Parasympathomimetic and Parasympatholytic Drugs

Easy-to-Remember Notes for Pharmacy Competitive Examinations

These notes focus on the high-yield concepts, drug classifications, mechanisms, uses, adverse effects and exam traps frequently tested in GPAT, NIPER, UPSC Drug Inspector, AIIMS Pharmacist, Railway Pharmacist, ESIC and State Pharmacist examinations.

1. First Understand the Basic Idea

The parasympathetic nervous system mainly uses acetylcholine (ACh) as its neurotransmitter.

Two important groups of drugs act on this system:

Parasympathomimetics

These drugs mimic or increase the action of acetylcholine.

Think:

Parasympathomimetic = Parasympathetic ON

They generally produce:

Miosis + Salivation + Bradycardia + Increased GI activity + Urination

Parasympatholytics

These drugs block the action of acetylcholine at muscarinic receptors.

Think:

Parasympatholytic = Parasympathetic OFF

They generally produce:

Mydriasis + Tachycardia + Dry mouth + Constipation + Urinary retention

2. Cholinergic Receptors

Acetylcholine acts through two major types of receptors:

Nicotinic receptors

Found mainly at:

• Autonomic ganglia

• Neuromuscular junction

• Adrenal medulla

Muscarinic receptors

Found mainly in:

• Heart

• Smooth muscles

• Glands

• Eye

• Urinary bladder

• Gastrointestinal tract

For most questions on parasympathomimetic and parasympatholytic drugs, remember the muscarinic receptors.

3. Muscarinic Receptors: M1, M2, M3

The easiest way to remember them:

M1 = Mind

Found mainly in:

• CNS

• Autonomic ganglia

• Gastric glands

M2 = Heart ❤️

Found mainly in:

• Heart

Effects:

• ↓ Heart rate

• ↓ AV conduction

M3 = Glands + Smooth Muscle

Found in:

• Salivary glands

• Bronchial glands

• GI tract

• Urinary bladder

• Eye

• Vascular endothelium

Effects:

• ↑ Secretions

• Bronchoconstriction

• ↑ GI motility

• Bladder contraction

• Miosis

Super-short memory

M1 = Mind
M2 = Heart
M3 = Glands & Smooth muscle

4. Classification of Parasympathomimetics

Parasympathomimetics are also called cholinomimetics.

They are divided into:

A. Direct-acting cholinomimetics

They directly stimulate cholinergic receptors.

Important examples:

• Acetylcholine

• Methacholine

• Carbachol

• Bethanechol

• Pilocarpine

• Cevimeline

Memory sequence

A-M-C-B-P-C

Acetylcholine
Methacholine
Carbachol
Bethanechol
Pilocarpine
Cevimeline

B. Indirect-acting cholinomimetics

They inhibit acetylcholinesterase (AChE).

Therefore:

AChE inhibition → ↑ Acetylcholine → ↑ Cholinergic activity

Important examples:

• Neostigmine

• Physostigmine

• Pyridostigmine

• Edrophonium

• Ambenonium

5. Direct-Acting Drugs

Acetylcholine

Acetylcholine is a direct cholinergic agonist.

It acts on both:

• Muscarinic receptors

• Nicotinic receptors

Major effects

• Bradycardia

• Miosis

• Increased salivation

• Increased GI motility

• Increased urination

• Bronchoconstriction

Important point

Acetylcholine is rapidly hydrolysed by cholinesterases.

Therefore:

Acetylcholine = Very short duration

6. Methacholine

Methacholine is predominantly a muscarinic agonist.

Important use

Bronchial challenge testing

It causes bronchoconstriction and can be used to assess airway hyperresponsiveness.

Exam memory

Methacholine → Methacholine challenge → Bronchial hyperreactivity

7. Carbachol

Carbachol acts on:

• Muscarinic receptors

• Nicotinic receptors

It is relatively resistant to cholinesterase hydrolysis.

Important use

Ophthalmology

It causes:

Miosis

Remember

Carbachol → Ciliary/eye → Miosis

8. Bethanechol

Bethanechol is a direct-acting muscarinic agonist.

