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Amitriptyline Metabolization

Amitriptyline is used to treat the symptoms of depression and anxiety disorders. It belongs to the family of the so-called tricyclic antidepressants (TCA) and acts by raising the amounts of certain natural substances present in the brain, which are necessary to maintain mental balance. It is also used to treat eating disorders, neuropathic pain such as fibromyalgia, postherpetic neuralgia (burning, stinging pain or discomfort that may persist for months or years after a herpes zoster infection) and to prevent migraine.

ACTION MECHANISM

Amitriptyline inhibits the mechanism responsible for the reuptake of serotonin and noradrenaline in adrenergic and serotonergic neurons, increasing their synaptic concentration.

It is a potent tricyclic antidepressant with intense sedative effect and rapid onset, with marked anticholinergic effects.

CONTRAINDICATIONS

Hypersensitivity to amitriptyline or other tricyclic antidepressants.

Amitriptyline is contraindicated in patients with recent myocardial infarction. The concomitant use of amitriptyline with MAOIs and cisapride is contraindicated.

PRECAUTIONS

Precautions should be taken when prescribing amitriptyline in patients with a history of epileptic seizures, liver dysfunction, renal failure, urinary retention, narrow-angle glaucoma or increased intraocular pressure, cardiovascular diseases (risk of arrhythmia, sinus tachycardia and prolongation of driving time, myocardial infarction, cerebrovascular accident), apoplexy, hyperthyroidism or with antithyroid treatment, manic-depressive illness (especially in the initial stages of treatment and after dose changes), schizophrenia.

Precautions should be taken if amitriptyline is taken simultaneously with MAOIs, alcohol or other CNS depressants, as it may produce an increased risk of suicide.

Take precautions when prescribing amitriptyline to treat children under 18 yearS old.

The treatment with amitriptyline should be interrupted several days before surgery.

Start and discontinue the treatment progressively. Dose adjustments should be based on the clinical response. The patient should be monitored until improvement due to the risk of suicide.

SIDE EFFECTS

Dry mouth, sedation, blurred vision, constipation, urinary retention, drowsiness, orthostatic hypotension, tachycardia, muscle tremors, nervousness or restlessness, parkinsonian syndrome.

Cardiac arrhythmia, myocardial depression, changes in the ECG (prolongation of the QT and QRS intervals). Sexual dysfunction, behavior and suicidal thoughts and bone fractures.

PHARMACOLOGIC INTERACTIONS

Amitriptyline potentiates its toxicity in concomitance with MAOIs. Do not initiate treatment until 14 days after the end of treatment with MAOIs.

Amitriptyline can potentiate the effect if taken together with other antidepressants.

Amitriptyline potentiates the effects of alcohol, barbiturates, benzodiazepines, anticholinergics/sympathomimetics (risk of paralytic ileus) and analgesic opioids.

There is risk of: delirium if amitriptyline is taken together with disulfiram and etclorvinol; agranulocytosis if amitriptyline is taken together with antithyroid drugs; serotonin syndrome in concomitance with serotonin enhancers; hyperpyrexia in concomitance with anticholinergics or neuroleptics.

Plasma levels of amitriptyline are increased with cimetidine, quinidine, antidepressants, phenothiazines, haloperidol, class 1C antiarrhythmic, propafenone, flecainide, fluoxetine, sertraline and paroxetine, P450 cytochrome inhibitors (ketoconazole, ritonavir, etc.).

Plasma levels of amitriptyline are diminished with barbiturates, inducers of P450 cytochrome (carbamazepine, phenytoin, hypericum ...).

BRAND NAMES

  • Deprelio ®
  • Tryptizol ®

Gene or region studied

  • CYP2D6
  • CYP2C19
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