Pharma-Cholinoceptor-blocking drugs.pptx

Pharma-Cholinoceptor-blocking drugs.pptx

1. Cholinoceptor -blocking drugs

2. Overview The cholinergic antagonists bind to cholinoceptors , but they do not trigger the usual receptor-mediated intracellular effects Also called cholinergic blockers , parasympatholytics or anticholinergic drugs Cholinoceptor antagonists are divided into muscarinic and nicotinic subgroups on the basis of their receptor affinities

3. Overview Cholinergic antagonists are subdivided according to their physiological site of action: Muscarin antagoni sts ( antamuscarinics , parasympatholytic drugs) Ganglionic blockers Neuromuscular-blocking drugs

4. Neuromuscular junction Effector organ M receptor Sympathatic Neuromuscular junction N M receptor Adrenal medulla Ganglionic transmittion Neuroeffector transmittion Parasympathatic Sympathatic innervation of adrenal medulla Somatic Effector organ α or β Adrenergic receptor Ganglionic blockers antimuscarinics Neuromuscular blockers N N receptor N N receptor N N receptor Acetylcholine Norepinephrine

5. Muscarinic antagonists (antimuscarinics) These are reversible (surmountable) competitive antagonists that compete with ACh and other muscarinic agonists for a common binding site on the muscarinic receptor These drugs block sympathetic neurons that are cholinergic innervating salivary and sweat glands The antimuscarinics are beneficial in a variety of clinical situations, because they do not block nicotinic receptors

6. Muscarinic antagonists ( antimuscarinics ) The class of drugs includes: Naturally occurring alkaloids ( atropine & scopolamine ) Semisynthetic derivatives of the naturally occurring alkaloids, which primarily differ from the parent compounds in their disposition in the body or their duration of action Synthetic muscarinic antagonists ( homatropine & tropicamide ) , some of which show selectivity for particular subtypes of muscarinic receptors

7. Muscarinic antagonists Atropine (prototype) does not distinguish among the M 1 , M 2 , and M 3 subgroups of muscarinic receptors Few synthetic antimuscarinic drugs demonstrate selectivity for one or another of these subgroups: M1 selective agents: pirenzepine , telenzepine M3 selective agents: darifenacin, solifenacin

8. Organ Effect Mechanism CNS Sedation, anti-motion sickness action, antiparkinson action, amnesia, delirium Block of muscarinic receptors, several subtypes Eye Cycloplegia (paralysis of the ciliary muscle of the eye) , mydriasis Block of M 3 receptors Bronchi Bronchodilation, especially if constricted Block of M 3 receptors GIT Relaxation, slowed peristalsis, reduced salivation Block of M 1 , M 3 receptors Genitourinary tract Relaxation of bladder wall, urinary retention Block of M 3 and possibly M 1 receptors Heart Bradycardia (at low doses) Tachycardia (at high doses) Block of presynaptic M1 receptors Block of M 2 receptors in the sinoatrial node Blood vessels Block of muscarinic vasodilation; not manifest unless a muscarinic agonist is present Block of M 3 receptors on endothelium of vessels Glands Marked reduction of salivation; moderate reduction of lacrimation, sweating; less reduction of gastric secretion Block of M 1 , M 3 receptors Effects of muscarinic blocking drugs

9. Muscarinic antagonists Clinical uses Central Nervous System Disorders Parkinson's Disease: Benzotropine, biperiden , and trihexylphenidyl Motion Sickness: Scopolamine (injection or by mouth or as a transdermal patch)

10. Muscarinic antagonists Clinical uses Ophthalmologic Disorders Examination of the retina and optic disc and for the accurate measurement of refractive error administered topically as eye drops or ointment Agents used: Atropine, scopolamine, cyclopentolate and tropicamide, homatropin Short-acting drugs ( e.g cyclopentolate and tropicamide) are favoured for ophthalmic application b/c complete recovery of accommodation occurs within 6 to 24 hours and 2 to 6 hours, respectively

11. Muscarinic antagonists Clinical uses Respiratory disorders: Ipratropium , tiotropium are used as an inhalational drug in asthma & chronic obstruction pulmonary disease (COPD) Gastrointestinal disorders Treatment of traveler's diarrhea : in combination with an opioid antidiarrheal drug (e.g. atropine & diphenoxylate combination Urinary Disorders Symptomatic relief in the treatment of urinary urgency caused by minor inflammatory bladder disorders Relief bladder spasm after urologic surgery eg . prostatectomy: Oxybutynin , darifenacin, solifenacin , tolterodine, fesoterodine (all are selective M3 antagonists), trospium (a nonselective antagonist)

12. Muscarinic antagonists Clinical uses Cholinergic poisoning Used for the treatment of poisoning caused by anticholinesterase organophosphorus insecticides or by the ingestion of mushrooms of Inocybe genus Atropine is used to antagonize/reverse the central and parasympathomimetic effects of the organophosphate anticholinesterase inhibitors

13. Toxicity (Adverse effect) of a ntimuscarinic agents Depend on the dose Includes: dry mouth, blurred vision ‘sandy eyes’, tachycardia, and constipation In children-  Atropine fever ( hyperthermic effects of atropine) In elderly  are susceptible to antimuscarinic toxicities including the eye and the bladder especially those with a history of prostatic hyperplasia

14. Contraindications Contraindications to the use of antimuscarinic drugs are relative, not absolute Antimuscarinic drugs are contraindicated in patients with glaucoma and elderly patients with a history of prostatic hyperplasia Because the antimuscarinic drugs slow gastric emptying, they may increase symptoms in patients with gastric ulcer (nonselective antimuscarinic agents should never be used to treat acid-peptic disease )