Cholinergic Drugs
Dr. Saira Jahan
Cholinergic Stimulants
increase activity at acetylcholine synapses.
Direct-Acting Cholinergic Stimulants
bind directly to the cholinergic receptor to activate it…
relativly specific
For instance, drugs that have a greater specificity for the
muscarinic cholinergic receptor are more beneficial. These
muscarinic cholinergic stimulants will primarily affect the
peripheral tissues while exerting a minimal effect on the
cholinergic receptors located in the autonomic ganglia and
the neuromuscular junction.
Systemic…Bethanechol…stimulate muscarinic cholinergic
receptors…GI and bladder atony after surgery.
carbachol and pilocarpine are limited to topical
use..glaucoma.
Methacholine..administered locally to the lungs via
inhalation to test for airway hyperresponsiveness when
Indirect-Acting
Cholinergic Stimulants
by inhibiting the acetylcholinesterase
enzyme…cholinesterase inhibitors or
anticholinesterase agents
Lack of specificity…
Neostigmine & pyridostigmine
TACRINE AND DONEPEZIL
ECHOTHIOPHATE
EDROPHONIUM
PHYSOSTIGMINE
Clinical Applications of Cholinergic
Stimulants
Alzheimer Disease… progressive neuro
degenrative disorde effect older
adults. ..cholinergic neurons…memory,
cognition,HMF
Indirect chole stimulant …tacrine , donepezil ,
galantamine, and rivastigmine effective in early
stages…prolong the effects of any acetylcholine
released from neurons that are still functioning
in the Cerebral cortex.
do not alter the progression…less effective in
advanced cases.
Gastrointestinal and Urinary Bladder Atony.
After surgery or other trauma to the viscera…
period of atony(loos of tone)in (smooth
muscles)SMCs…intestinal peristalsis is diminished
or absent, and bladder becomes distended, leading
to urinary retention.
Bethanechol (DA)and neostigmine(IDA)
Glaucoma…increase in intraocular
pressure by acumulatn of aques humor in
eye..impaired vision and blindness.
Cholinergic stimulation by para sysm…
increases the outflow of aqueous
humor...topically..carbachol & pilocarpine.
Myasthenia Gravis
autoimmune …skeletal NM junction…dec number
of [Link] at [Link]…
autoantibodies… skeletal muscle weakness and
profound fatigability…patient require respiratory
support
no cure…ambenonium, neostigmine, and
pyridostigmine… [Link] inhibit the
acetylcholinesterase enzyme at NM junction,
allowing the endogenous acetylcholine released
from the presynaptic terminal to remain at the
myoneural junction for a longer period of time.
Reversal of Neuromuscular Blockage
during general anesthesia to maintain skeletal
muscle paralytic:agents include curare like drugs
(e.g., tubocurarine,
gallamine, pancuronium).
accelerated recovery from the paralytic effects of
these NM blockers may be desired at the end of
the surgical procedure.
IND-A cholinergic stimulants are sometimes used.
Reversal of Anticholinergic-Induced CNS
Toxicity
Indirect-acting cholinergic stimulants (e.g.,
physostigmine)
it case delirium, hallucinations, and coma.
Adverse Effects of
Cholinergic Stimulants
Due to nonspecificity of these drugs.
bethanechol, relatively specific for muscarinic
receptors, may stimulte M receptors elsewhere…
improves GI tone & BC
Exaggerated parasympathetic activity release
more acetyl
Cont…
1. GI distress (nausea, vomiting, diarrhea,
abdominal cramping),
2. Increased salivation,
3. bronchoconstriction,
4. Bradycardia
5. Difficulty in visual accommodation.
6. Increased sweating and vasodilation of
facial cutaneous blood vessels (flushing)
Anticholinergic
Drugs
competitive antagonists of the postsynaptic
cholinergic receptors…blocks the receptor from
the effects of endogenously released acetylcholine.
Antimuscarinic or antinicotinic agents.
