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Drugs Suppressing

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Drugs Suppressing 1 NATIONAL PHARMACEUTICAL UNIVERSITY Department of Pharmacology Medicines suppressing the cental nervous system (CNS depressant) 2 Neuroleptics (ANTIPSYCHOTIC MEDICINES) Neuroleptics are psychotropic medicines that are able to reveal the inhibitory action on the CNS (without consciousness disturbing) eliminate hallucinations, delirium and stop the psychomotor excitation (motor and speech). 7 Classification of neuroleptics Derivatives of phenotiazine butyrophenone Thioxanthene *, dibenzodiazepine #, benzamide &, benzisoxazole $ Clozapine # Chlorpromazine Droperidol Chlorprothixene * Levomepromazine Haloperidol Sulpyrid & Perphenazine Risperidone $ hydrochloride 3 Pharmacological action Antipsychotic effect (elimination of delusions, aggression) is associated with blockade of dopaminergic D2 receptor reticular formation (removed activating influence on the cortex of the brain), nuclei, midbrain, limbic system, hypothalamus. With the same linked primary and side effects - extrapyramidal disorder, a syndrome similar to Parkinson's disease. Potential action is caused by blockade a-AR and reticular formation. Antiemetic effect is related to the blockade of dopaminergic (D2) and serotonin receptors "trigger zone“ of medula oblongata and termination of the signals in the emetic center. 4 The Hypothermic effect is the result of adreno- and serotonin receptors blockade and, therefore, decrease of the activity of the hypothalamic thermoregulation centres (decrease of the heat production and increase of the heat emission). The Antihistamine effect implemented by the blockade of H1- histamine receptors. The Hypotensive effect - the result of blockade of AR and a- dofaminoretseptors in the hypothalamus and peripheral vessels. The Neuroleptic (weakness, drowsiness, paralysis of will", motor inhibition) action - blockade of central and a-AR reticular formation, limbic system, hypothalamus. 5 Effects and related indications Pharmacodynamics (effects) → Indications Antipsychotic Psychosis (schizophrenia etc.) Potentiating Neuroleptanalgesia, potentiation (for medicines that suppress CNS) of narcosis Anti-emetic Uncontrolled vomiting of the central genesis (in pregnant women with anti-tumor therapy) Hypothermic Controlled hypothermia during narcosis Antihistaminic Severe neurodermitis Hypotensive Severe forms of arterial hypertension with psychomotor excitation (chlorpromazine only) 6 Side effects of typical neuroleptics and related contraindications Side effects → Contraindications Neuroleptic syndrome, drug- Depression, parkinsonism induced parkinsonism, dyspepsia Derivatives of phenotiazine, butyrophenone, thioxanthene called "typical" neuroleptics, as they lead to the development of medicinal parkinsonism ( D2 receptor in the black substance and striped body region)-extrapyramidal disorders. Risperidone, clozapine are atypical neuroleptics Atypical Antipsychotics, or Second Generation Antipsychotic Drugs These new medications were approved for use in the 1990s. Clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine, and aripiprazole are atypical antipsychotic drugs. With the discovery of clozapine in 1959, it became evident that this drug was less likely to produce extrapyramidal effects (physical symptoms such as tremors, paranoia, anxiety, dystonia, etc. as a result of improper doses or adverse reactions to this class of drug) in humans at clinically effective doses than some other types of antipsychotics. Clozapine was categorized as the first atypical antipsychotic drug. This category of drugs has also been of great value in studying the pathophysiology of schizophrenia and other psychoses. 8 The pharmacological “face” of neuroleptics Antipsychotic effect : Haloperidol Droperidol Closapine Chlorprothixene = Chlorpromazine =Perphenazine hydrochloride=Sulpyrid Levomepromazine Potentiating effect: Haloperidol Droperidol Levomepromazine Chlorpromazine. Anti-emetic effect : Haloperidol Perphenazine hydrochloride Droperidol Sulpyrid Chlorpromazine Neuroleptic effect : Derivatives of phenothiazine = butyrophenone thioxanthene Closapine Sulpyrid. 9 TRANQUILIZERS (ANXIOLYTICS, ATARACTICS, ANTIPHOBIC MEDICINES) Tranquilizers (in Latin tranquillare – „to make calm”) are medicines that remove selectively fair, anxiety, emotional tension increased restlessness and are used mainly in neuroses and the related states. 