1. Drugs acting on
Autonomic
Nervous System
(3)
1

2. 2
Part 2
Drugs Affecting the
Parasympathetic Nervous
System (PNS)

3. 3

4. Cholinergic Receptors
 Nicotinic Receptors:
 Located in the ganglia of both the PSNS
and SNS
 In vertebrates, nicotinic receptors are
classified into two subtypes based on
their primary sites of expression:
muscle-type nicotinic receptors and
neuronal-type nicotinic receptors
 Named “nicotinic” because can be
stimulated by the nicotine (found in
cigarette) 4

5.  Muscarinic Receptors:
 Located postsynaptically in:
 Smooth muscle
 Cardiac muscle
 Glands of parasympathetic fibers
 Effector organs of cholinergic
parasympathetic fibers
 Named “muscarinic” because can be
stimulated by the muscarine (found in
some poisonous mushrooms)
5

6. Cholinergic Agents
 Drugs that stimulate the
parasympathetic nervous system
(PSNS) - “rest and digest”
 Also known as:
Cholinergic agonists
Parasympathomimetics
 Mimic the effects of the PSNS
neurotransmitter Acetylcholine (Ach)
6

7. Cholinergic agents: mechanism
of action
A- Direct-acting (cholinergic agonists)
 Bind to cholinergic receptors,
causing stimulation
B- Indirect-acting (anticholinesterase)
 Inhibit the enzyme “cholinesterase”
 This result in more Ach is available
at the receptors
 They are classified into Reversible
and Irreversible 7

8. Indirect-Acting Cholinergic Agents
(Cholinesterase Inhibitors)
1- Reversible
 Bind to cholinesterase for a period of
minutes to hours
I. Short acting: (15 min) Edrophonium
II. Intermediate acting: (3-6 hrs.):
Physostigmine
III.Longer acting: (6-8 hrs.) Carbamate
IV.Newer & longer acting: Donepezil
8

9. 2- Irreversible (extreme long acting):
 Bind to cholinesterase and form a
permanent bond
 It force the body to make new
cholinesterase
9

10. Drug Effects of Cholinergic Agents
10
RESPONSE
LOCATION
Vasodilation
Blood vessels
CVS
Decreased contractility
Cardiac muscle
Decreased heart rate
Node
Increased motility
Muscles
GI
Increased secretion /
Increased salivation
Sphincters
Dilation (increased
frequency)
Bladder
sphincter
Genitourinary
Bronchoconstriction
Bronchial
muscle
Lung
Constriction / Decreased
intraocular pressure
Pupil
Eye

11. Drug Effects of Cholinergic Agents
 At recommended doses, the
cholinergics affect the muscarinic
receptors
 At high doses, cholinergics stimulate
the nicotinic receptors
 Desired effects: from muscarinic
receptor stimulation
 Many undesirable effects are due to
stimulation of the nicotinic receptors
11

12. Therapeutic uses of cholinergic agents
A- Direct-Acting Cholinergic Drugs
1. Glaucoma and intraocular surgeries:
Reduces intraocular pressure, E.g.:
• Acetylcholine
• Pilocarpine
(poor oral absorption used topically)
2. Urine retention :
Increases tone and motility of bladder
and GI tract, E.g.:
• Bethanechol
12

13. B- Indirect-Acting Cholinergic Drugs
1. Myasthenia gravis:
It Increase skeletal muscle contraction, E.g.:
• Physostigmine
2. Alzheimer's Disease:
It Prevents cognitive deterioration (maintain
memory and learning capabilities) by
increasing concentrations of acetylcholine in
the brain, E.g.:
• Donepezil
(It is not a cure but improve the patient
status) 13

14. Side effects of cholinergic agents
“SLUDGE” – cholinergic agents toxicity
• Salivation
• Lacrimation
• Urinary incontinence
• Diaphoresis
• Gastrointestinal upset (cramps & diarrhea)
• Emesis (vomiting)
Others:
• CVS: bradycardia, hypotension
• CNS: Headache, dizziness, convulsions
• Respiratory: Increased bronchial secretions,
bronchospasms 14

