2010/06/13

Amitriptyline

Trade name:
Damilena maleinat

The international name:
Amitriptyline (Amitriptyline)

Group Affiliation:
Antidepressant

Description of the active substance (INN):
Amitriptyline

Dosage form:
tablets, capsules, solution for intramuscular injection, tablets, coated tablets

Mode of action:
Antidepressant drug (tricyclic antidepressant). Also has some analgesic (of central genesis), H2-gistaminoblokiruyuschee and antiserotoninovoe action helps eliminate bed-wetting and reduces appetite. Possesses a strong peripheral and central anticholinergic effects associated with high affinity to the m-cholinergic receptors, a strong sedative effect connected with affinity for H1 -histamine receptors, and alpha-adrenoceptor blocking action. Has the properties of anti-arrhythmic drugs subgroups Ia, like quinidine at therapeutic doses slows ventricular conduction (in overdose can cause severe intraventricular block). The mechanism of antidepressant action is associated with an increase in the concentration of noradrenaline in the synapses and / or serotonin in the central nervous system (reduction of the reverse suction). The accumulation of these neurotransmitters is the result of inhibition of return of their capture membranes of presynaptic neurons. Prolonged use reduces the functional activity of beta-adrenergic and serotonin receptors of the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems are impaired in depressive states. When anxiety and depressive states reduces anxiety, agitation and depressive manifestations. Antiulcer mechanism of action is due to the ability to block histamine H2-receptors in parietal cells of the stomach, as well as to provide sedative and anticholinergic effects of m-(for stomach ulcers and 12 duodenal ulcer reduces the pain, accelerates healing of ulcers). Efficiency at bed-wetting is due, apparently, anticholinergic activity, which leads to an increase in the ability of the bladder to stretch, direct beta-adrenergic stimulation, the activity of alpha-adrenergic agonists, accompanied by increased tone of sphincter and the central blockade of seizure serotonin. have a central analgesic action, which is believed to be associated with changes in concentrations of monoamines in the CNS, especially serotonin, and the impact on the endogenous opioid system. The mechanism of action for bulimia nervosa is unclear (perhaps similar to those for depression). Showed a distinct effect of the drug in patients with bulimia as no depression, and if available, to the reduction of bulimia may occur without a concomitant weakening of the depression itself. In the conduct of general anesthesia, reduces blood pressure and body temperature. Did not inhibit MAO. Antidepressive action develops within 2-3 weeks after application.

Indications:
Depression (especially with anxiety, agitation and sleep disorders, including childhood, endogenous, involutional, reactive, neurotic, drug, with organic brain damage, alcohol withdrawal), schizophrenic psychoses, mixed emotional disturbances, disturbances in behavior (Activity and attention), nocturnal enuresis (except in patients with hypotonia of the bladder), bulimia nervosa, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic diseases, atypical facial pain, postherpetic neuralgia, posttraumatic neuropathy, diabetic or other peripheral neuropathy), headaches, migraine (prevention), peptic ulcer and 12 duodenal ulcer.

Contraindications:
Hypersensitivity, used in conjunction with MAO inhibitors and for 2 weeks before starting treatment, myocardial infarction (acute and subacute periods), acute alcohol intoxication, acute intoxication with hypnotics, analgesic and psychoactive drugs, angle-closure glaucoma, severe violations of AV and intraventricular conduction (block feet beam branch block, AV block II cent.), lactation period, children's age (up to 6 years - oral forms, up to 12 years with the / m and / in the introduction). C care. Chronic alcoholism, asthma, manic-depressive psychosis, depression of bone marrow hematopoietic diseases, CAS (angina, arrhythmias, heart block, CHF, myocardial infarction, hypertension), stroke, reduced motor function of the gastrointestinal tract (risk of paralytic ileus), intraocular hypertension , liver and / or renal failure, hyperthyroidism, prostatic hyperplasia, urinary retention, hypotension bladder, schizophrenia (possible activation of psychosis), epilepsy, pregnancy (especially the I term), advanced age.

