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 (approved for benign prostatic hypertrophy) are newer alpha1-selective agents. Minoxidil, hydralazine, and diazoxide are directly acting peripheral vasodilators. Fenoldopam is a dopamine
1 receptor agonist that has been approved by the FDA for in-hospital, short-term management of severe hypertension. Nesiritide is a recombinant human B-type natriuretic peptide that is used for the intravenous treatment of acutely decompensated congestive heart failure. Sildenafil is one of a class of agents used in the treatment of male erectile dysfunction. Nitroprusside (See Nitroprusside) and nitrates (See Nitrates and Nitrites) are discussed elsewhere.
Mechanism of toxicity. All these drugs dilate peripheral arterioles to lower blood pressure. A reflex sympathetic response 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.
Indoramin. A 43-year-old woman died 6 hours after ingesting 2.5 g; CNS stimulation and seizures were also reported.
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.
Minoxidil. Two adults developed profound hypotension (with tachycardia) that required pressor support after 1.3- and 3-g ingestions of topical minoxidil solutions.
is generally well tolerated in accidental pediatric ingestions.
Pharmacokinetics (see Table II–61)
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.
Specific levels. Blood levels of these drugs are not routinely available or clinically useful.
Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, and ECG monitoring.
Emergency and supportive measures
Maintain an open airway and assist ventilation if necessary (See Airway and Breathing).
Hypotension usually responds to supine positioning and IV crystalloid fluids. Occasionally, pressor therapy is needed (See Hypotension).
Specific drugs and antidotes. There is no specific antidote.
Decontamination (See Decontamination). Administer activated charcoal orally if conditions are appropriate (see Table I–38). Gastric lavage is not necessary after small to moderate ingestions if activated ...