Cholinergics 2

1. Scopolamine
 Peripheral effects: similar to atropine
 Central effects: greater and longer than atropine
 The most useful drug in motion sickness
Uses
Prevention of motion sickness
 before anesthetics
1. Antimuscarinic agents
Ipratropium
 quaternary derivative of atropine
Uses
 used as inhalation in:
1. asthmatic patients who are unable to take adrenergic agonists
2. chronic obstructive pulmonary disease (COPD)

2. Uses of atropine substitute:
1- Treatment of peptic ulcer (EX. Pirenzipine).
2- Antispasmodic (atropine, propantheline).
3- Antiparkinsonian (benztropine).
4- Treatment of bronchial asthma (ipratropium).
5- Mydriatics/Cycloplegics (cyclopentolate).
6- Treatment of nocturnal enuresis (Oxybutynin).
7- Pre-anaesthetic medication (atropine) to prevent vagal
attack (block M2), prevent asphyxia through decreasing
bronchial secretions and saliva in addition to central
stimulation of respiratory center.
8- Antiemetic and for treatment of motion sickness
(hyoscine & scopolamine).
1. Antimuscarinic agents

3. 2. Ganglion blockers
 Act on the nicotinic receptors of both parasympathetic
and sympathetic ganglia
1. Depolarizing blockers:
• In small dose, they stimulate the ganglia (initial
depolarization), but in large dose they cause maintained
depolarization (block) leading to blocking or inactivating
of the N1 in ganglia.
• Ex. Nicotine and lobeline (large dose)
• Not used clinically
2. Competitive (non depolarizing) ganglionic blockers:
• They competitively block N1. Ex. Hexamethonium,
trimethaphan, mecamylamine.

4. Ganglionic Blockers
Actions:
They suppress both sympathetic and parathympathetic NS and the net
effect depends on the predominant tone (which of the 2 systems is
more active).
1- Heart:
Tachycardia (by blocking parasympathetic NS)
Decreased contractility and orthoststic hypotension (by blocking the
sympathetic NS)
2- Eye:
Mydriasis & cycloplegia (by blocking parasympathetic NS)
3- GIT & UT:
Decreased motility leading to constipation and urine retention (by
blocking parasympathetic NS)
- Little used now, only trimethaphan (short duration) is used as IV
infusion to control hypertension. They were used as antihypertensive.

5. Ganglion Stimulants
2. Ganglion Stimulants
• Nicotine small dose
• Lobeline small dose
• Ach
• Carbachol

7. Neuromuscular blockers (NMBs)
They block neuromuscular junction (motor-end plate) leading to relaxation
of skeletal muscles.
Uses of NMBs:
1- Surgical operations (pre-anaesthetic medications).
2- Electroshock theapy and certain types of convulsions.
3- Endoscopy and endotrachial intubation.
Classification:
A- Competitive NMBs:
They block N2 receptors at motor-end plate decrease opening of sodium
Channels……… no depolarization ………relaxation.
Ex. 1- Long acting : Pancuronium,
2- Intermediate : Vecuronium, Atracurium
3- Short acting : Mivacurium.
NB. D-tubocurarine, gallamine not used now.

8. B- Depolarizing (non-competitive) NMBs:
They initially produce stimulation of N2 receptors persistent opening
of sodium channels sodium channels stay in the open state which
cannot respond to any stimuli (inactivated) muscle paralysis.
Ex. Suxamethonium (succinylcholine) and decamethonium.
Actions of NMBs:
1- Relaxation of skeletal muscles (eye muscles, face, neck, hands, feet,
limbs, and finally respiratory muscles). Recovery is in the opposite
direction.
2- Other effects: atropine like-effects and hypotension due to release of
histamine.
Neuromuscular blockers (NMBs)

9. Adverse effects:
1- Histamine release leading to hypotension and allergic reactions.
2- Atropine-like effects.
3- Prolonged apnea if pseudocholinesterase is genetically deficient no
hydrolysis of succinylcholine paralysis of respiratory muscles and
Apnea
4- Malignant hyperthermia (succinylcholine): usually when given with
halothane in this case patient treated by cooling and by administration
of dantrolene
5- Increased toxicity if used with aminoglycosides antibiotics because
aminoglycosides have neuromuscular blocking effect.
6- Hyperkalemia: Succinylcholine increases potassium release from
intracellular stores- dangerous in burn patients or patients with
massive tissue damage in which potassium has been rapidly lost from
within cells
Neuromuscular blockers (NMBs)

10. • Cholinesterase inhibitors: neostigmine, physostigmine,
pyridostigmine, and edrophonium -can overcome the action of
nondepolarizing neuromuscular blockers
• Halogenated hydrocarbon anesthetics: halothane- enhance
neuromuscular blockade by exerting a stabilizing action at the
neuromuscular junction.
• Aminoglycoside antibiotics: gentamicin or tobramycin- inhibit
acetylcholine release from cholinergic nerves by competing with calcium
ions, hence enhance actions of these agents.
• Calcium-channel blockers: These agents may increase the
neuromuscular block of competitive blockers as well as depolarizing
blockers.
Neuromuscular blockers and Drug interactions:

11. Types of skeletal muscle relaxants:
A- Central: acting on cerebral cortex and/or spinal cord:
Barbiturates, Benzodiazepines & Baclofen
B- Peripheral:
1- NMBs:
 Competitive NMBs
 Depolarizing NMBs
2- Direct skeletal muscle relaxant:
 Dantrolene: decreases Ca2+ release from endoplasmic reticulum.
3- Other Motor-end-plate blockers:
 Botulinum toxin: decrease ACh release.
 β-bungarotoxin, Mg2+ and aminoglycosides: decrease ACh release
and block N2
 Local anaesthetics: block nerve action potential propagation

12. Thank You