CNS Pharmacology Drugs - PowerPoint Presentation

1. CNS PharmacologyDrugs which depress central nervous system (CNS)Lecture №3

2. Central nervous system

3. Neuron

4. Central neurotransmittersBiogenic amines: dopamine, nor-adrenaline, adrenaline, serotonin, histamineAcetylcholine; mainly excitatory (e) in CNS vs., inhibitory (i) effects in the PNSAmino acids: GABA (i), glycine (i), glutamate (e), aspartate (e)Neuropeptides: vasopressin, oxytocin, endorphins, enkephalinesPurine nucleotides: adenosine, ATPNeurolipids: anandamide, 2-arachidonoyl glycerol, ceramide

5. Drug act in cnsDrug which depress CNSDrug which stimulate CNSDrug for narcosisHypnotic drugsNeurolepticTranquilizersSedative drugAnalgesics PsychostimulantsAntidepressantsNootropic drugAnalepticAdaptogens

6. Drugs for narcosis Narcosis Greek word ναρκωσις (narcosis) is derived from narke, is a state of drug-induced reversible inhibition of central nervous function, during which surgical procedures can be carried out in the absence of consciousness, responsiveness to pain, defensive or involuntary movements, and significant autonomic reflex responses.Main characteristic:Loss of consciousnessPain feelingsDepression of reflexesRelaxation of skeletal musclesPostnarcosis amnesia

7. Drugs for narcosisCharacteristics of the ideal anestheticRapid, pleasant induction and recovery of anesthesiaRapid changes in the depth of anesthesiaAdequate skeletal muscle relaxation to perform surgeryProduction of amnesiaAbility to provide analgesiaA wide safety marginNontoxic

8. General anestheticsInhalational agentsInjectable agents The modern practice of anesthesiology relies on the use of combinationsof intravenous and inhaled drugs ( balanced anesthesia techniques) to take advantage of the favorable properties of each agent while minimizing their adverse effects. The choice of anesthetic technique is determined by the type of diagnostic, therapeutic,or surgical intervention to be performed.

9. General anestheticsInhalational agentsInhalation Anesthetics : - gases:Nitrogenium oxydulatum - volatile liquids: Aether pro narcosi, Ftorotanum, Halotanum SevfluranumInhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration and, because of their rapid elimination, they do not contribute to postoperative respiratory depression.

10. Ether for narcosisNarcosis develops after 10-20 min, stage of excitation - 10-20 min, strongly expressed after-narcosis depression, high width of narcosis actionSide effects and complicationsbright stage of excitationIncreasing of tone of n. vagiIncreasing of secretion of salivary, bronchial glands, coughing; laryngospasm, bronschospasm, vomiting with the following aspiration of the masses bradycardia, stop of heart beatIncreasing of tone of sympathetic nervous systemTachycardia, hyperglycemia

11. Ftorotan (galotan)Power of narcosis action of ftorotan is higher than of ether, it has a large width of narcosis 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 expressedSide effects and complicationshypotension and heart stop,sensibilization (increased sensitivity) of myocardium towards catecholamines acute damage of liver – halothane hepatitis,teratogenic action

12. Nitrogen oxideSmall 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, traumas, burns, attacks of stenocardia and myocardium infarction, colics,pain relieving in post-operative period

13. XenonXenon interacts with many different receptors and ion channels, and like many theoretically multi-modal inhalation anesthetics, these interactions are likely complementary. Xenon is a high-affinity glycine-site NMDA receptor antagonist. However, xenon is different from certain other NMDA receptor antagonists in that it is not neurotoxic and it inhibits the neurotoxicity of ketamine and nitrous oxide, while actually producing neuroprotective effects.  Xenon inhibits nicotinic acetylcholine α4β2,   plasma membrane Ca2+ ATPase,  5-HT3 receptor. While neither anesthetic nor antinociceptive, this reduces anesthesia-emergent nausea and vomiting.Xenon has a minimum alveolar concentration (MAC) of 72% at age 40, making it 44% more potent than N2O as an anesthetic. Thus, it can be used with oxygen in concentrations that have a lower risk of hypoxia.

14. Intravenous Anesthetics:Short-acting drugs (10- 15 min):- Ketaminum (Kalipsol, Ketanest)- Propofol (Diprivan)- Propanididum (Sombrevin) Drugs with medim duration of action (20 - 50 min): - Thiopental-natrium Long-acting drugs: - Natrii oxybutyrasCause rapid loss of consciousness and induction is pleasant. However, they produce little muscle relaxation and frequently do not obtund reflexes adequately. Repeated administration results in accumulation and prolongs the recovery time. Since these agents have little if any analgesic activity, they are seldom used alone except in brief minor procedures.

