indication

For the treatment of depression and as aid to smoking cessation.

pharmacology

Bupropion, an antidepressant of the aminoketone class and a non-nicotine aid to smoking cessation, is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. Compared to classical tricyclic antidepressants, Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine. In addition, Bupropion does not inhibit monoamine oxidase. Bupropion produces dose-related central nervous system (CNS) stimulant effects in animals, as evidenced by increased locomotor activity, increased rates of responding in various schedule-controlled operant behavior tasks, and, at high doses, induction of mild stereotyped behavior.

mechanism of action

Bupropion selectively inhibits the neuronal reuptake of dopamine, norepinephrine, and serotonin; actions on dopaminergic systems are more significant than imipramine or amitriptyline whereas the blockade of norepinephrine and serotonin reuptake at the neuronal membrane is weaker for bupropion than for tricyclic antidepressants. The increase in norepinephrine may attenuate nicotine withdrawal symptoms and the increase in dopamine at neuronal sites may reduce nicotine cravings and the urge to smoke. Bupropion exhibits moderate anticholinergic effects.

toxicity

Symptoms of overdose include seizures, hallucinations, loss of consciousness, tachycardia, and cardiac arrest.

biotransformation

Reduction of the carbonyl groupand/or hydroxylation of the tert-butyl group of bupropion.

absorption

For sustained release, peak plasma concentrations are achieved within 3 hours.

half life

24 hours

route of elimination

Bupropion is extensively metabolized in humans. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of metachlorobenzoic acid, which is then excreted as the major urinary metabolite. Following oral administration of 200 mg of 14C-bupropion in humans, 87% and 10% of the radioactive dose were recovered in the urine and feces, respectively. However, the fraction of the oral dose of bupropion excreted unchanged was only 0.5%, a finding consistent with the extensive metabolism of bupropion.

drug interactions

Carbamazepine: Carbamazepine, a strong CYP2B6 inducer, may increase the metabolism of bupropion. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bupropion if carbamazepine is initiated, discontinued or dose changed.

Cyclosporine: Bupropion may decrease the therapeutic effect of cyclosporine.

Isocarboxazid: Possible severe adverse reaction with this combination

Phenelzine: Possible severe adverse reaction with this combination

Rasagiline: Possible severe adverse reaction with this combination

Rifabutin: Rifampin reduces bupropion levels

Rifampin: Rifampin reduces bupropion levels

Ritonavir: Ritonavir increases the effect and toxicity of bupropion

Thioridazine: Bupropion may increase the effect and toxicity of thioridazine.

Thiotepa: Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Bupropion, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Bupropion if Thiotepa is initiated, discontinued or dose changed.

Tranylcypromine: The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Bupropion. These agents should not be administered within 14 days of each other.

Triprolidine: The CNS depressants, Triprolidine and Bupropion, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Zuclopenthixol: Bupropion, a strong CYP2D6 inhibitor, may increase the serum concentration of zuclopenthixol by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zuclopenthixol if bupropion is initiated, discontinued or dose changed.