CHOLINERGIC BLOCKING DRUGS

Question 1

Define cholinergic blocking drugs (muscarinic and nicotinic)

Answer 1

Cholinergic blocking drug is an antagonism. The agent will bind to the cholinergic receptor and prevent the ACh from binding and activating the receptor.

There are 2 types of cholinergic antagonist which are nicotinic and muscarinic antagonist.

In nicotinic antagonist, the cholinergic antagonist will bind specifically to the nicotinic receptors and causes the ligand gated ion channel to open all the time. As for example, tubocurarine which is a muscle relaxant.

However, in muscarinic antagonist, the cholinergic antagonist will bind to the muscarinic receptors and causes the prevention of GPCR to be activated by the ACh. As for example, atropine.

Question 2

Classify muscarinic blockers according to their effects on various receptor subtypes.

Answer 2

Muscarinic receptor subtypes: M1,M2,M3,M4,M5

Gq: M1,M3,M5
Gi: M2,M4
Muscarinic antagonist will produce excitatory action for Gi and inhibitory reaction for Gq.
Muscarinic agonist will produce excitatory action for Gq and inhibitory reaction for Gi.

Gi in muscarinic antagonist: When cholinergic antagonist bind to M2 @ M4 which is a Gi, it will causes the adenyl cyclase not inhibited. Hence, the amount of cAMP produced is increases. Thus, it will produce an excitatory action

Gq in muscarinic antagonist: When cholinergic antagonist bind to M1 @ M3 @ M5, it will inhibit phospholipase C. This causes the IP3 and DAG to be inhibited as well. Hence, it will cause inhibitory action.

Question 3

State the prototype and essential examples for muscarinic blockers (atropine, scapolamine, ipratropium, and pirenzepine)

Answer 3

NATURAL ALKALOIDS:
Atropine
Scopolamine

SEMISYNTHETIC DERIVATIVES/ SYNTHETIC CONGENERS
Ipratropium bromide
Tropicamide
Pirenzepine

Question 4

Explain the mechanism of action of muscarinic blockers.

Answer 4

Atropine is muscarinic blocker. When atropine bind, it will block all muscarinic receptor subtypes. This is because, atropine is a non specific antagonist. However, it is a reversible antagonism. Hence, if the amount of ACh is much more higher, then atropine can unbind from the receptor and allow the ACh to bind, and activating the receptor.

Question 5

Discuss the organ system effects of atropine after topical and systemic administration.

Answer 5

CVS

dose: 1 to 2mg
- Tachycardia: d/t blockade of vagal innervation at M2 - excitatory action
- Vasodilation: blood flow increase and decrease blood pressure

EYE

dose: 1 to 2mg
- Relaxation of iris sphincter muscle: mydriasis - dilation of pupils
- Cycloplegia: weak ciliary muscle- near vision is affecter, increases intraocular pressure
- Dry eyes: reduced lacrimal gland secretion

CNS

• Reduce tremor in Parkinson disease: inhibit cholinergic excess of parkinsonism
• Correct the vestibular disturbance
• Prevent motion sickness
• Sedation

LUNG

• Bronchodilation
• Reduced bronchial secretion

URINARY

• Slows voiding:
• Relax smooth muscle in ureter and bladder wall

Question 6

Desc pharmacokinetics, adverse effects and contraindications of atropine.

Answer 6

PHARMACOKINETICS:

1. Absorptions - well orally and topically
2. Distribution - widely distributed, can cross blood brain barrier
3. Metabolism and excretion - rapid, 50% excreted unchanged, prolonged effect in eyes >72 hrs

ADVERSE EFFECTS:

1. CNS- restlessness - irratation, disorientation
2. EYES- blurred vision, increased intraocular pressure
3. CVS- arrhythmias (a problem with the rate or rhythm of your heartbeat) , cutaneous vasodilation
4. GUT- urinary retention
5. SKIN- not sweating
6. GIT- dry mouth, reduced peristalsis

CONTRAINDICATION

1. Glaucoma
2. Prostatic hyperplasia/ enlargement/ urinary tract obstruction
3. GI ileus

Question 7

List the clinical uses of antimuscarinic agents.

Answer 7

1. CHOLINERGIC POISONING
   - mushroom poisoning
   - overdose of anticholinesterase drug (pt myasthenia gravis)
   - organophosphate poisoning (insecticides)
2. TREATMENT
   - antimuscarinic therapy- atropine
   - cholinesterase regeneration- pralidoxime

Question 8

Explain atropine poisoning and its treatment.

Answer 8

Example: amitripthyline, clozapine, antihistamine

Use with caution: treating motion sickness and diarrhoea (diphenoxylate + atropine) in children

SYMPTOMS OF AP:
cant pee - urinary retension
cant see - blind
cant spit - dry mouth
cant shit - absent bowel sound
* flushed skin, mydriasis, hyperthermia, confused, hallucination, shaking

TREATMENT OF AP:

• symptomatic/ conservative treatment
• limit intestinal absorption
• physostigmine (reversible cholinesterase inhibitor)
• sedation- benzodiazepine

Question 9

TRUE/FALSE
ATROPINE:
A. BLOCKS MUSCARINIC CHOLINERGIC RECEPTOR NON SELECTIVELY
B. CAUSES IRREVERSIBLE ANTAGONISM
C. IS USED IN TREATMENT OF BRADYCARDIA
D. WORSEN THE TREMORS IN PT WITH PARKINSON’S DISEASE
E. OVERDOSE IS TREATED WITH ANTICHOLINESTERASE.

Answer 9

A. TRUE
B. FALSE (REVERSIBLE)
C. TRUE (TREAT DUMBBELL)
D. FALSE (IMPROVE)
E. TRUE

Question 10

TRUE/FALSE
ATROPINE:
A. CYCLOPLEGIA
B. TREAT GLAUCOMA
C. IS USED IN BENIGN PROTASTATE ENLARGEMENT
D. DECREASED GIT MOTILITY
E. CAUSE HYPERHIDROSIS

Answer 10

A. TRUE (CYCLOPLEGIA - CANNOT ACCOMODATE FOR NEAR VISION)
B. FALSE (INCREASED THE INTRAOCULAR PRESSURE. DECREASED INTRAOCULAR PRESSURE - PILOCARPINE AND NEOSTIGMINE)
C. FALSE (CONTRAINDICATED TO USE ATROPINE IN GLAUCOMA AS WELL AS BPH AND URINARY STONES)
D. TRUE (CHOLINERGIC DRUG AND ANTICHOLINESTERASE WILL INCREASED THE GIT MOTILITY AS WELL AS SECRETION)
E. FALSE (HYPERHIDROSIS OCCUR IN PT WHO CONSUME PILOCARPINE AND NEOSTIGMINE)