2. Overview
Drugs affecting the ANS are divided into two groups
according to the type of neuron involved in the
mechanism of action:
a) The cholinergic drugs: they act on receptors that are
activated by acetylcholine (Ach)
b) The adrenergic drugs: they act on receptors that are
activated by norepinephrine or epinephrine
3. Cholinergic Receptors (Cholinoceptors)
• Cholinoceptor denotes receptors that respond to
acetylcholine.
• Two families/subtypes of cholinoceptors were
named after the alkaloids originally used in their
identification: muscarinic (M) and nicotinic (N)
receptors.
4. I. Muscarinic (M) receptors
• These receptors, in addition to binding
acetylcholine, also recognize muscarine, but
show a weak affinity for nicotine.
• Five subclasses of muscarinic receptors: M1, M2,
M3, M4, and M5 have been identified
5. I. Muscarinic (M) receptors
• responsible for activating Ca+2-dependent
responses, such as secretion by glands and the
contraction of smooth muscle
6. II. Nicotinic (N) receptors
• These receptors, in addition to binding ACh, also
recognize nicotine, but show a week affinity for
muscarine.
• N receptors are located on plasma membranes
of postganglionic cells in all autonomic ganglia,
of muscles innervated by somatic motor fibers
(i.e. Neuromuscular junction), and of some CNS
neurons.
7. II. Nicotinic (N) receptors
• When the nicotnic AchR is stimulated, the
channel opens and allows Na+ to rush into the
cell
• This triggers depolarization of the cell and elicits
a neruronal action potential (in postganglionic
nerve) or muscle contraction (in skeletal
muscles).
8. Cholinomimetic agents
• Cholinomimetic drugs can elicit some or all of
the effects that acetylcholine (ACh) produces.
• Include agents that act directly (cholinoceptor
agonists/stimulants) or indirectly acting
mechanisms (cholinesterase inhibitors).
10. • Cholinergic receptor agonists mimic the effects
of ACh by binding directly to cholinoceptors
• The directly acting cholinomimetics can be
subdivided into:
• 1- Parasympathomimetic drugs: primarily work
through binding to muscarinic receptors.
• 2- Agents that stimulate nicotinic receptors.
11. • These agents can be divided into two groups:
• 1-Choline esters (acetylcholine, metacholine,
carbachol, & bethanechol)
• 2-Naturally occurring cholinomimetic alkaloids
(muscarine, nicotine, pilocarpine, & lobeline)
13. Direct acting cholinergic stimulants
Organ system effect
• Cardiovascular system:
1. Vasodilation.
2. Decrease in heart rate.
3. Decrease in the force of cardiac contraction
• Eye:
cause contraction of the smooth muscle of the:
1) Iris sphincter*: resulting in miosis
2) Ciliary muscle*: resulting in accommodation of
the eye for near vision
14.
15. Direct acting cholinergic stimulants
Organ system effect
c. Other Organ Systems
Respiratory system: bronchoconstriction & increase
tracheobronchial secretion
GIT: stimulation of salivation and acid secretion.
Genitourinary tract: promoting urination.
16. Direct acting cholinergic stimulants
Organ system effect
CNS: Muscarinic agonists are able to produce marked
CNS owing to activation of M1-receptors in the brain
areas involved in cognition.
17. Clinical uses of the direct acting
cholinomimetics
a) Glaucoma: cholinomimetics reduce
intraocular pressure by causing contraction of
the ciliary body so as to facilitate outflow of
aqueous humor (e.g pilocarpine and carbachol)
b) Bladder and bowel atony after surgery:
Bethanechol
c) Xerostomia associated with Sjögren's
syndrome and that caused by radiation damage
of the salivary glands: pilocarpine & cevimeline
18. Nicotinic receptors
• Direct acting nicotine agonists have no
therapeutic applications exept in smoking
cessation (nicotine and varenicline) and
producing skeletal muscle paralysis
(succinylcholine).
19. Nicotine replacement therapy
• To help patients stop smoking .
• Available in the form of gum, transdermal patch,
nasal spray, or inhaler.
20. Varenicline (Chantix®)
• Is a partial agonist at α4β2 nicotinic receptors.
• Varenicline prevents the stimulant effect of
nicotine at presynaptic α4β2 receptors that
causes release of dopamine.
• ADRs: nausea, insomnia, and exacerbation of
psychiatric illnesses, including anxiety and
depression
22. Indirect acting cholinomimetics
Acetylcholinesterase (AChE) is an enzyme that
specifically cleave ACh to (acetate and choline) and,
thus, terminates its action.
Inhibitors of AChE indirectly provide a cholinergic
action by prolonging the lifetime of acetylcholine (i.e.
they have both muscarinic and nicotinic effects)
23. Indirect acting cholinomimetics
• There are three chemical groups of cholinesterase
inhibitors:
(1) Simple alcohols bearing a quaternary ammonium
group, eg, edrophonium
(2) Carbamates (eg, neostigmine)
(3) Organophosphates (eg, echothiophate)
24. Therapeutic Uses and Durations of Action of Cholinesterase Inhibitors
Uses Approximate Duration of Action
Alcohols
Edrophonium Myasthenia gravis,
arrhythmias
5–15 minutes
Carbamates and related agents
Neostigmine Myasthenia gravis, 0.5–2 hours
Pyridostigmine Myasthenia gravis 3–6 hours
Physostigmine Glaucoma 0.5–2 hours
Ambenonium Myasthenia gravis 4–8 hours
Demecarium Glaucoma 4–6 hours
Organophosphates
Echothiophate Glaucoma 100 hours
Types and some uses:
25. Indirect acting cholinomimetics
Organ system effect
• Central nervous system (CNS)
In higher concentrations, they cause generalized
convulsions, which may be followed by coma and
respiratory arrest.
• Eye, Respiratory Tract, GIT, & Urinary Tract
The effects of the cholinesterase inhibitors are
qualitatively quite similar to the effects of the direct-
acting cholinomimetics.
26. Clinical uses
• Glaucoma: physostigmine, demecarium,
echothiophate, isoflurophate
• Gastrointestinal and Urinary Tracts:
Neostigmine to treatment of adynamic ileus and
atony of the urinary bladder.
• Myasthenia gravis:Carbamates
(Pyridostigmine, neostigmine , and
ambenonium): anticholinesterase agents used in
the long-term therapy for myasthenia gravis.
