Muscarinic Receptor Blockers

Question 1

Antimuscarinics

Answer 1

Competitive Antagonists of ACh @ Muscarinic Receptors
(Affinity; No intrinsic activity)

In Large Doses, may act @ Nicotinic Receptors.

Some may actually be Inverse Agonists (act by shifting receptor equilibrium to the inactive state)
__Implies that Muscarinic Receptors are Constitutively Active

All Muscarinic Receptors are NOT equally sensitive to the action of antimuscarinic drugs.
_Recall that there are 5 different subtypes of muscarinic receptors.

1) Alkaloids (naturally occurring)
2) Semi-Synthetics
3) Synthetic compounds

Question 2

Tertiary Antimuscarinics

Answer 2

Lipid-Soluble
Cross BBB
Enter CNS

1) Alkaloids:
_Atropine
_Scopolamine

2) Semisynthetic:
_Homatropine

3) Synthetic:
_*Dicyclomine (Bowel spasm)
_*Tropicamide (Eye)
_*Benztropin (Parkinson's)
_*Trihexyphenidyl (Parkinson's)

Question 3

Quaternary Antimuscarinics

Answer 3

Ionized
Can’t cross BBB

1) Ipratropium (COPD), Tiotropium

Question 4

Atropine

Answer 4

Tertiary Alkaloid
Lipid-Soluble
Cross BBB
Enter CNS

Found in
_Belladonna (Deadly Nightshade)
_Datura Stramonium (stinkweed)

Uses:
_Bradycardia or Heart Block due to Excess Vagal Tone
_Cholinergic Poisoning by Muscarine and/or Anticholinesterase Organophosphates
_Excessive Salivation (Hyperhidrosis)

Effects Vary with Dose:
_*Small Doses:
*Decreased Salivation and
*Decreased Sweating

_Larger Doses:
Dilated Pupils,
Blurring of Near Vision,
Tachycardia (Palpitations)

_Even Larger Doses: 
Difficulty Speaking and Swallowing, 
Restlessness and Fatigue, 
Headache, 
Hot Dry skin, 
Difficulty Urinating, 
Reduced GI Motility

**At Low Therapeutic doses, Atropine has almost no detectable CNS effects.
_CNS Stimulation is prominent with *Toxic doses:
Restlessness, Irritability, Disorientation, Hallucinations.

(Secretions are very, very sensitive to small doses of Atropine.)

Atropine Poisoning Symptoms:
_Dry Mouth, Thirst
_Blurred Vision (Cycloplegia), Photophobia (Mydriasis)
_Hot, Dry, Flushed Skin
_Increased Body Temperature
_Palpitations
_Restlessness, Excitement, Hallucinations

Red as a Beet
Hot as a Hare
Dry as a Bone
Blind as a Bat
Mad as a Hatter

1) Contraindicated in Prostatic Hypertrophy.

Atropine causes Urinary Retention, especially in Elderly Males
_B/c of Enlarged Prostate

2) Contraindicated in Narrow Angle Glaucoma (Angle Closure Glaucoma).

_B/c this occurs when the iris blocks the outflow canal of aqueous humor from the eye.
(Atropine would cause the Ciliary muscle to block the flow.)

3) Lomotil
(used to treat Diarrhea)
_Contains Atropine
_May be source of Atropine poisoning, especially in Children

Question 5

Scopolamine

Answer 5

Tertiary Alkaloid
Lipid-Soluble
Cross BBB
Enter CNS

CNS Depressant in Clinical Dosage

• -Drowsiness
• -Amnesia

Use: Anti-Emetic
(Motion Sickness)

In people with Severe Pain:
_Causes CNS Excitation and Hallucinations

Toxic Psychoses in Children and Elderly (not in other age groups)

Question 6

Therapeutic Uses of Antimuscarinics

Answer 6

1) *Cholinergic Poisoning by Muscarine and/or Anticholinesterase Organophosphates:
_Atropine

2) Reversal of Competitive Muscle (Nicotinic) Blockers:
_Atropine + Reversible Anticholinesterase

3) Cardiovascular:
Bradycardia or Heart Block due to Excess Vagal Tone:
_Atropine

4) Reduce Excessive Salivation (Hyperhidrosis):
_Atropine

5) *Anti-Emetic (Motion Sickness):
_Scopolamine

6) *Respiratory:
COPD: *Ipratropium, *Tiotropium

7) GI Tract:
Bowl Spasms:
_Dicyclomine

8) *GU Tract:
Urinary Frequency: 
_*Oxybutynin 
(Some M3 Selectivity)
_*Solifenacin and Darifenacin (Better M3 Selectivity)
_*Tolteridine (M3 Selective)
_Trospium (Non-Selective)

9) *Ophthalmological:
Mydriasis and Cycloplegia for Eye Exams:
_*Tropicamide
_Cyclopentolate
(Cycloplegia = paralysis of Ciliary muscle)

10) Parkinson’s:
_Benztropine
_*Trihexyphenidyl

Question 7

Adverse Effects of Antimuscarinics

Answer 7

1) Dry Mouth, Thirst
2) Mydriasis (Photophobia) and
3) Cycloplegia (Blurred Vision)
4) Urinary Retention
5) Constipation
6) Tachycardia
7) Hot, Flushed Skin and
8) Increased Body Temperature
9) Palpitations
10) Agitation and Delirium
11) Toxic Psychoses (Scopolamine in Children and Elderly)
12) Restlessness, Excitement, Hallucinations
13) Hypotension due to Ganglion Block (Really High, Toxic Doses, not at therapeutic doses)

Atropine:
_Contraindicated in Prostatic Hypertrophy (Elderly Men).
_Contraindicated in Narrow Angle Glaucoma

Scopolamine:
_CNS excitation in ppl in Severe Pain
_Toxic Psychoses in Children and Elderly (not in other age groups)

Question 8

Treatment of Antimuscarinic Toxicity

Answer 8

Physostigmine or Neostigmine

Benzodiazepine in Agitation or Seizures.