15. Thiopental-natriumAfter 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 effectscough, laryngeal and bronchial spasmIn 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 – nonreversible paralysis, contact with an artery – thrombosis with the following gangrene of the extremity

16. KETAMINUM (KALIPSOL, KETANEST)Ketamine hydrochloride injection is indicated as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation. Ketamine hydrochloride injection is best suited for short procedures but it can be used, with additional doses, for longer procedures.Usual Adult Dose for AnesthesiaIV:-Induction: 1 to 4.5 mg/kg IV; alternatively, 1 to 2 mg/kg IV at a rate of 0.5 mg/kg/min; (2 mg/kg dose provides 5 to 10 minutes of surgical anesthesia within 30 seconds)IM:-Induction: 6.5 to 13 mg/kg IV; (9 to 13 mg/kg IV provides 12 to 25 minutes of surgical anesthesia)-Maintenance: The maintenance dose should be adjusted according to the patient's anesthetic needs and whether an additional anesthetic is employed. Increments of one-half to the full induction dose may be repeated as needed for maintenance of anesthesia.

17. Propofol (Diprivan) Usual Adult Dose for AnesthesiaMost adult patients under 55 years of age and classified as ASA-PS I or II require 2 to 2.5 mg/kg of Propofol injectable emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol injectable emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia.Propofol is an intravenous sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of Propofol induces hypnosis with minimal excitation, usually within 40 seconds from the start of injection (the time for one arm-brain circulation)

18. Preanesthetics medication“It is the term applied to the administration of drugs prior to general anaesthesia so as to make anaesthesia safer for the patient” & to minimize adverse effects of anaesthesiaAIMS:Relief of anxiety & apprehension preoperatively & facilitate smooth induction Amnesia for pre- & post-operative events Potentiate action of anaesthetics, so less dose is neededAntiemetic effect extending to postoperative period Decrease secretions & vagal stimulation caused by anaesthetics Decrease acidity & volume of gastric juice to prevent reflux & aspiration pneumonia

19. Drugs use for premedicationМ-cholinoblockersAtropini sulfasNarcotic analgesicsMorphini hydrochloridum, Promedolum AntihistaminicDimedrolum, SuprastinumTranquilizersDiazepamumDecrease secretion of salivary glandsProphylaxis of laryngo- and bronchospasmProphylaxis of vagotony Potentiation of drugs for nacrosis Prophylaxis of allergic reactionsDecrease of anxiety, potentiation of nacrosis

20. NEUROLEPTANALGESIA – special type of general analgesia which include neuroleptic (droperidol) and narcotic analgesic (fentanil). Combined drug is talamonalMain peculiaritiesLow toxicityPotent antishock actionEvident antivomiting effectStability of hemodynamicsRapid onset (1-3 min), rapid termination of action (20-30 min)Usage:Extensive traumas, burns (the prophylactic of pain shock)Myocardium infarctionInitial narcosis

21. Hypnotic drugsThese drugs are able to cause sedation (with concomitant relief of anxiety) or to encourage sleep. Chemical classes of sedative-hypnoticsBarbiturates: Hexobarbital, Phenobarbital, Thiopental.Benzodiazepines: Chlordiazepoxide, Diazepam, Nitrazepam, OxazepamCarbamates: MeprobamateQuinazolones: MethaqualoneAlcohols: Ethanol

22. Sleep phases

23. Hypnotic drugstherapeutic classificationSedative/HypnoticsLormetazepam,Temazepam,Nitrazepam,FlurazepamAnxiolyticsDiazepam,Oxazepam,LorazepamAnticonvulsantsDiazepam,Nitrazepam,ClonazepamLorazepamCentral muscle relaxantsDiazepam,Flurazepam,Clonazepam

24. Hypnotic drugsIndication for usage of hypnotic drugsFor relief of anxietyFor sedation and amnesia before medical and surgical proceduresTreatment of epilepsy and seizure states.Premedication prior to anesthesiaIntravenous administration, as a component of balanced anesthesiaFor control of ethanol or other sedative hypnotic withdrawal statesFor muscle relaxation in specific neuromuscular disorders

25. Adverse effects of hypnotic drugsCNS – drowsiness, impaired concentration, mental and physical sluggishnessDrug hangover: hypnotic doses produce a feeling of tiredness well after the patient awakes. This drug hangover leads to impaired ability to function normally for many hours after waking. Occasionally, nausea and dizziness occurs.Precautions. Barbiturates induce the P-450 system and therefore may decrease the effect of drug that metabolized by these hepatic enzymes. Addiction. Abrupt withdrawal from barbiturates may cause tremors, anxiety, weakness, restlessness, nausea and cardiac arrest. Drug dependence (physiological and psychological). Poisoning leads to severe depression of respiration and central cardiovascular depression.

