2. Antidepressants. Classification. Mechanism of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.

Antidepressants Is a group of drugs used to treat depression, capable of improving pathologically altered mood and general mental state, restoring interest in life, activity and optimism in patients with depression.

Classification:

4. 3-cycle

BUT... Antidepressants - inhibitors of the action of monoamines (potentiation of the action of monoamines due to the violation of their reuptake):

a) indiscriminate monoamine reuptake blockers - imizine, amitriptyline, azafen, coaxil;

b) selective serotonin reuptake blockers - fluoxetine, sertraline, trazodone, paroxetine, fluvoxamine

c) selective blockers of the reuptake of serotonin and norepinephrine - venlafaxine, duloxetine, mianserin

5. Gink derivatives

B. Antidepressants - MAO inhibitors => an increase in the level of neurotransmitters in the brain tissue:

a) MAO inhibitors of irreversible indiscriminate action - nialamide;

b) reversible MAO inhibitors — moclobemide, befol;

6. 4-cycle - mixed mechanism (A + B): pyrazidol, incazan, maprotiline

Mechanism of action: inhibition of monoamine oxidase (MAO), localized in the mitochondria of adrenergic and serotonergic nerve endings in the central nervous system, as well as in the cells of the liver, myocardium and other tissues. As a result of enzyme inhibition, intracellular inactivation of monoamines - serotonin, norepinephrine, dopamine - is delayed and the release of mediators into the synaptic cleft increases when impulses arrive. Facilitation of synaptic transmission is accompanied not only by the restoration of mood, but also by the elimination of psychomotor retardation, which is often associated with depression.

Indications for use:

∙ asthenic-depressive syndrome;

∙ endogenous depression;

∙ menopause;

∙ alcoholic depression;

∙ neuroses and psychopathies;

∙ schizophrenia, accompanied by feelings of fear and anxiety;

∙ affective insanity;

∙ complex therapy of Alzheimer's disease and other involutional mental disorders;

∙ bulimia nervosa;

∙ dependence on benzodiazepines, withdrawal symptoms when they are canceled.

Side effects:

∙ drugs with a stimulating effect - anxiety, anxiety, insomnia, headache, confusion, delirium, disorientation, nightmares, tremors, paresthesia;

∙ drugs with a sedative effect - lethargy, drowsiness;

∙ peripheral M-anticholinergic effects;

∙ cardiotoxicity;

∙ orthostatic hypotension;

∙ violation of leukopoiesis by the type of leukopenia and agranulocytosis;

∙ dyspeptic disorders;

∙ increased appetite and weight gain;

∙ allergic reactions;

∙ in men - erectile dysfunction and ejaculation, gynecomastia,

in women - persistent galactorrhea.

Contraindications:

∙ violation of cerebral circulation;

∙ diseases of the blood system, blood-forming organs, liver, kidneys;

∙ decompensated heart failure, ischemic heart disease, angina pectoris, arterial hypotension, myocarditis;

∙ severe atherosclerosis;

∙ thyrotoxicosis, decompensated diabetes mellitus;

∙ pregnancy, breastfeeding;

∙ glaucoma, prostatic hypertrophy, constipation

∙ danger of sympathoadrenal crisis (convulsions, hyperthermia, coma)!

∙"Serotonin crisis" with the development of dyspeptic disorders, delirium, hyperthermia, arterial hypertension, muscle rigidity, myoclonus. decay of skeletal muscle!

Amitriptyline - antidepressant activity, acts in 10-14 days, there is no psychosedative, stimulating effect.

Imizin acts in 2-3 weeks.

Fluoxetine - high antidepressant activity, acts after 1-4 weeks, no sedative, does not change weight.

Maprotiline - similar to imizine, slowly absorbed.

Moclobemide - action is short, no ↑ blood pressure, sedation.

Nialamide - well tolerated.

3. Class I antiarrhythmic drugs (sodium channel blockers, or membrane stabilizers). Classification. Mechanism of action. Indications for use. Side effects. Contraindications Comparative evaluation of drugs.

Class I antiarrhythmics -substances that block fast sodium channels of the cell membrane, that is, inhibiting the rate of initial depolarization of cells with a fast electrical response.

Classification:

1) Subclass IA-quinidine, novocainamide.

2) Subclass IB-lidocaine, diphenine

3) Subclass IC-propafenone, etmosine.

Mechanism of action:

Quinidine inhibits the transmission of excitation from the vagus nerve to the heart (due to m-anticholinergic properties), and also somewhat reduces cardiotropic sympathetic (adrenergic) effects. The blocking effect on a-adrenergic receptors is also manifested in relation to peripheral vessels (the total peripheral resistance decreases slightly).

Indications: Supraventricular and ventricular premature beats, atrial tachycardia, AV tachycardia.

Side effects: ringing in the ears, headache, visual impairment. Diarrhea, nausea, and vomiting are often observed. Idiosyncrasy is sometimes noted. Thrombocytopenic purpura is a severe complication1. Atrioventricular and interventricular blocks are possible, as well as toxic tachyarrhythmia. Quinidine lowers blood pressure (total peripheral vascular resistance falls). In the presence of blood clots in the ears of the heart, embolism is sometimes observed (during the transition from atrial fibrillation to sinus rhythm).

Lidocaine - has a depressing effect on automatism (the rate of phase 4 - diastolic depolarization decreases). It does not affect the rate of rapid depolarization (phase 0) or slightly reduces it. In contrast to quinidine, the duration of the action potential (i.e., the repolarization phase) and, to a small extent, the effective refractory period, lidocaine decreases. On the ECG, a shortening of the Q-T interval is noted. The contractility of the myocardium lidocaine does not change or somewhat decreases. It has no vagolytic properties. It has an insignificant effect on hemodynamics. The drug is characterized by a rapidly developing and short-term effect (after a single injection it lasts for 10-20 minutes).

Indications: ventricular arrhythmias (extrasystoles and tachycardia arising from myocardial infarction, open heart surgery, in the postoperative period).

Subclass IC - pronounced arrhythmogenic activity, reduce automatism, more reduce conductivity, do not affect repolarization.

Side effects: ringing in the ears, headache, blurred vision, diarrhea, dyspepsia, decreased blood pressure.

Contraindications: idiosyncrasy, atrioventricular block, liver disease.

Novocainamide - decreases myocardial contractility less than quinidine, vagolytic activity is less pronounced. It is administered enterally and parenterally.

Diphenin - like lidocaine, absorbed slowly, cumulates. Applied for overdose with cardiac glycosides.