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Anti-cholinergic Drugs

Anticholinergic drugs work by blocking the actions of acetylcholine in the parasympathetic nervous system. They are competitive antagonists that bind to muscarinic receptors, reversibly blocking acetylcholine transmission. Atropine is a prototypical anticholinergic derived from deadly nightshade. It causes dilation of the pupils, increased heart rate, decreased secretions, and relaxed smooth muscles. Anticholinergics are used to treat Parkinson's disease, motion sickness, asthma, peptic ulcers, overactive bladder, and other conditions. Side effects include dry mouth, blurred vision, constipation, urinary retention, and excitement or delirium in overdose.

Health & Medicineâ—¦
Autonomic nervous system Lecture 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
Actions Cardiovascular 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
Actions CNS – • 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.
Actions Eye: • 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
Actions Respiratory 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 Uses Central 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 Uses CVS – • 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 Uses Respiratory 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 Uses Gastrointestinal: • 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 Uses Urologic 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 anticholinergics Body System Side/Adverse Effects Cardiovascular Increased heart rate, dysrhythmias CNS CNS excitation, restlessness, irritability, disorientation, hallucinations,delirium
Side Effects of anticholinergics Body System Side/Adverse Effects Eye Dilated pupils, decreased visual accommodation, increased intraocular pressure Gastrointestinal Decreased salivation, decreased gastric secretions, decreased motility
Side Effects of anticholinergics Body 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.
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