Direct and Indirect acting Drugs

1. Parasympathomimetic Drugs:
Direct and Indirect acting drugs
Lecture 3
Dr. Jasmine Chaudhary
Associate Professor
MMCP, Mullana

2. • Ester of carbamic acid
• Has both muscarinic and nicotinic actions
•Muscarinic actions are prominent on eye, GIT & urinary bladder
• DOA more than 30 min
•Used in treatment of glaucoma.
•Acetylcholine and Carbachol may be used for intraocular
use as a miotic in surgery

3. Bethanechol
• Not hydrolyzed by acetylcholinesterases
• Actions
• Directly stimulates M receptors causing increased intestinal motility &
tone
• It stimulates detrusor muscle of the bladder while trigone & sphincters
are relaxed causing expulsion of urine.
No nicotinic action, only muscarinic especially on GIT and urinary
system
• Therapeutic Uses:
• Urinary retention
• Helpful for postsurgical atony of the bladder and GI tract

4. Methacholine
• More selective on cardiovascular system.
• Weak nicotinic effect
• Methacholine is primarily used to diagnose bronchial hyperreactivity, which is
hallmark of asthma and also occurs in chronic obstructive pulmonary disease
• Therapeutic Uses:
• Urinary retention
• Helpful for postsurgical atony of the bladder and GI tract

5. Pilocarpine
An alkaloid, lipid soluble & is stable to hydrolysis by cholinesterases.
Therapeutic Use :
• Mainly used in the treatment of Glaucoma
• Also used to treat xerostomia/dry mouth as stimulates the secretion
of large amounts of saliva and sweat.
• Pilocarpine is used to stimulate sweat glands in a sweat test to
measure the concentration of chloride and sodium that is excreted in
sweat.

6. Indirect acting Cholinergic agonists
• They act through inhibition of Acetyl cholinesterase enzyme, so
increases Acetylcholine level in the synapse.
• Accumulation of acetylcholine then occurs which enhances the
activation of the nicotinic and muscarinic receptors.
• Anticholinesterase drugs are either reversible or irreversible
inhibitors of acetylcholinesterase

7. Physostigmine (Reversible)
•Highly toxic parasympathomimetic alkaloid, specifically, a reversible
cholinesterase inhibitor
•Used to treat glaucoma and delayed gastric emptying.
•It indirectly stimulates both nicotinic and muscarinic acetylcholine
receptors
•Only anticholinesterase capable of crossing the blood brain barrier as
is more lipid soluble.
•Used as an antidote for overdosage of anticholinergics such as
atropine, antihistamines, TCA, phenothiazines.

8. Neostigmine and Pyridostigmine (Reversible)
•Medication used to treat myasthenia gravis and urinary retention.
•Used as an antidote for tubocurarine and other nondepolarizing agents
in surgery.
•Pyridostigmine is an analogue of neostigmine with one quarter of its
potency

9. Edrophonium and Ambenonium exerts its actions against myasthenia gravis
by competitive reversible inhibition of acetylcholinesterase.
Edrophonium prevent respiratory paralysis in cobra bite also
Tacrine (Reversible)
Centrally acting acetylcholinesterase inhibitor and indirect cholinergic
agonist (parasympathomimetic) approved for the treatment of Alzheimer's
disease
It also acts as a histamine N-methyltransferase inhibitor.
Also described as an analeptic agent used to promote mental alertness

10. Isofluorphate,Echothiopate, Parathion and Malathion
Diisopropyl fluorophosphate (Isoflurophate), Echothiopate, Parathion and
Malathion are irreversible anti-cholinesterase cholinergic drug and are used as
organophosphorus insecticides.
Isofluorphate and Echothiopate are also used in ophthalmology as miotic agent in
treatment of chronic glaucoma.
Parathion
Malathion
Isofluorphate
Echothiopate

11. Cholinesterase reactivator
Pralidoxime (PAM)
• Pralidoxime is an antidote to organophosphate pesticides and chemicals
• It reactivates the enzyme cholinesterase by cleaving the phosphate-ester
bond formed between the organophosphate and acetylcholinesterase.

12. ADVERSE EFFECTS
(Overstimulation of Muscarinic and Nicotinic Receptors)
 Miosis
Salivation
Sweating
Bronchial constriction
Vomiting and diarrhea
Myasthenia gravis
Neuromuscular blockade (nicotinic effect)
CNS effects: high doses

13. Question Bank
• Give structure and use of Pralidoxime, Parathion, Tacrine,
Physostigmine
• Give synthesis and uses of carbachol.
•Write a note on direct acting drugs.