium nitroprusside?

-nonselective vasodilator that dilate both arteries and veins -release nitric oxide from drug or vascular endothelium

-used in hypertensive emergencies

-IV

-short half life

What is a special feature of hydrazaline MOA?

may increase cGMP and cause smooth m. relaxation

What are the therapeutic uses of vasodilators?

severe HTN

What is the therapeutic use of hydrazaline?

HTN in pregnancy

What are the therapeutic uses of minoxidil?

treat hair loss from androgenic alopecia

What are the adverse effects of hydralazine?

-induce anginal attacks and myocardial ischemia through reflex increases in CO in elderly with coronary artery disease

-lupus like syndrome

-dizziness

-headache

-sweating

-flushing

What are the adverse effects of minoxidil?

-induce anginal attacks and myocardial ischemia through reflex increases in CO in elderly with coronary artery

-exacerbation of angina

-massive fluid retention

-hair growth

-pericarditis

What are the side effects of nitroprusside?

-dizziness

-headache

-thiocynate and cyanide toxicity from rapid metabolism

What are the adverse effects of any vasodilating drug?

-hypotension accompanied with other SE

-reflex tachycardia

-increased myocardial contrations

-increased renin secretion

-fluid retention

-headache

-flushing

-palpitation

-dizziness

What are the calcium channel blockers?

-verapamil

-diltiazem

-amlodipine

-nifedipine

What is the MOA of calcium channel blockers?

-block voltage-dependent L-type calcium channels of cardiac and smooth muscle

-reduce intracellular Ca2+ to relax arteriolar smooth m. which causes vasodilation and lower BP

-reduce cardiac contractility

What are characteristics of dihydropyridines?

-strong vasodilators

-most likely to produce reflex tachycardia due to little or no inhibition of AV conduction

What CCBs do not produce reflex tachycardia because they depress AV and SA node?

-verapamil

-diltiazem

What is the order of CCBs based on their cardiac effects?

verapamil > diltiazem > nifedipine

What are the adverse effects of nifedipine?

-reflex tachycardia

-vascular side effects

-headache

-flushing

-dizziness

-peripheral edema

What are the adverse effects of verapamil?

-bradycardia in SA node dysfunction

-contraindicated in pt with SA or AV node abnormalities or CHF

-constipation

-gingival hyperplasia

-bradycardia

What are the adverse effects of diltiazem?

-bradycardia in SA node dysfunction

-contraindicated in pt with SA or AV node abnormalities or CHF

-flushing

-peripheral edma

-dizziness

-headache

What are the therapeutic uses of CCBs?

-HTN

-angina

-arrhythmia

What is the dopamine agonist agent?

fenldopam

What are some characteristics of fenoldopam?

-rapid acting

-IV

-for hypertensive emergencies

What is the MOA of dopamine agonists?

activate vascular D1 receptors and produces vasodilation in vascular beds including coronary and renal vessels

What are the adverse effects of dopamine agonists?

-headache

-nausea

What are the endothelin receptor antagonists?

-bosentan

-ambrisentan

What is the MOA of bosentan?

nonselective endothelin-1 receptor antagonist (ETa and ETb) which is a peptide produced by vascular endothelium

What is the MOA of ambrisentan?

selective ETa receptor antagonist

What is the therapeutic use of endothelin receptor antagonists?

pulmonary hypertension only

What are the adverse effects of endothelin receptor antagonists?

-headache

-cutaneous flushing

-edema formation

-liver injury

-birth defects