Amitriptyline increases. Amitriptyline - emergency or extreme case
Dosage form: tablets Ingredients:1 tablet contains:
active substance: Amitriptyline hydrochloride 0.0283 g (in terms of amitriptyline 0.0250 g);
Excipients: corn starch 0.078 g, lactose monohydrate 0.185815 g, colloidal silicon dioxide 0.001 g, medical gelatin 0.000885 g, magnesium stearate 0.003 g, talc 0.003 g.
Description: Tablets from white to white with a creamy tint, round, biconvex shape. Pharmacotherapeutic group: ATX antidepressant:N.06.A.A.09 Amitriptyline
Pharmacodynamics:Amitriptyline is a tricyclic antidepressant from the group of non-selective inhibitors of neuronal monoamine reuptake. It has a pronounced thymoanaleitic and sedative effect.
PharmacodynamicsThe mechanism of the antidepressant action of amitriptyline is associated with inhibition of the reverse neuronal uptake of catecholamines (norepinephrine, dopamine) and serotonin in the central nervous system.
Amitriptyline is an antagonist of muscarinic cholinergic receptors in the central nervous system and in the periphery, and also has peripheral antihistamine (III) and antiadrenergic properties.
Antidepressant action develops within 2-4 weeks after the start of use.
Pharmacokinetics:Absorption is high. Amitriptyline is rapidly and well absorbed from the gastrointestinal tract after oral administration. Time to reach maximum concentration (T
m ah) after ingestion 2-7.7 hours. The bioavailability of amitriptyline is from 33 to 62%, its active metabolite nortriptyline is 46-70%. The volume of distribution is 5-10 l/kg. Effective therapeutic concentrations in the blood of amitriptyline are 50-250 ng / ml, for nortriptyline (its active metabolite) 50-150 ng / ml. Maximum plasma concentration (C m ax) - 0.04-0.16 μg / ml. Passes through histohematic barriers, including the blood-brain barrier (including nortriptyline). Amitriptyline concentrations in tissues are higher than in plasma. Communication with plasma proteins 92 - 96%.Metabolism
It is metabolized in the liver by demethylation (CYP2D19, CYP3A isoenzymes) and hydroxylation (CYP2D6 isoenzyme) with the formation of active metabolites - nortriptyline, 10-hydroxyamitriptyline, 10-hydroxynortriptyline and inactive metabolites. The main active metabolite is the secondary amine, nortriptyline. Metabolites 10-hydroxyamitriptylip, 10-hydroxynortriptyline are also active, but their action is much less pronounced.
Amitriptyline and nortriptyline are conjugated with glucuronic acid, but these conjugates are inactive.
Demitylnortriptyline and amitriptyline-N-oxide are present in blood plasma in low concentrations and are practically devoid of pharmacological activity. In comparison with amitriptyline, all metabolites have a significantly less pronounced m-cholioblocking effect.
breeding
The plasma half-life is 9 to 46 hours for amitriptyline and 18 to 95 hours for nortriptyline. The mean total creatinine clearance is 39.2 ± 10.18 l/h. It is excreted mainly at night - 80%, partly with bile. Complete elimination within 7-14 days. Amitriptyline crosses the placental barrier and is excreted in breast milk. The concentration ratio breast milk / plasma is 0.4-1.5. When breastfeeding while taking amitriptyline, an average of 2% of the dose taken by the mother, in terms of body weight (in mg / kg), enters the child's body, in terms of body weight (in mg / kg). Equilibrium plasma concentrations of amitriptyline and nortriptyline in most patients are achieved within a week.
Elderly patients
In elderly patients, there is an increase in the half-life and a decrease in the clearance of amitriptyline due to a decrease in the metabolic rate.
Patients with impaired liver function
Impaired liver function can lead to a slowdown in the metabolism of amitriptyline and an increase in its plasma concentrations.
Patients with impaired renal function
Renal failure does not affect the kinetics of the drug. Indications:Endogenous depression and other depressive disorders.
Contraindications:Hypersensitivity to amitriptyline or excipients of the drug, lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
Simultaneous treatment with monoamine oxidase inhibitors (MAO) and two weeks before the start of treatment (see section "Interaction with other drugs"),
Heart failure in the stage of decompensation.
Insufficiency of coronary circulation.
Acute and recovery periods of myocardial infarction.
Violation of the conduction of the heart muscle.
Severe diseases of the liver and kidneys with severe dysfunction.
Peptic ulcer of the stomach and 12 duodenal ulcer in the acute stage.
Hyperplasia of the prostate.
Urinary retention, including with prostatic hyperplasia.
Bladder atony.
Pyloric stenosis, paralytic ileus.
Pregnancy, breastfeeding period.
Children's age up to 18 years.
Acute poisoning with alcohol, barbiturates or opioids.
Angle-closure glaucoma.
