Immipramine Research Paper

INTRODUCTION :
Imipramine belongs to a group of medicines called tricyclic antidepressants. It affects chemicals in the brain that may become unbalanced. It is generally used to treat symptoms of depression. However, it is also used to treat a completely unrelated condition in children, known as nocturnal enuresis (night-time bedwetting).
TRADE NAMES :
TofranilAntidepAntipresMicrodepPraminGENERIC NAME : Imipramine hydrochloride
ACTION : Antidepressant
AVAILABLE FORMS :
Tablets (imipramine hydrochloride)—10, 25, 50 mg; capsules (imipramine pamoate)—75, 100, 125, 150 mg
DOSAGE/ROUTE :
Adults
Depression: Hospitalized patients: initially, 100–150 mg/day PO in divided doses. Gradually increase to 200 mg/day as required. If no response
after 2 wk, increase to 250–300 mg/day. Total daily dosage may be given hs. Outpatients: initially, 75 mg/day PO, increasing to 150 mg/day. Dosages > 200 mg/day not recommended. Total daily dosage may be given hs. Maintenance dose is 50–150 mg/day.
Chronic pain: 50–200 mg/day PO.
Adolescent and geriatric patients
Depression: 30–40 mg/day PO; doses > 100 mg/day generally are not needed.
Pediatric patients ≥ 6 yr
Childhood enuresis: Initially, 25 mg/day 1 hr before bedtime.
If response is not satisfactory after 1 wk, increase to 50 mg nightly in children < 12 yr, 75 mg nightly in children > 12 yr.
Doses > 75 mg/day do not have greater efficacy but are more likely to increase side effects.
Do not exceed 2.5 mg/kg per day.
Early-night bedwetters may be more effectively treated with earlier and divided dosage (25 mg midafternoon, repeated hs).
Institute drug-free period after successful therapy, gradually tapering dosage.
MECHANISM OF ACTION:
Mechanism of action unknown. The TCAs are structurally related to the phenothiazine antipsychotic drugs (eg, chlorpromazine), but unlike the phenothiazines, TCAs inhibit the presynaptic reuptake of the neurotransmitters norepinephrine and serotonin; anticholinergic at CNS and peripheral receptors; sedative; the relation of these effects to clinical efficacy is unknown.
PHARMACOKINETICS :
Route - Oral
Onset - Varies
Peak - 2 to 4 hours
Metabolism: Hepatic 8–16 hr
Distribution: Crosses placenta; enters breast milk
Excretion: Urine
Imipramine is rapidly and almost completely absorbed from the gastrointestinal tract.
Peak plasma levels are reached in 2 to 5 hours, and plasma half-life ranges from 9 to 20 hours.
After oral administration of 50 mg 3 times daily for 10 days, the mean steady-state plasma concentration was 33 to 85 ng/mL for imipramine and 43 to 109 ng/mL for desmethylimipramine, an active metabolite.
Approximately 86% of imipramine is bound to plasma proteins.
It is excreted primarily as inactive metabolites, up to 80% in the urine and up to 20% in the feces.
Owing to the lower clearance of imipramine in plasma, elderly patients require lower doses of imipramine than patients in younger age groups.
DRUG INTERACTIONS : phenytoinany other antidepressant, or medication to treat mental illness bladder or urinary medicines such as darifenacin, tolterodine, solifenacinbronchodilators such as ipratropium or tiotropiumcold or allergy medicine that contains an antihistamine medication for Parkinson's disease; or medication to treat excess stomach acid, stomach ulcer, motion sickness, or irritable bowel
syndrome
Patients should be warned that, while taking imipramine their responses to alcoholic beverages, other CNS depressants (e.g., barbiturates, benzodiazepines or general anesthetics) or anticholinergic agents (e.g., atropine, biperiden, levodopa) may be exaggerated. When tricyclic antidepressants are given in combination with anticholinergics or neuroleptics with an anticholinergic action, hyperexcitation states or delirium may occur, as well as attacks of glaucoma.
Tricyclic antidepressants should not be employed in combination with antiarrhythmic agents of the quinidine type.
Since imipramine may diminish or abolish the antihypertensive effects of guanethidine, bethanidine, clonidine, reserpine, or alpha-methyldopa, patients requiring concomitant treatment for hypertension should be given antihypertensives of a different type (e.g., diuretics, vasodilators, beta-blockers).
Imipramine should be discontinued prior to elective surgery for as long as clinically feasible, since little is known about the interaction between imipramine and general anesthetics.

INDICATIONS :
Relief of symptoms of depression (endogenous depression most responsive); sedative effects of tertiary amine TCAs may be helpful in patients whose depression is associated with anxiety and sleep disturbance
Enuresis in children 6 yr or older
Unlabeled use: control of chronic pain (eg, intractable pain of cancer, peripheral neuropathies, postherpetic neuralgia, tic douloureux, central pain syndromes)CONTRAINDICATIONS :
Contraindicated with hypersensitivity to any tricyclic drug patients with aspirin allergy recent MI myelography within previous 24 hr or scheduled within 48 hr pregnancy lactation
PRECAUTIONS :
Use cautiously with preexisting CV disorders; seizure disorders (TCAs lower the seizure threshold); hyperthyroidism; angle-closure glaucoma, increased intraocular pressure, urinary retention, ureteral or urethral spasm; impaired hepatic, renal function; psychiatric patients (schizophrenic or paranoid patients may exhibit a worsening of psychosis with TCA therapy; manic-depressive patients may shift to hypomanic or manic phase); elective surgery.