26. antiseizure drugsClassification of seizure types. Partial seizuresSimple partial seizuresComplex partial seizuresPartial seizures secondarily generalized Generalized seizuresGeneralized tonic-clonic (grand mal) seizuresAbsence (petit mal) seizuresTonic seizuresAtonic seizuresClonic and myoclonic seizures

27. antiseizure drugs by groupsAMPA receptor antagonistsBarbiturate anticonvulsantsBenzodiazepine anticonvulsantsCarbamate anticonvulsantsCarbonic anhydrase inhibitor anticonvulsantsDibenzazepine anticonvulsantsFatty acid derivative anticonvulsantsGamma-aminobutyric acid analogsGamma-aminobutyric acid reuptake inhibitorsHydantoin anticonvulsantsMiscellaneous anticonvulsantsNeuronal potassium channel openersOxazolidinedione anticonvulsantsPyrrolidine anticonvulsantsSuccinimide anticonvulsantsTriazine anticonvulsants

28. antiseizure drugs by diseaseAntiepilepticСarbamazepinum (Finlepsin, Tegretol)Ethosuximidum (Suxilep) Natrii valproas (Convulex)AntiparkinsonicDopaniergic system activatorsLevodopaMіdantanumNakomCentral cholinoblockersCyclodolum (Parkopan)

29. antiparkinsonic drugs Parkinson’s disease (PD) is a progressive neurodegenerative disorder. It is caused by degeneration of substantia nigra in themidbrain, and consequent loss of DA-containing neurons in thenigrostrial pathway. Two balanced systems are important in theextrapyramidal control of motor activity at the level of the corpus striatum and substantia nigra; in the first the neurotransmitter isACh, in the second – DA.

30. antiparkinsonic drugs classificationDrugs acting on dopaminergic system:Dopamine precursors – Levodopa (l-dopa)Peripheral decarboxylase inhibitors – carbidopa andbenserazideDopaminergic agonists: Bromocriptyne, Ropinirole andPramipexoleMAO-B inhibitors – Selegiline, RasagilineCOMT inhibitors – Entacapone, TolcaponeDopamine facilitator - AmantadineDrugs acting on cholinergic systemCentral anticholinergics – Teihexyphenidyl (Benzhexol),Procyclidine, BiperidenAntihistaminics – Orphenadrine, Promethazine

31. antiparkinsonic drugs classificationDopamine and Tyrosine Are Not Used for Parkinson Disease Therapy, Why?Dopamine Doesn't Cross the Blood Brain BarrierHuge amount of tyrosine decreases activity of rate limiting enzyme Tyrosine Hydroxylase

32. NeurolepticsAntipsychotics, also known as neuroleptics or major tranquilizers, are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. They are increasingly being used in the management of non-psychotic disorders. Antipsychotics are usually effective in relieving symptoms of psychosis in the short term.Main effect: Antipsychotic – they reduce main symptoms of psychosis (delirium, hallucination, psychomotor activity). These drugs also have a calming effect & they keep consciousness

33. Classification of neurolepticsDerivatives of phenotiazine: aminasine, triftazine, etaperasine,Derivatives of tioxanten: chlorprotixenDerivatives of butyrophenon: haloperidol, droperidolDerivatives of piperasine-dibenzodiazepine: clozapineDerivatives of indole: reserpin, sulpyrid (eglonil)“Typical” – derivatives of phenotiazine, tioxanten, butyrophenon – they cause disorders of extrapyramidal system function – syndrome of parkinsonism “Atypical” – derivatives of indole, piperasine-dibenzodiazepine – they cause those negative reactions very rarely

34. The mechanism of action of neuroleptics1. Block a adreno-, dopamino-, cholino-, histamino- and serotoninergic receptors.Typical antipsychotics block postsynaptic dopamine receptors in the limbic system and increase dopamine turnover by blockade of the D2 receptor. The decrease in dopamine neurotransmission has been correlated to the antipsychotic effects of the phenothiazines. This D2 blockade is also responsible for their extrapyramidal and antiemetic effects.2. Decrease the permeability of cell membranes for electrolytes 3. They inhibit the enzyme tyrozine-hydroxylase, which convert aminoacid tyrosine to DOPA, one of the precursors of main mediators dopamine and norepinephrine.4. They inhibit the calmoduline activity. This enzyme converts Са++ into its active form, and influence on the main processes in the cells.5. They decrease the release of exciting aminoacids which can interfered with NMDA receptors and have activating action on the neurons.