Carefully:Amitriptyline should be used with caution in people suffering from alcoholism, with bronchial asthma, manic-depressive psychosis (MDP) and epilepsy (see Special Instructions), in elderly patients, with oppression of bone marrow hematopoiesis, hyperthyroidism, diseases of the cardiovascular system (angina pectoris, arterial hypertension), bipolar affective disorder (after exiting the depressive phase), intraocular hypertension, decreased motor function of the gastrointestinal tract (risk of paralytic ileus), concomitant use with selective serotonin reuptake inhibitors (SSRIs), schizophrenia (activation of psychosis is possible) .
Pregnancy and lactation:The use of the drug during pregnancy and breastfeeding is contraindicated. During pregnancy, amitriptyline should be used only if the intended benefit to the mother outweighs the potential risk to the fetus. The drug must not be used in III trimester of pregnancy, unless absolutely necessary. If the drug is used during pregnancy, the patient should be warned about the high risk of such use for the fetus, especially in the third trimester of pregnancy. During breastfeeding, you must either refuse to take the drug or stop breastfeeding. If this is not done, the child's condition should be monitored, especially during the first four weeks after birth. spastic events), amitriptyline should be discontinued gradually, starting a dose reduction at least 7 weeks before the expected birth. Dosage and administration:Assign inside (during or after a meal).
The initial daily dose for oral administration is 50-75 mg (25 mg in 2-3 doses), then the dose is gradually increased by 25-50 mg until the desired antidepressant effect is obtained. The optimal daily therapeutic dose is 150-200 mg (the maximum part of the dose is taken at night). In severe depression resistant to therapy, the dose is increased to 300 mg or more, up to the maximum tolerated dose (the maximum dose for outpatients is 150 mg / day). In these cases, it is advisable to start treatment with intramuscular or intravenous administration of the drug, while using higher initial doses, accelerating the increase in dosages under the control of the somatic state.
After obtaining a stable antidepressant effect after 2-4 weeks, the doses are gradually and slowly reduced. In the event of signs of depression with a decrease in doses, it is necessary to return to the previous dose.
If the patient's condition does not improve within 3-4 weeks of treatment, then further therapy is inappropriate.
In elderly patients with mild disorders, in outpatient practice, doses are 25-50-100 mg maximum, in divided doses or 1 time per day at night.
withdrawal syndrome
With long-term treatment, especially at high doses, with a sharp discontinuation of the drug, adverse reactions such as headache,
nausea, vomiting, diarrhea, irritability, malaise, insomnia, sleep disturbance with vivid unusual dreams, irritability. Side effects:Mainly associated with the anticholinergic effect of the drug: paresis of accommodation, blurred vision, increased intraocular pressure, dry mouth, constipation, intestinal obstruction, urinary retention, fever. All these phenomena usually disappear after adaptation to the drug or dose reduction. Some of the side effects listed below, eg headache, difficulty concentrating. sleep disturbance, anxiety, tremors, decreased libido can be symptoms of depression and usually improve with improvement in the depressive state.
The frequency of side effects is listed as: very common (>1/10): often (>1/100 to<1/10); нечасто (от >1/1000 to<1/100); редко (от >1/10000 to<1/1000); очень редко (<1/10000); частота неизвестна (частоту встречаемости побочного эффекта невозможно оценить на основании имеющихся данных).
From the binge system: very often headaches, drowsiness, tremor, dizziness; often - impaired concentration, increased fatigue, weakness, irritability, tinnitus, dysarthria, polyneuropathy, dysgeusia (taste disturbance), paresthesia, ataxia, agitation, extrapyramidal disorders, increased incidence of epileptic seizures, peripheral neuropathy, infrequently - insomnia, convulsions, anxiety; rarely akathisia.
On the part of mental activity: very often - confusion, disorientation, decreased libido; infrequently - a decrease in cognitive functions, hypomania, mania, anxiety, night "nightmares"; rarely - aggressiveness, delirium (in the elderly), hallucinations, in women - delayed orgasm, loss of ability to achieve orgasm; frequency unknown suicidal thoughts, suicidal behavior.
From the side of the cardiovascular system: very often - palpitations, tachycardia, orthostatic hypotension, heart rhythm disturbance, extrasystole; often atrioventricular block, bundle branch block, symptoms of heart failure, syncope; infrequently - an increase in blood pressure, non-specific changes in the ECG in patients who do not suffer from heart disease; rarely - myocardial infarction; very rarely - atrial fibrillation, ventricular fibrillation, cardiomyopathy.
From the digestive system: very often - dry mouth, constipation, nausea, heartburn, anorexia, darkening of the tongue, epigastric discomfort, gastralgia; often - inflammation of the oral mucosa, gum disease, irreversible dental caries, a sensation of "burning in the mouth", intestinal obstruction; infrequently - cholestatic jaundice, diarrhea, vomiting, swelling of the tongue, stomatitis; rarely - an increase in the salivary glands, paralytic ileus, impaired liver function, hepatitis.
From the urinary system: often - urinary retention.
From the reproductive system: often - a change in potency.
