Ganglionic stimulants and blockers suffi

Dr.Umer Sufyan.M

1. GANGLIONIC STIMULANTS & GANGLIONIC BLOCKERS Dr. UMER SUFYAN M MBBS , MD PHARMACOLOGY DEPARTMENT ACSR Govt MEDICAL COLLEGE, NELLORE

2. GANGLIONIC STIMULANTS

3. Drugs can act on sympathetic and parasympathetic ganglia producing either stimulation or blockade.

4. Ganglion No transmission of signals Blocks  I nhibition  Blocks predominant tone  Blocks reflexes.

5. Ganglionic stimulants have extremely limited therapeutic application but find use as in various experimental tools. Ganglionic blocking agents are effective in the treatment of hypertension etc…..

6. GANGLIONIC STIMULANTS Selective nicotinic agonists Nicotine (small dose) Lobeline Dimethyl phenyl piperazinium (DMPP) Tetramethyl ammonium (TMA) Varenicline Nonselective / muscarinic agonists Acetylcholine Carbachol Pilocarpine Anticholinesterases

7. A variety of agents, including Nicotine, Lobeline, and Di-Methyl Phenyl Piperazinium (DMPP), can stimulate ganglionic nicotinic receptors. Although these drugs have little or no therapeutic use, Offer only considerable interest like :- I) Drugs like Nicotine stimulate and block ganglionic receptors proved a valuable aid in identifying and localizing postganglionic fibers.

8. II) Nicotine’s use as a potent insecticide and rodenticide and its presence in tobacco smoke have endowed it with considerable toxicological interest.

9. Mechanism of Ganglionic Stimulation Nicotine, Lobeline, and DMPP etc….. Combine with ganglionic nicotinic receptors on the postsynaptic membrane Leads membrane depolarization, Influx of sodium and calcium ions Generation of a fast excitatory - - postsynaptic potential . stimulation of autonomic ganglia and a complex pattern of mixed sympathetic and parasympathetic responses.

10. ACTIONS : i ) Activation of nicotinic receptors on the plasma membrane of the cells of the adrenal medulla Exocytotic release of E and NE Ii ) Stimulation of nicotinic receptors at NMJ Contraction of skeletal muscle

11. Treatment of smoking cessation/ quiting tobacco chewing Majority of smokers (and tobacco chewers) wish to quit smoking/chewing, but fail to do so because of nicotine dependence. measure to help smokers quit is counseling and motivation . The goals of pharmacotherapy are: To reduce the craving for the satisfying (reward) effects of nicotine. To suppress the physical withdrawal symptoms of nicotine.

12. The drugs currently utilized for the above goals are : Nicotine replacement Partial agonists of α4β2 NRs ( Varenicline ) Antidepressants ( Bupropion )

13. Nicotine transdermal :- patches releasing 7, 14, 21 mg nicotine per 24 hr respectively. In smoking > 20 cigarettes /day-start with 30 cm2 patch, shift to Smaller patches every 5–8 days & treat for 3–4 weeks (max. 12 weeks).

14. Nicotine chewing gum :- 1, 2, 4 mg chewing gum Smoking >20 cigarettes/day— Start with 4 mg gum chewed and retained in mouth for 30 min when urge to smoke is felt. After a few days change over to 2 mg gum and then to 1 mg gum. Not more than 15 pieces to be used in a day.

15. Varenicline :- Initially 0.5 mg OD, gradually increase upto 1 mg BD according to need, for not more than 12 weeks; then taper off. Bupropion :- This atypical antidepressant inhibits reuptake of DA and NA, and has been marketed as a sustained release tablet specifically for smoking cessation. Clinical efficacy has been rated equivalent to nicotine replacement

16. GANGLION BLOCKERS

17. GANGLION BLOCKERS Ganglion blockers are competitive antagonist at NN receptors in autonomic ganglia. Net effect of the blocker is to reduce the predominant tone. Effects are predictable and depend on the relative dominance in terms of PANS and SANS.

18. GANGLION BLOCKING AGENTS A. Competitive blockers Quaternary ammonium compounds Hexamethonium , Pentolinium Mecamylamine , Pempidine Monosulfonium compound :- Trimethaphan camforsulfonate B. Persistent depolarising blockers Nicotine (large dose) Anticholinesterases (large dose)

19. The competitive ganglion blockers were used in the 1950s for hypertension and peptic ulcer , but have been totally replaced now because they produce a number of intolerable side effects

20. Trimethaphan is an ultrashort acting ganglion blocker; has been occasionally infused i.v . to produce controlled hypotension and in hypertensive emergency due to aortic dissection.

21. Mecamylamine : alone or in combination with Nicotine patch been tried for smoking cessation. It appears to block the reward effect of nicotine. Constipation occurred in many subjects, and it is not an approved drug. “At present there is no clinical relevance of ganglion blockers.”

22. THANK YOU