Adverse effects:
Anticholinergic effects: blurred vision, cycloplegia, mydriasis, increased intraocular pressure (only persons with local anatomical predisposition - a narrow angle of anterior chamber), tachycardia, dry mouth, confusion, delirium or hallucination, constipation, paralytic ileus, difficulty urinating , reduction of perspiration. the nervous system: drowsiness, asthenia, fainting, anxiety, disorientation, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, agitation, restlessness, manic state, hypomanic state, aggressiveness, memory impairment, depersonalization, increased depression, reduced ability to concentrate, insomnia, nightmares, dreams, yawning, asthenia, activation of the symptoms of psychosis, headache, myoclonus, dysarthria, tremor of small muscles, especially the hands, arms, head and tongue, peripheral neuropathy (paresthesia), myasthenia gravis, myoclonus, ataxia, extrapyramidal syndrome, quickening and strengthening of epileptic seizures, EEG changes. On the part of the SSA: tachycardia, palpitations, dizziness, orthostatic hypotension, nonspecific ECG changes (ST interval and T wave) in patients not suffering from heart disease; arrhythmia, blood pressure lability (decreased or increased blood pressure), violation of intraventricular conduction (increasing complex QRS, change the interval PQ, bundle branch block feet). On the part of the digestive system: nausea, rarely - hepatitis (including dysfunction liver and cholestatic jaundice), indigestion, vomiting, stomachalgia, increased appetite and body weight, or decreased appetite and weight, sores, taste changes, diarrhea, darkening of the tongue. On the part of the endocrine system: an increase in size (swelling) of testicles, gynecomastia, an increase the size of breasts, galactorrhea, decreased or increased libido, reduced potency, hypo-or hyperglycemia, hyponatremia (decreased production of vasopressin), a syndrome of inappropriate secretion of ADH. From the side of hematopoiesis: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia. Allergic reactions: skin rash, itching, skin rash, photosensitization, edema of the face and tongue. Other: Hair loss, tinnitus, edema, hyperpyrexia, swollen lymph nodes, urine retention, thamuria, hypoproteinemia. withdrawal symptoms: the sudden cancellation after long-term care - nausea, vomiting, diarrhea, headache, malaise, sleep disturbances, unusual dreams, unusual excitement, with the gradual abolition after long-term care - irritability, restlessness, sleep disturbances, unusual dreams. Communication with the drug intake is not installed: volchanochnopodobny syndrome (migratory arthritis, the appearance of antinuclear antibody and positive rheumatoid factor), abnormal liver function, ageusia. Local reaction to the in / in the introduction: thrombophlebitis, lymphangitis, burning sensation, allergic skin reaktsii.Peredozirovka. Symptoms. On the part of the CNS: drowsiness, stupor, coma, ataxia, hallucinations, anxiety, psychomotor agitation, reduced ability to concentrate, disorientation, confusion, dysarthria, hyperreflexia, muscular rigidity, choreoathetosis, epileptic syndrome. On the part of the SSA: BP decrease, tachycardia , arrhythmia, a violation of intracardiac conduction, characteristic of tricyclic antidepressants intoxication, ECG changes (especially the QRS), shock, CH, in very rare cases - cardiac arrest. Other: respiratory depression, apnea, cyanosis, vomiting, hyperthermia, mydriasis, increased sweating, oliguria or anuria. The symptoms develop within 4 h after the overdose, reach a maximum after 24 h and lasts 4-6 days. If you suspect an overdose, especially in children, the patient should be hospitalized. Treatment: Ingestion: gastric lavage, the appointment of activated charcoal, symptomatic and supportive therapy, in severe anticholinergic effects (lowering of blood pressure, arrhythmias, coma, myoclonic epileptic seizures) - the introduction of inhibitors cholinesterase (application Physostigmine is not recommended because of the increased risk of convulsions); maintenance of blood pressure and water and electrolyte balance. Showing the control functions of SSA (including ECG) within 5 days (relapse can occur after 48 h and later), anticonvulsant therapy, mechanical ventilation and other resuscitation. Hemodialysis and forced diuresis are ineffective.