It is resistant to hydrolysis by acetylcholinesterase.

Main uses

1. Postoperative urinary retention

2. Neurogenic bladder

Mechanism

Bethanechol stimulates muscarinic receptors in the urinary bladder:

M3 stimulation → detrusor contraction → urination

Adverse effects

Excessive cholinergic stimulation may cause:

• Salivation

• Sweating

• Diarrhea

• Abdominal cramps

• Bradycardia

• Bronchoconstriction

Easy memory

BETHANECHOL → Bladder

9. Pilocarpine

Pilocarpine is a direct muscarinic agonist.

Important uses

1. Glaucoma

2. Xerostomia (dry mouth)

In the eye

Pilocarpine causes:

Miosis + Ciliary muscle contraction

This facilitates aqueous humour outflow.

In salivary glands

Pilocarpine:

↑ Salivation

Memory

PILO = Pupil Little

Pilocarpine makes the pupil little/smaller.

Therefore:

Pilocarpine → Miosis + Salivation

10. Cevimeline

Cevimeline is a muscarinic agonist with relative preference for M1/M3 receptors.

Main use

Xerostomia

Especially useful for dry mouth associated with Sjögren syndrome.

Memory

Cevimeline → “C” for saliva? Think “Cevimeline = dry mouth treatment".

11. Indirect Parasympathomimetics

These drugs inhibit acetylcholinesterase.

Normal situation

ACh → AChE → inactive products

After AChE inhibition

AChE blocked → ACh accumulates → cholinergic effects increase

This is the central concept behind indirect parasympathomimetics.

12. Neostigmine

Neostigmine is a reversible acetylcholinesterase inhibitor.

It is a quaternary ammonium compound.

Therefore:

Poor penetration into CNS

Important uses

• Myasthenia gravis

• Reversal of non-depolarizing neuromuscular blockade

• Postoperative urinary retention

• Paralytic ileus

Important combination

Neostigmine + Atropine/Glycopyrrolate

Why?

Neostigmine increases ACh.

This can produce unwanted muscarinic effects such as:

• Bradycardia

• Salivation

• Bronchial secretions

• Bronchospasm

Atropine or glycopyrrolate blocks these muscarinic effects.

Exam trap

Neostigmine does NOT significantly cross the BBB.

13. Physostigmine

Physostigmine is also a reversible AChE inhibitor.

But there is a very important difference from neostigmine.

Physostigmine is a tertiary amine.

Therefore:

Physostigmine crosses the BBB.

Major use

Antimuscarinic poisoning

For example, severe atropine toxicity.

Very important comparison

PhysostigmineNeostigmineTertiary amineQuaternary ammoniumCrosses BBBPoor CNS penetrationUsed in antimuscarinic toxicityUsed in myasthenia/reversalCentral effects possibleMainly peripheral

Memory

PHYSO → Physically enters the brain

14. Pyridostigmine

Pyridostigmine is a reversible AChE inhibitor.

Major use

Myasthenia gravis

It is a quaternary compound and has poor CNS penetration.

Exam association

Pyridostigmine → Myasthenia gravis

15. Cholinergic Toxicity

Too much acetylcholine produces cholinergic toxicity.

Remember: DUMBBELSS

D – Diarrhea
U – Urination
M – Miosis
B – Bradycardia
B – Bronchospasm
E – Emesis
L – Lacrimation
S – Salivation
S – Sweating

Key idea

Cholinergic toxicity = “Too wet and too slow.”

16. Organophosphate Poisoning Organophosphates inhibit acetylcholinesterase, causing excessive acetylcholine.

Clinical features

• Miosis

• Salivation

• Lacrimation

• Sweating

• Bronchospasm

• Bradycardia

• Diarrhea

• Urination

Treatment

Atropine + Pralidoxime

Atropine

Blocks muscarinic receptors.

It treats the major muscarinic manifestations.

Pralidoxime (2-PAM)

Can reactivate phosphorylated AChE if administered before significant aging of the enzyme.

Exam trap

Atropine does NOT directly reactivate AChE.

Pralidoxime reactivates AChE, when used appropriately before aging.

