Direct Acting Cholinergic Mimetics PDF

DIRECT ACTING CHOLINOMIMETICS. Introduction- Parasympathetic effects  Cholinomimetics Are drugs that mimic acetylcholine (Ach) Divided into either: Ach receptor stimulants (direct acting cholinomimetics) Cholinesterase inhibitors (indirect acting cholinomimetics). 1. DIRECT...

DIRECT ACTING CHOLINOMIMETICS. Introduction- Parasympathetic effects  Cholinomimetics Are drugs that mimic acetylcholine (Ach) Divided into either: Ach receptor stimulants (direct acting cholinomimetics) Cholinesterase inhibitors (indirect acting cholinomimetics). 1. DIRECT ACTING CHOLINOMIMETICS Divided into: a) Choline esters eg. Acetylcholine, Carbachol, Methacholine and Bethanecol b) Alkaloids eg. Muscarine, Nicotine, Lobeline, Pilocarpine, Arecholine & Oxotremorine  Pharmacokinetics Choline esters are relatively lipid insoluble Poorly absorbed Poor penetration into the CNS Variable hydrolysis by cholinesterase  Properties of Choline esters Choline ester Susceptibility Action on Action on to Muscarinic Nicotinic cholinesterase receptors receptors Acetylcholine ++++ +++ +++ Methacholine + ++++ Nil Carbachol Negligible ++ +++ Bethanechol Negligible ++ Nil  Note: Acetylcholine undergoes very rapid hydrolysis IV bolus injection- effect lasts 5-20 seconds IM and SC injections produce only local effects Methacholine and Bethanechol have nil effect on nicotinic receptors due to presence of a β- methyl group.  Bethanechol Negligible CVS effects Acts chiefly on the bladder & bowels Preferable to carbachol because of this partial selectivity  Methacholine Effective orally 3 times more resistant to hydrolysis by cholinesterase compared to Ach Longer duration of action than ACh  ALKALOIDS a. Mainly muscarinic b. Mainly nicotinic action action Natural Natural  Nicotine  Muscarine  Lobeline  Pilocarpine  Arecholine Synthetic  Dimethylphenyl- Synthetic piperazinium (DMPP)  Oxotremorine  Alkaloids i. Muscarine Quartenary amine Occurs in poisonous mushrooms (Amanita muscaria & Inocybe spp.) Has only muscarinic actions Not used therapeutically Toxic when ingested Less well absorbed in the gut compared to tertiary alkaloids  ii. Tertiary alkaloids Include  Pilocarpine  Lobeline  Nicotine Are well absorbed Nicotine is derived from the plant Nicotiana tabacum It is a lipophilic liquid capable of absorption through the skin  Acetylcholine actions a. Muscarinic i. Heart SA Node  Decreased rate of impulse generation (negative chronotropy) Atria  Decrease in contractile strength(negative inotropy) Atrioventricular Node  Decrease in conduction velocity (negative dromotropy)  ii. Lung Bronchial muscle Contraction (Bronchoconstriction) Bronchial glands Stimulation of secretion  iii. GIT Increased motility Relaxation of sphincters Stimulate secretions Leads to evacuation of bowel contents  iv. Urinary bladder Contraction of detrusor muscles Relaxation of trigone & sphincter Ureter - increased peristalsis v. Glands Sweat/salivary/lacrimal/nasopharyngeal- Increased secretions  vi. Eye Sphincter (circular) muscle of iris Contraction (miosis) Ciliary muscle Contraction for near vision  Increased aqueous outflow Reduction in intraocular pressure  b. Nicotinic Skeletal muscles Application of ACh to motor endplate leads to skeletal muscle contraction  Choline esters- Clinical uses Ach not used because of its transient & non- selective action Bethanechol has been used in  Postoperative paralytic ileus  Postoperative/postpartum nonobstructive urinary retention  Neurogenic bladder atony  Congenital megacolon  Gastroesophageal reflux  Other Clinical uses Dry mouth with Sjogren’s syndrome (pilocarpine, cevimeline) Diagnosis of bronchial airway hyperreactivity (methacholine)  Adverse effects Excessive salivation, sweating Nausea, diarrhoea, abdominal cramps Urinary urgency Cutaneous vasodilatation Bronchoconstriction Hypotension  Features of mushroom poisoning– treat with Atropine 1-2mg every 30 mins  Contraindications 1. Bronchial Asthma 2. GI or urinary tract obstruction THE END.