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Chapter 196: Antihypertensives

Frank LoVecchio; Dan Quan

INTRODUCTION

An estimated 29% of adults in the United States have hypertension; thus, antihypertensives are commonly found in patient homes.1 Several classes of drugs used to treat hypertension are discussed in this chapter: diuretics, sympatholytic agents, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and vasodilators (Table 196-1). Calcium channel blockers and β-blockers, also used in the treatment of hypertension, are discussed elsewhere (see Chapter 195, “Calcium Channel Blockers,” and Chapter 194, “Beta-Blockers”).

TABLE 196-1Summary of Antihypertensive Drugs
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TABLE 196-1 Summary of Antihypertensive Drugs
Class Drug Mechanism of Action Clinical Presentation With Toxicity Comments
Diuretics

Chlorothiazide

Chlorthalidone

Hydrochlorothiazide

Indapamide

Metolazone

 Inhibition of distal tubule sodium chloride absorption

Hypovolemia

Hypokalemia

Hypercalcemia

 Metabolic complications, such as hypokalemia, glucose intolerance, and hyperuricemia seen with increased therapeutic thiazide doses.

Bumetanide

Furosemide

 Inhibition of sodium-potassium-chloride symporter in renal loop of Henle

Hypovolemia

Hypocalcemia

Hypokalemia

Hypomagnesemia

  

Amiloride

Triamterene

 Inhibition of sodium absorption and potassium elimination in renal distal collecting duct

Hypovolemia

Hyperkalemia

  

Eplerenone

Spironolactone

 Mineralocorticoid antagonist

Hypovolemia

Hyperkalemia

  
Sympatholytics

Doxazosin

Prazosin

Tamsulosin

Terazosin

 α1-Adrenergic receptor antagonist Hypotension Phenylephrine may be used for refractory hypotension.

Clonidine

Guanabenz

Guanfacine

α2-Adrenergic receptor agonist

Imidazoline receptor agonist

µ-Receptor opioid agonist

Hypotension

Bradycardia

Neurologic depression

Dopamine considered agent of choice for hypotension.

Phenylephrine may be used for refractory hypotension.

Oxymetazoline

Tetrahydrozoline

 Imidazoline receptor agonist

Hypotension

Bradycardia

Neurologic depression

  

Guanadrel

Methyldopa

Reserpine

 Decreased norepinephrine release

Hypotension

Bradycardia

Hemolytic anemia (idiosyncratic reaction to methyldopa)

  
Angiotensin-converting enzyme inhibitors

Benazepril

Captopril

Enalapril

Fosinopril

Moexipril

Perindopril

Quinapril

Trandolapril

Inhibition of ACE

Inhibition of bradykininase

Hypotension

Hyperkalemia

Angioedema (idiosyncratic)

Cough (idiosyncratic)

Epinephrine, corticosteroids, and antihistamines have no proven benefit in ACEI-induced angioedema.

Icatibant 30 milligrams SC or C1 esterase inhibitor [human] 1000 U IV appear effective in ACEI-induced angioedema.
Angiotensin receptor blockers

Candesartan

Eprosartan

Irbesartan

Losartan

Telmisartan

Valsartan

 Angiotensin II receptor antagonist

Hypotension

Hyperkalemia

Angioedema (less common than with ACE inhibitors)

 Epinephrine, corticosteroids, or antihistamines have no proven benefit in ARB-induced angioedema.
Vasodilators Hydralazine Arteriolar vasodilation

Hypotension

Lupus-like syndrome (idiosyncratic reaction to hydralazine)

  
Minoxidil Arteriolar vasodilation

Tachycardia

Increased myocardial oxygen demand

  
Sodium nitroprusside Arteriolar and venous vasodilation (via nitric oxide release)

Hypotension

Tachycardia

Thiocyanate toxicity (after prolonged infusion)

Cyanide toxicity (very rare)

Thiosulfate should be administered if cyanide toxicity is considered.

 

Many pharmacies mix sodium nitroprusside and thiosulfate to avert cyanide toxicity.

Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; ACEI = angiotensin-converting enzyme inhibitors.

For most of these agents, life-threatening toxicity is not expected in acute overdose.2 In nearly all cases, good supportive care is adequate. The initial approach to the patient with potential overdose of an antihypertensive drug is fairly uniform. Secure the airway as necessary, establish IV access, provide continuous cardiac monitoring, and obtain an ECG. A bolus of crystalloid solution is first-line treatment for hypotension. If a ...

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