Antihypertensive drugs

Question 1

Diuretic examples

Answer 1

Thiazides
Loop (furosemide)
K+ sparing (spironolactone)

Question 2

Diuretic MOA

Answer 2

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

Question 3

Indications, CIs and SEs of diuretics

Answer 3

Indications: HTN, edema
CI: hypovolemia, severe electrolyte abnormalities
SEs: electrolyte disturbances (Na, K), dehydration, subsequent renal dysfunction

Question 4

Beta-blocker types

Answer 4

cardioselective (b1): atenolol, metoprolol
b1&b2: propanolol, nadolol, timolol
mixed alpha & beta: labetolol, carvedilol
partial agonists: pindolol, acebutolol (selectivity is relative)

Question 5

MOA of beta-blockers

Answer 5

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

Question 6

Indications, CIs and SEs of b-blockers

Answer 6

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

Question 7

Ca-channel blocker types

Answer 7

DHP

• Nifedipine
• amlodipine
• felodipine
• nicardipine

Question 8

DHP MOA

Answer 8

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)

Question 9

Indications, CIs and SEs of DHPs

Answer 9

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!)

Question 10

ACEi prototypes

Answer 10

captopril, ramipril, -prils

Question 11

ACEi MOA

Answer 11

ACE converts AI –> AII and breaks down bradykinin
vasodilation (AII, bradykinin)
decrease Na and H2O resorption (reduced aldosterone)

Question 12

Indications, CIs and SEs of ACEi

Answer 12

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

Question 13

ARB prototypes

Answer 13

Losartan - sartan

Question 14

ARB MOAs

Answer 14

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)

Question 15

Indications, CIs and SEs of ARBs

Answer 15

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

Question 16

Alpha 1 blocker prototypes

Answer 16

Prazosin

-zosin

Question 17

a-1 blocker MOAs

Answer 17

inhibits v/c –> reduce arteriolar resistance increase venous capacitance –> lower peripheral resistance

Question 18

a1 blocker Indications, CIs and SEs

Answer 18

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.

Question 19

Direct renin inhibitor prototypes

Answer 19

Aliskiren

Question 20

Direct renin inhibitor MOAs

Answer 20

directly inhibits renin

Does not allow any compensatory mechanism (shuts down RAAS)

Question 21

Indications, CIs and SEs for direct renin inhibitors

Answer 21

Indications: HTN, heart failure (investigating)

CIs: pregnancy

SEs: generally well-tolerated, diarrhea

Question 22

Aldosterone antagonist prototypes

Answer 22

spironolactone, eplerenone

Question 23

MOAs of andosterone antagonists

Answer 23

blocks aldosterone receptors in CD

Question 24

Indications, CIs and SEs - aldosterone antagonists

Answer 24

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

Question 25

Direct vasodilator prototypes

Answer 25

Hydralazine

Question 26

Hydralazine MOA

Answer 26

relaxes arteriolar smooth muscle, does not affect venous smooth muscle. exact MOA unclear

Question 27

Indications, CIs and SEs - hydralazine

Answer 27

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)

Question 28

HTN pharmacological therapy regimen

Answer 28

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