Parasympathomimetic and Parasympatholytic.pptx

Parasympathomimetic and Parasympatholytic powerpoint presentation

1. PARASYMPATHOMIMETIC AND PARASYMPATHOLYTIC Presented by SABITRI PRADHAN M.Pharm,GIPS Pharmacology, 1st semester 1

2. CONTENTS PARASYMPATHOMIMETIC Introduction Synthesis and Release of Acetylcholine Types of Cholinergic Receptors( Muscarinic and Nicotinic) Classification of Drugs Therapeutic uses of Cholinergic Drugs Side effects of Cholinergic Drugs PARASYMPATHOLYTIC Introduction Mechanism of action Classification Drug uses Pharmacological action Toxicity of Anticholinergic Contraindication Reference 2

3. PARASYMPATHOMIMETIC 3

4. INTRODUCTION Parasympathomimetic/Cholinergic drugs/ Cholinomimetic drugs/ Cholinoceptor activating drugs are agent which produce the action similar to those seen by the stimulation of parasympathetic nervous system. Parasympathomimetic drugs activate the parasympathetic nervous system(PSNS). PSNS performs maintenance activities and conserves body energy. Acetylcholine is both pre-and postganglionic neurotransmitter. Acetylcholine released at the cholinergic synapses and neuroeffector junctions, mediates its pharmacological action through cholinergic receptors. 4

5. SYNTHESIS AND RELEASE OF ACETYLCHOLINE 5

6. TYPES OF CHOLINERGIC RECEPTORS CHOLINERGIC RECEPTORS: 1) Muscarinic Receptor M1 M2 M3 M4 M5 2) Nicotinic Receptor Nm or N1 Nn or N2 6

7. MUSCARINIC RECEPTOR 7

8. NICOTINIC RECEPTOR 8

9. CLASSIFICATION 9

10. DIRECT PARASYMPATHOMIMETIC MOA: They directly stimulate muscarinic or nicotinic parasympathetic receptors or both. The drug include are- A) Choline esters: Acetylcholine,Methacholine,CarbacholandBethanechol (Urecholine). Acetylcholine: Synthesis: 10

11. It is synthesized from its two immediate precursors, choline and acetyl coenzyme A It has a short action A quaternary ammonium compound It affect in both muscarinic and nicotinic receptors Uses: As miotic Myasthenia gravis Carbachol : Not metabolized by cholinesterases Longer duration of action than Ach Muscarinic actions on Eye,GIT , UT   Contd … 11

12. Contd …. Uses: Mainly in glaucoma Urinary retention and paralytic ileus Bethanechol : Prominent muscarinic actions on GIT,UT No nicotinic action Longer duration of action Uses: In paralytic ileus In urinary retention 12

13. Contd … B) Natural Alkaloid Pilocarpine : It is chief alkaloid obtain from the leaves of shurb Pilocarpus jaborandi. It crosses BBB. It has muscarinic action and also mild nicotinic action Uses: Ophthalmic use: for initial treatment of open glaucoma To counteract mydriasis produce by atropine As sialagogue : used to stimulate salivary secretion in patients after laryngeal surgery. 13

14. INDIRECT ACTING PARASYMPATHOMIMETIC (ANTICHOLINESTERASE) MOA Acetylcholinesterase ( AchE ) is a enzyme which degrades acetylcholine to inactive products: choline and acetic acid. These agents act by inhibiting the AchE , by reversible or irreversible binding which indirectly increase the concentration of acetylcholine in the synaptic cleft and ultimately at the respective cholinergic receptors. 14

15. Contd … The drug include: Reversible Inhibitors of AChE: The reversible anticholinesterase drugs have a similar structure to Ach. They combine with the anionic and their esteric site of AChE. This complex is less readily hydrolysed than AChE-Ach complex. It results in a temporary inhibition of the enzyme This inhibition prolong the duration of action of Ach released in the synaptic cleft. 15

