Cholinergic_Antagonists [1].ppt

CHOLENARGIC ANTAGONIST.

1. Cholinergic
antagonists
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2. Cholinergic antagonists are divided in two
subgroups on the basis of their specific receptor
affinities:
● Muscarinic antagonists
● Nicotinic antagonists
Cholinergic antagonists

3. •Antagonist of AchRs act by binding
directly to the agonist site.
•Competitively blocking stimulation of
the receptor.

4. ● Muscarinic antagonists (i.e. antimuscarinic
drugs).
● These agents selectively block the muscarinic
synapses of the parasympathetic nerves.
● The effects of parasympathetic innervations are
interrupted, and
● Allow sympathetic responses to predominate.
● Nicotinic antagonists (i.e. ganglion-blocker and
neuromuscular junction blocker).
Cholinergic antagonists

5. The neuromuscular
junction (NMJ).
At the NMJ, motor neurons
innervate a group of muscle
fibers.
•The area of muscle fibers
innervated by an individual
motor neuron is referred to as
the end-plate region.
•Motor neuron is depolarized,
its synaptic vesicles fuse with
the presynaptic membrane.
•Releasing ACh into the S cleft.
•ACh receptors of the NMJ are
exclusively nicotinic.

6. •Antimuscarinic agents:
•atropine,
•scopolamine,
•ipratropium block muscarinic receptors
causing inhibition of all muscarinic
functions.
•In addition, these drugs block the few
exceptional sympathetic neurons that are
cholinergic –
•eg. Those innervating sweat glands.
Antimuscarinic agents

7. •The most commonly encountered
anticholinergics are
–Either naturally occurring alkaloids
–Or synthetic quaternary ammonium compounds
•Alkaloids are relatively selective for antagonistic
activity at muscarinic receptors
•Synthetic compounds demonstrate antagonism
at nicotinic receptors

8. - Atropine and
Scopolamine are
belladona alkaloids
(competitive inhibitors)
-scopolamine permeates
the BBB
-Atropine: negligible
effect on the CNS at
therapeutic doses.
- Scopolamine even at
low doses has
prominent CNS effects.

9. Mechanism of drug action
- Competitively block muscarinic receptors
- Salivary, bronchial, and sweat glands are
most sensitive to atropine
- Smooth muscle and heart are intermediate
in responsiveness
-In the eye, causes pupil dilation and difficulty for
far vision accomodation
-Relaxation of the GI, slows peristalsis

10. •Atropine, a belladonna
alkaloid, has a high
affinity for muscarinic
receptors, where it
binds competitively,
preventing
acetylcholine from
binding to that site.
Atropine

11. •Atropine is isolated from the plant Atropa
belladonna.
•‘Bella donna’ means ‘beautiful woman’.
•In the old days, in Italy atropine was used
by young women to augment their looks
before attending festivities.
•It widens the pupils of the eyes, and it
prevents sweating, therefore leading to
accumulation of heat and to red cheeks.
•Dilation of pupil was considered a mark of
beauty.

12. •Atropine is both a central and peripheral
muscarinic blocker.
•General actions last about 4 hours except
when placed topically in the eye, where the
action may last for days.

13. Atropine is clinically used
•To induce mydriasis
•To reverse symptomatic sinus bradycardia
•To inhibit excessive salivation and mucous
secretion during surgery
•To prevent vagal reflexes induced by
surgical trauma of visceral organs
•To counteract the effect of muscarinic
poisoning from certain mushrooms.

14. Atropine (Contd.)
•Because of its marginal activity at nAChR
– high dose of atropine is required for
effects to be seen in NMJ.
•Because nicotinic receptors are primarily
responsible for excitatory transmission at
autonomic ganglia, atropine produces
partial block at these sites only at relatively
high doses.

15. •Depending on the dose, atropine may cause
dry mouth, blurred vision, "sandy eyes",
tachycardia, and constipation.
•Effects on the CNS include restlessness,
confusion, hallucinations, and delirium, which
may progress to depression, collapse of the
circulatory and respiratory systems and death.
•In older individuals, the use of atropine to
induce mydriasis and cycloplegia is considered
too risky since it may exacerbate an attack of
glaucoma in someone with a latent condition.
Adverse effects:

16. Scopolamine
•Differs from Atropine for substantial CNS
effects.
•Frequently used for the prevention and
treatment of motion sickness, as an anti-
emetic, and in the hospital setting, as an
adjunct to end of life comfort care
medications to effect mild sedation and
management of oral secretions.

17. Scopolamine (Contd.)
•A transdermal patch system has been
developed to effect slow absorption and
long duration of the anti-motion sickness
effect (plasma level is not increased and no
undesirable CNS effect).
•It can be used to ameliorate nausea,
particularly that associated with
chemotherapy.
•Can be given IV during procedures to
minimize oral secretions.

18. Ipratropium
•Synthetic quaternary ammonium
compound for the treatment of COPD.
•Less effective in treating asthma.

19. Nicotinic Receptor Antagonists
•Selective NRA are used primarily to
produce nondepolarizing (competitive)
neuromascular blockade during surgical
procedure.
•Nondepolarizing NMJ blockers such as
Tubocurare, act by antagonizing nAChR
directly.
•Thus preventing endogenous ACh binding
and subsequent muscle cell depolarization.
•Leads to flaccid paralysis

20. •In selecting a specific agent – primary
consideration is its duration of action.
•Long lasting agents (d-Tubocurarine,
pancuronium)
•Intermediate duration agents (Vecuronium,
rocuronium)
•Rapidly degraded compounds
(mivacurium)