ADVERSE EFFECTS :
(Adverse effects in Italics are most common; those in Bold are life-threatening.)
Adult use
• CNS: Sedation and anticholinergic effects, dry mouth, blurred vision, disturbance of accommodation for near vision, mydriasis, increased intraocular pressure; confusion, disturbed concentration, hallucinations, disorientation, decreased memory, feelings of unreality, delusions, anxiety, nervousness, restlessness, agitation, panic, insomnia, nightmares, hypomania, mania, exacerbation of psychosis, drowsiness, weakness, fatigue, headache, numbness, tingling, paresthesias of extremities, incoordination, motor hyperactivity, akathisia, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms, seizures, dysarthria, tinnitus, altered EEG
• CV: Orthostatic hypotension, hypertension, syncope, tachycardia, palpitations, MI, arrhythmias, heart block, precipitation of CHF, stroke
• Endocrine: Elevated or depressed blood sugar, elevated prolactin levels, inappropriate ADH secretion
• GI: Dry mouth, constipation, paralytic ileus, nausea, vomiting, anorexia, epigastric distress, diarrhea, flatulence, dysphagia, peculiar taste, increased salivation, stomatitis, glossitis, parotid swelling, abdominal cramps, black tongue, hepatitis
• GU: Urinary retention, delayed micturition, dilation of the urinary tract, gynecomastia, testicular swelling in men; breast enlargement, menstrual irregularity and galactorrhea in women; increased or decreased libido; impotence
• Hematologic: Bone marrow depression, including agranulocytosis; eosinophilia, purpura, thrombocytopenia, leukopenia
• Hypersensitivity: Rash, pruritus, vasculitis, petechiae, photosensitization, edema (generalized, facial, tongue), drug fever
• Withdrawal: Abrupt discontinuation of prolonged therapy: nausea, headache, vertigo, nightmares, malaise
• Other: Nasal congestion, excessive appetite, weight gain or loss; sweating (paradoxical effect in a drug with prominent anticholinergic effects), alopecia, lacrimation, hyperthermia, flushing, chills
Pediatric use for enuresis
• CNS: Nervousness, sleep disorders, tiredness, convulsions, anxiety, emotional instability, syncope, collapse • CV: ECG changes of unknown significance when given in doses of 5 mg/kg/day • GI: Constipation, mild GI disturbances • Other: Adverse reactions reported with adult use
NURSING IMPLICATIONS :
Collect History: Hypersensitivity to any tricyclic drug or to tartrazine; recent MI; myelography within previous 24 hr or scheduled within 48 hr; preexisting CV disorders; seizure disorders; hyperthyroidism; angle-closure glaucoma, increased intraocular pressure, urinary retention, ureteral or urethral spasm; impaired hepatic, renal function; psychiatric patients; elective surgery; pregnancy; lactation
Physical Examination: Weight; Temperature; skin color, lesions; orientation, affect, reflexes, vision and hearing; Pulse, BP, auscultation, orthostatic BP, perfusion; bowel sounds, normal output, liver evaluation; urine flow, normal output; usual sexual function, frequency of menses, breast and scrotal examination; liver function tests, urinalysis, CBC, ECG
Limit drug access for depressed and potentially suicidal patients.
Give IM only when oral therapy is impossible. Do not give IV.
Give major portion of dose night if drowsiness, severe anticholinergic effects occur (note that elderly may not tolerate single daily dose therapy).
Reduce dosage if minor side effects develop; discontinue if serious side effects occur. Arrange for CBC if patient develops fever, sore throat, or other sign of infection during therapy.
PATIENT EDUCATION :
Take drug exactly as prescribed.
Do not stop taking drug abruptly or without consulting your health care provider.
Avoid prolonged exposure to sunlight or sunlamps; use a sunscreen or protective garments.
These side effects may occur: headache, dizziness, drowsiness, weakness, blurred vision (reversible; safety measures may need to be taken if severe; avoid driving or performing tasks that require alertness); nausea, vomiting, loss of appetite (small frequent meals, frequent mouth care may help); dry mouth (sucking sugarless candies may help); disorientation, difficulty concentrating, emotional changes; changes in sexual function, impotence, changes in libido.
Report dry mouth, difficulty in urination, excessive sedation, fever, chills, sore throat, palpitations.
CONCLUSION :
Imipramine, sold as Tofranil and also known as melipramine, is a HYPERLINK "http://en.wikipedia.org/wiki/Tricyclic_antidepressant" \o "Tricyclic antidepressant" tricyclic antidepressant (TCA) of the HYPERLINK "http://en.wikipedia.org/wiki/Dibenzazepine" \o "Dibenzazepine" dibenzazepine group. Imipramine is mainly used in the treatment of major depression and enuresis (inability to control urination).It has also been evaluated for use in panic
disorder.