Dosage and administration:
Inside, not liquid, immediately after a meal (to reduce the irritation of the mucous membrane of the stomach). The initial dose for adults - 25-50 mg at night, then increase the dose for 5-6 days to 150-200 mg / day in 3 divided doses (maximum dose is taken on the part of the night). If within 2 weeks of no improvement occurred, the daily dose increased to 300 mg. With the disappearance of signs of depression reduce the dose to 50-100 mg / day and continue treatment at least 3 months. In old age with lung disorders prescribed in doses of 30-100 mg / day (at night), after reaching the therapeutic effect of switching to the minimum effective dose - 25-50 mg / day. V / m or / to (enter slowly) in a dose 20-40 mg 4 times a day, gradually replacing ingestion. Duration of treatment - no more than 6-8 months. In nocturnal enuresis in children 6-10 years - 10-20 mg / day for the night, 11-16 years - 25-50 mg / day. Children as an antidepressant: 6 to 12 years - 10-30 mg or 1-5 mg / kg / d fractional, in adolescence - 10 mg 3 times a day (if necessary, up to 100 mg / day). For the prevention of migraine, chronic pain neurogenic nature (in m . hour long headaches) - from 12.5-25 to 100 mg / day (maximum dose taken part in the night).

Cautions:
Before treatment is necessary to monitor blood pressure (in patients with low or labile blood pressure, it can be reduced even more) during treatment - control peripheral blood (in some cases may develop agranulocytosis, and therefore it is recommended to monitor blood picture, especially when increase in body temperature, the development of influenza-like symptoms and sore throat), with long-term therapy - control functions of the SSA and the liver. In elderly and patients with diseases of the SSA shows control of heart rate, blood pressure, ECG. The ECG may result in clinically insignificant changes (smoothing of the T wave, depression of segment ST, the expansion of the complex QRS). Parenteral use is possible only in hospital under medical supervision, compliance with bed rest in the first days of therapy. Caution is necessary when a dramatic shift in the vertical position from the "lying" or "sitting." During the period of treatment should eliminate the use of ethanol. Assign no earlier than 14 days after discontinuation of MAO inhibitors, beginning with small doses. At the reception following the sudden cessation of long-term treatment may develop the syndrome of "cancel." Amitriptyline at doses above 150 mg / day lowers the threshold for seizure activity (it should take into account the risk of epileptic seizures in susceptible patients, as well as the presence of other predisposing factors, the emergence of cramps, such as traumatic brain injury of any etiology, the simultaneous use of antipsychotic drugs (neuroleptics) during the period of non-ethanol or cancellation of drugs with anticonvulsant properties, such as benzodiazepines). pronounced depression of the peculiar risk of suicidal actions, which may persist until a substantial remission. In this regard, early treatment may be in combination with the drug from the group of benzodiazepines, or antipsychotic drugs and constant medical control (charging proxies storage and issuing of drugs). In patients with cyclic affective disorders during the depressive phase of the therapy may develop manic or hypomanic (requires dose reduction or withdrawal of the drug and the appointment of antipsychotic drugs). After coping with these states, if there are indications, treatment at low doses may be renewed. Because of the possible effects of cardiotoxicity requires careful when treating patients with thyrotoxicosis or patients receiving thyroid hormone drugs. In conjunction with electroconvulsive therapy shall be appointed only with careful medical supervision . In predisposed patients and elderly patients may result in the development of drug psychoses, mainly at night (after the withdrawal of the drug are within a few days). It can cause paralytic ileus, mainly in patients with chronic constipation, elderly, or patients who are forced to comply bed rest. Prior to the general or local anesthesia should alert the anesthesiologist that the patient is taking amitriptyline. Because anticholinergic actions may reduce watery, and the relative increase in mucus in the tear fluid, which can cause damage to the corneal epithelium in patients who use contact lenses. Prolonged use of an increase in the incidence of dental caries. Can be increased need for riboflavin. The study of reproduction in animals showed adverse effects on the fetus, and adequate and strictly controlled studies in pregnant women has not held. Pregnant women should use the drug only if the intended benefits to the mother outweighs the potential risk to the fetus. Penetrates into breast milk and may cause drowsiness in infants. In order to avoid the development of the syndrome of "cancellation" in neonates (manifested wheezing, drowsiness, intestinal colic, increased nervous excitability, hypotension or hypertension, tremor or spastic phenomena) receiving amitriptyline gradually canceled at least 7 weeks prior to delivery. Children are more susceptible to acute overdosage, which should be considered dangerous and potentially fatal for them. In the period of treatment to be careful when driving vehicles and other lesson potentially hazardous activities that require high concentration and speed of psychomotor reactions.

