Актуальная Медицина - Desipramine hydrochloride (PDH)

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Desipramine hydrochloride  (PDH)

Norpramin, Pertofrane

 

·        Pharmacologic classification: dibenzazepine tricyclic antidepressant

·        Therapeutic classification: antidepressant, antianxiety agent

·        Pregnancy risk category C

 

How supplied

Available by prescription only

Tablets: 10mg, 25 mg, 50 mg, 75mg, 100mg, 150 mg

Pertofrane

Capsules: 25 mg, 50 mg

 

Indications, route and dosage

Depression

Adults: 75 to 150 mg P.O. daily in divided doses, increasing to a maximum of 300 mg daily. Alternatively the entire dosage can be given at bedtime.

Elderly patients and adolescents: 25 to 50 mg P.O. daily, increasing gradually to a maximum of 100 mg daily.

 

Pharmacokinetics

·        Absorption: Desipramine is absorbed rapidly from the Gl tract after oral  administration.

·        Distribution: Desipramine is distributed widely into the body, including the CNS and breast milk. Drug is 90% protein-bound. Peak effect occurs in 4 to 6 hours; steady state, within 2 to 11 days, with full therapeutic effect in 2 to 4 weeks.

·        Metabolism: Desipramine is metabolized by the liver, a significant first-pass effect may explain variability of serum concentrations in different patients taking the same dosage.

·        Excretion: Drug is excreted primarily in urine.

 

Contraindications and precautions

Desipramine is contraindicated in patients with known hypersensitivity to tricyclic antidepressants, trazodone, and related compounds; in the acute recovery phase of myocardial infarction (M) because of its potential arrhythmogenic effects and ECG changes; in patients in coma or severe respiratory depression because of added CNS depressant effects; and during or within 14 days of therapy with monoamine oxidase inhibitors.

            Desipramine should be used cautiously in patients with other cardiac diseases (arrhythmias, congestive heart failure (CHF), angina pectoris, valvular disease, or heart block); respiratory disorders; epilepsy and other seizure disorders; scheduled electroconvulsive therapy; bipolar disease, glaucoma, hyperthyroidism, or patients taking thyroid replacement; Type I and Type II diabetes; prostatic hypertrophy, paralytic ileus, or urinary retention; hepatic or renal dysfunction; or Parkinson’s disease; and in those undergoing surgery using general anesthesia.

             If product contains tartrazine, drug may precipitate asthma in patients with aspirin allergy.

 

 

Adverse reactions

·         CNS: drowsiness, dizziness, sedation, excitation, tremor weakness, headache, nervousness, seizures, peripheral neuropathy, extrapyramidal symptoms, anxiety, vivid dreams, confusion (more marked in elderly patients).

·         CV: orthostatic hypotension, tachycardia, arrhythmias, Ml, stroke, heart block, CHF, palpitations, hypertension (including some surgical patients), ECG changes.

·         EENT: blurred vision, tinnitus, mydriasis, increased intraocular pressure.

·         Gl: dry mouth, constipation, nausea, vomiting, anorexia, diarrhea, paralytic ileus, jaundice.

·         GU: urine retention.

·         Other: sweating, photosensitivity , hypersensitivity (rash, urticaria, drug fever, edema).

   After abrupt withdrawal of long-term therapy, nausea, headache, and malaise (does not indicate addiction) may occur.

   Note: Drug should be discontinued (not abruptly) if signs of hypersensitivity occur. Monitor carefully for the following: urine retention, extreme dry mouth, rash, excessive sedation, seizures, tachycardia, sore throat, fever, or jaundice. Dizziness, fatigue, or orthostatic hypotension may indicate need for reduced dosage.

 

Overdose and treatment

The first 12 hours after acute ingestion are a stimulatory phase characterized by excessive anticholinergic  activity (agitation, irritation, confusion, hallucinations, parkinsonian symptoms, hyperthermia, seizures, urine retention, dry mucous membranes, pupillary dilatation, constipation, and ileus). This is followed by CNS depressant effects, including hypothermia, decreased or absent reflexes, sedation, hypotension, cyanosis, and cardiac irregularities, including tachycardia, conduction disturbances, and quinidine-like effects on the ECG.

       

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