Amitriptyline

General characteristics. Structure:

Active ingredient: 25 mg Amitriptylini hydrochloridum.

Excipients: lactose, corn starch, dibasic calcium phosphate, gelatin, magnesium talc stearate, colloid silicon dioxide, methylparaben.

Antidepressant with antidepressive, anxiolytic, sedative, antineuralgic (it is central analgetic), antiulcerous and antibulemichesky action.

Pharmacological properties:

Pharmacodynamics. Inhibits the return capture of neurotransmitters (noradrenaline, serotonin, etc.) presynaptic nerve terminations of neurons, causes accumulation of monoamines in a synaptic gap and strengthens a postsynaptic impulsation. At prolonged use reduces functional activity (desensitization) of beta and adrenergic and serotoninovy receptors of a brain, normalizes adrenergic and serotonergic transfer, recovers the balance of these systems broken at depressions. Blocks m-holino-and histamine receptors of TsNS.

Pharmacokinetics. At intake it is quickly and well soaked up from a GIT. Bioavailability of amitriptyline at different ways of introduction makes 30-60%, its metabolite - a nortriptilin - 46-70%. _Cmax in blood after intake is reached in 2,0-7,7 h. Therapeutic concentration in blood for amitriptyline - 50-250 ng/ml, for a nortriptilin - 50-150 ng/ml. Linkng with blood proteins makes 95%. Easily passes, as well as нортриптилин, through gistogematichesky barriers, including GEB, placental, gets into breast milk.  _T1/2 makes 10-26 h, at a nortriptilin - 18-44 h. In a liver is exposed to biotransformation (demethylation, a hydroxylation, N-oxidation) and forms active - нортриптилин, 10-hydroxy-amitriptyline, and inactive metabolites. It is removed by kidneys (mainly in the form of metabolites) within several days.

At alarming depressions reduces alarm, agitation and depressive manifestations. Antidepressive action develops within 2-4 weeks after an initiation of treatment.

Indications to use:

• Depressions of any etiology. It is especially effective at it is disturbing - depressions, owing to expressiveness of sedation. Does not cause an aggravation of productive symptomatology (nonsense, hallucinations) unlike antidepressants with a promoting effect.

• The mixed emotional frustration and disturbances in behavior, phobic frustration.

• Children's enuresis (except for children with a hypotonic bladder).

• Psychogenic anorexia, bulimic neurosis.

• Neurogenic pains of chronic character, for prevention of migraine.

Route of administration and doses:

Appoint inside (in time or after food).

The initial daily dose at intake makes 50-75 mg (on 25 mg in 2-3 receptions), then the dose is gradually increased by 25-50 mg, before obtaining desirable antidepressive effect. The optimum daily therapeutic dose makes 150-200 mg (the maximum part of a dose is accepted for the night). At heavy depressions, resistant to therapy, the dose is increased to 300 mg and more, to the most tolerable dose. In these cases it is reasonable to begin treatment with intramuscular or intravenous administration of drug, applying at the same time higher initial doses, accelerating building of dosages under control of a somatic state.

After obtaining lasting antidepressive effect in 2-4 weeks of a dose gradually and slowly reduce. In case of symptoms of a depression at decrease in doses it is necessary to return to a former dose. At the sudden termination of reception after prolonged treatment development of a withdrawal is possible. If the condition of the patient does not improve within   3-4 weeks of treatment, then further therapy is inexpedient.

At patients of advanced age at easy disturbances, in out-patient practice, doses make 25-50-100 mg (max) in the divided doses or 1 time a day for the night. For prevention of migraine, chronic pains of neurogenic character (including long headaches) from 12,5-25 mg to 100mg/days.

To children, as antidepressant: from 6 to 12 years - 10-30 mg/days or 1-5 mg/kg/days are fractional, at teenage age - on 10 mg 3 times a day (if necessary to 100 mg a day).

For treatment of night enuresis to children 6 years - 12,5-25 mg for the night are more senior (the dose should not exceed 2,5 mg/kg of body weight).

Features of use:

With care apply at an ischemic heart disease, arrhythmia, heart failure.

Treatment by amitriptyline elderly and children has to take place under careful somatic control and using the minimum doses of drug, raising them gradually, in order to avoid development of delirious frustration, a hypomania and other complications.

Due to a possibility of suicide attempts at patients with a depression regular observation of patients, especially in the first weeks of treatment, and also appointment in minimum necessary doses is necessary for decrease in risk of overdose. In the absence of improvement of a condition of the patient within 3-4 weeks it is necessary to reconsider treatment tactics.

