cholinergic antagonists. anti- muscarinic agents sites of action 1. secretions by salivary,...

Cholinergic antagonists

Anti- muscarinic agents

sites of action• 1. Secretions by salivary, bronchial and sweat

glands.• 2. The eye and cardiac responses mediated by

the vagus.• 3. Urinary bladder and GI tract.• 4. Gastric secretions.

Naturally occurring

• Atropine ( belladonna )

• Scopolamine

• Homatropine

• ATROPINE – high affinity for muscarinic receptors. acts both centrally and peripherally.

• Mydriasis, cycloplegia.• Eneuresis in children• Low doses- bradycardia.• High doses—tachycardia• Dilates cutaneous vasculature

• Atropine uses• In ophthalmology –mydriatic/ cycloplegic• Spastic disorders of GI and lower urinary tract.• To treat OP poisoning• To suppress respiratory secretions prior to

surgery.

Synthetic quaternary ammonium antimuscarinic agents.

• Ipratropium

• Propantheline

Synthetic tertiary amine muscarinic antagonists

• Cyclopentolate

• Tropicamide

• Dicyclomine

• Pirenzipine

CNS• Due to its greater lipid solubility, scopolamine

has significant CNS effects even at low therapeutic doses.

• An adjunct for anesthesia due to an ability to decrease short term memory.

• Motion sickness (scopolamine)• Antipsychotic therapy: used to treat the

extrapyramidal symptoms

Eye

• Mydriasis

• Refract the eye during ophthalmic examinations.

• Caution : glaucoma

Heart

• Low doses initially produce bradycardia, but later doses produce tachycardia.

• Some times in Surgery/catheterization

Lung

• Broncho -dilation: Ipratropium• Mainly used as inhalation in treating asthma and

COPD.• Atropine prior to surgery will decrease the

respiratory secretions

GI tract

• Salivary secretions decrease

• Can cause dry mouth and difficulty in swallowing

• Only Pirenzepine has some potency to decrease hyperacidity..

Other uses

• With an opioid to relax the ureter in renal colic.

• To increase the capacity and decrease the frequency of bladder contractions, i.e.enuresis in children.

• To decrease the frequency of urination in spastic paraplegia.

Toxic effects• decreased concentration and memory• drowsiness• sedation• excitation• ataxia• asynergia• disorientation• hallucinations• coma

ATROPINE PSYCHOSIS

• Disorientation, confusion, recent loss of memory, agitation, incoherent speech, restlessness, hallucinations, anxiety and delirium.

• Treatment – symptomatic only and discontinue the drug immediately.

Therapeutic uses of muscarinic antagonists

• 1. Premedication• · Atropine• · Given before operations to prevent unwanted M

stimulation.• · Want to eliminate bronchial secretions (don't want the

patient to choke on their own secretions)• · Want to block vagal stimulation to the heart and lungs

(want to keep airways open)• · During induction of anesthesia, there may be excessive

vagal stimulation, which we want to eliminate.

• Anticholinesterase toxicity• Toxicity due to over dose of physostigmine and

other anticholinesterases

• Atropine is used to treat this condition by blocking all M receptors.

• 2. Antispasmodic• · Hyoscine N butyl Bromide• · A quaternary derivative• · Treats colic• 3. Bronchodilator (asthma)• · Ipratropium• · A quaternary derivative• · Given by inhalation, get a local effect

• Homatropine• · Much shorter action than atropine• · It is the drug of choice when doing

investigations of the eye, since it dilates the pupil for a short time only.

• 4.Treatment of peptic ulcers• · Pirenzepine• · Selective M1 antagonist• · Not as good as H2 antagonists (e.g.

cimetidine) or proton pump inhibitors (e.g. omeprazole)

• 5. Parkinson's disease • · Benztropine, trihexiphenidyl

also used to treat the extrapyramidal symptoms due to Antipsychotic drugs

• 6. Motion sickness

· Hyoscine, scopolamine

• REMEMBER • S --- salivation• L --- lacrimation• U --- urination• D --- diaphoresis• G --- GI• E --- Eye & emesis

GANGLIONIC BLOCKERS

• NICOTINE

• TRIMETHAPHAN

• MECAMYLAMINE

SITE OF ACTION

• ALL NICOTINIC RECEPTORS

• IN ANS ( BOTH SNS AND PNS )• IN CNS

NICOTINE

DOSAGE

• LOW DOSE

• HIGH DOSE

GANGLION

• STIMULATION

• BLOCK

CNS/ NICOTINE

• LOW DOSE- EUPHORIA,RELAXATION

• HIGH DOSE- central respiratory paralysishypotension- medullary paralysis

PERIPHERAL EFFECTS

• COMPLEX• HR RAISES• B.P.- RAISES• GIT- MOTILITY RAISES

OTHERS

• TRIMETHAPHAN- SHORT ACTING• HTN EMERGENCIES

• used in surgery, particularly neurosurgery, to produce a relatively bloodless operative field (controlled hypotension).

• MECAMYLAMINE- LONG ACTINGCHR. CASES of HTN

Neuromuscular Blocking Drugs

Mainly during surgery to produce complete muscle relaxation, without giving higher anesthetic doses.

Neuro muscular blocking drugs• Atracurium• Doxacurium• Mivacurium • Pancuronium• Rocuronium• Succinylcholine• Tubocurarine• Vecuronium

Atracurium• safe in renal failure, used in critically ill patients

for mechanical ventilation. • Short duration of action – so suitable for short

surgical procedures.

Rocuronium & Succinylcholine • Rapid onset of action – so used mainly in

tracheal intubation in patients with gastric contents.

Vecuronium – short duration of action , so used in short surgical procedures.

Imp side effects

• Tubocurarine – induce histamine release and also lower B.P.

• Pancuronium – Increased H.R.• Succinylcholine – malignant hyperthermia,

hyperkalemia and increased Intraocular pressure.