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Home , Benzobarbital, Droperidol, Gidazepam

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NATIONAL PHARMACEUTICAL UNIVERSITY Department of Pharmacology

Medicines suppressing the cental nervous system (CNS depressant) 2

Neuroleptics ( 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 *, dibenzodiazepine #, &, $

Clozapine # Droperidol * Sulpyrid & $ hydrochloride 3

Pharmacological action Antipsychotic effect (elimination of delusions, aggression) is associated with blockade of 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 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 effect implemented by the blockade of H1- 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, are atypical neuroleptics Atypical , or Second Generation Antipsychotic Drugs

These new were approved for use in the 1990s. Clozapine, , , , , risperidone, , , , and are 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, , 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 = butyrophenone  thioxanthene  Closapine  Sulpyrid. 9

TRANQUILIZERS (, 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 Derivatives of diphenylmetanum and other chemical groups

Diazepan Hydroxysine* Meprobamat

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 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 ()

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 ++++ +/+ + , , , spasmolytic () Diazepam +++ +/+ ++ Chlordiaze- ++ +/+ + poxide Lorazepam ++ - + Accumulation, anticonvulsant, hypnotic

Alprazolam + - + Anticonvulsant,

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 compounds * origin and Combined **

Persenum** * 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 ++ + , mint oil

Valocordin + + Sodium bromide, Convallaria, Belladonna, 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. 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 -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 doses) Mild neuroses, neurotic syndrome

Side effects → Contraindications Apathy, drowsiness, weakness Activities that require the rapid psychomotor reactions Most sleeping drugs causes the violation of the structure sleep syndrome "aftereffect", "return", “withdrawal", physical and psychological dependence, addiction, cummulation (especially ). Closest to the ideal of sleeping drugs - zopiklon and . 24

Classification of medicines

Derivatives of Derivatives of Combined medicines benzodiazepine, cyclopyrrolone, barbituric acid ,* methylbutamide** Nitrozepam Reladorm Phenobarbital  Zolpidem* ( + Cyclobarbital* ** diazepam) 25

The pharmacological «face» of hypnotic medicines Phenobarbital  reladorm  bromisoval zolpidem = zopiclon 

Medicines Sleep Accu- Addiction Effective in disorder of Withdra- Disorder After duration mulati wal of the action -on Falling Sleep sleep asleep duration phases Phenobarbital 8-10 +++ +++ + + +++ + +++ Cyclobarbital 5-6 ++ +++ + +++ + ++ Nitrazepam 6-8 + ++ + + ++ + ++ Zopiderm 6-8 - + + + -  

Zopiclone 6 - + + -  

Bromisoval 6 ++ - + -  ++

Reladorm 6 ++ +++ + + +++  ++ 27

Anticonvulsants Anticonvulsant medicines decrease or stop convulsions in pathological states of the organism

Mechanism of action Inhibition the pathological activity of neurons in epileptic foci of motor cortex areas and subcortical structures by reducing the utilization of O2, energetic and exciting action of amino acids (glutaminum and aspartamum), blocking Ca- and Na-channels in the epileptic foci, stimulation of GABA- ergic inhibitory mechanisms 30

Classification

Benzodiazepines Valproates Barbiturates

Diazepam Valproic acid Phenobarbital

Succinimides Iminostilbens Others

Ethosuccimide Tolperizone 28 Effects and related indications

Pharmacodynamics (effects) → Indications

Anticonvulsant effect Convulsions of different origin (epilepsy, craniocerebral traumas, tumours of the CNS, meningitis)

Side effects → Contraindications

CNS inhibition, mental confusion, Activities that require attention, drowsiness, depression, tolerance depression 29

The principles of correct usage of : - Individually assemble the necessary combination of drugs; - Increase the dose gradually; - Evaluate the effectiveness of drugs in a few weeks of treatment (number of convulsions should decrease by 50%); - If necessary to make the gradual replacement of one drug, reducing its dose, the second (in increasing doses); - Conduct continuous therapy (discontinuation of the drug allowed after 4-5 years in the absence of pathological changes in electroencephalogram). 34

Antiparkinsonian medicines Pharmacodynamics (effects) → Indications Antiparksionian effect Parkinsons desease, Parkinson syndrome

Side effects → Contraindications Antiholynergic tachycardia glaucoma, constipation

Dophaminenergic psychosis

Antiglutamatergic Epilepsy,

All medications must be taken with brief intervals (1-2 days / week) for the prevention of tolerance (habituation). 31

The pharmacological «face» of anticonvulsants Medicines Convulsive attacks: Epyleptic status SE Other effects g\s Benzobarbital + - + Sedative, hypnotic - Phenobarbital + + ++ - Diazepam  + +++ Sedative, hypnotic, - tranquilizing Clonazepam + + ++ + Carbamazepine + - +++ Antidepressant, - normothymic, analgesic Valproic acid + - + + Ethosuccimide - - + Tranquilizing, analgesic + Tolperizone - - + Sedative, hypnotic + 33 Drugs for parkinsonism treatment Drugs used to treat Parkinson disease and syndrome of parkinsonism, including medicinal parkinsonism. Mechanism of action At these diseases in the CNS is disturbed balance of neurotransmitters: the quantity of and content is increased. These means restoring the balance between dopaminergic and cholinergic brain systems. The mechanism of action of drugs are divided into: I. - blocking the central (reducing the influence of acetylcholine in the CNS) and peripheral M-cholinoreceptors. II. Dopaminergic - restore the dopamine deficiency in the CNS. III. Antyglutamatergic - reduce the exciting action of glutamate neurons in the CNS, which develop on the background of dopaminergic system failure. 35

Classification of medicines

Anticholinergic Dophaminer- Antiglutamatergic (cholinolytic) gic ones ones

Trihexiphenydil Levodopa Levodopa + carbidopa (Nacom) Selegiline 32 Mechanism of action CNS Dopaminergic ending

Levodopa Levodopa

DOPA decarboxylase

Dopamine

Selegiline

Dopamine release Amantadine Dopamine reuptake Bromocriptine

Amantadine

Postsinaptic D2-receptors 36

The pharmacological «face» of antiparkinsonian medicines

Medicines Antiparkinsonian Side Other effects effect effects

Levodopa +++ + The maximum effect in a month.Little impact on the autonomic and mental disorders, a characteristic (gold standard phenomenon of "inclusion and exclusion" therapy)

Nacom + +, Combination: levodopa, carbidopa. The effect is rapid, (briefly) tolerance less toxic Selegiline ++ + Antidepressant.The need to combine with levodopa or nakomom Trihexilphe- + ++ Cholinolytic nydil Amantadine + +, Cholinolytic, antiviral tolerance Thank you!