1 / 43

DRUGS acting on the PARASYMPATHATIC NERVOUS SYSTEM

DRUGS acting on the PARASYMPATHATIC NERVOUS SYSTEM. Dr. Naila Abrar. Parasympathetic Nervous System. Muscarinic Nicotinic Autonomic neuroeffector Ganglia & NMJ junctions Acetylcholine. GPCR. Ion Channels. CHOLINOCEPTORS. Nicotinic Ion channel. Muscarinic

lori
Download Presentation

DRUGS acting on the PARASYMPATHATIC NERVOUS SYSTEM

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. DRUGS acting on the PARASYMPATHATIC NERVOUS SYSTEM Dr. Naila Abrar

  2. Parasympathetic Nervous System Muscarinic Nicotinic Autonomic neuroeffector Ganglia & NMJ junctions Acetylcholine GPCR Ion Channels

  3. CHOLINOCEPTORS Nicotinic Ion channel Muscarinic GPCR

  4. PARASYMPATHOMIMETIC DRUGSor CHOLINERGIC DRUGSor CHOLINOMIMETIC DRUGS

  5. CLASSICIFICATION • Directly Acting • Indirectly Acting

  6. A. Directly Acting Cholinergic Drugs • CHOLINE ESTERS • CHOLINOMIMETIC ALKALOIDS

  7. CHOLINE ESTERS - Acetylcholine - Methacholine - Carbachol - Bethanechol

  8. II.CHOLINOMIMETIC ALKALOIDS a. Mainly MuscarinicAgonists • Natural Alkaloids: - Muscarine - Pilocarpine - Arecholine • Synthetic Alkaloid: - Oxotremorine • Mainly Nicotinic Agonists • Natural Alkaloids: - Nicotine - Lobeline • Synthetic Alkaloids: - Dimethylphenyl-piperazinium(DMPP)

  9. B. Indirectly Acting Cholinergic Drugs(Anticholinesterases) I- REVERSIBLE II- IRREVERSIBLE Organophosphates Therapeutically useful -ecothiopate War gases -sarin, tuban, soman Insecticides -parathion, malathion, DFP, TEPP, OMPA • Carbamates • Tertiary amines-physostigmine • Quaternary ammonium compounds- neostigmine, pyridostigmine, tacrine, ambenonium, demecarium • Alcohols- edrophonium • Miscellaneous- tacrine, galantamine, rivastigmine, donepezil

  10. PHARMACOKINETICS • Esters-Quaternary ammonium gp • Choline esters are poorly absorbed and poorly distributed into CNS • Methacholine is resistant to hydrolysis by cholinesterase • Carbamic acid esters carbachol and bethanechol- most resistant-longer duration of action

  11. Pharmacokinetic (contd.) • Pilocarpine, nicotine, lobeline-tertiary natural compounds- well absorbed • Muscarine, quaternary amine is toxic when ingested present in certain mushrooms • Excretion chiefly through kidneys

  12. MECHANISM OF ACTION of directly acting cholinomimetics • Activation of muscarinic receptors on effector cells directly to alter organ function • Interaction with muscarinic receptors on nerve terminals to inhibit release of their neurotransmitter

  13. MECHANISM OF ACTION of directly acting cholinomimetics Muscarinic- GPCR • Inhibitory effects (M2 & M4) • Inhibition of adenylyl cyclase- decrease of cAMP (GPCR-Gi/Go) • Excitatory effects (M1,M3,M5) • Increase activity of IP3 & DAG (GPCR-Gq/11)

  14. MECHANISM OF ACTION of directly acting cholinomimetics Nicotinic – pentameric ion channel • Na+ & K+ move down conc. gradient • Depolarization • Skeletal muscle-Action potential propagation-contraction • Prolonged agonist occupancy-depolarizing blockade