From the endocrine system: infrequently - galactorrhea; rarely - swelling of the testicles; frequency unknown - gynecomastia.
On the part of the hematopoietic organs: rarely - inhibition of bone marrow hematopoiesis, purpura.
From the immune system: infrequently skin rash, itching, urticaria; rarely - photosensitivity, angioedema; very rarely - allergic inflammation of the alveoli and lung tissue (pneumonia, Leffler's syndrome);
From the skin and subcutaneous tissue: very often hyperhidrosis; infrequently - swelling of the face.
On the part of the body as a whole: very often increased appetite; often - fatigue, changes in body weight with prolonged use, nasal congestion; rarely - hair loss, swollen lymph nodes, hyperpyrexia, violation of liver function tests, increased alkaline phosphatase in the blood, pollakiuria, loss of appetite; very rarely - allergic vasculitis.
On the part of the organs of vision: often - blurred vision, disturbance of accommodation, dilated pupils, increased intraocular pressure; rarely - paresis of accommodation. On the part of the hearing organs: rarely - tinnitus, auditory hallucinations.
On the part of laboratory and instrumental data: very often - an increase in intraocular pressure; often changes in the EEG, impaired intraventricular conduction (prolongation of the QT interval, expansion of the QRS complex on the ECG), "jumping" blood pressure, decreased production of antidiuretic hormone, hyponatremia; rarely - stump or hyperglycemia, glucosuria. impaired glucose tolerance, agranulocytosis, leukopenia, eosinophilia. thrombocytopenia, increased activity of "liver" transaminases.
Overdose:Symptoms
Reactions to overdose in different patients can vary significantly.
Symptoms may develop slowly and imperceptibly, or abruptly and suddenly. During the first hours there is drowsiness or agitation, disorientation, confusion. dilated pupils, fever, shortness of breath, dysarthria, agitation and hallucinations.
Anticholinergic symptoms (mydriasis, tachycardia, urinary retention, dry mucous membranes, slowed intestinal motility), convulsions, convulsive seizures, muscle rigidity, fever, sudden depression of the central nervous system, depression of consciousness up to coma, respiratory depression. Symptoms from the cardiovascular system: arrhythmias (ventricular tachyarrhythmia, cardiac arrhythmias like torsade des pointes, ventricular fibrillation). The ECG is characterized by PR interval prolongation, QRS complex widening, QT interval prolongation, T-wave flattening or inversion, ST-segment depression, and intracardiac conduction block of varying degrees, which can progress to cardiac arrest. The expansion of the QRS complex usually correlates with the severity of toxic effects due to acute overdose. Heart failure, low blood pressure, cardiogenic shock. Metabolic disorders: metabolic acidosis, hypokalemia. After awakening, confusion, agitation, hallucinations, ataxia are again possible.
Treatment
Termination of therapy with amitriptyline, hospitalization (in the intensive care unit).
Treatment is symptomatic and supportive. Probing and gastric lavage, even if a long time has passed after taking the drug inside, with the preliminary appointment of activated charcoal. Careful observation, even if the case seems uncomplicated. Monitoring the level of consciousness, pulse, blood pressure and respiration. Frequent monitoring of electrolytes in blood serum and blood gases. Airway control, if necessary, should be carried out using intubation. To prevent possible respiratory arrest, it is recommended to use a ventilator. Showing constant ECG monitoring and control of heart function for 3-5 days. because relapse can occur after 48 hours or later. With the expansion of QRS intervals, heart failure and ventricular arrhythmias, a positive effect can be achieved by shifting the pH to the alkaline side (due to the introduction of bicarbonate or moderate hyperventilation) and by rapid infusion of hypertonic sodium chloride solution (100-200 mmol Na +). It is possible to use appropriate antiarrhythmics, for example, lidocaine for ventricular arrhythmias at a dose of 50-100 mg IV (1-1.5 mg/kg), then 1-3 mg/min by IV infusion. If necessary, cardioversion, defibrillation is performed. For the treatment of circulatory failure, plasma expanders should be used, and in severe cases, dobutamine infusions should be used at an initial rate of 2-3 mcg/ct per minute with an increase in dose depending on the response. With agitation and convulsions, diazepam may be used. Hemodialysis and forced diuresis are not very effective. Interaction:Amitriptyline enhances the inhibitory effect on the central nervous system of the following drugs: neuroleptics, sedatives and hypnotics, anticonvulsants, analgesics, anesthetics, alcohol; shows synergism when interacting with other antidepressants. Tricyclic antidepressants, including amitriptyline, are metabolized by the CYP2D6 isoenzyme of the hepatic cytochrome P450. The CYP2D6 isoenzyme in humans has several isoforms. CYP2D6 isoenzymes can inhibit various psychotropic drugs, for example, antipsychotics, selective serotonin reuptake inhibitors (SSRIs) with the exception of citalopram (a very weak inhibitor of the CYP2D6 isoenzyme)
