Hypotension from antidepressant drugs

These result from the drug s sympathoplegic actions. The major adverse effect is postural hypotension. This effect can be almost totally prevented by concomitant administration of a tricyclic antidepressant agent such as protriptyline. Nausea and vomiting may occur after the intravenous administration of a bolus of bretylium. 

Limited effectiveness and toxicity are the major reasons for switching a patient from one antidepressant drug to another. SSRIs are sometimes superior to tiicychcs in their clinical efficacy, and in this case amitriptyline had not proved effective after a reasonable trial (8 weeks). At that time, the depressive symptoms in this patient included feelings of worthlessness and possibly suicidal ideation. Tricyclic overdose is especially dangerous in depressed patients, who often use medications close at hand in attempting suicide. Ingestion of just a 2-week supply of amitriptyline can cause severe hypotension, cardiac arrhythmias, seizures, coma, and death ( one-prescription lethal ). 

Because neuronal uptake is necessary for the hypotensive activity of guanethidine, drugs that block the catecholamine uptake process or displace amines from the nerve terminal (see Chapter 6) block its effects. These include cocaine, amphetamine, tricyclic antidepressants, phenothiazines, and phenoxybenzamine. 

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility hypovolemia resulting from vomiting, diarrhea, or fluid sequestration peripheral vascular collapse due to blockade of -adrenoceptor-mediated vascular tone or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, tricyclic antidepressants, digitalis, and theophylline. 

Data are sparse that conclusively establish that altered drug effects result from impaired ANS function/ perhaps due to the difficulty in ascribing a particular drug effect to a particular ANS function. However/ increased orthostatic hypotension seen at baseline/ in addition to drugs that cause sympathetic blockade/ such as typical neuroleptics and tricyclic antidepressants/ is likely to be a contributing factor to the increased incidence of hip fracture noted in patients receiving these drugs (41). Similarly the... 

Tricyclic antidepressants reverse the hypotensive effects of postganglionic blocking agents, guanethidine, reser-pine, clonidine, and alpha-methyldopa, and the addition of a tricyclic can result in loss of blood pressure control (159,179). Sudden withdrawal of a tricyclic compound from a patient stabilized with these compounds can also result in serious hypotension. An additional reason for avoiding drugs such as reserpine, methyldopa, and... 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

---