1. Cholinergic Antagonist
Course Coordinator
Jamaluddin Shaikh, Ph.D.
School of Pharmacy, University of Nizwa
Lecture-16
October 31, 2011

2. Cholinergic Antagonist
Cholinergic antagonists bind to cholinoceptors, but do not trigger receptor-mediated intracellular effects
Types of antagonists:
1. Selectively block muscarinic synapses of the parasympathetic nerves
2. Ganglionic blockers, show a preference for the nicotinic receptors of the sympathetic and parasympathetic ganglia
3. Neuromuscular blocking agents, interfere with transmission of efferent impulses to skeletal muscles

3. Peripheral Nervous System

4. Cholinergic Antagonists
Antimuscarinic agents
Atropine
Scopolamine
Ipratropium
Ganglionic Blocker
Nicotine
Mecamylamine
Neuromuscular Blocker
Pancuronium
Tubocurarine
Atracurium
Mivacurium
Succinylcholine

5. Antimuscarinic agents
Cholinergic Antagonists
Antimuscarinic agents
Atropine
Scopolamine
Ipratropium
Ganglionic Blocker
Nicotine
Mecamylamine
Neuromuscular Blocker
Pancuronium
Tubocurarine
Atracurium
Mivacurium
Succinylcholine

6. Antimuscarinic agents: Atropine
A tertiary amine, has high affinity for muscarinic receptors, preventing ACh from binding
Atropine acts both centrally and peripherally
General actions last about 4 hours

7. Atropine: Actions Eye: Gastrointestinal (GI): Urinary system:
Blocks all cholinergic activity, resulting in mydriasis, unresponsiveness to light. In narrow-angle glaucoma, intraocular pressure may rise dangerously
Gastrointestinal (GI):
Reduce activity of the GI tract
Although gastric motility is reduced, hydrochloric acid production is not significantly affected.
Urinary system:
Reduce hypermotility states of the urinary bladder

8. Atropine: Actions, continued…..
Cardiovascular:
At low doses: decrease cardiac rate (bradycardia)
At higher doses: cardiac rate increases modestly
Secretions:
Blocks the salivary glands, producing a drying effect on the oral mucous membranes
Sweat and lacrimal glands are also affected

9. Atropine: Therapeutic Use
Ophthalmic:
Topical atropine exerts mydriatic effect
May induce an acute attack of eye pain due to sudden increases in eye pressure in individuals with narrow-angle glaucoma
Antidote for cholinergic agonists:
Used for the treatment of overdoses of cholinesterase inhibitor insecticides and some types of mushroom poisoning
Antisecretory:
Used as an antisecretory agent to block secretions in the upper and lower respiratory tracts prior to surgery
Glaucoma is an eye disorder in which the optic nerve suffers damage

10. Atropine: Pharmacokinetics & Adverse Effects
Readily absorbed
Partially metabolized by the liver
Eliminated primarily in the urine
Half-life is about 4 hours
Adverse effects:
Dry mouth, blurred vision, tachycardia, and constipation
Effects on CNS include restlessness, confusion, hallucinations,
Children are sensitive to the rapid increases in body temperature

11. Scopolamine Tertiary amine alkaloid, produces effects like atropine
Therapeutic uses:
Therapeutic use is limited to prevention of motion and to blocking short-term memory
Pharmacokinetics and adverse effects:
Similar to those of atropine

12. Ipratropium A quaternary derivative of atropine
Useful in treating asthma in patients who are unable to take adrenergic agonists
Beneficial in the management of chronic obstructive pulmonary disease. It is inhaled for these conditions
Does not enter the systemic circulation or the CNS

13. Cholinergic Antagonists
Antimuscarinic agents
Atropine
Scopolamine
Ipratropium
Ganglionic Blocker
Nicotine
Mecamylamine
Neuromuscular Blocker
Pancuronium
Tubocurarine
Atracurium
Mivacurium
Succinylcholine

14. Ganglionic Blockers: Nicotine
A component of cigarette smoke
No therapeutic benefit and is deleterious to health
Depending on the dose, nicotine depolarizes autonomic ganglia, resulting first in stimulation and then in paralysis of all ganglia
The stimulatory effects include increased blood pressure and cardiac rate
At higher doses, the blood pressure falls because of ganglionic blockade

15. Neuromuscular Blocker
Cholinergic Antagonists
Antimuscarinic agents
Atropine
Scopolamine
Ipratropium
Ganglionic Blocker
Nicotine
Mecamylamine
Neuromuscular Blocker
Pancuronium
Tubocurarine
Atracurium
Mivacurium
Succinylcholine

16. Neuromuscular Blocking Drugs
Block cholinergic transmission between motor nerve endings and the nicotinic receptors on the neuromuscular end plate of skeletal muscle
Structural analogs of acetylcholine
Clinically useful during surgery for producing complete muscle relaxation

17. Nondepolarizing Blockers
Mechanism of Action
At low doses:
Interact with the nicotinic receptors to prevent the binding of acetylcholine
Prevent depolarization of the muscle cell membrane and inhibit muscular contraction
At high doses:
Block the ion channels of the end plate

18. Nondepolarizing Blockers, continued….
Therapeutic uses:
Used in anesthesia during surgery
Pharmacokinetics:
Injected intravenously
Quaternary amines structure, making them orally ineffective, and do not cross the blood-brain barrier
Many of the drugs are not metabolized
Excreted unchanged in the bile
Adverse effects:
Tubocurarine: lowering blood pressure
Pancuronium: increased heart rate