CHAPTER 2-156: VASODILATORS

INTRODUCTION

A variety of vasodilators and alpha receptor blockers are used in clinical medicine. Nonselective alpha-adrenergic blocking agents (eg, phenoxybenzamine, phentolamine, and tolazoline) have been used in clinical practice since the 1940s. The first selective alpha₁ blocker, prazosin, was introduced in the early 1970s; doxazosin, indoramin, terazosin, trimazosin, urapidil, and tamsulosin are newer alpha₁-selective agents. Minoxidil, hydralazine, and diazoxide are directly acting peripheral vasodilators. Fenoldopam is a dopamine-1 receptor agonist approved for short-term management of severe hypertension. Nesiritide is a recombinant peptide that is used for the intravenous treatment of acutely decompensated congestive heart failure. Sildenafil, tadalafil, vardenafil, and avenafil are used in the treatment of male erectile dysfunction. Nitroprusside and nitrates are discussed elsewhere.

MECHANISM OF TOXICITY

All these drugs dilate peripheral arterioles to lower blood pressure. A reflex sympathetic response often results in tachycardia and occasionally cardiac arrhythmias. Prazosin and other, newer, alpha₁-specific agents are associated with little or no reflex tachycardia; however, postural hypotension is common, especially in patients with hypovolemia.

TOXIC DOSE

The minimum toxic or lethal doses of these drugs have not been established. Fatalities have been reported with indoramin overdose and excessive IV doses of phentolamine.

1. Indoramin. A 43-year-old woman died 6 hours after ingesting 2.5 g; CNS stimulation and seizures were also reported.

2. Prazosin. A young man developed priapism 24 hours after an overdose of 150 mg. A 19-year-old man became hypotensive after taking 200 mg and recovered within 36 hours. Two elderly men who ingested 40–120 mg were found comatose with Cheyne–Stokes breathing and recovered after 15–18 hours.

3. Minoxidil. Two adults developed profound hypotension (with tachycardia) that required pressor support after 1.3- and 3-g ingestions of topical minoxidil solutions.

4. Sildenafil is generally well tolerated in accidental pediatric ingestions.

5. Pharmacokinetics (see Table II–66)

CLINICAL PRESENTATION

Acute overdose may cause headache, nausea, dizziness, weakness, syncope, orthostatic hypotension, warm flushed skin, and palpitations. Lethargy and ataxia may occur in children. Severe hypotension may result in cerebral and myocardial ischemia and acute renal failure. First-time users of alpha₁ blockers may experience syncope after therapeutic dosing.

DIAGNOSIS

Is based on a history of exposure and the presence of orthostatic hypotension, which may or may not be accompanied by reflex tachycardia.

1. Specific levels. Blood levels of these drugs are not routinely available or clinically useful.

2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, and ECG monitoring.

TREATMENT

1. Emergency and supportive measures

   1. Maintain an open airway and assist ventilation if necessary.

   2. Hypotension usually responds to supine positioning and IV crystalloid fluids. Occasionally, pressor therapy is needed (Hypotension).

2. Specific drugs and antidotes. There is no specific antidote.

3. Decontamination. Administer activated charcoal orally if conditions are ...