PSYCHOTROPIC DRUGS PSYCHOTROPIC DRUGS Drugs with depressive type

PSYCHOTROPIC DRUGS

PSYCHOTROPIC DRUGS Drugs with depressive type of action 1. 2. 3. 4. Neuroleptics (antipsychotics) Tranquilizers (anxiolytics) Sedative drugs Normotymics (tymoleptics, tymoanaleptics) Drug with stimulative action 1. 2. 3. 4. Antidepressants Psychomotor stimulants Nootropic drugs Drugs which increase general tone (adaptogens) Psychotomimetics (psychodysleptics) 1. 2. LSD Cannabis sativa L.

NEUROLEPTICS Derivatives of phenotiazine: aminazine, triftiazine, etaperazine, tioridazine Derivatives of tioxanten: chlorprotixen Derivatives of butyrophenon: haloperidol, droperidol Derivatives of piperasinedibenzodiazepine: clozapine Derivatives of indole: reserpin, sulpyrid (eglonil)

NEUROLEPTICS “Typical” – derivatives of phenotiazine, tioxanten, butyrophenon – they cause disorders of extrapyramidal system function – syndrome of parkinsonism “Atypical” – derivatives of indole, benzodiazepine – they cause those negative reactions very rarely

Aminazine (chlorpromazine) 1951 – aminazine was introduced into clinical practice It brought considerable changes into situations of psychiatric clinics Before appearance of aminazine for treatment of psychologically sick patients insulin or electric shock were widely used, in some cases - lobotomy

Phenothiazine derivatives

Thioxanten derivateves

Butyrophenon derivatives

piperasine-dibenzodiazepine derivatives (Clozapin, Clozapine, Faza. Clo, Leponex, Zaponex, Clopin Eco. )

Mechanism of action of neuroleptics Influence on dopamine (D 2), noradrenergic, serotoninergic, GABAergic, cholinergic receptors

Properties of neuroleptics Antipsychotic action - they eliminate productive symptoms of psychosis (delirium and hallucinations), affective disorders They eliminate psychomotor excitation consciousness is present

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Administration of antipsychotic action of neuroleptics Treatment of psychosis Schizophrenia Maniac-depressive psychosis Alcohol psychosis Reactive psychosis In a case of psychomotor excitation of various etiology

Delirium tremens – alcohol psychosis

Influence of neuroleptics on psychical activity 1. Drugs with psychosedative action – they cause condition of psychomotor indifference (apathy, decreasing of moving activity, retarded emotions and wishes, disappearance of initiative) Aminazine, clozapine (leponex), chlorprotyxen, haloperidol, droperidol Peculiarities of usage: psychosis with manifestations of excitation Contraindications: psychosis with retardness, inertia, depression, stupor, apatho-abulic syndrome

Neuroleptics with psychosedative action

Influence of neuroleptics on psychical activity 2. Drugs which stimulate psychical activity (increase mimics and liveliness, increase moving activity, improve the mood) Triftazin, ethaperazin, moditen, majeptil Peculiarities of usage: psychosis with psychomotor retardness, apatho-abulic conditions, stupor conditions Contraindications: affective disturbances, mania, psychomotor excitation

Drugs which stimulate psychical activity

Other properties and indications for administration of neuroleptics Drugs with psychosedative action – for potentiation of action of hypnotic drugs, opioid and nonopioid analgesics, drugs for general anesthesia, local anesthetics, for example, neuroleptanalgesia Anti-emetic action (elimination of vomiting of central origin): brain tumors, radial and chemical therapy, intestinal impassability, intoxication with heart glycosides, apomorphine and other drugs Decreasing of body temperature (only in the case of simultaneous hypothermia) Decreasing of blood pressure (alpha-adrenoblocking properties – aminazine, droperidol) – in case of hypertensive crisis, lungs, brain edema

Side effects of neuroleptics Extrapyramidal disorders: muscular hypertonus, general constraint, tremor of hands, tongue, mandible, head, seizure contractions of muscles, vegetative crisis For treatment – cyclodol (levodopa is contraindicated because it diminishes therapeutic effect of neuroleptics) Orthostatic collapse Complicated nose breathing, hypostatic, aspirate pneumonia Dyspeptic disorders: anorexia, changes of taste Abdominal pain Constipation Damage of the liver (cholestasis) Granulocytopenia (especially clozapin) Hyperglycemia, dysmenorrhea, galactorrhea, hyperthyrosis, gynecomastia, impotence Aminazine has a considerable irritative action

syndrome of parkinsonism

Parkinsone syndrome treatment Cyclodolum Levodopa is contraindicated

TRANQUILIZERS Agonists of benzodiazepine receptors: - derivatives of benzodiazepine – chlozepid, sybazon, phenazepam, gidazepam Agonists of serotonine receptors: buspyrone Drugs with other mechanisms of action: - derivatives of diphenilmethan: amisyl - derivatives of propanediole: meprotan