16. Contd … Physostigmine: Its an alkaloid obtain from the dried ripe seeds of Physostigmine venenosum It is highly lipid soluble and shows better absorption in all the body compartments including CNS and can cross BBB It is highly toxic and so has only limited use It is having intermediate duration of action(30min-2hrs) Uses: Ophthalmic use: for the treatment of glucoma Belladonna(atropine poisoning) 16

17. Cond … Edrophonium : A quaternary ammonium compound that binds to the anionic site of the enzyme only It is mainly used for diagnostic purposes The ionic bond formed is readily reversible Duration of action: 5-15 min Neostigmine : Hydrolysed by esterases in liver and plasma Duration of action: 3-5 hrs Direct action on nicotinic(Nm) receptor of skeletal muscle. 17

18. Contd … MOA B) Irreversible inhibitors of AChE These agents are called irreversible blockers because they phosphorylated the esteric site of AChE irreversibly by forming a covalent bond Pentavalent organo-phosphorous cmpounds containing fluoride or organic group During the process, this group is released leaving the remaining part of drug molecule attached covalently with the esterstic site of AChE through its phosphorous atom After phosphorylation, AChE becomes inactive and very stable due to covalent bonding. Recovery depends on new synthesis(few weeks) Ecothiophate (exception): is having a quaternary nitrogen which can also bind to the anionic site of the enzyme-slow hydrolysis-not strictly irreversible. 18

19. Therapeutic uses of parasympathomietic drugs Myasthenia gravis: Edrophonium to diagnose Neostigmine, pyridostigmine and distigmine to treat To stimulate bladder and bowel after surgery: Bethanechol,Carbachol,Distigmine To improve cognitive function in Alzheimer’s disease: Rivastigmine, gallantamine, donepezil Physostigmine in belladonna poisoning 19

20. Side effects of Parasympathomimetic Drugs Diarrhoea Urination Miosis,muscle weakness Bronchorrhea Bradycardia Emesis Lacrimation sweating. 20

21. Contd … PARASYMPATHOLYTIC 21

22. INTRODUCTION Parasympatholytic/Anti-Cholinergic/ Cholinolytic drug are those that block or inhibit the parasympathetic nervous system Also called cholinergic blocking agents or parasympatholytics Often referred to as anticholinergics or antimuscarinics It works as an antagonist 22

23. Mechanism of Action Act by occupying receptor sites at parasympathetic nerve endings, thereby leaving fewer receptor sites free to respond to acetylcholine Distribution of receptors is broad so effects of anticholinergics will be diffuse. Atropine causes reversible(surmountable) blockade of cholinomimetic actions at muscarinic receptors – blockade by a small dose of atropine can be overcome by a larger concentration of acetylcholine or equivalent muscarinic agonist Atropine is highly selective for muscarinic receptors, does not distinguish between the M1, M2, and M3 Some quaternary amine antimuscarinic agents have significant ganglion- blocking actions. 23

24. Classification 24

25. Drugs uses Atropine: prototype. Antidote in OP poisoning Ipratropium: Useful in rhinorrhea,also excellent bronchodilator Scopolamine: depresses CNS and causes amnesia, drowsiness,euphoria,relaxation and sleep. Given parenterally, orally and transdermally. Benztropine: temporary use in Parkinson’s disease. Trihexyphenidyl: contraindicated in glaucoma Flavoxate: relieves dysuria,urgency,frequency,and pain with GU infections Oxybutynin: has direct antispasmodic effects on smooth muscle and anticholinergic effects. 25

26. Pharmacological Action ATROPINE CVS effects- Decreased cardiovascular response to vagal stimulation resulting in tachycardia Mainly tachycardia due to antagonism of the vagal affect CNS At normal doses atropine stimulates medullary centers, however at higher doses produce excitement, agitation, hallucination and coma Depresses vestibular excitation and has anti motion sickness properties Supresses tremor and rigidity of parkinsonism by blocking cholinergic overactivity in basal ganglia. 26

