Antihypertensive drugs (general)

Primary HTN want to treat the heart/blood vessels/kidney

Want to decrease TPR, CO, body fluid volume, BP (last one may result in reflex tachycardia &/or edema from renin activity)

Drugs altering sympathetic activity (alpha 2 agonists)

Clonidine & Methyldopa (prodrug)

W/ alpha 2 stimulation = decrease in sympathetic outflow and decrease in TPR/HR

Uses: mild/moderate HTN

Opiate w/drawl (clonidine) for the autonomic SE's

HTN management during pregnancy (methyldopa)

SE: Positive Coombs test (methyldopa)

CNS depression

Edema

DI: TCA's decrease anti-HTN effects

Drugs altering sympathetic activity (interfering w/ storage vesicles)

Reserpine

Destroys NE vesicles

Periphery causes decreased CO and TPR

CNS causes decreased NE, DA, 5HT

SE: depression (often severe!)

edema, increases GI secretions

Guanethidine

 Accumulates in nerve endings and taken up and binds to vessicles inhibiting NE release

SE: diarrhea, edema

DI: TCA's block reuptake

Drugs altering sympathetic activity (alpha 1 blockers)

Prazosin, Doxazosin, Terazosin

Decreases arteriolar AND venous resistance (watch for reflex tachycardia)

Uses: HTN, BPH

SE: "1st dose" syncope d/t dilation

orthostatic hypotension -from venous dilation

urinary incontinence

Drugs altering sympathetic activity (beta blockers)

Propranolol, metoprolol, acebutolol etc.

SE: cardiovascular depression

fatigue

sexual dysfunction

increases LDLs and TGs

Caution in: asthmatics

vasospastic disorders

diabetics

Direct acting vasodilators (drugs acting through NO)

SEVERE HTN

Hydralazine:decreases TPR, arteriolar dilation ONLY

SE: SLE-like syndrome in slow acetylators

Edema

Reflex tachycardia

Nitroprusside: decreases TPR via dilation of both arteries and veins

Uses: DOC for HTN emergencies

SE: Cyanide toxicity (Sodium nitrite or amyl nitrite are the antidotes along w/ sodium thiosulfate)

Drugs acting to open K+ channels (hyperpolarize)

Minoxidil

 Causes hyperpolarization of smooth muscle results in arteriolar vasodilation

Uses: HTN emergencies, severe HTN, baldness

SE: hypertrichosis (hair grows)

hyperglycemia

edema

reflex tachycardia

Calcium channel blockers

Block L-type Ca2+ channels in heart and vessels

Causes decreased TPR (in those more specific for aterioles...end in -dipine)

Prototype = nifedipine

Uses: HTN, angina, antiarrhythmics (verapamil/diltiazem only for the last)

SE: reflex tachycardia

gingival hyperplasia (PHENYTOIN does too!)

constipation (verapamil)

Diuretics

ACE inhibitors

angiotensin converting enzyme (aka kininase II) converts angiotensin I --> II

Angiotensin II causes increased aldosterone secretion and vasoconstriction (inhibits this!)

Captopril (other -prils)

also prevents the degredation of bradykinin

Uses: mild/moderate HTN, protective of diabetic nephropathy, CHF

SE: dry cough (from bradykinin)

hyperkalemia (not secreting from kidney)

acute renal failure in renal artery stenosis

Angioedema (rapid swelling in nose, mouth, throat)

Contraindication in pregnancy

ARB's

Block the angiotensin II from binding to the AT-1 receptors so you get decreased aldosterone secrection and vasodilation but doesn't interfer w/ bradykinin breakdown

Losartan (other -sartan's)

Uses: mild/moderate HTN, protective of diabetic nephropathy, CHF

SE: hyperkalemia, acute renal failure in renal artery stenosis, angioedema

Contraindication: pregnancy D

HTN + comorbid condition (angina)

HTN + comorbid condition (diabetes)

use ACEI's or ARB's

HTN + comorbid condition (heart failure)

HTN + comorbid condition (post MI)

HTN + comorbid condition (BPH)

HTN + comorbid condition (dyslipidemia)

Pulmonary HTN

Bosentan: endothelin is a powerful vasoconstrictor and this drug is an ET(a) receptor antagonist

SE:assoc w/ vasodilation(flushing, HA, hypotension)

Epoprostenol: prostacyclin (PGI2)

Sildenafil: inhibits phosphodiesterase type V

increases cGMP, get pulmonary aa. relaxation