parasympathomimetic

1. PARASYMPATHOMIMETICS (
CHOLINERGIC AGONISTS)

3. TYPES OF CHOLINE ESTERASE ENZYMES
Acetyl-Choline Esterase (A.Ch.E.)
True-Ch.E.
Butyryl-Choline
Esterase
(B.Ch.E.)Pseudo-Ch.E.
1- Sites All cholinergic sites + CNS + RBCs Liver & Plasma
2- Substrates - Endogenous A.Ch.
Methacholine(Parasympathomimetic)
- Exogenous A.Ch.
- Butyrylcholine
- Succinylcholine (N-M
blocker)
- Procaine (Local
anesthetic)
Propanidid (I.V.
general anesthesia)

6. EFFECTS OF DIRECT-ACTING CHOLINOCEPTOR
STIMULANTS.
 Organ Response
 Eye
 Sphincter muscle of iris Contraction (miosis).
 Ciliary muscle Contraction for near vision and
outflow of aqueous humor
 Decrease of Intraocular pressure .


7.  Heart
 Sinoatrial node(SA) Decrease in rate (negative
chronotropy)
 Atria Decrease in contractile strength (negative
inotropy).
 Atrioventricular node (AN)Decrease in conduction
velocity (negative dromotropy).

8.  Blood vessels
 Arteries Dilation (via endothelium-derived relaxing
factor, or EDRF
 Veins Dilation (via EDRF).
 Lung
Bronchial muscle Contraction (bronchoconstriction)
 Bronchial glands Stimulation secretion

9.  Gastrointestinal tract
 Motility Increase
 Sphincters Relaxation
 Secretion Stimulation

10.  Urinary bladder
 Detrusor Contraction
 Trigone and sphincter Relaxation

 Glands
 Increase Sweat, salivary, lacrimal, nasopharyngeal
Secretion

11. DIRECT-ACTING CHOLINERGIC AGONISTS
 Acetylcholine
 Susceptibility to Cholinesterase
 Have Muscarinic and Nicotinic Action
 very rapidly hydrolyzed in the gastrointestinal
tract
 Acetylcholine is available as an ophthalmic
surgical aid for the rapid production of miosis .

12. BETHANECHOL
 completely resistant to hydrolysis by
cholinesterases .
 has mainly muscarinic actions, showing some
selectivity on gastrointestinal tract and urinary
bladder motility.
 Bethanechol directly stimulates muscarinic
receptors.

13.  Therapeutic applications
 It is used to stimulate the atonic bladder, particularly
in postpartum or postoperative, nonobstructive
urinary retention.
 Adverse effects
 Sweating, salivation, flushing, decreased blood
pressure, nausea, abdominal pain, diarrhea, and
bronchospasm

14. CARBACHOL (CARBAMYLCHOLINE)
 completely resistant to hydrolysis by
cholinesterases.
 Carbachol has both muscarinic as well as nicotinic
actions.
 Therapeutic uses
 carbachol is rarely used therapeutically except in
the eye as a miotic agent to treat glaucoma by
causing pupillary contraction and a decrease in
intraocular pressure.

 Adverse effects:
 At doses used ophthalmologically, little or no side
effects occur due to lack of systemic penetration .

15. PILOCARPINE
 Pilocarpine exhibits muscarinic activity and is used
primarily in ophthalmology.
 Pilocarpine is administered orally in 5- to 10-mg
doses given three times daily for the treatment of
xerostomia that follows head and neck radiation
treatments or that is associated with Sjogren's
syndrome.

16. THERAPEUTIC USE IN GLAUCOMA
 Pilocarpine is the drug of choice in the emergency
lowering of intraocular pressure of both narrow-angle
(also called closed-angle) and wide-angle (also called
open-angle) glaucoma.
 Adverse effects
 Pilocarpine can enter the brain and cause CNS
disturbances. It stimulates profuse sweating and
salivation.

17. CEVIMELINE
 Is a newer agonist with activity at M3 muscarinic
receptors. These receptors are found on lacrimal
and salivary gland epithelia.
 Cevimeline has a long-lasting sialogogic action and
may have fewer side effects than pilocarpine . It
also enhances lacrimal secretions in Sjogren's
syndrome .

18. INDIRECT-ACTING CHOLINERGIC AGONSISTS:
ANTICHOLINESTERASES (REVERSIBLE)
 Physostigmine
 Actions
 Inhibits of acetylcholinesterase enzyme that
indirectly provide a cholinergic action by prolonging
the lifetime of acetylcholine produced endogenously
at the cholinergic nerve endings. This results in the
accumulation of acetylcholine in the synaptic space.

19. PHYSOSTIGMINE
 Its duration of action is about 30 minutes to 2 hours,
and it is considered an intermediate-acting agent.
 Physostigmine can enter and stimulate the
cholinergic sites in the CNS.

20. THERAPEUTIC USES
 It is used to treat glaucoma
 Physostigmine is also used in the treatment of
overdoses of drugs with anticholinergic actions,
such as atropine, phenothiazines, and tricyclic
antidepressants.

21. ADVERSE EFFECTS:
 convulsions when high doses are used.
 Bradycardia
 paralysis of skeletal muscle.

22. NEOSTIGMINE
 Unlike physostigmine, neostigmine is more polar,
is absorbed poorly from the GI tract, and does not
enter the CNS. Its effect on skeletal muscle is
greater than that of physostigmine, and it can
stimulate contractility before it paralyzes.
 Neostigmine has an intermediate duration of action,
usually 30 minutes to 2 hours.

23. NEOSTIGMINE
 It reversibly inhibits acetylcholinesterase in a
manner similar to that of physostigmine.
 It is used to stimulate the bladder and GI tract.
 Neostigmine has found use in symptomatic
treatment of Myasthenia gravis.
 Adverse effects of neostigmine include those of
generalized cholinergic stimulation, such as
 salivation,
 flushing,
 decreased blood pressure,
 nausea,
 abdominal pain,
 diarrhea, and
 bronchospasm.

24. PYRIDOSTIGMINE AND AMBENONIUM
 Pyridostigmine and ambenonium are other
cholinesterase inhibitors that are used in the
chronic management of myasthenia gravis.
 Their durations of action are intermediate (3 to 6
hours and 4 to 8 hours, respectively) but longer
than that of neostigmine.
 Adverse effects of these agents are similar to those
of neostigmine

25. EDROPHONIUM
 The actions of edrophonium are similar to those
of neostigmine, except that it is more rapidly
absorbed and has a short duration of action of 10 to
20 minutes
 . Edrophonium is used in the diagnosis of
Myasthenia gravis. Intravenous injection
of edrophonium leads to a rapid increase in muscle
strength. Care must be taken, because excess drug
may provoke a cholinergic crisis. Atropine is the
antidote.

26. INDIRECT-ACTING CHOLINERGIC AGONSISTS:
ANTICHOLINESTERASES (IRREVERSIBLE)
 A number of synthetic organophosphate
compounds have the capacity to bind covalently to
acetylcholinesterase.
 Related compounds, such as parathion
(organophosphours compound), are employed as
insecticides.

27. ECHOTHIOPHATE
 Therapeutic uses:
 An ophthalmic solution of the drug is used directly
in the eye for the chronic treatment of open-angle
glaucoma. The effects may last for up to one week
after a single administration.