Interaction:
When the joint application of ethanol and drugs which depress the central nervous system (including other antidepressants, barbiturates, and general anesthetics benzadiazepinov), possibly a considerable increase in inhibitory action on CNS, respiratory depression and hypotensive effect. Increases the sensitivity to drinks containing ethanol. Increases anticholinergic effects of drugs with anticholinergic activity (eg phenothiazines, antiparkinsonian drugs, amantadine, atropine, biperidena, antihistamine drugs), which increases the risk of side effects (from the central nervous system, eyes, intestines and bladder). When combined with the use of antihistamine drugs, clonidine - strengthening of inhibitory action on CNS, with atropine - increases the risk of paralytic ileus, with drugs causing extrapyramidal reactions - the severity and frequency of extrapyramidal effects. With simultaneous application of amitriptyline, and indirect anticoagulants (coumarin derivatives or indadiona) may increase anticoagulant activity of the past . Amitriptyline may increase the depression caused by SCS. When combined with the use of anticonvulsant drugs may be increased inhibitory action on the central nervous system, reducing the threshold for seizure activity (when used in high doses) and reduced the effectiveness of the latter. drugs for the treatment of thyrotoxicosis increase the risk of agranulocytosis. reduces the effectiveness of phenytoin and alpha-blockers. microsomal oxidation inhibitors (cimetidine), extend T1 / 2, increase the risk of toxic effects of amitriptyline (may require dose reduction of 20-30%), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine, oral contraceptives) reduce the concentration in plasma and reduce the effectiveness of amitriptyline. Fluoxetine and fluvoxamine increase the concentration of amitriptyline in plasma (may require reducing the dose of amitriptyline to 50%). In a joint application with holinoblokatorami, phenothiazines and benzodiazepines - are mutually reinforcing sedative and central anticholinergic effects and increased risk of epileptic seizures (threshold decrease seizure activity), phenothiazines, in addition, may increase the risk of neuroleptic malignant syndrome. In case of simultaneous application of amitriptiliina with clonidine guanetidinom, betanidinom, reserpine and methyldopa - decrease the hypotensive effect of the latter; with cocaine - the risk of cardiac arrhythmias. Estrogensoderzhaschie Oral contraceptive drugs and estrogens may increase the bioavailability of amitriptyline; antiarrhythmic drugs (like quinidine) increase the risk of arrhythmias (possibly slow metabolism of amitriptyline). The combined use of disulfiram and other inhibitors atsetaldegidrogenazy provoke delirium. incompatible with MAO inhibitors (possible increase in the frequency of periods hyperpyrexia , severe convulsions, hypertensive crises, and the patient's death). Pimozid and probucol may increase cardiac arrhythmia, which is manifested by the lengthening of the QT interval on ECG. intensifies the effect of the SCA epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (including if when these drugs are part of local anesthetics), and increases the risk of cardiac arrhythmia, tachycardia, severe hypertension. In a joint appointment with the alpha-adrenostimulyatorov for intranasal administration, or for use in ophthalmology (with significant systemic absorption) can increase the vasoconstrictor action of the latter. In a joint reception with thyroid hormones - the mutual reinforcement of therapeutic effects and toxic effects (including cardiac arrhythmia and a stimulating effect on CNS). M-holinoblokatory and antipsychotic drugs (neuroleptics) increase the risk of hyperpyrexia (especially during hot weather). At a joint appointment with etc. gematotoksichnymi drugs may gain gematotoksichnosti.