Anticholinergic drugs Dr. S. Parthasarathy MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics- PhD ( physiology), IDRA

What are they ? Anticholinergic drugs competitively antagonize the effects (parasympathetic) of the neurotransmitter acetylcholine at cholinergic postganglionic sites designated as muscarinic receptors Inverse agonist ?? Change the receptor to inactive state !!

Muscarinic cholinergic receptors are present in the heart, salivary glands, and smooth muscles of the gastrointestinal and genitourinary tract. Anticholinergic means – anti muscarinic Nicotinic means – ganglion blockers like hexamethanonium – not discussed

Nicotine and muscarine – alkaloids

Why nicotinic blockers don’t block neuromuscular junction ?? Nicotinic receptors – Nn Nicotinic receptors – Nm Curare in high doses can also block ganglion Hexamethonium in high doses can also block NMJ

Receptor subtypes M1 M2 M3 M4 M5 location CNS Stomach Heart Airway Salivary Endothelium heart Effects H+ ion secretion Others Constrict Brady Vasodilation Salivation bronchoconstrict ----- ------

Classification Natural Atropine , scopolamine Semisynthetic Homatropine , ipratropium Synthetic Propantheline ,Oxyphenonium, clidinium, Pipenzolatemethylbromide, Isopropamide, Glycopyrrolate. --- numerous

Tertiary amines Atropine , scopolamine Quarternary ammonium Glycopyrrolate

The three musketeers – similarity Atropine Glycopyrrolate

Atropine Tropic acid + tropine Scopolomine Glycopyrollate Tropic acid with scopine ( hyoscine) Glycopyrollate Quarternary ammonium compound

Atropine Alkaloid of atropa belladona Deadly nightshade 1880s – reduce vagal tone in anaesthesia 1915 – inhibit secretions in anesthesia

Action and uses Decrease secretions when do we utilize this property ?? Children Downs syndrome Ether Airway surgeries

To prevent or reverse bradycardia Scoline ‘ Fentanyl High spinal Neostigmine Beta blockade Surgical stimuli – ECT, sphincter stretching Gut traction , oculocardiac reflex

Low doses and brady ? Initial brady why ? blocking of muscarinic M2 receptors on the post ganglionic parasympathetic neurons, transiently increasing the amount of acetylcholine in the synapse Usually complete vagal block needs 3 mg of atropine Tachycardia more marked in children than elderly Increase AV conduction Dilation of vessels of face and a rash Usually BP unchanged – unless brady - depression

Be specific

CNS Stimulates medulla stimulates respiratory centre Auditory hyperacusis Restlessness Delirium- later sedation with atropine Short term memory loss – anesthesia useful ? Scopolamine – sedation more Motion sickness – scopolamine Benzatropine – parkinsons

RS and glands Sweat bronchial and salivary secretions are stopped – dry mouth Bronchial relaxation Ipratropium yes – tiotropium is long acting

Paralysis of sphincter of iris Dilation of pupil – homatropine drops Loss of accommodation more with local atropine than with parenteral

Peptic Ulcer •Decrease gastric acid secretion •Selective M1 blocker, Pirenzepine,Telenzepine Decreased pancreatic secretions gut spasm,IBS Travellers diarhoea Anti emetic effect LES relax - ? Aspiration risk

Atropine fever in children Atropine bladder Precipitation of BPH in elderly

In OPC poisoning The recommended starting dose of atropine is 2 mg IV bolus. Subsequent doses of 2-5mg every 5-15 minutes should be for adequate atropinization increased heart rate (>100 beats/min.), moderately dilated pupils, a reduction in bowel sounds, a dry mouth (axillae) and a decrease in bronchial secretions.

In OPC poisoning Shots of atropine every 5 minutes Atropinised in one hour Then every hour he/ she may need 10- 20 % of the dose received in the first hour as one hour infusion Inbetween atropinisation lost– one more bolus and increase the infusion rate by 10 % CNS features – no Glycopyrollate

Pharmacokinetics Atropine is readily absorbed from gut and conjunctival membranes. Scopolamine is absorbed across the skin, (Transdermal route). Partially metabolised by the liver. Eliminated primarily in the urine. Half life of about 4 hours. IV and IM routes – OK

Doses Atropine glycopyrollate IV dose (mic./Kg) 10-20 5 -10 onset 1 minute Duration 3 hours 6 hours Tachycardia ++++ ++ antisialogogue +++ CNS side effects CACS + --- Antiemetic ---- Pupil size --

Scopolamine Scopolia cariolica Sedative, ( DIFFERENCE BETWEEN ATROPINE) amnesia and antiemetic with antisialogogue Less tachycardia What more we want as a premedicant !! 0.3 mg to 0.6 mg IV /IM

Poison Hot as a hare: increased body temperature Blind as a bat: mydriasis (dilated pupils) Dry as a bone: dry mouth, dry eyes, decreased sweat Red as a beet: flushed face Mad as a hatter: delirium

ABCDs – pneumonic   Anorexia Blurred vision Constipation/Confusion Dry Mouth Sedation/Stasis of urine

Why 0.6 mg atropine One grain = 60 mg 0.6 mg – 1/ 100 grain Hence ampoules were prepared like that

Summary What is it Classification Dose Difference Indication Uses Eyes Salivary Gut Pancreas Bladder Bronchus Sweat Skin

Carry home message !! Don’t sleep