Anticholinergic

Drugs
•Red : important
•Black : in male / female slides
•Pink : in female’s slides only
•Blue : in male’s slides only
•Grey: Extra, Doctor’s notes

OBJECTIVES:
By the end of this lecture , you should be able to:

✓ Identify the classification of anticholinergic drugs

Describe pharmacokinetics and dynamics of muscarinic

✓
antagonists.

✓ Identify the effects of atropine on the major organ systems.

list the clinical uses of muscarinic antagonists.

✓ know adverse effects & contraindications of anticholinergic

drugs.

✓ Identify at least one antimuscarinic agent for each of the

following special uses: mydriasis, cyclopedia, peptic ulcer &
parkinsonism.

Editing File
 Anticholinergic Drugs - Antimuscarinic
classifications:

According to Source
Natural Synthetic / Semisynthetic

Atropine (Hyoscyamine) Homatropine (Semisynthetic)

Hyoscine (Scopolamine) Tropicamide

Pharmacokinetics of Atropine and Ipratropium

Hyoscine:
● Lipid soluble Pirenzepine
● Good Oral absorption
● Good distribution Benztropine
● Can cross BBB (have CNS effect)
● Hyoscine has better BBB penetration Oxybutynin
● 50% of ATROPINE is metabolized in
liver and 50% excreted unchanged in Darifenacin
urine.
● HYOSCINE is more completely
Glycopyrrolate
metabolized.
● ATROPINE has t1/2 of 3–4 h.

According to structure
Tertiary amines Quaternary ammonium
“Lipid soluble“ “Water soluble“

Atropine (Hyoscyamine) Glycopyrrolate

Hyoscine (Scopolamine) Ipratropium

According to selectivity
Non-selective Selective

Pirenzepine (M1)
Atropine (Hyoscine)

Hyoscine (Scopolamine) Darifenacin (M3)

Ipratropium
 Mechanism of action:
Reversible competitive blockade of muscarinic
receptors, some like atropine block nicotinic
receptors in toxic doses
(reverses muscarinic effects of cholinergic drugs).
● Salivary, bronchial, and sweat glands are
most sensitive
● Gastric glands and gastric smooth muscles
are the least.
● Smooth muscle and heart are
intermediate.
● Atropine & hyoscine can block all
muscarinic receptors because they are
(not selective).

REVIEW For Mechanism of actions:

For your understanding only!
★ Muscle Relaxants “ Neuromuscular Blockers”
peripherally acting :Act by blocking neuromuscular
junction or motor end plate ”nicotinic receptors” leading to
skeletal muscle relaxation. e.g=Atracurium

★ Cholinomimetics: Drugs that produce actions similar to

stimulation of parasympathetic system or similar to
Acetylcholine

Direct: Indirect:

Cause direct Acts indirectly by

stimulation of inhibiting
cholinergic Acetyl
receptors cholinesterase
“muscarinic or act on both
nicotinic muscarinic and
receptors” nicotinic
receptors.

e.g Carbachol e.g Neostigmine

 Pharmacodynamics Actions:

- Atropine (clinical dose) → stimulation followed by sedation

it stimulates medullary centers including vagal, vasomotor, and respiratory
high dose: cortical excitation, restlessness, hallucinations, disorientation, and delirium
followed by respiratory depression and coma
- Hyoscine → Sedation (both drugs are pre-anesthetics)
- Antiemetic (block vomit center) and Antiparkinsonian effects (block basal ganglia)

- Bradycardia followed by tachycardia (blocks M2 receptors in SA node)

why initial bradycardia? At low doses, atropine (non-selective) inhibits pre-synaptic M1 receptors that inhibit Ach release. This “double” inhibition leads
to an increase of Ach-->bradychardia
- ↑AV conduction
- No BP influence, but decreases vasodilation caused by cholinergic agonists
- Toxic dose → Cutaneous vasodilation (atropine flush)

- Passive mydriasis (circular muscle paralysis) (active mydriasis is due to radial muscle contraction)
- Cyclopegia (ciliary muscle paralysis→ loss of near accommodation → blur )
- ↑IOP (not suitable for glaucoma) + ↓Lacrimal secretion (sandy eye).

- Bronchodilation + ↓ Secretion (leads to viscosity)

- ↓ Motility (antispasmodic) → constipation

- ↓ Gastric acid production
- ↓ Salivary secretions (dry mouth)
- ↑ Sphincter contraction (urinary retention)
- Smooth muscle relaxation

- Sphincter contraction (urinary retention→ can occur in men with prostatic hyperplasia)
- Relaxation of urinary bladder smooth muscles

- ↓ Sweating (dry skin)

in children, a modest dose can cause atropine fever
 Drugs Organ Clinical uses

Benztropine AND Parkinsonism

Benzhexol CNS
Hyoscine Vomiting (Motion sickness)
Preanesthetic

Tropicamide AND Ophthalmic Ophthalmoscopic examination (fundus

homatropine disorders examunation) of retina
Atropine substitute with short
duration of action

Glycopyrrolate AND ● Intestinal spasm.