17. Classification of Parasympatholytics

Parasympatholytics are mainly antimuscarinic drugs.

Important examples:

Non-selective antimuscarinics

• Atropine

• Scopolamine

• Homatropine

• Tropicamide

• Glycopyrrolate

• Ipratropium

• Tiotropium

Urinary antimuscarinics

• Oxybutynin

• Tolterodine

• Solifenacin

• Darifenacin

• Trospium

18. Atropine

Atropine is the prototype antimuscarinic drug.

It competitively blocks muscarinic receptors.

Effects of atropine

OrganEffectHeart↑ Heart rateEyeMydriasisCiliary muscleCycloplegiaSalivary glands↓ SalivationGI tract↓ MotilityBladderUrinary retentionBronchiBronchodilationSweat glands↓ Sweating

Easy memory

ATROPINE = Anti-parasympathetic

19. Important Uses of Atropine

1. Symptomatic bradycardia

Atropine blocks vagal effects on the heart.

2. Organophosphate poisoning

It antagoni muscarinic effects of excess acetylcholine.

3. Psesreanaesthetic medication

Reduces excessive secretions.

4. Ophthalmology

Produces:

• Mydriasis

• Cycloplegia

20. Atropine Toxicity

Excessive atropine causes:

• Dry mouth

• Dry skin

• Mydriasis

• Tachycardia

• Hyperthermia

• Urinary retention

• Confusion

• Hallucinations

Classic memory

“Dry as a bone, blind as a bat, red as a beet, hot as a hare, mad as a hatter.”

The phrase helps remember antimuscarinic toxicity.

Antidote

Physostigmine

Why?

Because it crosses the BBB and increases acetylcholine in the CNS and periphery.

21. Scopolamine

Scopolamine is an antimuscarinic with important central effects.

Main use

Motion sickness

Memory

Scopolamine → Sea sickness

22. Tropicamide

Tropicamide is a short-acting antimuscarinic.

Main use

Ophthalmic examination

Produces:

• Mydriasis

• Cycloplegia

Exam memory

Tropicamide = short-acting mydriatic

23. Glycopyrrolate

Glycopyrrolate is a quaternary ammonium antimuscarinic.

Because of its positive charge:

It poorly crosses the BBB.

Uses

• Reduction of salivary secretions

• Reduction of respiratory secretions

• Used with neostigmine during reversal of neuromuscular blockade

Important comparison

Atropine → CNS penetration possible
Glycopyrrolate → minimal CNS penetration

24. Ipratropium

Ipratropium is an inhaled antimuscarinic bronchodilator.

Main use

COPD

It can also be used in certain asthma settings.

Mechanism

M3 blockade → ↓ bronchoconstriction → bronchodilation

Memory

Ipratropium → Inhaled antimuscarinic

25. Tiotropium

Tiotropium is a long-acting inhaled antimuscarinic bronchodilator.

Main use

COPD maintenance therapy

Memory

Tiotropium → Long-acting “tropium” bronchodilator

26. Antimuscarinics in Overactive Bladder

Important drugs:

• Oxybutynin

• Tolterodine

• Solifenacin

• Darifenacin

• Trospium

Mechanism

Muscarinic blockade → ↓ detrusor contraction → ↓ urgency and frequency

Common adverse effects

• Dry mouth

• Constipation

• Blurred vision

• Urinary retention

Special point

Darifenacin → relative M3 selectivity

27. Parasympathomimetic vs Parasympatholytic

• Feature Parasympathomimetic Parasympatholytic

• Basic action Mimics/enhances ACh Blocks muscarinic ACh action

• Heart ↓ HR ↑ HR

• Pupil Miosis Mydriasis

• Salivation ↑ ↓

• GI motility ↑ ↓

• Urination ↑ ↓

• Bronchi Constriction Dilatation

• Secretions ↑ ↓

• Example Bethanechol Atropine

Golden rule

Cholinergic = WET & SLOW
Anticholinergic = DRY & FAST

28. Most Important Drug–Use Associations

Memorize this table before the examination:

