الحلقة 6 من كورس كلنيكال فارما (ANS)

Antimuscarinic Agents – Anticholinergic – Cholinergic Blockers

A: Natural Belladonna Alkaloids:-

Atropine /dl-Hyoscyamine (Isopto®Atropine) (AtroPen®)

Information -Atropine is a tertiary amine belladonna alkaloid.

- Has high affinity to muscarinic receptor.

- It's competitive antagonist  prevent ACh from binding to

those sites.

- It's pass BBB  CNS effects.

- It has peripheral and central effect.

- Antidote for cholinergic agonists.

Pharmacological

action

Eye

-Passive Mydriasis due to weakening of constrictor

(circular) pupil muscle (allow radial muscle to

contract).

- Cycloplegia  paralysis of the ciliary muscle loss

of the ability to accommodate.

- Increase IOP in patient with closed angle glaucoma

due to narrowing of anterior chamber angle.

- Decrease lacrimation Dry or sandy eye.

Cardiovascular

system

In small dose

A) Bradycardia: (initial

decrease heart rate)

 due to:

1: Central activation of vagal

afferent outflow.

2: Blocking of M1 receptor

on the inhibitory

presynaptic neurone

increase ACh M2.

B) Minimal effect on blood

vessels.

In high dose

A) Tachycardia: (moderate

increase heart rate) due to

blocking the muscarinic

receptors (M2) on sinoatrial

(SA) node.

B) Vasodilatation effect:

especially in facial area

Atropine flush.

GIT

(Antispasmodic Effect)

- Inhibit GIT motility  decrease tone  relaxation of wall.

- Not significance effect on gastric HCl production:

* It's not effective in peptic ulcer but some derivatives

(Atropine substitute) are used for in peptic ulcer e.g.

Pirenzepine and Telenzepine  Which are selective M1

antagonist  decrease acid secretion with less side effect

than atropine.

Urinary

bladder

- Urine retention  Cause relaxation to urinary bladder

wall and contraction to sphincter(Difficult micturition).

- N.B: So it's contraindicated in urinary tension especially

urinary tension which associated with prostatic

hyperplasia.

Respiratory

system

- Slight bronchodilator and decrease bronchial secretion.

- N.B: So it's used before administration of inhalant

anaesthetics e.g. halothane to reduce secretion in the

trachea and the possibility of laryngospasm.

- Atropine substitute e.g. Ipratropium and Tiotropium

more effective and less side effects (selectivity), so  used

in bronchial asthma.

Glands

- Decrease all secretions: -

Decrease Lacrimation (Dry or sandy eye)

Decrease Salivation (Xerostomia; dry mouth)

Decrease Sweating (increase body temperature)

- Cause atropine fever in children .

CNS

- In normal dose little CNS effects.

- In toxic dose  CNS excitation (restlessness, hallucinations

and disorientation).

- Has anti-tremors effect in Parkinson's disease  due to

blocking muscarinic receptors in braindecrease ACh

activity.

Uses

and

Dosage

A) Ophthalmologic Disorders:-

1) Used before eye examination:

- Measurement of refractive errors (Myopia or Hyperopia).

- Examination of retina by inducing mydriasis.

* Atropine substitute (Short-acting) e.g. Cyclopentolate and Tropicamide

more preferred than Atropine in eye examination due to short duration of

action.

2) Uveitis and iritis treatment (inflammation of the uvea/iris):

- Mydriasis and ciliary muscle relaxation desirable in acute inflammatory

conditions of the iris and uveal tract.

* Atropine substitute (Long-acting) e.g. Homatropine more preferred than

atropine in uveitis and iritis.

DRUG DURATION OF ACTION(DAYS) USUAL CONCENTRATION %

Atropine 7-10 0.5-1

Homatropine 1-3 2-5

Cyclopentolate 1 0.5-2

Tropicamide 0.25 0.5-1

B) Gastrointestinal Disorders:-

1) Antispasmodic  Relax the GI tract.

* Atropine substitute e.g. Hyoscine N-Butylbromide more preferred than

atropine as antispasmodic agent.

2) Antidiarrheal > often combined with opioid antidiarrheal drug e.g.

Diphenoxylate (lomotil®)  Diphenoxylate + Atropine.

C) Urinary Disorders:-

1) Urinary incontinence S Contraction to bladder sphincter.

2) Bladder spasm after urologic surgery Relax bladder wall.

3) Overactive bladder syndrome (OAB).

* Atropine substitute e.g. Oxybutynin and Solifenacin more selective than

atropine in urinary disorders.

D) Cardiovascular Disorders:-

1) Treat bradycardia (Atropine cause temporarily increase heart rate).

2) Reduce AV heart block(associated with digitalis toxicity or myocardial infarction).

Usual adult dose: 0.4 to 1 mg IV one time (repeated every 1 to 2 hours as needed

to achieve an adequate heart rate or promote normal AV node

conduction or within 5 to 10 minutes if the initial effect is

inadequate).

Usual pediatric dose: 0.01 to 0.03 mg/kg IV every 5 minutes for 2 to 3 doses as

needed.

E) Respiratory Disorders:-

1) Preanesthetic medication:

-Atropine become part of routine preoperative medication when anesthetics

such as halothane were used due to:

- Anti-secretory agent (block salivary secretion and decrease secretion in the trachea

which can accelerate reflex bronchoconstriction)

- Bronchodilator agent (prevent episodes of reflex laryngospasm).

- Protect heart from arrhythmia (particularly bradycardia).

Usual adult dose: 0.4-0.6 mg 30-60 minutes Pre-operative, repeat every 4- 6

hours as needed.

Usual pediatric dose: 0.01 mg/kg/dose 30-60 minutes Pre-operative, repeat

every 4-6 hours as needed.

G) Cholinergic Poisoning (Antidote for Cholinergic Agonists):

Atropine is used for the treatment of organophosphate (insecticides, nerve

gases) poisoning, overdose of clinically used anticholinesterases such as

physostigmine and in some types of mushroom poisoning.

Usual dose: 0.05 mg/kg/dose IV repeated every 3-5 min. as needed, doubling

the dose if previous dose not treat signs of parasympathomimetic

activity.

F) Central Nervous System Disorders:-

1) Parkinson's disease (Adjuvant therapy):

* Atropine substitute e.g. Benztropine used with L-dopa in management

Parkinson's symptoms.

2) Motion sickness:

- Certain vestibular disorders respond to antimuscarinie drugs.

- Scopolamine is one of the oldest remedies for seasickness.

Scopolamine or Hyoscine (Transderm Scop®)

Information

Scopolamine another tertiary amine plant alkaloid, produces peripheral

effects similar to those of atropine.

* It differs from atropine in the following

- It is more potent in mydriasis, cycloplegia and decrease secretion.

- It is less potent in heart and bronchial muscle.

- It is greater action on the CNS (produces amnesia and drowsiness).

- It is longer duration of action.

Uses Scopolamine is one of the most effective anti-motion sickness drugs.

- The therapeutic use of scopolamine is limited to prevention of motion

sickness and postoperative nausea and vomiting.

It is available as a topical patch (Transderm Scop®) that provides effects

for up to 3 days.

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