Antihypertensive drugs Flashcards
Diuretic examples
Thiazides
Loop (furosemide)
K+ sparing (spironolactone)
Diuretic MOA
Inhibit reabsorption of Na
Loop diuretics and thiazides also act as vasodilators (esp important for thiazides)
requires functioning kidneys
thiazides weaker than loop because it acts distal to where most of Na reabsorption occurs
Indications, CIs and SEs of diuretics
Indications: HTN, edema
CI: hypovolemia, severe electrolyte abnormalities
SEs: electrolyte disturbances (Na, K), dehydration, subsequent renal dysfunction
Beta-blocker types
cardioselective (b1): atenolol, metoprolol
b1&b2: propanolol, nadolol, timolol
mixed alpha & beta: labetolol, carvedilol
partial agonists: pindolol, acebutolol (selectivity is relative)
MOA of beta-blockers
block b1: reduce HR and SV, renin secretion
direct inhibitory effect on SNS
mixed a and b antagonists - vasodilation
useful for MI
avoid in elderly - youth respond better
Indications, CIs and SEs of b-blockers
Indications: HTN, chronic heart failure, arrhythmias, angina, post-MI , other non-cardio indications (migraine, public speaking anxiety, glaucoma, tremor)
CIs: non-selective for asthmatics
2nd degree heart block
acute heart failure
bradycardia
SEs: fatigue, bradycardia/block, hypotension
CNS effects - insomnia, nightmares, depression
Raynaud’s phenomenon (cold extremities)
hypoglycemia, lipid profiles (increase triglycerides, decreased HDL) impotence
Ca-channel blocker types
DHP
- Nifedipine
- amlodipine
- felodipine
- nicardipine
DHP MOA
L-type Ca channel antagonists (block influx of ca through L-type channels, inhibit contraction of smooth muscle –> vasodilation)
DHPs have greater selectivity for the vasculature (non-DHPs have greater selectivity at the heart)
Indications, CIs and SEs of DHPs
Indications: HTN, prevent coronary spasm in variant angina, prevent cerebral artery spasm after brain hemorrhage
CIs: pregnancy (teratogenic), conditions in which tachycardia is harmful, CAD, aortic/mitral stenosis
SEs: vasodilation-related symptoms: flushing, dizziness, tachycardia, headache
baroreceptor-mediated reflex tachycardia
Metabolized by CYP3A4 (grapefruit juice!)
ACEi prototypes
captopril, ramipril, -prils
ACEi MOA
ACE converts AI –> AII and breaks down bradykinin
vasodilation (AII, bradykinin)
decrease Na and H2O resorption (reduced aldosterone)
Indications, CIs and SEs of ACEi
Indications: HTN, CHF, post-MI
CIs: pregnancy (fetal hypotension), renal dysfunction
SEs: dry cough (increased bradykinin), hyperkalemia (reduced aldosterone), hypotension, renal dysfunction (vasodilates efferent arteriole, decrease GFR - more prominent in volume-depleted patients) and overall reduces systemic BP
ARB prototypes
Losartan - sartan
ARB MOAs
Angiotensin antagonist (AT1)
blocks action of AII –> vasodilation, natriuresis (less aldosterone)
Effect of ARB is downstream of ACE
No effect on bradykinin
More complete inhibition of AII activity (alternate pathways rather than ACE)
Indications, CIs and SEs of ARBs
Indication: HTN, chronic CHF, ACEi patients who cannot tolerate cough
CIs: pregnancy (teratogen)
SEs: well-tolerated dizzienss, hypotension hyperkalemia when used with K+ supplements, or K+ sparing diuretics renal failure angioedema, much more rare than ACEi
Alpha 1 blocker prototypes
Prazosin
-zosin
a-1 blocker MOAs
inhibits v/c –> reduce arteriolar resistance increase venous capacitance –> lower peripheral resistance
a1 blocker Indications, CIs and SEs
Indications: HTN, congestive heart failure
SEs: postural hypotension, reduce plasma triglycerides and total LDL, increase HDL
rarely used; not indicated as monotherapy - use with diuretics, b-blockers, etc.
Direct renin inhibitor prototypes
Aliskiren
Direct renin inhibitor MOAs
directly inhibits renin
Does not allow any compensatory mechanism (shuts down RAAS)
Indications, CIs and SEs for direct renin inhibitors
Indications: HTN, heart failure (investigating)
CIs: pregnancy
SEs: generally well-tolerated, diarrhea
Aldosterone antagonist prototypes
spironolactone, eplerenone
MOAs of andosterone antagonists
blocks aldosterone receptors in CD
Indications, CIs and SEs - aldosterone antagonists
Indications: +thiazide/loop diuretic to treat edema + hypertension, particularly useful for primary aldosteronism, heart failure
CIs: peptic ulcers
SEs: hyperkalemia (K+ sparing diuretic)
spironolactone may cause xgynecomastia, impotence, decreased libido, hirsutism, GI symptoms
Direct vasodilator prototypes
Hydralazine
Hydralazine MOA
relaxes arteriolar smooth muscle, does not affect venous smooth muscle. exact MOA unclear
Indications, CIs and SEs - hydralazine
Indications: hypertension
CIs: extreme caution in elderly, CAD (due to reflex tachycardia)
SEs: headache, nausea, flushing, hypotension, palpitations, tachycardia, angina pectoris Immunological reactions (lupus) --> arthralgia, arthritis, fever and pericardial effusion
Rarely used
can be used in patients who cannot tolerate ACEi or AT1 antagonists, and in pregnant women in hypertensive emergencies (e.g. preeclampsia)
HTN pharmacological therapy regimen
1st line: low-dose thiazide
2nd line: combination, add ACEi/ARB (if ACEi-intolerant)/DHP (long-acting)
Note CIs (e.g. asthmatics)
Relative CIs
- COPD: beta-blockers
- Gout: thiazides
- HF: non-DHP, alpha blockers
- renal insufficiency: potassium-sparing diuretics
-depression: b-blockers, central a-agonists, reserpine
