108 PART III Cardiovascular Drugs

DRUG SUMMARY TABLE: Drugs Used in Hypertension

Mechanism Clinical Toxicities,
Subclass of Action Applications Pharmacokinetics Interactions

Diuretics (see also Chapter 15)

Hydrochlorothiazide, Block Na/Cl transporter in Hypertension, mild Oral Hypokalemia,
chlorthalidone distal convoluted tubule edema Duration: 8–12 h hyperglycemia,
hyperuricemia,
hyperlipidemia
Furosemide Block Na/K/2Cl transporter in Hypertension, heart Oral, parenteral Hypokalemia,
thick ascending limb failure, edema, Duration: 2–3 h hypovolemia,
hypercalcemia ototoxicity

Sympathoplegics
Centrally acting
Clonidine Agonist at α2 receptors • in Hypertension Oral and transdermal Sedation, danger of
CNS this results in decreased Oral duration: 2–3 days • severe rebound
SANS outflow transdermal 1 wk hypertension if suddenly
stopped
Methyldopa Prodrug converted to Hypertension Oral Sedation, induces
methylnorepinephrine in CNS, Duration: 12–24 h hemolytic antibodies
with result like clonidine

Ganglion blockers
Hexamethonium Obsolete prototype nicotinic None Oral, parenteral Severe orthostatic
acetylcholine (ACh) receptor hypotension,
blocker in ganglia • blocks all constipation, blurred
ANS transmission vision, sexual
dysfunction
Trimethaphan: IV, rarely used short-acting ganglion blocker for hypertensive emergencies, controlled hypotension
Mecamylamine: oral ganglion blocker, several hours’ duration, experimental use in smoking cessation

Postganglionic neuron blockers

Reserpine Blocks vesicular pump (VMAT) Obsolete in Oral Sedation • severe
in adrenergic neurons hypertension, Duration: 5 days psychiatric depression
Huntington’s disease (high doses)
Guanadrel: blocks reuptake of norepinephrine (NET) and depletes stores; oral, long duration; severe orthostatic hypotension (guanethidine, a
similar drug, was withdrawn in the United States)

Alpha blockers
Prazosin Selective α1 blocker • reduces Mild hypertension, Oral First dose orthostatic
peripheral vascular resistance • benign prostatic Duration: 6–8 h hypotension
prostatic smooth muscle tone hyperplasia
Doxazosin, terazosin: similar to prazosin but longer duration of action

Beta blockers
Propranolol Prototype nonselective β Hypertension • many Oral, parenteral Bronchospasm in
blocker • reduces cardiac other applications (see Duration: 6–8 h (extended asthmatics • excessive
output • possible secondary Chapter 10) release forms available) cardiac depression,
reduction in renin release sexual dysfunction,
sedation, sleep
disturbances
Atenolol, metoprolol: like propranolol but β1-selective; fewer adverse effects
Labetalol, carvedilol: combined α and β blockade; oral and parenteral

(Continued)
 CHAPTER 11 Drugs Used in Hypertension 109

DRUG SUMMARY TABLE: Drugs Used in Hypertension (Continued)

Mechanism Clinical Toxicities,
Subclass of Action Applications Pharmacokinetics Interactions

Vasodilators, oral
Calcium channel blockers
Verapamil, diltiazem Prototype L-type calcium Hypertension, angina, Oral, parenteral Excessive cardiac
channel blockers • combine arrhythmias Duration: 6–8 h depression • constipation
moderate vascular effect with
strong cardiac effect
Nifedipine, other dihydropyridines: oral and parenteral; greater vasodilator than cardiodepressant effects

Older oral vasodilators

Hydralazine Probably causes release of Hypertension (also Oral Tachycardia, salt and
nitric acid (NO) by endothelial used in heart failure in Duration: 6–8 h water retention,
cells • causes arteriolar dilation combination with lupus-like syndrome
isosorbide dinitrate)

Minoxidil Prodrug, sulfate metabolite Severe hypertension • Oral, topical Marked tachycardia, salt
+
opens K channels, causes male-pattern baldness Duration: 6–8 h and water retention •
arteriolar smooth muscle hirsutism
hyperpolarization and
vasodilation

Vasodilators, parenteral
Nitroprusside Releases NO from drug Hypertensive Parenteral only Excessive hypotension •
molecule emergencies • cardiac Duration: minutes • requires prolonged infusion may
decompensation constant infusion cause thiocyanate and
cyanide toxicity
+
Diazoxide K channel opener in smooth Hypertensive Parenteral for hypertension, Hyperglycemia • edema,
muscle, secretory cells emergencies oral for insulinoma excessive hypotension
• hypoglycemia due
to insulin-secreting
tumors
Fenoldopam D1 agonist • causes arteriolar Hypertensive Parenteral only, very short Excessive hypotension
dilation emergencies duration

Renin antagonist
Aliskiren Renin inhibitor • reduces Hypertension Oral Angioedema, renal
angiotensin I synthesis Duration: 12 h impairment

Angiotensin antagonists
ACE inhibitors
Captopril ACE inhibitor • reduces Hypertension, diabetic Oral Hyperkalemia • teratogen
angiotensin II synthesis renal disease, heart Half-life: 2.2 h but large • cough
failure doses provide duration of
12 h
Benazepril, enalapril, lisinopril, others: like captopril but longer half-lives
Angiotensin II receptor blockers (ARBs)
Losartan Blocks AT1 receptors Hypertension Oral Hyperkalemia • teratogen
Duration: 6–8 h
Candesartan, irbesartan, others: like losartan

ACE, angiotensin-converting enzyme; ANS, autonomic nervous system; CNS, central nervous system; SANS, sympathetic autonomic nervous system.