ANTICHOLINERGIC DRUGSANTICHOLINERGIC DRUGSANTICHOLINERGIC DRUGSANTICHOLINERGIC DRUGS

Profs. Abdulqader Alhaider and Hanan HagarPharmacology Department

What students should know:What students should know:Student should be able to : Student should be able to :

• Describe Kinetics of muscarinic antagonists Describe Kinetics of muscarinic antagonists • The effects of atropine on the major organ systems.The effects of atropine on the major organ systems.• To list the clinical uses of muscarinic antagonistsTo list the clinical uses of muscarinic antagonists.• To know adverse effectsTo know adverse effects & contraindications of anticholinergic & contraindications of anticholinergic drugs.drugs.• To identify at least one antimuscarinic agent for each of theTo identify at least one antimuscarinic agent for each of the following special uses:mydriasis, cyclopedia, peptic ulcer & following special uses:mydriasis, cyclopedia, peptic ulcer & parkinsonism.parkinsonism.

Anticholinergic drugsAnticholinergic drugs

are drugs that block cholinergic receptors. Two types are available

1. Nicotinic blockers (antinicotinics).Ganglionic blockers (not used Clinically Why?)

Neuromuscular blockers (Skeletal Muscle Relaxants)

2. Muscarinic blockers (antimuscarinics)Naturally occurring alkaloids (e.g: Atropine)

Synthetic atropine substitutes.

Anticholinergic drugsAnticholinergic drugs

Antimuscarinics(Parasympatholytics)

Antinicotinics

synthetic atropine substitutes

Ganglionic blockers

Neuromuscular blockers

Anticholinergic drugs Anticholinergic drugs

Naturally occurring alkaloids

• History (Thousants of years)•Atropine (Hyoscyamine)• Hyoscine (scopolamine)• Esters of tropic acid and tertiary amines• Lipid soluble• Good oral absorption• Good distribution• Cross blood brain barrier (have CNS actions)

Natural alkaloids

Muscarinic antagonistsMuscarinic antagonists

Synthetic atropine substitutes

Muscarinic antagonistsMuscarinic antagonists

Tertiary amines

Lipid solublecentral actions

BenztropineHomatropineTropicamaidePirenzepineOxybutynin

Tertiary amines

Lipid solublecentral actions

BenztropineHomatropineTropicamaidePirenzepineOxybutynin

Quaternary amines

Polar, water solubleNo CNS effects

IpratropiumGlycopyrrolate

N+N+

Quaternary amines

Polar, water solubleNo CNS effects

IpratropiumGlycopyrrolate

N+N+

Muscarinic antagonistsMuscarinic antagonists

Quaternary aminesQuaternary amines

DRUG Pharmacokinetics

Natural alkaloidsAtropine (Hyosyamine)Hyoscine (scopolamine)

Tertiary amines, lipid soluble, well absorbed, well distributed, good penetration to CNS

Synthetic atropine substitutes

Benztropine Tertiary amine

Tropicamide Homatropine

Tertiary amines

Ipratropium Quaternary amines, not absorbed well, poor distribution, no CNS effects

Pirenzepine Tertiary amine

GlycopyrrolateOxyphenonium

Quaternary amines

Oxybutinin Tertiary amine

Antimuscarinic drugs Antimuscarinic drugs

Mechanism of action

• Reversible competitive blockade of muscarinic

receptors.

Can antimuscarinic drugs reverse the action of

Ach on skeletal muscles?

Antimuscarinic drugs Antimuscarinic drugs

CNS– CNS depression – Antiemetic effect (block vomiting center)– antiparkinsonian effect (block ACH at

basal ganglia).

– Toxic dose: Hyperthermia - excitement-hallucination.

Pharmacological Effects ofPharmacological Effects ofAntimuscarinic Drugs Antimuscarinic Drugs

Cardiovascular system (CVS) Tachycardia (increase heart rate) AV conduction ( + ve dromotropic effect) Therapeutic dose: Vasodilatation induced

by cholinomimetics. Toxic dose: Cutaneous vasodilatation

(atropine flush).

Respiratory system Bronchial Relaxation (bronchodilator) Bronchial secretion viscosity

EyePassive mydriasis

due to paralysis of circular muscleCycloplegia (loss of near accommodation) due to paralysis of ciliary muscle.Loss of light reflex. Increase I.O.P (worsens glaucoma). Lacrimal secretion sandy eye

Secretions

Salivary secretion ( Dry mouth ). Sweating Dry skin Fever in infants and

children. Bronchial secretion Viscosity Lacrimal secretion Sandy eye

GIT– Relaxation of smooth muscles. GIT motility Antispasmodic effect. Sphincter contractions– Constipation

Urinary Tract– Relaxation of smooth muscles of ureters.– Sphincter contraction. – Urinary retention (worsens prostate

hypertrophy).

Hyoscine (SCOPOLAMINE)

What is difference between atropine and hyoscine?

Hyoscine has• Shorter duration of action• More CNS depressant action• Antiemetics action in motion sickness• Amnesic action. • Less CVS effect

Can you put a question for exam?

Cholinergic actions Anticholinergic actions

Eye

1. Contraction of circular muscle of iris (miosis)

2. Contraction of ciliary muscles for near vision

1. Mydriasis

2. Cycloplegia

relaxation of ciliary muscles

Heart

bradycardia ( heart rate ) Tachycardia ( heart rate)

Urinary bladder

Contraction of muscles

Relaxation of sphincter

Relaxation of muscles

contraction of sphincter

Cholinergic drugs Anticholinergic drugsExocrine glands

Increase of sweat, saliva, lacrimal, bronchial, intestinal secretions

Decrease all secretion

GIT

peristalsis

secretion

relaxation of sphincter

peristalsis secretionContraction of sphincter

Lung

1. Bronchoconstriction

2. bronchial secretion

1. Bronchodilatation2. Decrease secretion

Drugs organ Uses

Atropine CNS Cardiac Arrest How?Rx of pesticide Toxicity

Hyoscine CNS Preanesthetic medication, Motion sickness, antispasmodic

Benztropine CNS Parkinson's disease

TropicamideHomatropine

Eye Fundus examination of eye

Ipratropium Respiratory system

asthma, COPD, inhalation

Pirenzepine Stomach Peptic ulcer

GlycopyyrolatePropantheline

GIT Antispasmodics in hypermotility

Oxybutynin GUT Urinary urgency, Urinary incontinence

Uses of antimuscarinic drugs Uses of antimuscarinic drugs

• Adverse effects (usually can be observed with antidepressant s and antipsychotics)– Eye: Blurred vision – Mydriasis – CVS: Tachycardia - Atropine flush– GUT: Urinary retention – GIT: Constipation, paralytic ileus– Secretions: Dryness of mouth , Sandy eye– Increased body temperature.– CNS: sedation, hallucination, excitation (Toxic dose).

• Treatment– Gastric lavage.– Anticonvulsant.– Cooling blanket.

• Antidote: Physostigmine ( IV slowly).

• Treatment of anticholinergic Toxicities – Gastric lavage.– Anticonvulsant.– Cooling blanket.

• Antidote: Physostigmine ( IV slowly).

Contraindications– Glaucoma (angle closure glaucoma)– Tachycardia– Prostate hypertrophy in old patients.– Constipation, paralytic ileus, intestinal

obstruction.– Children in case of atropine

Thank you

Questions ?