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Cholinotpopic Drugs

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Cholinotpopic Drugs Lecture №1 Introduction in pharmacology. Cholinotpopic drugs Lector: Head of the pharmacology department, doctor of medicine Voloshchuk Nataliya Ivanovna Sciences about medicines «Pharmacology” - “Pharmacy” - Part of the medical science Part of the medical science which study which study preparing action and and identification the drugs introduction of drugs Sciences about medicines PHARMACY PHARMACOLOGY Pharmacognosy PRESCRIPTION Pharmaceutical chemistry GENERAL Pharmaceutical analysis PRIVATE (special) Pharmaceutical technology CLINICAL The organization and economic of pharmacy Pharmacology is medical and biological science which uses experimental researches (on animals) and clinical trials (on volunteers and patients) and study the action of medicines (drugs) on the human organism, mechanisms of the drugs-organism interaction. The main problems of pharmacology: Pharmacology takes part in the synthesis of medicines (drugs). Pharmacology establishes action and studies mechanisms of action of medicines and biologically active substances on a human body and animals. Pharmacology investigates mechanisms of drugs-organism interaction, i.e. pharmacodynamics and pharmacokinetics of preparations in experiment and clinical practice. Pharmacology defines and scientifically proves contra-indications and indications to medical application of drugs for the purpose of prophylactic and treatment of diseases. The general classification of drugs Drugs, influence the Drugs, influence the peripheral effector organs nervous system Drugs, influence the central Antimicrobic and nervous system antiparasital drugs Drugs, influence the metabolic processes Drugs, influence the peripharal nervous system Pharmacology of cholinotropic drugs central peripheral nervous system nervous system (CNS) efferent afferent autonomic somatic (vegetative) sympathetic parasympathetic Efferent nervous fibres supply skeletal muscles – somatic; regulate funtions of internal organs - vegetative Synaps - is a place of contact of long fibre ending (axon) of one neuron with a body of other one or cell of active organ (effector cell) Anatomical differences of parasympathetic nervous system versus sympathetic 1. The place of outlet from CNS Parasympathetic: Cranial part of CNS - III - n. oculomotorius VII - n.facialis (chorda tympany) IХ - n. glossopharyngeus Х - n. vagus; Sacral: n.pelvicus Sympathetic: Thoraco-lumbalis (truncus sympathicus) 2. The place of the ganglia’s localization, and the length of the pre- and postganglionic fibers Parasympathetic ganglia are in or near the wall of the innervated organ, parasympathetic preganglionic nerves are long and postganglionic ones are short. Sympayhetic ganglia are near the spinal cord; therefore, preganglionic fibers are short and postganglionic fibers are long. Physiological differences Sympathetic and parasympathetic actions often oppose each other Кафедра фармакологии и клинической фармакологии ДГМА - 2007 CholinergicCholinergic synapsesynapse NaNa++ CholinCholin AcetylAcetyl--CoCoАА ++ CholinCholin CholinacetylaseCholinacetylase AcetylcholineAcetylcholine CaCa2+2+ АCh, АТФ, Р PresynapticPresynaptic CholineCholine++AcetasAcetas Acethylcholine membranemembrane AcethylcholinesteraseAcethylcholinesterase КК++ NaNa++ ММ--,, NN--cholinoreceptorscholinoreceptors ofof postsynapticpostsynaptic membranemembrane Classification of cholinoreceptors М-ch.r N-ch.r (muscarinic) (nicotinic) Excitation of these receptors with ACh or cholinomimetics stimulates the main functions of cells, tissues, organs Blockade of these receptors causes the opposite effect: decreases all these functions М-ch.r.. CNS N-ch.r. N-ch.r. N-ch r. N-ch.r. adrenoreceptors М-ch.r.. Localisation of cholinoreceptors М-cholinoreceptors localized: miocardium, smooth muscles of bronchi, stomach, intestine, uterus, urine bladder, internal muscles of the eye in the exocrine glands: (bronchial, lachrymal glands, salivary glands, glands of GIT In the central nervous system М-ch.r.. CNS N-ch.r. N-ch.r. N-ch r. N-ch.r. adrenoreceptors М-ch.r.. N-cholinoreceptors localized: Sympathetic and parasympathetic ganglias Neuro-muscular synapses (skeletal muscles) Central nervous system Classification of cholinergic drugs 1. M-, N-cholinomimetics (Acetylcholinum) 2. Anticholinesterase drugs (Proserinum, Galanthamini hydrobromidum, Pirydostygmini bromidum) 3. M-, N- cholinoblockers (Cyclodol) 4. M-cholinomimetics (Pilocarpini hydrochloridum) 5. M-cholinoblockers (Atropini sulfas, Platyphyllini hydrotartras) 6. N-cholinomimetics (Cytitonum, Lobelinum); 7. N-cholinoblockers: а) ganglionblockers (Benzohexonium, Pentaminum); б) myorelaxants (Tubocurarini chloridum, Dithylinum) M-, N- cholinomimetics Acetylcholinum