pharmacology lecture

1. GANGLIONIC
STIMULANTS &
GANGLIONIC
BLOCKERS
Dr. Maria Qammar
PHARMACOLOGY DEPARTMENT

2. GANGLIONICSTIMULANTS

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

4. Ganglion
No transmission of signals
Blocks  Inhibition
 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 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. o 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. GANGLIONBLOCKERS

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 BLOCKINGAGENTS
A. Competitive blockers Quaternary
ammonium compounds
 Hexamethonium, Pentolinium
 Mecamylamine, Pempidine
Monosulfonium compound :-
 Trimethaphan
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

21. 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.

22. 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.

23. Adverse effects of Ganglion Blocking
Drugs:
 Excessive orthostatic hypotension
 Sexual dysfunction.
 Constipation
 Urinary retention
 Precipitation of Glaucoma
 Blurred vision
 Dry mouth

24. THANK YOU