| Indication | Labeled indications: depression and insomnia. Unlabeled indications: chronic and neuropathic pain, anxiety, idiopathic urticaria. |
| Pharmacodynamics | Doxepin, a tricyclic antidepressant of the dibenzoxepin type, is used to treat depression and anxiety and, topically, pruritus associated with eczema. Doxepin has substantial anticholinergic and sedative effects. |
| Mechanism of action | The mechanism of action of doxepin is not completely understood. It is thought that Like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. Doxepin may also act on histamine H1-receptors, resulting in sedative effects, and β-adrenergic receptors. |
| Absorption | Well-absorbed from the GI tract. Peak plasma concentrations occur within 2 hours of oral administration. |
| Volume of distribution | Not Available |
| Protein binding | Highly bound to plasma proteins. |
| Metabolism | Extensively metabolized in the liver via the same pathways as other TCAs. N-demethylation produces an active metabolite, N-desmethyldoxepin. |
| Route of elimination | Not Available |
| Half life | 6 - 24.5 hours |
| Clearance | Not Available |
| Toxicity | LD50=26 (mg/kg) (in mice, iv); LD50=16 (mg/kg) (in rats, iv); Cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia. |
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