  15. ACETYLCHOLINE CHEMISTRY An ester of acetic acid and choline

  16. SYNTHESIS, STORAGE, RELEASE & INACTIVATION

  17. Pharmacological actions/ Organ system effects: • Muscarinic Actions • Nicotinic Actions

  18. EYE: • M3 • Miosis (constriction of pupil)- contraction of papillary sphincter ms. • Spasm of accommodation (contraction of ciliary muscle)- eye fixed for near vision • Decrease in intraocular pressure • Conjunctival hyperemia • Lacrimation

  19. CVS (Heart & Blood Vessels) • Negative chronotropic effect-bradycardia M2 -Decreases rate of spontaneous depolarization • Negative dromotropic effect- decrease in conduction velocity in AV node-(inhibiting Ca channels) • Negative inotropic effect- decreased cardiac output (hyperpolarization, decrease cAMP & epinephrine release) • Vasodilation- fall in blood pressure- NO

  20. RESPIRATORY SYSTEM • M3 • Bronchial muscle contraction • Bronchial gland stimulation- increase tracheobronchial secretions

  21. GIT • M3 • Increase motility • Relaxation of sphincters • Increase tone of LES

  22. URINARY BLADDER • M3 • Detrusor muscle contraction • Relaxation of sphincters • Promote micturition

  23. Exocrine glands- M3 - Increase in salivation, sweat, lacrimation • Central Nervous System - M1 - Cortical arousal, or activation • Peripheral nervous system - Stimulation of ganglia both the systems are activated

  24. Neuromuscular junction - Na+ and K+ entry into cell- depolarization - Skeletal muscle contraction

  25. THERAPEUTIC USES • Glaucoma (pilocarpine) • Accommodative estropia • Induction of miosis (Ach, carbachol) • Postoperative ileus (bethanechol) • Congenital megacolon (bethanechol) • Atony of urinary bladder – post op, diabetic autonomic neuropathy (bethanechol)

  26. THERAPEUTIC USES (contd.) • Dry mouth with Sjogren’s syndrome (pilocarpine, cevimeline) • Diagnosis of bronchial airway hyperreactivity (methacholine)

  27. ADVERSE EFFECTS • Signs of muscarinic excess. • Salivation, sweating • Difficulty in visual accommodation • NVD, abd. cramps • Urinary urgency • Cutaneous vasodilatation • Bronchoconstriction • Hypotension

  28. CONTRAINDICATIONS • Bronchial asthma • GI or urinary tract obstruction • Peptic ulcer • Recent myocardial infarction • Coronary insufficiency • Hyperthyroidism

  29. MUSHROOM POISONING • Signs of muscarinic excess-salivation, sweating, NVD, visual disturbances, headache, abd. Colic,urinary urgency, bradycardia, bronchospasm, hypotension, shock • Atropine (1-2mg I/M every 30mins)

  30. ACUTE NICOTINE TOXICITY • CNS stimulation, cause convulsions, coma and respiratory arrest. • Skeletal muscle depolarization and respiratory paralysis. • Hypertension and cardiac arrhythmia.

  31. CHRONIC TOBACCO USE • Increased risk of vascular disease. • Sudden coronary death. • Aggravation of peptic ulcer in smokers.

  32. Other Choline Esters Methacholine Carbachol Bethanechol

  33. METHACHOLINE • Both muscarinic and nicotinic actions. • Muscarinic actions are more prominent on CVS than on GIT and urinary bladder. • Duration of action 30 min. • Paroxymal atrial tachycardia.

  34. CARBACHOL • Not destroyed by cholinesterase. • Longer duration of action and potent than methacholine. Therapeutic uses • Post operative abdominal distention, paralytic ileus, urinary retention and glaucoma.

  35. BETHANECHOL • Weak but prolonged effect Therapeutic uses • Difficulty in micturition, gastric distention following surgery.

  36. PILOCARPINE • Pilocarpus microphyllus (jaborandi) • Tertiary amine-enters CNS • More muscarinic effects Therapeutic uses • Glaucoma (other options available) • Reverse effects of mydriatics • Xerostomia • Break adhesions

More Related