15. Anticholinergic
(Cholinergic blocking agents)
 Drugs that block or inhibit the actions of
acetylcholine (Ach) in the PNS
 Also known as:
Parasympatholytics
Cholinergic antagonists
 Competitive antagonists; compete with
Ach and block the cholinergic receptors
 As a result, Ach is unable to bind to the
receptor site and cause the cholinergic
effect 15

16. 1. Antimuscarinic agents
 The majority of anticholinergic drugs
2. Antinicotinic agents
 Skeletal neuromuscular blockers
16
Types of anticholinergics

17. 17
Sites of actions of cholinergic antagonists

18. Antimuscarinics: drug effects
18
RESPONSE
LOCATION
Small doses: decrease heart rate
Large doses: increase heart rate
AV/ SA
Node
CVS
Decreased motility
Muscles
GI
Decreased secretion / Decreased
salivation
Sphincters
Constriction (retention)
Bladder
sphincter
Genitourinary
Bronchodilation /Decreased bronchial
secretions
Bronchial
muscle
Lung
Dilation
Pupil
Eye
Small doses: decrease muscle
rigidity & tremors
Large doses: drowsiness,
hallucinations
CNS

19. 1- Atropine
• SA node dysfunction
• Bradycardia
• 2nd degree heart block
• Decreasing the production of saliva and
secretions of the airway prior to surgery
• Antispasmodic (stomach, intestines, &
other organs)
• Eye drop for examination and surgeries
19
Therapeutic uses of antimuscarinics
agents

20. 2- Scopolamine / Hyoscine
• Nausea and vomiting
• Motion sickness (where it is often applied as
a transdermal patch behind the ear)
• Gastrointestinal, renal or biliary spasms
• Irritable bowel disease
• “Truth drug” in combination with other drugs
3- Dicyclomine
• Peptic ulcer disease and hypersecretory state
• Irritable bowel disease 20

21. 4- Benztropine
 Antiparkinson drug, “Decreases muscle
rigidity and muscle tremors”
5- Atrovent
 Bronchodilator/ decrease secretions from
nose, pharynx and bronchi. It is used for:
• Chronic bronchitis
• Asthma
• Chronic obstructive pulmonary disease
21

22. Antimuscarinics: side effects
Body System Side/Adverse Effects
Cardiovascular Increased heart rate,
dysrhythmias
CNS CNS excitation, irritability,
hallucinations
Eye Dilated pupils, increased
intraocular pressure
Gastrointestinal Decreased salivation, gastric
secretions and motility
Genitourinary Urinary retention 22

23. They are used for:
• Producing complete muscle relaxation
with anesthetics during surgeries or
mechanical ventilation
• Facilitating intubation
23
Therapeutic uses of Antinicotinic
Neuromuscular blockers

24. Example:
1- Tubocurarine
• It was the first used neuromuscular
blocker, but now rarely used because safer
alternatives
2- Atracurium
• Onset of action: 90 second
• Duration of action: ≤ 30 minutes
• Widely used
• Should be refrigerated 24

25.  These drugs may cause paralysis of the
diaphragm and bronchospasm
 Also, neuromuscular blockers may
facilitate histamine release, which causes
hypotension, flushing, and tachycardia
 Some drugs may trigger a transient
release of large amounts of potassium
from muscle fibers
 This puts the patient at risk for life-
threatening complications, such as
hyperkalemia and cardiac arrhythmias 25
Side effects of Antinicotinic
Neuromuscular blockers

26. 26

27. 1- SA node, also known as sinus node,
is a group of cells located in the wall of
the right atrium of the heart which have
the ability to produce an electrical
impulse that travels through the heart
causing it to contract
2- AV node, also known as
atrioventricular node, it is a part of the
electrical conduction system of the
heart and electrically connects the atria
and ventricles
27