Hypertension Flashcards
What is the pharmacological strategy of antihypertensive drugs? WHat reflexive homeostatic actions may occur?
Decrease TPR, CO (HR, SV), &/or volume. Reflexive tachycardia may occur with increased sympathetic activity. Reflexive increases in renin leading to edema may occur due to decreased volume.
Which diuretics are used to treat hypertension? What is the major mxn by which these drugs lower HTN? Which can be used in those with renal failure? These can be combined with what class of drugs to prevent hypokalemia? Over time, how do diuretics affect HR, CO, renin.
Thiazides (hydrochlorthiazide, chlorthalidone, indapamid, metolazone – in order of increasing potency) used for mild-moderate HTN. Loop diuretics (furosemide) used for severe HTN in the setting of CHF, cirrhosis, GFR
Short-acting ACEi? Long-acting ACEi? Which is converted to a more active metabolite? (And what is that metabolite?
Captopril. Lisinopril, Benazepril, Quinapril, Ramipril, Enalapril (–> Enalaprilat [more active]). (HINT: end in ‘pril’ !!)
Mxn of action of ACEis? Thus, what is the major mxn by which HTN is reduced? Uses? Side effects? Contraindications? What are the effects on HR, CO, volume & renin?
MOA: Blocks endothelial ACE from converting
angiotensin I to angiotensin II (potent vasoconstrictor); as a side effect, also prevents breakdown of bradykinin (potent vasodilator) HTN is reduced due to decreased TPR. Uses: mild-moderate HTN, CHF, left ventricular hypertrophy, post- MI (prevents left ventricular remodeling), may reduce the risk of diabetes pts at risk, chronic kidney disease & proteinuria. Side effects: Dry cough, hyperkalemia, acute renal failure in renal artery stenosis, angioedema. Contraindications? Contraindicated: pregnancy, renal artery stenosis, hyperkalemia, prior angioedema. No effect on HR, CO, volume. Increased renin.
Angiotensin receptor blockers (ARBs) ?
Losartan, Valsartan, Irbesartan. (HINT: end in ‘sartan’ !!)
Mxn of action of ARBs? Thus, what is the major mxn by which HTN is reduced? Uses? Side effects? Contraindications? What are the effects on HR, CO, volume & renin?
MOA: Competitive inhibition of angiotensin II in
vascular endothelium. HTN is lowerd due to decreased TPR. Uses: mild-moderate HTN, CHF, left ventricular hypertrophy, post- MI (prevents left ventricular remodeling), may reduce the risk of diabetes pts at risk, chronic kidney disease & proteinuria. Side effects: Hyperkalemia, acute renal failure in renal artery stenosis, angioedema, dry cough – much less frequent than with ACE-I. Contraindicated in pregnancy, renal artery stenosis, hyperkalemia, prior angioedema. No effect on HR, CO, volume. Increased renin.
Renin inhibitor? Is this drug effective?
Aliskirin – not very effective.
Non-dihydropyridine calcium-channel blockers? Dihydropyridine calcium-channel blockers? Which affects the heart greatest? Which affects the blood vessels greatest? Which affects the heart and blood vessels at relatively equal amounts?
Verapamil, Diltiazem. Amlodipine, Nifedipine. Verapamil affects the heart. Dihydropyridines affect the blood vessels. Diltiazem affects both. (NOTE: This is a spectrum!)
Mxn of action of non-dihydropyridine calcium-channel blockers? Thus, what is the major mxn by which HTN is reduced? Uses? Side effects? Contraindications? What are the effects on volume & renin?
Interact with L-type voltage gated plasma membrane Ca channel --> decreased calcium entry into vascular smooth muscle --> causes decreased contractility. HTN lowered due to decreased SV --> CO. Also: decrease firing rate of aberrant pacemaker sites, decrease conduction velocity, prolongs repolarization in SA and AV node (--> decreases HR --> CO). Cause vasodilation in the peripheral vessels, though less so than dihydropyridines. Uses: Hypertension, angina, class IV anti-arrhythymic. Side effects: constipation (most common), bradycardia, leg edema, worsening heart failure (negative inotropes!), headache, flushing. Contraindications: overt decompensated heart failure, bradycardia, sinus node dysfunction, high-degree AV block. Increased volume and renin.
Mxn of action of dihydropyridine calcium-channel blockers? Thus, what is the major mxn by which HTN is reduced? Uses? Side effects? Contraindications? What are the effects on volume & renin?
MOA: Interact with L-type voltage gated plasma membrane Ca channel –> decreased
calcium entry into vascular smooth muscle. HTN lowered due to decreased TPR. These have less heart-specific effects. Uses: Hypertension, Raynaud’s, angina (3rd choice drug). Side effects: Reflex tachycardia – note that this will worsen angina!! (lipophilic agents gain entry to brain and depress vasomotor center, rapidly dropping BP, causing reflexive sympathetic activation; long-acting are less lipophilic), gingival hyperplasia, constipation, leg edema, headache, flushing. Contraindication: overt decompensated heart failure, bradycardia, sinus node dysfunction, high-degree AV block. Increased volume and renin.
Non-selective B-blocker? Selective B1 blockers? Combined aB blockers? Which are long-acting? Which has a very short half life? Overall, what can we expect in using BBs to treat HTN?
Propanolol. Metoprolol, Atenolol, Bisoprolol + Nadolol (long-acting), Esmolol (short-acting) Labetolol, Carvedilol. (HINT: end in ‘lol’ !!). Overall, only a very modest reduction in BP can be expected from BBs – inferior to thiazides, ACEi/ARBs, & CCBs.
What is the MOA of BBs? What are the unique uses of carvedilol, labetalol, and esmolol? Side effects?
Reduce CO, inhibit renin release, reduce NE release, decrease central vasomotor activity (sympathetic tone). If B1 specific, cardioselectivity can be achieved. If combined alpha effects, vasodilation is also achieved. Carvedilol: ACS or CHF. Labetolol: HTN urgency. Esmolol: IV for AV nodal blocking. Side effects: bronchospasm, bradycardia (negative chronotrope), CHF (negative ionotrope), masking of hypoglycemia symptoms, fatigue + decreased exercise capacity + lethargy, depression (crosses BBB), sexual dysfunction. B1 selectives are less likely to give bronchospasm, hypoglycemic awareness, or depression.
Alpha1 adrenergic blockers?
Terazosin, Doxazosin, Prazosin
Alpha1 adrenergic mxn? Uses? Side effects?
MOA: Blocks post-synaptic α1-adrenergic receptor antagonist on vascular smooth muscle. Uses:
BPH; second-tier meds for HTN. Side effects: Orthostatic hypotension, fluid retention, worsening angina
(secondary to reflex tachycardia).
Vasodilators?
Hydralazine (+ Nitroprusside), Minoxidil (+ Diazoxide)
