Cholinergic Agents

Cholinergic Receptors
Muscarinic Receptor Nicotinic Receptor
Types of Receptor Metabotropic (G protein coupled) Ionotropic (Ion channel coupled)
receptor receptor
1. Activation of Phospholipase C 1. Coupled with cation channels
2. Formation of 2. Mediate fast excitatory synaptic
a. Inositol Triphosphate (IP3) transmission
Effects Upon Activation b. Diacyl Glycerol (DAG)
3. Inhibition of Adenylate Cyclase
a. Activation of K+ channels
b. Closure of Ca2+ channels
Types Locations Types Locations
M1  CNS NM  Skeletal muscle
M2  CNS NN  Autonomic ganglia
 Heart  Adrenal medulla
M3  CNS NCNS  Brain
 Smooth muscle  Spinal cord
 Endothelium
Subdivisions
 Secretory glands
M4  CNS
 Heart
M5  CNS
 Salivary glands
 Iris
 Mononuclear blood cells
 Cholinoreceptor Stimulants
Direct Acting (Receptor Agonists) Indirect Acting (Cholinesterase Inhibitors)
Muscarinic and Nicotinic Agonists Reversible Inhibitors
 Acetylcholine  Short Acting
 Carbachol o Endrophonium
 Medium Acting
o Neostigmine
o Pyridostigmine
o Physostigmine
Muscarinic Agonists Irreversible Inhibitors
 Pilocarpine  Organophosphates
 Bethanecol o Isoflurophate
Nicotinic Agonists o Echothiophate
 Nicotine  Soman
 Suxamethonium Chloride  Malathion
Adverse Effects  Salivation  GIT hypersensitivity
 Diaphoresis  Headache
 Colic  Cycloplasm
Major Contraindications  Asthma  Hyperthyroidism
o Choline ester may induce o Choline ester may induce Atrial Fibrillation
bronchoconstriction in Hyperthyroid patient
 Peptic Ulcer  Coronary Vascular Disease
o Choline ester increases gastric secretion o Choline ester leads to vasodilation
o May further exacerbate blood flow
Signs of Toxicity  Nausea  Urinary urgency
Antidote = Atropine  Vomitting diarrhea  Salivation
 Cutaneous vasodilation  Sweating
 Bronchoconstriction
 Pharmacological Effects of Cholinergic Agents
Organs Effects Organs Effects
 Contract the Spincther Papilae of the Iris  Negative Chronotropic (heart rate)
o Leading to Miosis o Mediated by M2 receptors
 Contract the Ciliary muscle o Decrease phase 4 Diastolic Depolarization
o Reduced far vision accomodation leading to  Prolong the membrane potential to reach
Cycloplasm threshold level
o Pull the iris away from the Anterior Chamber  Negative Dromotropic (conduction velocity)
o Open the Trabeculae Meshworks o Excessive vagal tone can lead to massive
Eyes  These 2 will lead to drainage of Aqueous humor away
Heart Bradycardia
from Anterior Chamber through the Canal of Schlemm  May lead to a partial or total heart block
o Reduce the Intraocular pressure o Reduction of Ca2+ channels opening mediates
reduction in heart rate
 Negative Ionotropic (heart contractility)
o Prominently affecting Artial rather than Ventricular
o Due to reduction in inward movement of Ca2+
 Marked vasodilation, due to  Intestinal effects
o Relaxation of smooth muscle cells through o Increase in
endothelial release of  Peristalsis
 Nitric Oxide  Tone
 Endothelium-derived Relaxing Factor (EDRF)  Contraction amplitude
o Inhibition of Post-Ganglionic release of o Mediated by M3
Norepinephrine by Ach o M2 reduces cAMP formation
Blood Vessels o Direct stimulation through Vagus nerve GIT  Glandular effects
 Ach may cause vasoconstriction during Endothelial o Strongly stimulate
damage  Salivary glands
 Gastric glands
o Lessly stimulate
 Pancreatic gland
 Small intestine gland
 Relax most spinchters
 Contraction of Detrusor muscle of the Urinary Bladder  Bronchoconstriction
 Relax the Trigone and Bladder Spinchter  Increase mucus secretion by Tracheobronchial glands
Genitourinary
o Increase maximal voluntary voiding pressure
Tract o Decrease bladder capacity
 Mediated by M2 and M3 receptors Respiratory
 Increase secretion of
o Thermoregulatory sweat glands
Miscellaneous o Lacrimal gland
o Nasopharyngeal gland
 Parasympathomimetic Agents
Muscarinic and Nicotinic Agonists
Drugs Mechanism of Action Clinical Indications
Acetylcholine Excitatory Effects Experimentally due to its short half in
 Inhalation  M3 receptors respect to its extensive metabolism by
o Constriction of Sphincter Papilae
 Miosis
 Acetylcholinesterase
 Reduce intraocular pressure  Plasma Cholinesterase
Carbachol o Increase GIT motility and secretion  Miotic agent
 Eye drops o Stimulates
 Bronchial glands
 Salivary glands
 Sweat glands
 Lacrimal glands
o Contract smooth muscle of
 Uterus
 Bronchioles
 Ureters
 Urinary bladder
Depressive Effects
 M2
o Negative Inotropic
o Negative Chronotropic
o Vasodilation
Muscarinic Agonists
Drugs Mechanism of Action Clinical Indications
Pilocarpine  Miosis  Glaucoma
 Eye drops  Cycloplasm
 Decrease intraocular pressure
Carbachol  Stimulates smooth muscle of GIT  Postoperative Abdominal Distension
 Tablet  Stimulates Detrusor muscles of Urinary Bladder  Gastric Atony
 Gastroparesis
 Injection  Urinary incontinence
 Xerostomia
 Sjogren syndrome
Methacholine Chloride  Synthetic Choline ester  Bronchial challenge test
o Use to diagnose bronchial hypersensitivity
 Inhalation  Non-selective Muscarinic agonist Other therapeutic is limited due to extensive
 Bradycardia
 Hypotension