Anticholinergic agent

Anticholinergic agent
defination, classification, SAR, structure, etc

1. Cholinergic A ntagonist Presented by - Ashok Gautam Skb college of pharmacy

2. Cholinergic antagonist These drugs block the response of Ach in the muscarine receptor by competitively binding to it and inhibiting any response . They have opposite pharmacological response of Ach

3. SAR The R1 or R2 groups must be carbocyclic or heterocyclic The R3 group can be hydrogen, hydroxyl (- OH ), hydroxymethyl (- CH2OH ), amide The X is mostly Ester in most potent derivatives but it can be a ether oxygen or absent completely The N substituent cab be both quaternary ammonium salt or tertiary amine with different alkyl groups The distance between the ring substituted carbon and nitrogen is not fixed but maximum potency requires about 2 carbon units (Note: The SAR does not say anything about selectivity for muscarinic subtypes) General framework of Anticholinergics

4. M edical use In Sooth muscle spasm I n cold n flu (to reduce nasal secretion) P reviously in ulcer (but now replaced by H2 antagonist and proton inhibitors) Overactive bladder (to much urination) Motion sickness Treat organophosphate poisoning Parkinson (brain disease where nerves start degrading and person slowly goes crazy)

5. SAR of Cholinergic Agent v/s and Anticholinergic Agent A) Nitrogen group In agonist the N can only be quanternary but In antagonist N can be both quanternary or tertiary Methacholone Orphendrine

6. B) Ethylene group In agonist the no of ethylene is fixed at only 2 but In antagonist no of ethylene can range from 2-4 Bethanecol carbamate Glycopyrrolate

7. C) Selectivity In agonist the methyl substitution in ethylene group controls selectivity of muscarinic or nicotinic but In antagonist no such feature is present . Still It only antagonizes muscarinic only Methacholone Muscarinic selective

8. Classification Solanaceous alkaloid and analogs Atropine Hyoscyamine Scoplamine Homatropine Ipratropium and Tiotropium B) Synthetic Cholinergic blocking agent 1) Aminoalcohol Esters Clinidium bromide Cyclopentolate Dicyclamine Glycopyrrolate Mepenzolate Methantheline Oxyphencyclimine Propantheline Oxybutynin Solifenacin

9. 2 ) Aminoalcohol Ethers Benztropine Orphenadrin 3) Aminoalcohol Biperiden Procyclidine Trihexethyl chloride Tolterodine 3) Aminamides Isopropamide Tropicamide Darifenacin 4) Miscellaneous Diphemanil Ethopropazine Papaverine

10. Atropine Atropine Anticholinergic, blocks muscarinic receptors Alkaloid extracted from Solanaceae plant first anticholinergic . It is an E ster of tropine and tropic acid and used as a sulphate Salt in racemic from At therapeutic does it can penetrate the brain and stimulate the CNS Uses Treat Bardycardia Reduce secretion before surgery Treat Iritis (painful inflammation of eye) Organophosphate poisoning (only to decrease muscarinic action, not an antidote like PAM) MOA – It competitively binds to muscarinic receptor and antagonizes it thus blocking all cholinergic effects

11. Hyoscyamine Hyoscyamine It is the levorotary isomer of atropine USE: various gastrointestinal disorders including spasms, peptic ulcers , irritable bowel syndrome , pancreatitis , and cystitis . U sed to relieve some heart problems , control some of the symptoms of Parkinson's disease , control of respiratory symptoms

12. Scopolamine Scopolamine In the form of a levorotatory Action on the higher nerve centers T ransdermal patch of scopolamine is available side effects: include sleepiness, blurred vision , dilated pupils , and dry mouth U se: Postoperative nausea and vomiting and sea sickness , Motion sickness (where it is often applied as a transdermal patch behind the ear ), Gastrointestinal spasms, Renal or biliary spasms, Aid in radiology and endoscopy , Irritable bowel syndrome , Clozapine -induced hypersalivation , Eye inflammation

13. Ipratropium bromide Ipratropium It is a Q uaternary ammonium derivative of atropine used in inhalation therapy to produce dilation of bronchial smooth muscle for acute asthmatic attacks . The drug produces bronchodilation by competitive inhibition of cholinergic receptors bound to smooth muscle of the bronchioles

14. Tiotropium bromide Tiotropium bromide Used in an inhalation device to deliver the drug into the lungs. It is indicated in the treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema L ong-acting, 24-hour

15. 1) Aminoalcohol Esters Clinidium bromide Clinidium bromide Marketed alone and in combination with the minor tranquilizer chlordiazepoxide ( Librium) in a product known as Librax . For the treatment of GI complaints is the use of an anxiety-reducing agent together with an anticholinergic agent

16. Cyclopentolate Cyclopentolate It is used only for its effects on the eye , A cts as a parasympatholytic . When placed in the eye, it quickly produces cycloplegia and mydriasis . Usefulness in refraction studies . Can be used , as a mydriatic in the management of iritis , iridocyclitis , keratitis

17. Dicyclamine Dicyclamine Used for its spasmolytic effect on various smooth muscle spasms, particularly those associated with the GI tract. It is also useful in dysmenorrhea, pylorospasm , and biliary dysfunction .

18. Glycopyrrolate Mepenzolate Methantheline Oxyphencyclimine

19. 2) Aminoalcohol Ethers Benztropine Has anticholinergic, antihistaminic, and local anesthetic properties. Its anticholinergic effect makes it applicable as an antiparkinson agent . It is about as potent anticholinergic as atropine

20. Orphenadrin Orphenadrin Closely related to diphenhydramine structurally but has much lower antihistaminic activity and much higher anticholinergic action It does reduce voluntary muscle spasm , however, by a central inhibitory action on cerebral motor areas .

21. 3) Aminoalcohol Biperiden Biperiden Has a relatively weak visceral anticholinergic , but a strong nicotinolytic action in terms of its ability to block nicotine induced convulsions Has a relatively strong musculotropic action , which is about equal to that of papaverine , in comparison with most synthetic anticholinergic drugs

22. Procyclidine Procyclidine Effective peripheral anticholinergic A bility to relieve voluntary muscle spasticity by its central action Treatment of Parkinson syndrome Reduce muscle rigidity in postencephalitic , arteriosclerotic, and idiopathic types of the disease

23. 4) Aminoamides Isopropamide Isopropamide Potent anticholinergic , Producing atropine-like effects peripherally L ong duration of action . A single dose can provide antispasmodic and antisecretory effects for as long as 12 hours . USE:- It is used as adjunctive therapy in the treatment of peptic ulcer and other conditions of the GI tract associated with hypermotility and hyperacidity .

24. Tropicamide Tropicamide Effective anticholinergic for ophthalmic use P roduces short acting mydriasis and cycloplegia To achieve mydriasis , either 0.5 % or 1.0% concentration may be used Treatment of acute iritis , iridocyclitis , and keratitis

25. 5) Miscellaneous Diphemanil Ethopropazine Papaverine

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