[CA2 M4]: PCOL Antihypertensives

Drugs that lower BP by decreasing fluid/blood volume and preload, and some with vasodilatory effect

Diuretics

Effects: Interfere with sympathetic control, decreases central sympathetic outflow

Sympathoplegic agents

Effects: Reduces venous contraction/tone, heart rate, contractile force of the heart, cardiac output, and total peripheral resistance.

Sympathoplegic agents

Clinical applications: Hypertension, cancer pain, opioid withdrawal, pre-eclampsia

Alpha-2 agonists

Used in HTN in pregnancy (4)

Nifedipine, methyldopa, hydralazine, labetalol

S/E: sedation, rebound HTN, dry mouth, hemolytic anemia yielding a (+) Coomb's test

Alpha-2 agonists

Alpha-2 agonist yielding a (+) Coombs test and causes hemolytic anemia

Methyldopa

Taper use before discontinuing to

avoid rebound hypertension.

Alpha-2 agonists

Antidote: for alpha-2 agonists

Phentolamine, phenoxybenzamine

Peripheral effects as rapid IV bolus or very high oral doses, CNS effect as slow IV infusion or prolonged doses

Alpha-2 agonists

Alpha-2 agonists effect as rapid IV bolus or very high oral doses

Peripheral (Vasoconstriction - increased BP)

Alpha-2 agonists effect as slow IV infusion or prolonged doses

CNS (inhibit sympa - decreased BP)

Drug class: Clonidine

Alpha-2 agonists

Drug class: Methyldopa

Alpha-2 agonists

MOA: Block nicotinic ganglia

receptors

Ganglion blockers

Clinical applications: hypertension

(obsolete)

Ganglion blockers, post-ganglionic blockers

S/E: Postural hypotension, dry mouth, blurred vision, constipation, sexual dysfunction

Ganglion blockers

Drug class: hexamethonium

Ganglion blockers

Drug class: trimethaphan

Ganglion blockers

Drug class: mecamylamine

Ganglion blockers

MOA: deplete the adrenergic nerve

terminal of its norepinephrine stores

Reserpine

MOA: block the release of

norepinephrine

Guanethidine, Guanadrel, Bretylium

S/E: Sedation, severe psychiatric depression, suicidal ideations

Post-ganglionic blockers

Avoid in pt with history of depression

Post-ganglionic blockers

Effect: decreased sympathetic activation of certain tissues or organs

Alpha-1 blockers, beta blockers

Clinical applications: benign prostatic hyperplasia, HTN

Alpha-1 blockers

S/E: 1st dose orthostatic HTN (given at bedtime), reflex tachycardia, dizziness, drowsiness, headache, weakness

Alpha-1 blockers

Drug class: -Zosin

Alpha-1 blockers

Most selective Alpha-1 blocker for prostatic smooth muscle

Tamsulosin

Commonly used alpha-1 blocker for HTN

Prazosin

Alpha-1 blocker with longer half-life than Prazosin

Doxazosin, Terazosin

Effects: lowers PVR and BP, miosis, nasal stuffiness, increased urinary output

Alpha-1 blockers

Clinical applications: angina prophylaxis, HTN, arrhythmias, migraine, performance anxiety, hyperthyroidism, glaucoma, chronic heart failure

Beta blockers

Not used in acute HF as it may further depress the heart

Beta blockers

S/E: Bradycardia, bronchospasms, AV block, HF, CNS sedation, erectile dysfunction, increased VLDL, decreased HDL

Beta blockers

Most common SE of beta blockers

Bradycardia

May mask symptoms of hypoglycemia (tremors, tachycardia, anxiety) in diabetic pt

Beta blockers

Combined alpha and beta blockade

Carvedilol, labetalol

Effect: Beta blocker that lowers BP, negative ICD, decreases renin release

Beta-1 blocker

Effect: Beta blocker that increases PVR, causes bronchoconstriction and decreases IOP by decreasing aqueous humor

Beta-2 blocker

⭐️ MOA: increase nitric oxide release

Hydralazine, nitrovasodilators, Na nitroprusside

Effects: Relaxes vascular smooth muscle

Direct vasodilators

Clinical applications: HTN, HF, Pre-eclampsia

Hydralazine

⭐️ S/E: Edema, reflex tachycardia, myocardial ischemia, drug-induced lupus

Hydralazine

⭐️ Used in HTN emergencies in pregnant pt

Hydralazine

⭐️ Used in CHF if combined with ISDN, for African-American pt

Hydralazine

⭐️ MOA: opens K channels, causing hyperpolarization

Diazoxide, Minoxidil

⭐️ Clinical applications: HTN crisis (alternative), alopecia (topical)

Minoxidil

⭐️ Clinical application: HTN crisis (alternative), hypoglycemia due to insulinoma

Diazoxide

⭐️ S/E: Edema, reflex tachycardia, salt and water retention, hypertrichosis, hirsutism

Minoxidil

⭐️ S/E: hyperglycemia (inhibits insulin release from beta cells)

Diazoxide

⭐️ Requires concomitant use of diuretics and BBs to block compensatory side effects

PAVD (Diazoxide, Minoxidil)

Stimulates hair follicles to differentiate

and grow.

