Autonomic nervous systemLecture 3

Anticholinergic Drugs

Dr. Mohit Kulmi

• Drugs that block or inhibit the actions of acetylcholine (ACh) in the parasympathetic nervous system (PSNS)

• Also called cholinergic blocking agents or parasympatholytics

• Often referred to as anticholinergics or antimuscarinics

Mechanism of Action• Competitive antagonists• Compete with acetylcholine• Block acetylcholine at the muscarinic receptors

in the PSNS• Reversible blockade of acetylcholine at

muscarinic receptors by competitive binding • (reversal by increasing acetylcholine or agonist

----> decreased blockade) • Once these drugs bind to receptors, they inhibit

nerve transmission at these receptors.

Atropine• Prototype antimuscarinic drug - derived from

Atropa belladonna (deadly nightshade) and Datura stramonium (thorn apple)

• History: • during the Italian renaissance dilated pupils

were considered desirable• plant extracts were used as cosmetic eye drops• hence the name belladonna or "beautiful lady"

in Italian

ActionsCardiovascular effects-• Decreased cardiovascular response to vagal

stimulation resulting in tachycardia• Mainly, tachycardia due to antagonism of the

vagal affect.

• Vascular– no (direct) effect – except, dilate cutaneous vessels (red as a beet)– block hypotensive effect of muscarinic agonists

ActionsCNS –• At normal doses atropine stimulates medullary

centers, However, at higher doses produce excitement, agitation, hallucinations and coma.

• Depresses vestibular excitation and has anti motion sickness properties

• Supresses tremor and rigidity of parkinsonism by blocking cholinergic overactivity in basal ganglia.

ActionsEye:• Dilated pupils (mydriasis)• Blocks muscarenic innervations on the circular muscles

(Mydriasis) and relaxes cilairy muscles (Cycloplegia)• worsens glaucoma

Gastrointestinal:• Relax smooth muscles of GI tract• Decrease intestinal and gastric secretions• Decrease motility and peristalsis • antispasmodic effect• Sphincter contraction

ActionsRespiratory system - • Decreases bronchial secretion (used as preanesthetic

Medication,COPD)• Dilated bronchial airways (used for treatment of

Asthma)Genitourinary -• Relaxes detrusor muscle• Increased constriction of internal sphincter• Result: urinary retention• Relaxation of smooth muscles of ureters.• Therefore, they are contraindicated for prostate

hypertrophy patients.

Glandular – • Salivary secretion (Dry mouth)• gastric Acid (used for Peptic Ulcer )• Sweating Dry skin Fever in infants and

children.• Bronchial Secretion (used for COPD)

Therapeutic UsesCentral Nervous System Disorders-• Parkinson’s disease – Benztropine,

Trihexyphenidyl• Those who cannot take Levodopa• Helpful in decreasing salivation, spasticity and

tremors• Motion Sickness (Scopolamine)• Drug-induced extrapyramidal reactions(due to

antipsychotics)

Therapeutic UsesCVS – • Atropine is used to increase heart rate in

symptomatic bradycardias.• Sinus node dysfunction• Symptomatic second-degree heart block• Sinus or nodal bradycardia (due to myocardial

infarction)

Therapeutic UsesRespiratory system-

• Decreased secretions from nose, mouth, pharynx, bronchi

• Relaxed smooth muscles in bronchi and bronchioles

• Decreased airway resistance• Bronchodilation

Respiratory agents are used to treat: • Exercise-induced bronchospasms• Chronic bronchitis• Asthma• Chronic obstructive pulmonary disease• Ipratropium as inhalation (or Tiotropium)

Therapeutic UsesGastrointestinal:• Blockade of PSNS results in:• Decreased secretions• Relaxation of smooth muscle• Decreased GI motility and peristalsis

Gastrointestinal agents are used to treat:• Peptic Ulcer: Pirenzepine• As antispasmodic :Butylscopolamine• Irritable bowel disease: Propantheline• GI hypersecretory states

Therapeutic UsesUrologic disorders-• Antispasmodic effects seen in overactive

bladder and in urinary incontinence - Oxybutynin

• Detrusor hyper-reflexia, • Enuresis

-Increase bladder capacity-Decrease bladder pressure

Therapeutic Uses

Opthalmological Disorders-• Homatropine,tropicamide• Accurate measurement of refractive error in

uncooperative patients (e.g, children)• Examination of retina (Mydriasis)

Side Effects of anticholinergicsBody System Side/Adverse Effects

Cardiovascular Increased heart rate, dysrhythmias

CNS CNS excitation, restlessness, irritability, disorientation, hallucinations,delirium

Side Effects of anticholinergicsBody SystemSide/Adverse Effects

Eye Dilated pupils, decreased visual accommodation, increased intraocular pressure

Gastrointestinal Decreased salivation, decreased gastric secretions, decreased motility

Side Effects of anticholinergicsBody System Side/Adverse Effects

Genitourinary Urinary retention

Glandular Decreased sweating

Respiratory Decreased bronchial secretions

Toxicity of Anticholinergics• Anticholinergic overdose syndrome (Belladona

poisoning- consumption of seeds or berries of belladona or dhatura plant) is characterized by: Hyperthermia, delirium, dry mouth, tacycardia, ileus, urinary retention. Seizures, coma and respiratory arrest may occur.

• Treatment – Gastric lavage with tannic acid, cold sponging or ice bags, Physostigmine s.c. or i.v., diazepam to control convulsions.

Contraindications• Glaucoma• Prostatic hypertrophy • Urinary tract obstruction• Gastrointestinal tract obstruction• Infectious diarrhea• Reflux esophagitis• Tachyarrhythmias • Angina• Hyperthyroidism• Pregnancy

Individual Drugs• Atropine - prototype. Antidote in OP Poisoning.• Ipratropium - Useful in rhinorrhea. Also

excellent bronchodilator.• Scopolamine - depresses CNS and causes

amnesia, drowsiness, euphoria, relaxation and sleep. Also good for motion sickness. Given parenterally, orally and transdermally.

• Benztropine - temporary use in Parkinson’s disease. Useful for dystonic reactions caused by antipsychotics.

Individual Drugs• Trihexyphenidyl - also used for treating EPS

by some antipsychotics. Contraindicated in glaucoma.

• Flavoxate - relieves dysuria, urgency, frequency, and pain with GU infections

• Oxybutynin - has direct antispasmodic effects on smooth muscle and anticholinergic effects. Decreases frequency of voiding.

Thank you!