• Drug Remember

• Bethanechol Urinary retention

• Methacholine Bronchial challenge

• Carbachol Miosis

• Pilocarpine Glaucoma + xerostomia

• Cevimeline Xerostomia

• Neostigmine Myasthenia + reversal

• Physostigmine Antimuscarinic poisoning

• Pyridostigmine Myasthenia gravis

• Atropine Bradycardia + organophosphate poisoning

• Scopolamine Motion sickness

• Tropicamide Short-acting mydriasis

• Glycopyrrolate Poor CNS penetration

• Ipratropium Inhaled bronchodilator

• Tiotropium Long-acting bronchodilator

• Oxybutynin Overactive bladder

• Darifenacin Relative M3 selectivity

29. High-Yield Competitive Exam Traps

Trap 1

Which cholinomimetic crosses the BBB?

✅ Physostigmine

❌ Neostigmine

Trap 2

Which antimuscarinic crosses the BBB?

✅ Atropine

❌ Glycopyrrolate has very limited CNS penetration.

Trap 3

Drug causing miosis?

✅ Pilocarpine

❌ Atropine causes mydriasis.

Trap 4

Drug causing mydriasis?

✅ Atropine/Tropicamide

❌ Pilocarpine causes miosis.

Trap 5

Treatment of muscarinic effects in organophosphate poisoning?

✅ Atropine

Trap 6

Drug that reactivates phosphorylated AChE?

✅ Pralidoxime

Trap 7

Drug used for antimuscarinic poisoning?

✅ Physostigmine

Trap 8

Quaternary antimuscarinic with poor CNS penetration?

✅ Glycopyrrolate

Trap 9

Antimuscarinic used for motion sickness?

✅ Scopolamine

Trap 10

Antimuscarinic used for overactive bladder?

✅ Oxybutynin / Tolterodine / Solifenacin / Darifenacin / Trospium

30. Last-Minute Revision Formula

Parasympathomimetics

DIRECT

ACh – Methacholine – Carbachol – Bethanechol – Pilocarpine – Cevimeline

INDIRECT

Neostigmine – Physostigmine – Pyridostigmine

Remember their major uses:

Bethanechol → BLADDER
Pilocarpine → PUPIL + SALIVA
Methacholine → BRONCHIAL TEST
Neostigmine → REVERSAL + MYASTHENIA
Physostigmine → ATROPINE TOXICITY
Pyridostigmine → MYASTHENIA

Parasympatholytics

Atropine – Scopolamine – Tropicamide – Glycopyrrolate – Ipratropium – Tiotropium – Oxybutynin

Remember:

Atropine → Bradycardia + OP poisoning
Scopolamine → Motion sickness
Tropicamide → Eye examination
Glycopyrrolate → Poor BBB penetration
Ipratropium/Tiotropium → COPD
Oxybutynin → Overactive bladder

One-Minute Super Revision

M1 = Mind
M2 = Heart
M3 = Glands & Smooth muscle

• Bethanechol = Bladder

• Pilocarpine = Pupil small + Saliva

• Neostigmine = Neuromuscular reversal

• Physostigmine = Passes BBB

• Atropine = Anti-muscarinic

• Scopolamine = Sea sickness

• Tropicamide = Short-acting eye drug

• Glycopyrrolate = Doesn't cross BBB well

• Ipratropium/Tiotropium = Bronchodilation

• Organophosphate poisoning = Atropine + Pralidoxime

• Cholinergic toxicity = DUMBBELSS

• Anticholinergic toxicity = Dry + Fast + Dilated + Confused

  Golden Rule for MCQs

If the question says:

• Miosis + salivation + bradycardia → think CHOLINERGIC

• Mydriasis + dry mouth + tachycardia → think ANTICHOLINERGIC

• Atropine poisoning → think PHYSOSTIGMINE

• Organophosphate poisoning → think ATROPINE + PRALIDOXIME

• Urinary retention → think BETHANECHOL

• Motion sickness → think SCOPOLAMINE

• Myasthenia gravis → think PYRIDOSTIGMINE/NEOSTIGMINE

• Click the below link to access MCQs

https://drive.google.com/file/d/11DMliJgp1Unhu3jijCJTfYF7LSlvc9YE/view?usp=drive_link