Autonomic pharmacology. Indirect acting cholinergic stimulants Lector prof. Posokhova K.A.

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)

Cholinergic synaps

Influence of parasympathetic and sympathetic nervous system on function of organs Eye m. sphincter pupillae m. dilatator pupillae m. ciliaris contraction (miosis) absent innervation contraction (close sight) absent innervation contraction (midriasis) dilation (far sight) Heart Excitability Conduction Power of contractions Frequency of contraction dicreasing slowing down dicreasing increasing speeding up increasing Vessels Skin, mucous membranes Mesentraium, organs of abdominal cavity Skeletal muscles Heart, brain absent innervation -’’ - dilation - ’’ - contraction -’’ – Bronchi Circular muscles Glandular secretion contractoin increasing dilation decreasing Stomach, intestines Perystaltics Tonus of sphyncters Glandular secretion increasing decreasing increasing decreasing increasing decresing Urinary bladder Detrusor Sphyncter contraction dilation contraction Glands (secretion) Salivary Sweat incresing (liquid secret, large quantity) increasing (small quantity) - ’’ -

Cholinergic nervous fibres are: 1) preganglionic (sympathetic and parasympathetic); 2) all postgnglionic parasympathetic; 3) postganglionic sympathetic which supply sweat glands and vessels of skeletal muscles; 4) somatic nerves; 5) nerves which supply adrenal medulla and carotic sinuses; 6) neurons of CNS Adrenergic nervous fibres are: 1) postganglionic sympathetic, except those which supply sweat glands and vessels of skeletal muscles; 2) neurons of CNS

Cholinergic drugs 1) M-, N-cholinomimetics (acetylcholine, carbacholine); 2) Anticholinesterase drugs – cholinesterase inhibitors (proserin, galanthamine hydrobromide, pirydostygmine bromide, armine); 3) M-, N- cholinoblockers (amisyl, cyclodol); 4) M-cholinomimetics (pilocarpin, aceclidyn); 5) M-cholinoblockers (atropine sulphate, platyphyllin hydrotartrate, scopolamine hydrobromide, metacinum); 6) N-cholinomimetics (cytyton, lobelin); 7) N-cholinoblockers: а) ganglionblockers (benzohexonium, pentamin, hygronium, arphonade); б) myorelaxants (tubocurarinum chloride, dytylinum, melliktin)

AcetylcholineCarbacholine M-, N-cholinomimetics

Carbacholine 0,5-1 % solutions of carbacholine - eye drops for treatment of glaucoma The drug is never used orally and with injections because of its consideralbe toxicity !

AmizylCyclodol M-, N-cholinoblockers

Amizyl Indications for administration neurotic disorders, Parcinoson’s disease and other extrapyramidal disorders, for premedication before narcosis, for diseases which are accompanied with spasm of smooth muscles, for dilation of pupil in ophtalmology neurotic disorders, Parcinoson’s disease and other extrapyramidal disorders, for premedication before narcosis, for diseases which are accompanied with spasm of smooth muscles, for dilation of pupil in ophtalmology The drug is administered orally 0,001-0,002 g The drug is administered orally 0,001-0,002 g 3-4 times per day, as eye dropps % solution is used as eye dropps % solution is used Side effects : dryness of mucous membranes, tachycardia, dilation of pupils, disturbances of accomodation. Side effects : dryness of mucous membranes, tachycardia, dilation of pupils, disturbances of accomodation. The drug is contraindicated in case of glaucoma!

Cyclodol Anticholinergic drug, preferably blocks central N-cholinoreceptors and peripheral M-cholinoreceptors Usage Parcіnson’s disease, Parcіnson’s disease, medicamentous parcinsonism

Proserinum, Galanthamini hydrobromidum, Armin, Pirydostygmini bromidum Anticholinesterase drugs

Proserinum Proserinum is an anticholinesterase drug of reverse action, its effect lasts for 2,5-4 hours. Indications for administration  Impairment of nerve conduction after polyomyelitis, paralysis, neurities, traumas  overdosing with M- cholinoblockers

Galanthamini hydrobromidum Duration of action of Galanthamini hydrobromidum is longer than of Proserinum, that’s why it can be administered 1-2 times per day Indications for administration Impairment of nerve conduction after polyomyelitis, paralyses, neuritis, traumas, overdosing with M-cholinoblockers

Pirydostigmini bromide (calimin ) Usage  myastenia gravis  after traumas, neuritis, paralyses  in a period of recovery after polyomyelitis, encephalitis

myastenia gravis

Anticholinesterase drugs are contraindicated in cases of epilepsia, hyperkinesias, bronchial asthma, stenocardia, bradycardia

POC (phosfororganic compounds as insecticides)

nausea, vomiting, diarrhea, abdominal pain nausea, vomiting, diarrhea, abdominal pain quick contraction of pupils, disturbance of visus (spasm of accomodation) quick contraction of pupils, disturbance of visus (spasm of accomodation) increasing of salivation and sweating increasing of salivation and sweating bronchospasm bronchospasm tachy- or bradicardia tachy- or bradicardia seizures, excitement, loss of consciousness, coma seizures, excitement, loss of consciousness, coma Death is caused by breath insufficiency, bronchospasm and lungs edema Acute poisoning with anticholinesterase drugs (POC)

 Treatment should be started immediately (WHO)  stomach lavage with solution of Sodium hydrocarbonate salt laxatives, enterosorbents salt laxatives, enterosorbents siphon enema siphon enema  the poison should be carefully washed away from the skin  forced diuresis, in complicated cases - hemosorbtion, hemodialysis Usage of antagonist is necessary!!! – atropine sulphate. It should be introduced intravenously repeatedly, 2-4 ml of 0,1 % solution with the interval of minutes. Appearance of tachycardia, dilation of pupils, dryness in the mouth are the criteria of sufficiency of atropine sulfate dose. Also reactivators of cholinesterase which renew activity of this enzyme are administered – dipyroxym, alloxym, isonitrosyn Treatment of acute poisoning

Depending on severity of poisoning dipyroxym is introduced once or a few times. An average dose of the drug in heavy cases is 3-4 ml of 15 % solution. The total dose of alloxym is 0,4-1,6 g (0,075 g every 1-3 hours). If necessary - artificial ventilation should be performed to a patient. And after symptomatic treatment is carried on. Treatment of acute poisoning