Amoxapin

The common adverse effects of amoxapine therapy include, but are not limited to, insomnia, palpitations, tachycardia, hypotension, and constipation. Furthermore, research has indicated that amoxapine may trigger hypomanic states in individuals with underlying bipolar disorder. Amoxapine has been observed to induce noradrenaline-mediated contraction of the urethra in guinea pigs and rats in various laboratory studies, leading to elevated urethral resistance. In addition, the drug has been associated with instances of painful ejaculations relieved by the administration of tamsulosin. Notably, tricyclic antidepressants (TCAs), including amoxapine, are correlated with an increased risk of seizures, especially in older patients and those with epilepsy. Therefore, it is recommended to use SSRIs or SNRIs in patients with a history of epilepsy and seizures.

Signs and Symptoms of Overdose

Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects, particularly grand mal convulsions, occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Renal failure may develop two to five days after toxic overdose in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomuolysis and myolobinurla is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Amoxapine

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.

Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Compounds that specifically inhibit the reuptake of serotonin in the brain.

Rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single dose.

60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine.

Widely distributed in body tissues with highest concentrations found in lungs, spleen, kidneys, heart, and brain. Lower concentrations can be detected in testes and muscle.