Table of Contents
Introduction
Physostigmine is a reversible acetylcholinesterase inhibitor that increases acetylcholine levels at cholinergic synapses. Unlike quaternary ammonium anticholinesterases, physostigmine is a tertiary amine and can cross the blood-brain barrier, allowing central nervous system effects. It is commonly used in the treatment of anticholinergic toxicity.
Mechanism of Action (Step-wise)
- Physostigmine reversibly inhibits the enzyme acetylcholinesterase (AChE).
- Acetylcholinesterase normally breaks down acetylcholine in the synaptic cleft.
- Inhibition of AChE prevents acetylcholine degradation.
- This increases acetylcholine concentration at cholinergic synapses.
- Increased acetylcholine stimulates muscarinic receptors in parasympathetic organs.
- This causes effects such as miosis, increased secretions, and bradycardia.
- Increased acetylcholine also stimulates nicotinic receptors at neuromuscular junctions.
- Physostigmine crosses the blood-brain barrier because it is a tertiary amine.
- Increased central acetylcholine reverses CNS manifestations of anticholinergic toxicity.
- The overall effect is enhanced cholinergic transmission in both peripheral and central nervous systems.
A key exam point is that physostigmine is a reversible acetylcholinesterase inhibitor that crosses the blood-brain barrier.
Pharmacokinetics
Physostigmine can be administered intravenously or intramuscularly. It is well distributed and penetrates the central nervous system due to its lipid solubility. It has a relatively short duration of action because acetylcholinesterase inhibition is reversible. It is metabolized in the liver and excreted via the kidneys.
Clinical Uses
Physostigmine is primarily used for the treatment of anticholinergic toxicity caused by agents such as atropine and antihistamines. It may also be used occasionally in glaucoma, although newer agents are preferred.
Adverse Effects
Common adverse effects are related to excessive cholinergic stimulation and include salivation, sweating, nausea, diarrhea, bronchospasm, and bradycardia. Excessive dosing may cause seizures and cholinergic crisis. Careful monitoring is required during administration.
Comparative Analysis
| Feature | Physostigmine | Neostigmine | Atropine |
|---|---|---|---|
| Mechanism | Reversible AChE inhibition | Reversible AChE inhibition | Muscarinic receptor blockade |
| CNS penetration | Yes | No | Yes |
| Main use | Anticholinergic toxicity | Myasthenia gravis | Bradycardia, organophosphate poisoning |
| Muscarinic effects | Increased | Increased | Decreased |
| BBB crossing | Yes | Minimal | Yes |
| Type | Tertiary amine | Quaternary amine | Tertiary amine |
Physostigmine differs from neostigmine because it crosses the blood-brain barrier and can reverse central anticholinergic symptoms. Compared to atropine, it enhances cholinergic activity instead of blocking it.
MCQs
- Physostigmine inhibits which enzyme?
a) Monoamine oxidase
b) Acetylcholinesterase
c) Cyclooxygenase
d) ATP synthase
Answer: b) Acetylcholinesterase
- Physostigmine increases levels of:
a) Dopamine
b) Acetylcholine
c) Serotonin
d) Histamine
Answer: b) Acetylcholine
- Physostigmine is classified as a:
a) Irreversible inhibitor
b) Reversible inhibitor
c) β blocker
d) Calcium channel blocker
Answer: b) Reversible inhibitor
- Physostigmine crosses the blood-brain barrier because it is a:
a) Quaternary amine
b) Tertiary amine
c) Peptide
d) Steroid
Answer: b) Tertiary amine
- Physostigmine stimulates:
a) Cholinergic transmission
b) Adrenergic transmission
c) Dopaminergic transmission
d) Histaminergic transmission
Answer: a) Cholinergic transmission
- Physostigmine is used in:
a) Asthma
b) Anticholinergic toxicity
c) Diabetes
d) Hypertension
Answer: b) Anticholinergic toxicity
- A common muscarinic effect is:
a) Tachycardia
b) Bradycardia
c) Mydriasis
d) Dry mouth
Answer: b) Bradycardia
- Excessive physostigmine may cause:
a) Hyperglycemia
b) Seizures
c) Hypertension
d) Hypercalcemia
Answer: b) Seizures
- Physostigmine increases acetylcholine at:
a) Cholinergic synapses
b) Dopaminergic synapses
c) Adrenergic synapses
d) Histaminergic synapses
Answer: a) Cholinergic synapses
- Compared to neostigmine, physostigmine:
a) Does not cross BBB
b) Crosses BBB
c) Has no CNS effects
d) Is irreversible
Answer: b) Crosses BBB
- Physostigmine may cause:
a) Bronchodilation
b) Bronchospasm
c) Hyperglycemia
d) Mydriasis
Answer: b) Bronchospasm
- Physostigmine reverses toxicity caused by:
a) Atropine
b) Insulin
c) Morphine
d) Digoxin
Answer: a) Atropine
FAQs
What is the mechanism of action of physostigmine?
It reversibly inhibits acetylcholinesterase, increasing acetylcholine levels.
Why can physostigmine affect the CNS?
Because it is a tertiary amine that crosses the blood-brain barrier.
What is its main clinical use?
Treatment of anticholinergic toxicity.
How does physostigmine differ from neostigmine?
Physostigmine enters the CNS, while neostigmine does not significantly cross the BBB.
What are common cholinergic side effects?
Salivation, bradycardia, diarrhea, and sweating.
Can physostigmine cause seizures?
Yes, especially in excessive doses.
References
Goodman & Gilman’s The Pharmacological Basis of Therapeutics – Cholinergic Drugs
https://accessmedicine.mhmedical.com/book.aspx?bookid=3191
Katzung: Basic and Clinical Pharmacology – Cholinomimetic Drugs
https://accessmedicine.mhmedical.com/content.aspx?bookid=3382
Tripathi: Essentials of Medical Pharmacology – Cholinergic Drugs
https://www.jaypeedigital.com
Harrison’s Principles of Internal Medicine – Poisoning and Drug Toxicity
https://accessmedicine.mhmedical.com