Minoxidil

⭐️ Drug class: hydralazine

Pure arteriolar VD

⭐️ Drug class: diazoxide

Pure arteriolar VD

⭐️ Drug class: minoxidil

Pure arteriolar VD

⭐️ Activates baroreflex or RAAS in monotherapy

Pure Arteriolar VD

⭐️ Remedy for baroreflex or RAAS activation of PAVD

(a) address RT

(b) adrress edema

Combination tx:

(a) PAVD + BB

(b) PAVD + Diuretics/ACEi/ARBs

⭐️ MOA: Block voltage-gated L-type calcium channels (most important in cardiac and smooth muscles)

CCBs

CCB: Vascular>Cardiac

Dihydropyridine CCBs

CCB: Cardiac>Vascular

Non-DHP CCBs

Effect: Leads to reduced intracellular

calcium concentration and reduced

muscle contractility

CCBs

⭐️ Clinical applications: angina, HTN

DHP CCBs

⭐️ Clinical Applications: Antiarrhythmic, Angina, HTN, Supraventricular tachycardia, Migraine

Non-DHP CCBs

⭐️ S/E: pretibial edema (common), reflex tachycardia, gingival hyperplasia, constipation, nausea, flushing, dizziness

DHP CCBs

⭐️ Intrinsically long-acting CCB

Lercanidipine, Amlodipine, Lacidipine (LAL)

⭐️ CCB class based on DOA which are safe (no RT, no edema)

Intrinsically long-acting, Modified long-acting

⭐️ Generic: Versant XR / Plendyl XR

Felodipine XR

⭐️ Most cardioselective CCB

Verapamil

⭐️ CCB with intermediate effect (heart and artery)

Diltiazem

⭐️ DOA related to safety

CCB

S/E: Gingival hyperplasia

Amlodipine, Verapamil

⭐️ S/E: bradycardia, pretibial edema (common), HF, AV block, gingival hyperplasia, constipation, nausea, flushing, dizziness

Non-DHP CCB

⭐️ S/E: constipation (most common extracardiac S/E)

Verapamil

CCB: may cause arrhythmias

DHP

CCB: can cause excessive cardiac depression, never used in acute HF

Non-DHP

⭐️ Drug class: nitroprusside

Vasodilator (parenteral), Mixed VD

⭐️ Drug class: Fenoldopam

Vasodilator (parenteral), D1 agonist

⭐️ MOA: D1 activation

Fenoldopam

Effect: Arteriolar and venous vasodilation

Nitroprusside

Effect: Arteriolar vasodilation of the renal arterioles and splanchnic blood

vessels

Fenoldopam

⭐️ Clinical applications: HTN emergency (1st line), acute HF, cardiogenic shock

Nitroprusside

Clinical applications: HTN emergency

Fenoldopam

⭐️ S/E: Hypotension, CN toxicity, headache

Nitroprusside

S/E: Hypotension, hypokalemia (increased renal blood flow)

Fenoldopam

Very light sensitive vasodilator; most effective and strongest (arterio- and venodilation)

Nitroprusside

Short DOA: 10 min; not commonly used

Fenoldopam

Increases renal and splanchnic blood flow, diuresis, decreases BP, and causes vasodilation

D1 Agonists

⭐️ MOA: inhibits renin (prevents conversion of AT to AT1)

Aliskiren

Effects: inhibits RAAS, reduced BP

Agents that block prod. or action of AT

S/E: Hyperkalemia, increased serum creatinine, renal impairment, headache, diarrhea, rash, angioedema

Aliskiren

Contraindicated in pregnancy; during the 2nd and 3rd trimester of pregnancy

causes fetal renal agenesis, impairment of renal function, and increased fetal mortality.

Aliskiren

⭐️ MOA: Inhibits the enzyme

angiotensin-converting enzyme, decreases ATII and aldosterone

ACEi

⭐️ MOA: causes an increase in

endogenous vasodilators of the

kinin family (bradykinin)

ACEi

⭐️ ACEi which are not prodrugs (3)

Captopril

Lisinopril

Enalaprilat (IV)

⭐️ Clinical applications: HTN, HF, diabetic nephropathy, albuminuria, CKD with or without DM

ACEi, ARBs

⭐️ S/E: Cough (common), angioedema (common), teratogenicity, hyperkalemia, taste disturbance, hypotension

ACEi

T/F: ACEi and ARBs are contraindicated in pregnancy

T

Causes increased levels of bradykinin

which can irritate the airways and

trigger a cough reflex.

ACEi

Delays progression of diabetic

nephropathy (renoprotective).

ACEi, ARBs