During reception of amitriptyline driving of vehicles, service of mechanisms and other types of the works demanding the increased concentration of attention is forbidden. During treatment it is necessary to avoid alcohol intake.

Reception of amitriptyline is possible not earlier than in 14 days after cancellation of MAO inhibitors.

Side effects:

Generally connected with cholinolytic effect of drug - accommodation disturbance, increase in intraocular pressure, dryness in a mouth, a chair delay, impassability of intestines, an urination delay, fervescence, drowsiness. All these phenomena usually pass after adaptation to drug or decrease in doses.

From TsNS: drowsiness, dizziness, tremor.

From cardiovascular system: tachycardia, orthostatic hypotension, increase in pressure, disturbance of conductivity, change of an ECG.

Allergic reactions: skin rash, etc.

From a GIT: nausea, vomiting, anorexia, stomatitis, taste disturbances, a sensation of discomfort in epigastriums, seldom abnormal liver functions.

From endocrine system: gynecomastia, galactorrhoea, change of secretion of ADG, decrease in a libido, potentiality.

Others: an agranulocytosis and other changes of blood, skin rash, a hair loss, a hyperadenosis, increase in body weight at prolonged use.

Amitriptyline in doses higher than 150 mg/days reduces a threshold of convulsive activity therefore it is necessary to consider risk of developing of convulsive attacks at patients with those in the anamnesis, and at that category of patients who are predisposed to it because of age or injuries.

Patients with depressive phase MDP, can pass into a maniacal stage.

Interaction with other medicines:

Amitriptyline exponentiates oppression of TsNS the following drugs: neuroleptics, sedative and hypnagogues, anticonvulsant drugs, central and narcotic analgetics, anesthetics, alcohol.

At combined use of amitriptyline with neuroleptics, and/or anticholinergic drugs there can be a febrile temperature reaction, paralytic intestinal impassability. Amitriptyline exponentiates hypertensive effects of catecholamines, but inhibits effects of the drugs influencing release of noradrenaline.

Amitriptyline can reduce anti-hypertensive action of sympatholytics (Octadinum, a guanetidin and drugs with the similar mechanism of action).

At a concomitant use of amitriptyline and Cimetidinum increase in concentration in amitriptyline plasma is possible. Inductors of a microsomal oxidation (barbiturates, carbamazepine) reduce concentration of amitriptyline in plasma

It is incompatible with MAO inhibitors. The concomitant use of amitriptyline with MAO inhibitors can lead to a lethal outcome. Having rummaged in treatment between reception of MAO inhibitors and tricyclic antidepressants has to make not less than 14 days!

Contraindications:

• Dekompensirovanny heart diseases.

• Acute and recovery period of a myocardial infarction.

• Disturbances of conductivity of a cardiac muscle.

• Idiopathic hypertensia of the III stage.

• Acute diseases of a liver and kidneys, with the expressed disturbance of functions.

• Blood diseases.

• Peptic ulcer of a stomach and 12 perstny guts in an aggravation stage.

• Glaucoma.

• Prostate hypertrophy.

• Bladder atony.

• Pylorostenosis, paralytic impassability of intestines.

• Simultaneous treatment by MAO inhibitors.

• Pregnancy, breastfeeding period.

• Children up to 6 years (injection forms up to 12 years).

• Hypersensitivity to amitriptyline.

Overdose:

Symptoms: drowsiness, disorientation, confusion of consciousness, hallucination, delirium, expansion of pupils, fervescence, asthma, dysarthtia, excitement, hallucinations, convulsive attacks, muscle tension, stupor, coma, vomiting, arrhythmia, hypotonia, heart failure, respiratory depression.

Treatment: the gastric lavage, reception of suspension of absorbent carbon, laxatives, maintenance of body temperature, monitoring of function of cardiovascular system since a recurrence can come not less than 5 days in 48 hours and later.

At heavy cholinolytic symptoms (hypotension, arrhythmia, a coma) - administration of physostigmine 1-Z of mg everyone a 1/2-2chasa in oil or in/in (to children administration of physostigmine is begun with 0,5 mg, then the dose is repeated with a 5-minute interval for definition of a minimal effective dose, but it is no more than 2 mg). Physostigmine should be applied only at patients in a coma, with respiratory depression, epileptic seizures, heavy hypotension and the expressed cardiac arrhythmia. The hemodialysis and an artificial diuresis are inefficient.

Storage conditions:

List B. To store in the place protected from moisture and light at a temperature not above + 25 °C. To store in the place, unavailable to children. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

On 50 tablets in banks polymeric or on 10 tablets in a blister strip packaging. To one bank, or 5 blister strip packagings together with a leaf insert place in a pack from a cardboard.