Сholini alfosceras (Gliaton, Cereton) Cholinomimetic with central action on the CNS Mechanism of action: Indications for use: Being introduct into the . Acute period of brain organism destroys to the trauma CHOLINE (takes part in the . Distrophic-degenerative biosynthesis of acetylcholine) and GLICEROPHOSPHATE syndromes (precursor of . involution changes of CNS phosphatidylcholine) . Cerebro-vascular • Improve nerve transmission insufficiency in cholinergic synapses Side effects: • Improve cerebral blood circulation, metabolic Nausea, stomachache, processes in the brain, conscious disturbances restore conscious during (seldom) brain traumas M-, N- cholinoblockers Amizyl Cyclodol Cyclodol Anticholinergic drug, preferably blocks central N-cholinoreceptors and peripheral M-cholinoreceptors Usage Parcіnson’s disease, medicamentous parcinsonism M-cholinergic drugs M- cholinomimetics M-cholinomimetics Pilocarpini hydrochloridum Aceclidinum Рilocarpini hydrochloridum Pharmacodinamics Contraction of pupil, improvement of outflow of intraocular liquid and relief intraocular pressure Dilation of eye vessels Usage Treatment of glaucoma Improvement of eye nutrition in a case of thrombosis of retinal central vein, acute obstruction of retinal arteries, optic nerve atrophy Systemic (resorbtive) action of the drug is not used because of its high toxicity. The most dangerous manifestation of poisoning with pilocarpinum is edema of lungs Aceclidinum Pharmacodinamics Miosis, decrease of intraocular pressure, spasm of accomodation Increase of tonus and peristalsis of smooth muscles of digestive tract organs, urinary bladder Increase of tonus of uterus and bronchial muscles Usage treatment of glaucoma prophylaxis and treatment of postoperative atony of stomach, intestines, urinary bladder stopping of post delivery uterus bleedings The drug is contraindicated in case of bronchial asthma, pregnancy, stenocardia Acute poisoning with substances of M-cholinomimetic action (overdosing of drugs, consumption of mushrooms) Clinical signs diarrhea, stomachache contraction of pupils, disorders of accomodation increasing of salivation, vomiting disorders of breathing because of bronchial spasm confusion, consciousness, seizures, coma Treatment measures for organism purifying form poison intravenous introduction of 0,1 % Atropine sulfate solution – 2 ml every 10 min. (until appearance of dryness in mouth and dilation of pupils) symptomatic treatment N-cholinergic drugs N-cholinomimetics Cytitonum (content alkaloid CYTIZINUM) Lobelini hydrochloridum Cytizinum Pharmacodynamics increases tone of respiratory center of medulla oblongata reflectively increases arterial pressure due to reflective excitation of vascular-motor center Usage Входить до складу таблеток «Теофедрин» (Theophedrinum), які застосовують для лікування бронхіальної астми; «Табекс» (“Tabex”) - застосовуть з метою полегшення відвикання від паління Acute poisoning with nicotine Clinical picture nausea, vomiting, salivation, abdominal pain, diarrhea, dizziness, headache, cold sweat, weakness, loosing of consciousness, tachy- or bradycardia, cardiac arrhythmias, seizures, breathing depression Death is caused by sharp depression of respiratory center and paralysis of breathing musculature Chronic poisoning with nicotine Chronic diseases of respiratory system, Lung cancer and Malignant tumors of other localisation, Ischemic heart disease, Obliterating endarteritis, Gastric and duodenal ulcer disease Women Depression of female sex hormones production, yellow face, early wrinkles, damaging of teeth, harsh voice, sometimes male type hair growth Men Deep, nonreversible changes of spermatozoids Anticholinesterase drugs • Proserinum REVERSIBLE acting (block of • Galanthamini cholinesterase lasts hydrobromidum some hours) • Pirydostygmini bromidum IRREVERSIBLE acting (block of cholinesterase lasts till 30 days) Phosphor-organic compounds Military gases (insecticides) (Zarin, Zoman, V-gases) The main peculiarities of anticholinesterase’ drugs They influence on the both: M- and N-cholinorecepors Their action is more physiologically They cause selective action (act in the synapses with lack of acetylcholine only) Pharmacodynamic of anticholinesterase’ drugs Miosis, intraocular pressure Spasm of accomodation bronchial tone and other smooth musculature secretion; Bradicardia and depression of the heart work Improve nerve conductivity to the skeletal muscles Improve nerve transmission in the ganglia's Stimulation of catecholamines release in suprarenal glands Indications for use of anticholinesterase drugs . Myasthenia gravis, peripheral paresis and paralysis, trauma, poliomyelitis . Postoperative gastrointestinal atony, uterus and bladder, atonic constipation . Glaecoma . Overdose and poisoning of cholinoblokers (Atropinum),
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