TRANQUILIZERS

Properties of tranquilizers Anxiolytic properties – eliminate feeling of anxiety, restlessness, fear, aggressiveness, irritability, cause peace, careness, decreasing of moving activity Hypnotic (somnolent) action Myorelaxing action (of central genesis) Antiseizure action

Duration of action of tranquilizers Drugs of long lasting action: diazepam, phenazepam, chlozepid Drugs of medium action duration: lorazepam, alprazolam Drugs of short action duration: midazolam

“DAY” TRANQUILIZERS Gidazepam Mezapam (rudotel) Grandaxyn (tophizopam) Trioxazyn Buspyron

Administration of tranquilizers Anxiolytic action Treatment of neurosis, accompanied by fear, anxiety, exertion, increased irritability, insomnia In case of headache and heart pain of neurotic origin, so called organic neurosis In case of abstinence in alcohol and drugs addicts In case of diencephalons crisis (sybazon) Tranquilizers do not diminish productive symptoms of psychosis!

Usage of tranquilizers Hypnotic action – they cause sleep, which is very close to physiological one according to its parameters Nitrazepam Phenazepam Diazepam Chlozepid Depression of CNS – for atharalgesia Sibazon Midazolam

Administration of tranquilizers Anti-seizure and myorelaxing action (depression of CNS structures, braking polysynaptic spinal reflexes) sybazon, fenazepam In a case of seizures of any etiology (epileptic status, tetanus, poisoning with seizure causing poisons) sibazon is introduced intravenously (intramuscularly) – 2 -4 ml of 0, 5 % solution repeatedly (maximum daily dose – 14 ml) To eliminate muscle tension in a case of radiculitis, arthritis, myositis, bursitis

Seizures (tetanus) drug of a first choice - Sibazon

SIDE EFFECT OF TRANQUILIZERS Psychological and physical addiction Prophylaxis: 1. Duration of treatment course should not be more than 2 months 2. Repeated course – not earlier than after 3 weeks break Sleepiness, reeling walk, retarded reactions tranquilizers should not be administered in ambulatories to people whose professions are connected with quick reactions Paradox reaction of excitation, insomnia Dizziness, decreasing of libido, disturbances of menstrual cycle Uncontrolled urination, defecation, ataxia, dysarthria Acute poisoning in case of overdosing

FLUMAZENIL (ANEXAT) ANTAGONIST OF TRANQUILIZERS

Combination of tranquilizers with alcohol-containing drinks is absolutely contraindicated (pathological alcohol intoxication)

SEDATIVE DRUGS Bromides Drugs of plant origin: valerian, dog nettle, melissa, passiflora etc. They do not cause addiction, somnolence, myorelaxation, ataxia

Valeriana

PASSIFLORA

Leonurus L. dog nettle

ADMINISTRATION OF SEDATIVE DRUGS Neurosis Neurasthenia Hysteria Increased irritability Insomnia Primary stages of essential hypertension

Bromism Cause – accumulation of bromide ions in organism in case of their prolonged administration as a result of material accumulation Symptoms: rhinitis, cough, conjunctivitis, skin rash, general weakness, memory disorders Treatment: sodium chloride (10 -20 g / day), a lot of drinking (3 -5 l / day), regular and frequent cleaning of skin and digestive tract

Hypnotic agents

DRUGS FOR GENERAL ANESTHESIA

General anesthesia = Narcosis (from the Greek narkosis – numbness, rigidity) – Generalized reversible depression of the central nervous system such that perception of all senses is ablated, condition which is characterized by loss of consciousness, pain feelings, depression of reflexes and relaxation of skeletal muscles and which is obtained by administration of drugs for general anesthesia

“Gentlemen, this is no humbug. ” 1846 TG Morton: First public demonstration of ether administration for excision of neck mass

CLASSIFICATION OF GENERAL ANESTHETICS Intravenous agents primarily used for induction • Barbiturates (Thiopental-sodium) • Benzodiazepines (Midasolam, diazepam) • Etomidate • Ketamine • Propofol • Propanidid • Sodium oxybutyrate • Predion

Unitary Hypothesis General anesthesia can be caused by a remarkable number of structurally diverse molecules

Molecular Mechanism(s) of General Anesthesia Xe Isoflurane Halothane . . . Molecular (lipids & receptors) Cellular (synapses)