SOURCE:atropine …The prototypical antiM-antich
drug..naturally occurring… extract of plants
belladonna and jimsonweed…semisynthetic, and
synthetic agents have been developed.
MOA:they block the postsynaptic cholinergic
muscarinic receptor.
Cont…
ANISOTROPINE IPRATROPIUM
ATROPINE MEPENZOLATE
BELLADONA METHENTHELINE
CLIDINIUM OXYBUTYRINE
CYCLOPENTOLATE PROPANTHELINE
DICYCLOAMINE SCOPOLAMINE
HOMATROPINE
HYOSCYAMINE
Clinical Applications of
Antimuscarinic Drugs
Stimulation of the gastrointestinal tract via
parasympathetic cholinergic neurons generally produces an
increase in gastric secretions and an increase in
gastrointestinal motility.
Consequently, certain antimuscarinic anticholinergics tend
to reverse this stimulation by blocking the effects of
endogenously released acetylcholine. Clinically, these drugs
are used as an adjunct in peptic ulcer.
Also, antimuscarinic anticholinergic drugs have been
approved for treatment of irritable bowel syndrome.
This condition is characterized by hyperactivity of
gastrointestinal smooth muscle and includes problems such
as irritable colon and spastic colon. These antimuscarinic
agents are sometimes referred to as antispasmodics
because of their reported ability to decrease
Parkinson Disease
movement disorder caused by a deficiency of the
neurotransmitter dopamine in the basal ganglia…
leads to an overactivity of central cholinergic
synapses.
benztropine, biperiden, and trihexyphenidyl….
preferentially block the central muscarinic
cholinergic synapses but also affect other
peripheral muscarinic receptors…side effects dry
mouth, constipation, and urinary retention, which
are caused by their antagonistic effect on
muscarinic receptors located outside of the brain.
Their primary effect, however, is to decrease the
influence
of central cholinergic synapses in parkinsonism.
Cardiovascular System
Atropine reverses the effects of excessive vagal
discharge and is used to treat the symptomatic
bradycardia that may accompany MI…also useful
in treating other cardiac arrhythmias such as
atrioventricular nodal block and ventricular
asystole.
Motion Sickness
…Scopolamine ..block cholinergic transmission
from areas of the brain and brainstem that mediate
motion-related nausea and vomiting (i.e., the
vestibular system and reticular formation).
Transdermally via small patches.
Preoperative Medication.
Atropine…occasionally used preoperatively to
decrease respiratory secretions during general
anesthesia…newer inhalation forms of GA.
Urinary Tract
…to alleviate urinary frequency and
incontinence caused by hypertonicity of the
urinary bladder.
detruser-cont, sphincter-relax
by inhibiting contraction of the bladder
detrusor muscle, thus allowing the bladder to
fill more normally, with a decrease in
frequency of urination and a lesser chance of
incontinence.
Respiratory Tract
atropine and some synthetic derivatives
(ipratropium, tiotropium) have been used to treat
bronchospasms occurring in patients with asthma
and chronic obstructive pulmonary disease
as a second choice for patients of asthma…Ist
choice…B2 agonists(salbutamol)
Ist choice in COPD.
Eye
Atropine and similar antimuscarinics block the
acetylcholine-mediated contraction of the pupillary
sphincter muscle, thus causing dilation of the pupil
During an ophthalmologic exam…applied
topically…for detailed inspection.
Cholinergic Poisoning
…eating wild mushrooms, exposed to certain
pesticides, or being exposed to certain types of
chemicals…inhibit the acetylcholinesterase enzyme
throughout the body.
require emergency treatment with atropine or an
analogous anticholinergic agent. In cases of severe
poisoning, fairly high doses of these drugs must
often be administered for several days.
Side Effects of Anticholinergic
1. dryness of the mouth,
2. blurred vision,
3. urinary retention,
4. constipation, and
5. tachycardia.
6. confusion, dizziness, nervousness, and
drowsiness…drugs that cross the BBB.
Thank You