27. Contd … Eye: Dilated pupils( mydriasis ) Blocks muscarinic innervations on the circular muscles( Mydriasis ) and relaxes ciliary muscles( cycloplegia ) Worsens glaucoma Gastrointestinal : Relax smooth muscle of GI tract Decrease intestinal and gastric secretions Antispasmodic effect 27

28. Contd … Respiratory system: Decreases bronchial secretion(used as preanesthetic medication,COPD ) Dilated bronchial airways(used in asthma treatment) Genitourinary: Relaxes detrussor muscle Relaxation of smooth muscle of ureters Glandular: Decreases salivary secretion(dry mouth) Decreases gastric acid(used for peptic ulcer) Decreases sweating(dry skin) Decreases bronchial secretion(used for COPD) 28

29. Toxicity of Anticholinergics Anticholinergic overdose syndrome (Belladonna poisoning-consumption of seeds or berries of belladonna or dhatura plant) is characterized by: Hyperthermia, delirium, dry mouth, tachycardia, urinary retention. Seizures, coma and respiratory arrest may occur. Treatment: Gastric lavage with tannic acid, cold sponging or ice bags, Physostigmine s.c . or i.v ., diazepam to control convulsions. 29

30. Contraindications Glaucoma Prostatic hypertrophy Urinary tract obstruction Gastrointestinal tract obstruction Infectious diarrhea Angina Hyperthyroidism pregnancy 30

31. Reference Sharma H.L., Sharma K.K., Principles of pharmacology, Paras medical publisher;2007. Tripathi K.D., Essentials of medical pharmacology, JP Medical Ltd;2013. Goodman L.S., Goodman and Gilman’s the phamacological basis of therapeutics;1996. Shah H.P., Ritter J.M., Rang and Dale’s pharmacology, Elsevier Ltd;2016. 31

32. Important Questions 1)Which of the following structure is supplied with parasympathetic division? A. sweat glands B. blood vessels of skeletal muscle C. skin D. none of the above 2) What is other the name of parasympathetic division? A. thoracolumbar outflow B. thoracosacral outflow C. craniosacral outflow D. craniolumber outflow 3) ANS is a part of which nervous system? A) central nervous system B. somatic nervous system C. peripheral nervous system D. all of the above 32

33. Contd … 4) Acetylcholine is synthesised and packaged in the presynaptic terminal before being released to act on the postsynaptic receptors. Which of these statements about that process in parasympathetic postganglionic neurons is not true? A) Acetylcholine is synthesised by the action of choline -o- acetyltransferase on choline and acetyl coenzyme A. B) Release of neurotransmitter is triggered when voltage sensitive calcium channels open to allow the influx of calcium. C) The released acetylcholine acts on postsynaptic nicotinic receptors. D)  Choline is recycled by being taken back up into the presynaptic terminal. 5) The postganglionic neuron releases what neurotransmitter in the parasympathetic nervous system? A) Arginine B) Norepinephrine C) Dopamine D) Acetylcholine 33

34. Contd … 6) The autonomic nervous system A) enables us to act on the external environment B)transmits motor information to the brain C)regulates the internal environment D) is located within the brain 7) Which of the following generally acts to conserve energy? A)somatic nervous system B)peripheral nervous system C)sympathetic nervous system D)parasympathetic nervous system 8) Parasympathetic nerve arises from which region of the nervous system? A) Cranio sacral B)Lumbar C)Cervical D) Thoracolumbar 34

35. Contd … 9) Muscarinic receptor are located in? A)Sensory carotid sinus baroreceptor zone B)Autonomic effector cells C)Autonomic ganglia D) Skeletal muscle neuromuscular junction 10) Indicate the location of M2 cholinoreceptor type- A)Heart B) Glands C)Endothelium D) Smooth muscle 35

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