35. Use of antipsychotic activity of neuroleptics Treatment of psychosesschizophrenia manic-depressive psychosis alcoholic psychosis reactive psychosis psychomotor agitation of different etiologyUsed for potentiation of action of hypnotic, narcotic and nonnarcotic analgesics, drugs for narcosis, local anesthetics, neuroleptanalgesia.Anti-emetic action (elimination of vomiting of central genesis): brain tumors, radial and chemical therapy, intestinal impassability, intoxication with heart glycosides, apomorphine and other drugsDecreasing of body temperature in case of hypothermiaDecreasing of blood pressure (alpha-adrenoblocking properties – aminasine, droperidol) – in case of hypertensive crisis, lungs edemaComplex treatment of epilepsy (myorelaxation of skeletal muscles) In combination with narcotic analgetics for treatment of chronic pain with severe anxiety.

36. Adverse effects of neurolepticsExtrapyramidal disorders: muscular hypertonus, general constraint, tremor of hands, tongue, mandible, head, seizure contractions of muscles, vegetative crisis (For treatment – cyclodol (levodopa is contraindicated)Orthostatic collapseDyspeptic disorders: anorexia, changes of tasteAbdominal painDamage of the liver (cholestasis)Granulocytopenia (especially clozapin)Hyperglycemia, dysmenorrhea, galactorrhea, gynecomastia, impotenceAminasine has a considerable irritable action

37. TranquilizersA tranquilizer is a drug that acts on the central nervous system and is used to calm, decrease anxiety, or help a person to sleep. Often called depressants because they suppress the central nervous system and slow the body down, they are used to treat mental illness as well as common anxiety and sleeplessness. Available only by prescription, they can cause dependence and certain ones can easily be abused.

38. TranquilizersAnxiolytic actionTreatment of neurosis, accompanied by fear, anxiety, tenseness, increased irritability, insomniaIn case of headache and heartache of neurotic origin, so called organic neurosisIn case of abstinence in alcohol and drugs addictsIn case of diencephal crisis (sibazon)Tranquilizers do not eliminate productive symptoms of psychosis!Hypnotic action – they cause sleep, which is very close to physiological one according to its parameters (Nitrazepam, Phenazepam, Diazepam, Chlozepid

39. Indication for usage of TranquilizersDepression of CNS – for atharalgesia (Sibazon, Midazolam)Anti-seizure and myorelaxing action (depression of CNS structures, braking polysynaptic spinal reflexes) - Sibazon, PhenazepamIn case of seizures of any etiology (epileptic status, tetanus, poisoning with seizure causing poisons) Sibazon is introduced i.v (i.m.) – 2-4 ml of 0,5% solution To eliminate muscular tension in case of radiculitis, arthritis, myositis bursitis – drugs which practically don’t have myorelaxing properties

40. Adverse effects of TranquilizersPsychological and physical dependence Prophylaxis: Duration of treatment course should not be more than 2 months Repeated course – not earlier than after 3 weeksSleepiness, reeling walk, retarded reactions Tranquilizers should not be administered in ambulatories to people whose professions are connected with quick reactionsParadox reaction of excitation, insomniaDizziness, decreasing of libido, disturbances of menstrual cycle Uncontrolled urination, defecation, ataxia, dysartria Acute poisoning in case of overdosing

41. “day” TranquilizersGidazepamMezapam (rudotel)Grandaxyn (tophizopam)TrioxazynBuspyron

42. Sedative drugDrugs which increase inhibition processes and decrease excitation processes in brain cortex and thus cause calming effect on the CNSBromides (KBr, NaBr)Drugs of plant origin: valerian, dog nettle, melissa, pasiflora etc.Combine drugs: Corvalolum, Novo-pasit, PersenThey do not cause addiction, somnolence, myorelaxation, ataxia

43. Indication for usage of sedative drugsNeurosesNeurastheniaHysteria HyperexcitabilityInsomniaInitial stages of hypertony, ischemia, tachycardia

44. Thank for your attention