Page 205 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 11 Antihypertensive Agents 191

and brain injury. Rather, blood pressure should be lowered by nitroprusside, nitroglycerin, labetalol, calcium channel blockers,
about 25%, maintaining diastolic blood pressure at no less than fenoldopam, and hydralazine. Esmolol is often used to manage
100–110 mm Hg. Subsequently, blood pressure can be reduced to intraoperative and postoperative hypertension. Diuretics such as
normal levels using oral medications over several weeks. The paren- furosemide are administered to prevent the volume expansion that
teral drugs used to treat hypertensive emergencies include sodium typically occurs during administration of powerful vasodilators.

SUMMARY Drugs Used in Hypertension

Pharmacokinetics,
Subclass, Drug Mechanism of Action Effects Clinical Applications Toxicities, Interactions
DIURETICS
• Thiazides: Block Na/Cl transporter in Reduce blood volume and Hypertension, mild heart
Hydrochlorothiazide, renal distal convoluted tubule poorly understood vascular failure
chlorthalidone effects
• Loop diuretics: Block Na/K/2Cl transporter in Like thiazides • greater efficacy Severe hypertension, heart See Chapter 15
Furosemide renal loop of Henle failure
• Spironolactone, Block aldosterone receptor in Increase Na and decrease K Aldosteronism, heart
eplerenone renal collecting tubule excretion • poorly understood failure, hypertension
reduction in heart failure
mortality
SYMPATHOPLEGICS, CENTRALLY ACTING
• Clonidine, Activate α 2 adrenoceptors Reduce central sympathetic Hypertension • clonidine Oral • clonidine also as patch •
methyldopa outflow • reduce norepinephrine also used in withdrawal Toxicity: sedation • methyldopa
release from noradrenergic from abused drugs hemolytic anemia
nerve endings
SYMPATHETIC NERVE TERMINAL BLOCKERS
• Reserpine Blocks vesicular amine Reduces all sympathetic effects, Hypertension but rarely Oral • long duration (days) •
transporter in noradrenergic especially cardiovascular, and used Toxicity: psychiatric depression,
nerves and depletes reduce blood pressure gastrointestinal disturbances
transmitter stores
• Guanethidine, Interferes with amine release Same as reserpine Same as reserpine Severe orthostatic
guanadrel and replaces norepinephrine hypotension • sexual
in vesicles dysfunction • availability
limited

` BLOCKERS
• Prazosin Selectively block α 1 Prevent sympathetic Hypertension • benign Oral • Toxicity: Orthostatic
• Terazosin adrenoceptors vasoconstriction • reduce prostatic hyperplasia hypotension
• Doxazosin prostatic smooth muscle tone
a BLOCKERS
• Metoprolol, others Block β 1 receptors; carvedilol Prevent sympathetic cardiac Hypertension • heart failure See Chapter 10
• Carvedilol also blocks α receptors; stimulation • reduce renin • coronary disease
• Nebivolol nebivolol also releases nitric secretion
oxide
• Propranolol: Nonselective prototype β blocker
• Metoprolol and atenolol: Very widely used β 1 -selective blockers
VASODILATORS
• Verapamil Nonselective block of L-type Reduce cardiac rate and output Hypertension, angina, See Chapter 12
• Diltiazem calcium channels • reduce vascular resistance arrhythmias
• Nifedipine, Block vascular calcium Reduce vascular resistance Hypertension, angina See Chapter 12
amlodipine, other channels > cardiac calcium
dihydropyridines channels
• Hydralazine Causes nitric oxide release Vasodilation • reduces vascular Hypertension • minoxidil Oral • Toxicity: Angina,
• Minoxidil Metabolite opens K channels resistance • arterioles more also used to treat hair loss tachycardia • Hydralazine:
in vascular smooth muscle sensitive than veins • reflex Lupus-like syndrome •
tachycardia Minoxidil: Hypertrichosis
(continued)