● Biliary and renal colics.
Hyoscine butyl-
● Irritable bowel syndrome.
bromide

Peptic Ulcer
(because pirenzepine acts on M1 receptors, which are
Pirenzepine GIT responsible for gastric acid secretion from stomach parietal
cells, inhibiting those receptors leads to reduced secretion
of gastric acid)

Irritable bowel syndrome, colonic

dicyclomine diverticular disease

Used for treatment of Traveler's diarrhea

Atropine AND with opioid
Extra: Opioid drugs cause constipation.
diphenoxylate

Urinary incontinence & Urinary urgency

Oxybutynin AND GUT caused by minor inflammatory bladder
disorders.
Darifenacin

Bronchial asthma & chronic obstructive

Ipratropium Respiratory pulmonary disease (COPD).
(inhalation) disorders

Preanesthetic
CVS and CNS Sinus bradycardia.
Atropine IV/IM
Used to increase heart rate through vagolytic
Atropine effects, causing increase in cardiac output.

Cholinergic Mushroom poisoning.

Atropine reverses muscarinic effects of cholinergic
poisoning poisoning.
Cholinesterase inhibitors (insecticides)

-
Others
Hyperhydrosis “excessive sweating”
Adverse effects:
Can’t pee, Can’t See, Can’t spit, Can’t shit

● CNS: ● Urinary tract:

1-confusion 2-agitation
Urinary retention
3 -delirium

● CVS: ● GIT:
1-Tachycardia 2-Hot flushed Constipation
skin(dilation of cutaneous blood vessels )

● Eyes: ● Secretions:
1-Blurred vision 1-Dryness of mouth 2-Sandy eyes
2-Mydriasis (pupil dilation) 3-Hyperthermia

Contraindications:

● Prostate
● Tachycardia
(secondary to thyrotoxicosis Hypertrophy
or cardiac insufficiency) (urinary retention)

● Glaucoma ● Constipation
(angle closure glaucoma) ● Paralytic ileus

● Children in case of
Atropine
(Atropine flush)
 Summary

Drug Organ Uses

Atropine Pre-anesthetic medication,

Antispasmodic

CNS

Hyoscine Pre-anesthetic medication,

Antispasmodic,Vomiting
(Motion sickness).

Benztropine Parkinson's disease

homatropine AND Eye Fundus examination

Tropicamide (ophthalmic examination)

Ipratropium Respiratory System Asthma, COPD

(Inhalation)

Pirenzepine Peptic ulcer

GIT

Glycopyrrolate Antispasmodics in
hypermotility

Oxybutynin GUT Urinary urgency, Urinary

Darifenacin incontinence
 QUIZ

MCQs:
1-A patient is brought into the emergency room. Upon examination you find the following: a high
fever, rapid pulse, no bowel sounds and dilated pupils that do not respond to light. His lungs are
clear. His face is flushed and his skin is dry. He is confused, disorientated and reports 'seeing
monsters'. Based on these symptoms, you suspect he has been 'poisoned'. Which of the
following, is the MOST obvious cause of poisoning?

A-Neostigmine. B-Physostigmine. C-Atropine Sulfate. D-Acetylcholine

2-Which of these drugs acts SELECTIVELY?

A-Darifenacin. B-Atropine. C-Hyoscine. 4-Ipratropium.

3-You are working in the post anesthesia care unit of a hospital. You have just
received a patient back from surgery and you are monitoring his status. Knowing
that the patient has received atropine, which of the following
statements/observations is UNEXPECTED?

A-The patient is complaining of extreme thirst.

B-The patient complains he is unable to clearly see the clock located just across from him.
C-The patient's heart rate is elevated.
D-The patient reports he has cramping and diarrhea.

4-One of these cases using Antimuscarinic drugs is contraindicated:

A-Glaucoma. B-Parkinson’s disease. C-Sinus bradycardia. D-Bronchial Asthma.

5-Mydriasis is known as:

A-Ciliary Muscle Contraction. B-Pupil Dilation. C-Pupil Constriction. D-Ciliary Muscle Relaxation.

SAQ:
1-What is the mechanism of action of Antimuscarinic drugs?
2-List FOUR Adverse Drug Reactions of Antimuscarinic drugs
3-A patient diagnosed with Colonic Diverticular Disease, what drug can you give
him ?
4-Can antimuscarinic drugs reverse the action of neostigmine on skeletal muscles?
5-Enumerate one case in which Antimuscarinic drug is contraindicated:
6-Name TWO drugs used for treatment of Parkinsonism
 Answers

MCQs:

1-C
Physostigmine is the treatment for the toxicity because it can cross the BBB
therefore it increases the concentration of Ach resulting in treating the
toxicity
2-A
3-D
4-A
5-B

SAQ:

1-Reversible competitive blockade of muscarinic receptors

(reverses muscarinic effects of cholinergic drugs).
2-Constipation, Urinary retention, Mydriasis, Tachycardia.
3-Dicyclomine.
4- No, Neostigmine acts on both (N and M receptors) but in
skeletal muscles it acts on the nicotinic receptor
5-Glaucoma.
6-Benzhexol + Benztropine
 GOOD LUCK

Team Leaders:
Nouf Alshammari Zyad Aldosari

Team sub-leader:
May Babaeer

Team Members:
Omar Alshenawy
Omar Alghadir

Sources:
Team 435.
Dr’s slides.