2. ANTICHOLINERGIC DRUGS Prof. Alhaider Pharmacology Department Prof. Hanan Hagar Pharmacology Department

3. What students should know: Student should be able to : Describe Kinetics of muscarinic antagonists Describe Kinetics of muscarinic antagonists The effects of atropine on the major organ systems. The effects of atropine on the major organ systems. To list the clinical uses of muscarinic antagonists To list the clinical uses of muscarinic antagonists. To know adverse effects & contraindications of anticholinergic drugs. drugs. To identify at least one antimuscarinic agent for each of the To identify at least one antimuscarinic agent for each of the following special uses:mydriasis, cyclopedia, peptic ulcer & following special uses:mydriasis, cyclopedia, peptic ulcer & parkinsonism. parkinsonism. Anticholinergic drugs

4. are drugs that block cholinergic receptors. Anticholinergic drugs

5. Antimuscarinics (Muscarinic antagonists) Antinicotinics synthetic atropine substitutes Ganglionic blockers Neuromuscular blockers Anticholinergic drugs Naturally occurring alkaloids

6. Include drugs as Atropine - Hyoscine Esters of tropic acid and tertiary amines Lipid soluble Good oral absorption Good distribution Cross blood brain barrier (have CNS actions) Natural alkaloids Muscarinic antagonists

7. Benztropine Homatropine Tropicamaide Pirenzepine Ipratropium Glycopyrrolate Oxybutynin Synthetic Muscarinic antagonists

8. Antimuscarinic drugs are competitive antagonists of the binding of ACh to muscarinic receptors. Mechanism of action of antimuscarinic drugs

9. Eye  Passive mydriasis (paralysis of circular muscle)  Cycloplegia (loss of near accommodation) (paralysis of ciliary muscle)  Loss of light reflex.  increase intraocular pressure (IOP) # glaucoma   Lacrimal secretion  sandy eye Respiratory system  Bronchial relaxation (bronchodilation)   Bronchial secretion   viscosity Pharmacological effects of antimuscarinic drugs

10. Cardiovascular system (CVS)  Tachycardia (increase heart rate)   AV conduction (+ve dromotropic effect)  Toxic dose: cutaneous vasodilatation  (flushing). Secretions  salivary secretion  (dry mouth).  sweating  dry skin  fever in infants and children  bronchial secretion   viscosity  lacrimal secretion  sandy eye  Gastric acid secretion

11. Gastrointestinal tract (GIT) –  Gastric acid secretion – Relaxation of smooth muscles. –  GIT motility  Antispasmodic effect. –  Sphincter contractions – Constipation Urinary Tract – Relaxation of smooth muscles of ureters. – Sphincter contraction. – Urinary retention.

12. Central Nervous System –Sedation –Antiemetic effect (block vomiting center) –antiparkinsonian effect (block basal ganglia). Large doses: can produce Hyperthermia - excitement-hallucination, coma

13. Hyoscine What is difference between atropine and hyoscine? Hyoscine has Shorter duration of action More CNS depressant action Less CVS effect Has antiemetic effect (used in motion sickness) Can produce amnesia.

14. Muscarinic antagonistsMuscarinic agonists  passive mydriasis (relaxation of circular muscles)  relaxation of ciliary muscles (Cycloplegia) loss of accomodation Eye  Miosis (contraction of circular muscle)  near vision a ccommodation (contraction of ciliary muscles) Tachycardia Heart bradycardia relaxation of muscles contraction of sphincter Urinary retention Urinary bladder contraction of muscles relaxation of sphincter Increased urination

15. Muscarinic antagonistsMuscarinic agonists ↓decrease all secretion dry skin, dry mouth, sandy eyes Exocrine glands ↑ Increase of sweat, saliva, lacrimal, bronchial, intestinal secretions  ↓peristalsis  ↓secretion  contraction of sphincter constipation GIT  ↑peristalsis  ↑secretion  relaxation of sphincter diarrhea  bronchodilation  ↓decrease secretion Respiratory system  bronchoconstriction  ↑bronchial secretion

16. Uses of antimuscarinic drugs  Fundus examination of eye  Antiemetic in motion sickness  Pre-anesthetic medication  Antispasmodic  Parkinson's disease  Asthma  Peptic ulcer  Treatment of overdoses of cholinesterase inhibitors

17. Uses Drugs Pre-anesthetic medication Antispasmodic Atropine Antiemetic in motion sickness Pre-anesthetic medication antispasmodic Hyoscine Parkinson's diseaseBenztropine Fundus examination of eyeHomatropine Asthma Chronic obstructive pulmonary disease(COPD) inhalation Ipratropium Peptic ulcerTelenzepine Antispasmodics in hypermotilityGlycopyyrolate Uses of antimuscarinic drugs

18. Side effects of antimuscarinics Eye: blurred vision – mydriasis CVS: tachycardia - cutaneous flush (atropine flush) GUT: urinary retention GIT: constipation, paralytic ileus Secretions: dryness of mouth, sandy eye, hyperthermia CNS: hallucination, excitation (Toxic dose). Treatment of overdose of antimuscarinics –Gastric lavage. –Anticonvulsant. –Cooling blanket. –Antidote: Physostigmine (IV slowly).

19. Contraindications –Glaucoma (angle closure glaucoma) –Tachycardia –Prostate hypertrophy in old patients. –Constipation, paralytic ileus. –Children in case of atropine

20. Question Can antimuscarinic drugs reverse the action of Ach on skeletal muscles?

21. Thank you Questions ?