Ganglionic stimulants and blockers suffi

GANGLIONIC STIMULANTS &

GANGLIONIC BLOCKERS

Dr. UMER SUFYAN M

MBBS, MD

PHARMACOLOGY DEPARTMENT

ACSR Govt MEDICAL COLLEGE, NELLORE

GANGLIONIC STIMULANTS

• Drugs can act on sympathetic and

parasympathetic ganglia producing

either stimulation or blockade.

Ganglion

No transmission of signals

Blocks Inhibition

Blocks predominant tone

Blocks reflexes.

• 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…..

GANGLIONIC STIMULANTS

Selective nicotinic agonists

Nicotine (small dose)

Lobeline

Dimethyl phenyl

piperazinium (DMPP)

Tetramethyl ammonium

(TMA)

Varenicline

Nonselective /

muscarinic agonists

Acetylcholine

Carbachol

Pilocarpine

Anticholinesterases

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.

II) Nicotine’s use as a potent insecticide and

rodenticide and its presence in tobacco smoke

have endowed it with considerable

toxicological interest.

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.

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

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.

o The drugs currently utilized for the above

goals are :

Nicotine replacement

Partial agonists of α4β2 NRs

( Varenicline)

Antidepressants ( Bupropion)

• 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).

• 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.

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

GANGLION BLOCKERS

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.

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)

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

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.

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.”

THANK YOU