Effects of General Anesthesia Low Dose Effects High Dose Effects • Amnesia • Deep sedation • Euphoria • Muscle relaxation • Analgesia • Diminished motor responses • Hypnosis • Diminished autonomic responses • Excitation • Hyperreflexia • Myocardial protection from ischemia • Cardiovascular/respiratory depression • Hypothermia

Measures of Anesthetic Potency • MAC: minimum alveolar concentration • MAC is the concentration of anesthetic that produces immobility in 50% of patients exposed to a noxious stimulus. • MACawake: MAC at which response to commands are lost • amnesia, loss of awareness • MACBAR: blunt autonomic response • MACintubation: response to intubation

Surgical interventions are performed on 1 st and 2 nd levels, approximately till half of 3 rd level of third stage of narcosis

Ftorothane (halothane) Power of narcosis action of ftorothan is higher than of ether, it has a large width of narcotic action, doesn’t irritate mucous membranes of breath tracts, doesn’t cause laryngeal and bronchial spasm, speed of development of narcosis – 3 -5 min. , after narcosis depression is not expressed Side effects and complications hypotension and cardiac arrest, sensitization (increased sensitivity) of myocardium towards catecholamines acute damage of liver – halothane hepatitis, teratogenic action

Nitrogenous oxide Small power and width of narcosis action, stage of excitation is present, quick entry and exit from narcosis (1 -2 min) Administration as an analgesic: pregnancy, teeth extraction, bandaging in case of burns, cleaning and revisions of wounds, iscemic heart attacks and myocardium infarction, colics, traumas, acute pancreatitis, pain relief in post-operative period

Induction Speed

Anesthetic of the Future: Xenon • Rare gas extracted from air • Very expensive to produce • Close to ideal anesthetic • Low blood and tissue solubility (rapid induction/recovery) • Potent • Not metabolized • Nonflammable • Minimal side effects

Drugs for noninhalative narcosis

Thiopental-sodium After administration of the drug narcosis develops in 1 -2 min. , awakening occurs in 20 -30 min. Administration introduction narcosis, basis narcosis, mononarcosis in case of short-lasting operative interventions (dentistry, gynecology, traumatology), anti-seizure drug. Side effects cough, laryngeal and bronchial spasm In case of rapid introduction – depression of centers of medulla oblongata. In case of contact of the drug with skin, it’s separation may occur, contact with nervous trunk or near it – irreversible paralysis, contact with an artery – thrombosis with the following gangrene of the extremity

Propanidid (sombrevin) Narcosis develops after 30 -40 sec from the beginning of intravenous introduction of the drug (“on the edge of the needle”). Stage of surgical narcosis lasts for 3 -4 min Administration for mononarcosis during short operative interventions in surgery, dentistry, gynecology, urology, painful diagnostic procedures, sometimes – for introduction into narcosis Side effects and complications Frequent breathing (tachypnoe) with the following stopping of breathing (apnoe), phlebitis and thrombosis in the place of introduction anaphylactic reactions

Sodium oxybutyrate in case of intravenous introduction narcosis develops after 15 -40 min. id administered orally sleep comes after 30 -60 min. duration of narcosis is 1, 5 -3 hours. It manifests antihypoxia properties Administration mononarcosis – to perform long-lasting surgeries but with small traumatic effect premedication, introduction and basis narcosis. drug of choice for narcosis in case of intoxications, sepsis, disturbance of functions of parenchymatous organs, analgesia during child-delivery. to decrease psycho-motor excitation, seizures, insomnia Side effects motor excitation seizure twitching of extremities and tongue vomiting hypopotassiumemia.

Ketamine hydrochloride (ketalar, kalipsol) During intravenous introduction of the drug narcosis develops after 1530 sec, lasts for 8 -10 min, during intramuscular introduction – after 2 -3 min, lasts for 20 -30 min Administration introduction and basis narcosis mononarcosis during surgeries which don’t need muscular relaxation as a part of combined narcosis Side effects during coming out of narcosis – unpleasant dreams, delirium, hallucination, seizures, nausea, vomiting, increasing of blood pressure, increasing of frequency and power of heart contractions The drug is able to raise intracranial pressure, oxygen consumption by brain and intraoccular pressure

PROPOFOL (DIPRIVAN) drug with ultra-short action Narcosis develops after 30 -40 sec after intravenous introduction, lasts for 3 -5 min Administration Mononarcosis Polycomponent narcosis Artificial ventilation of lungs Positive moments: can’t be accumulated, doesn’t have afternarcosis depression, possesses anti-vomiting action Negative moments: doesn’t have analgesic action (it is often combined with fentanil, ketamine), possible hypotension, short apnoe