14 Classification of tranquilizers Derivatives of benzodiazepines Derivatives of diphenylmetanum and other chemical groups Diazepan Alprazolam Hydroxysine* Phenazepam Lorazepam Meprobamat Chlordiazepoxide Gidazepam Medazepam, Gidazepam, Trimetosine are “day time” tranquilizers as they cause less inhibition of CNS than other medicines, therefore,they can be used in day time. 10 The mechanism of action They decrease the excitability of subcortical regions of the brain (the limbic system, thalamus, the reticular formation, the hypothalamus), that are responsible for emotional reactions, inhibit the interaction between these structures and the brain cortex. Benzodiazepines stimulate mainly benzodiazepine receptors and that leads to activation of GABA-receptors and intensification of the inhibitory functions of GABA . 11 Benzodiazepines GABA Extracellular compartment Membrane Ion of neuron channel Cytoplasm The mechanism of Benzodiazepines action 12 Effects and related indications Pharmacodynamics (effects) → Indications Аnxiolytic Neuroses Stress-protective Stress-reaction Hypnotic Insomnia (especially caused by negative emotions) Sedative Neurogenic diseases Anticonvulsant Convulsions (epilepsy) Potentiating Premedication 13 Side effects and related contraindications Side effects → Contraindications Drowsiness, weakness, Activities that require rapid disorders of attention and psychomotor reactions. Long- locomotion, tolerance, addiction term courses of treatment. Increase of doses 15 The pharmacological «face» of tranquilizers Medicines Tranquili- Addiction/ Side Other effects zing effect tolerance effects Phenazepam ++++ +/+ + Anticonvulsant, hypnotic, sedative, spasmolytic (diazepam) Diazepam +++ +/+ ++ Chlordiaze- ++ +/+ + poxide Lorazepam ++ - + Accumulation, anticonvulsant, hypnotic Alprazolam + - + Anticonvulsant, antidepressant Gidazepam + - Anticonvulsant, potentiating, stimulating Hydroxysi- - + Analgesic, myorelaxant, antiemic ne Meproba- + ++/+ ++ Anticonvulsant mat 16 Sedative Medicines Sedative medicines (in Latin sedatio is calming) are medicines that cause a moderate sedative effect as a result of decrease of CNS excitability and its reactivity of different stimuli The mechanism of action They increase of the inhibitory processes in the CNS and decrease of the excitability of the reticular formation and the brain cortex. 19 Classification of medicines Plant Bromide compounds * origin and Combined ** Persenum** Sodium bromide* Valerian extract Corvalol** (Valocordin) Novo-passit** Valocormide** 17 Effects and related indications Pharmacodynamics (effects) → Indications Sedative Neuroses, increased irritability, neurogenic disease, insomnia Stress-protective Stress-reaction Potentiating Intensification of effects of CNS depressants, the early stage of hypertension Side effects → Contraindications Decrease of the mental and Activities that require rapid physical activity, feeling of psychomotor reactions fatigue, drowsiness 18 The features of sedative medicines is the lack of significant side effects because they are widely used in outpatient practice and in elderly patients. At long use drugs generates bromine "bromizm": general retardation, drowsiness, weakening of memory, apathy, decreased potency, tearing, cough, running nose, skin rash. Treatment: immediately stop taking the drug, the introduction of large numbers of sodium chloride (20 g per day) and need to drink a lot. 20 Pharmacological «face» of sedative drugs Preparations Effects Composition/other effects Sedative Spasmolytic Sodium +++ Anticonvulsant bromide Urticae ++ Canine Tincture Valerian + + Spasmolytic extract Persen + + Mint, Melissa Corvalol ++ + Phenobarbital, mint oil Valocordin + + Sodium bromide, Convallaria, Belladonna, Menthol Novo-passit ++ + Guaphenesine, extracts of Crataegus, Humulus, Hypericum, Milissa, Passiflora, Sambucus 21 Hypnotic medicines Disorders of sleep (insomnia, hyposomnia) are one of the states that are common and occur independently (primary insomnia), and at the different somatic and psychiatric pathologies (the secondary insomnia). If the sleep disorder is repeated more than 4 times a week, which requires pharmacological correction as insomnia (violation of physiological rhythms in the CNS) leads to overexcited, fatigue, exhaustion of the brain and, consequently, to different forms of pathology of neurogenic origin. Hypnotics are products that tend to restore the process of falling asleep, sleep duration and depth of their violation. 22 The mechanism of action of sedative medicines Inhibit some brain structures (mainly cerebral cortex). Weaken the activating reticular formation of the discharges in the cerebral cortex. In the mechanism of action of benzodiazepine and barbituric acid an important part plays their relationship with benzodiazepine receptors and barbiturate-benzodiazepine-GABA receptor complex, leading to strengthening of the natural inhibitory neurotransmitter GABA (gamma amino butyric acid) 23 Hypnotics Pharmacodynamics (effects) → Indications Hypnotic Disorder of sleep Potentiating Intensification of the effects of CNS depressants Sedative(low
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