Uujuu

1. Session 10-Lecture 2
Membrane and receptor module
Drugs affecting the ANS
By: Ass. Prof. D.Gulala. I. Qader

2. Parasympathomimetics
Drugs affecting the ANS
Mimic acetylcholine action
cholinergic = muscarinic agonists= parasympathomimetics

3. Drugs that increase the
parasympathetic nervous system
response:
How does this change occur?
They produce responses similar to
parasympathetic neurotransmitters
acetylcholine
▪ Salivation
▪ Lacrimation
▪ Urinary incontinence
▪ Diarrhea
▪ Gastrointestinal
cramps
▪ Emesis
Through binding to parasympathetic
receptors (M,N)

4. Classification of cholinergic agonists
1. Direct acting cholinergic
receptor agonists: (Bind to
cholinergic receptors, activating
them)
2. Indirect acting cholinergic
receptor agonists: (acetylcholine
esterase inhibitors

5. Clinical pharmacology of cholinergic receptor agonists
Drug Receptor
Cholinesteras
e
Sensitivity Clinical
Use
Acetylcholi
ne
M,
N
Ye
s
Intraocular use for miosis during
surgery
Carbach
ol
M,
N
N
o
Intraocular use for miosis during
surgery,
glaucom
a
Pilocarpin
e
M N
o
Glaucom
a
Bethanech
ol
M N
o
Urinary retention, post-operative
ileus
M=Muscarin
ic
N=Nicotini
c

6. Indirect
acting
cholinergics
⚫ Do not act directly on the Ach
receptors
⚫ Cause non-specific cholinergic
stimulation.
⚫ Two mechanisms of action:
1. Inhibit the enzyme acetylcholine
esterase (reversibly or irreversibly)
2. Stimulate the release of
acetylcholine from the vesicles
(spider venom)

7. Indirect acting cholinergics:acetylcholine esterase inhibitors
All are nonspecific – act on muscarinic & nicotinic receptors at all
sites: parasympathetic NS, ganglia, NMJ.
Reversible inhibition of enzyme:
⚫ Drugs: Physostigmine, neostigmine, pyridostigmine.
⚫ Uses: GI atony, bladder atony, glaucoma, myasthenia gravis and atropine
poisoning
Edrophonium uese to diagnose myasthenia gravis
Donepezil, rivastigmine, galanthamine to slow the progression of
Alzheimer’s disease
Irreversible inhibition of enzyme:
⚫ Drugs (echothiophate)
⚫ Insecticides (malathion, parathion)
⚫ Nerve gases used in warfare (Sarin,Tabun).

8. Parasympatholytic
Cholinergic antagonists
Drugs affecting the ANS
8

9. Classifications of anticholinergic
Antimuscarinic
1. Atropine
2. Scopolamine
3. Ipratropium, tiotropium
4. Cyclopentolate
5. Tropicamide
Neuromuscular blockers (nicotinic blocker)
(Cisatracurium, pancuronium, rocuronium, vecuronium,
⚫ Tubocurarine, Succinylcholine….etc) Neuromuscular blocking
drugs are used to induce complete skeletal muscle relaxation in
surgery

10. Antimuscarinic
These agents (for example, atropine and scopolamine) block
muscarinic receptors, causing inhibition of all muscarinic
functions. In addition, these drugs block the few
exceptional sympathetic neurons that are cholinergic, such
as those innervating sweat glands.
Mechanism of action
• Blocks muscarinic receptors
• Salivary, bronchial, and sweat glands are most sensitive to
atropine
• Smooth muscle and heart are intermediate in responsiveness
10

11. SYNTHETIC ATROPINE DERIVATIVES
ORGAN DRUG
APPLICATION
❑ Eye tropicamide, cyclopentolate Pupil dilation
❑ CNS Benztropine Treat Parkinson’s disease
Scopolamine Prevent/Reduce motion sickness
❑ Bronchi Ipatropium, tiotropium Bronchodilate in Asthma, COPD
❑ GI Methscopolamine Reduce motility/cramps
Pirenzepine PU
❑ GU Oxybutinin Treat transient cystitis
Postoperative bladder spasms

12. Drugs acting at the
cholinergic nerve terminal

13. Receptor Regulation in Autonomic Applications
In many clinical conditions the targeted receptor eg
B1R in atenolol will be upregulated whereas in
stimulation with salbutamol B2R could be
downregulated. This phenominon occurs mainly due
to a biological response to signal transduction that will
modify gene transcription to return homeostasis.
So that in case of chronic (eg > 2 weaks ) use of
atenolol then B1R could be expressed in many folds
higher than basal level. This will cause rebound
phenominon or tachyphylaxis i.e there will be the
inverse symptoms like tachycardia, hypertension when
atenolol is suddenly withdrown.

14. Action Potential
Na+
Effect of chronic β-receptor blockade
Presynaptic neuron
H+
Effector organ
Ca2+
Na+
Tyrosine
Tyrosine
Dopamine
DA
NE
Uptake 1
Na+
, Cl-
NE
NE
NE
NE
NE
MAO

15. Action Potential
Na+
Effect of chronic β-receptor blockade:
Receptor up-regulation
H+
Effector organ
Ca2+
Na+
Tyrosine
Tyrosine
Dopamine
DA
NE
Uptake 1
Na+
, Cl-
NE
NE
NE
NE
NE
MAO

16. Action Potential
Na+
Effect of chronic β-receptor blockade:
Receptor up-regulation
H+
Effector organ
Ca2+
Na+
Tyrosine
Tyrosine
Dopamine
DA
NE
Uptake 1
Na+
, Cl-
NE
NE
NE
NE
NE
MAO