Parasympatholytics

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Parasympatholytics

• Dr. Zaker

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(No Transcript)
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Cholinergic receptors
Nicotinic receptors Muscarinic receptors
Present in Autonomic ganglia (NN) Adrenal medulla (NN) Motor endplate (NM) CNS (Spinal cord mainly) (NN) Present in Effector organ supplied by Parasymp Sweat glands BV CNS (Brain Mainly)
Blocked By Ganglion blocker (Nicotine, LD, in ganglia) Neuromucular blocker (eg. Curare in skeletal muscles) Blocked by Atropine
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Drug affecting ANS neuromuscular junction
Sympathetic Sympathetic Parasympathetic Parasympathetic Drugs acting on NMJ
Sympatho-mimetics Sympatho-lytics Parasympatho-mimetics Parasympatho-lytics NMJ Blocking Agents
Adrenergic agonists Adrenergic antagonists Cholinergic agonists Cholinergic antagonists Cholinergics
1. a receptors 2. ß receptors a-antagonist ß-antagonist Selective ß Mixed type Nicotinic Muscarinic 1. Muscarinic antagonists 2. Ganglion blocking drugs 1. Competitive non-depolarizing (Curare, Pancuronium)
Direct acting Indirect acting Direct acting Indirect acting 2. Non competitive depolarizing (Decamethonium, Succinylcholine)
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Classification of Cholinergic drugs

• Muscarinic antagonists (Parasympatholytics)
• (Atropine, hyoscine, homatropine)
• Ganglion blocking drugs
• (Hexamethonium, gallamine)
• Neuromuscular blocking drugs
• (Calcium antagonists, hemicholinium, magnesium
  ions)

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MUSCARINIC RECEPTOR ANTAGONISTS

• They produce reversible blockade of the action of
  ACh at muscarinic receptors competitively. They
  have affinity for muscarinic receptors, no
  efficacy, and slow dissociation rate.
• Classified as
• Natural belladonna Alkaloids Atropine, Hyoscine
  (Scopolamine) Both are tertiary ammonium
  alkaloids
• Synthetic derivatives Homatropine, Ipratropium,
  Pirenzepine (Selective M1 antagonist)

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Atropine

• Pharmacokinetics
• Absorbed orally, can be given by Inj. Metabolized
  in liver, distribution to all tissue, t1/2 2hr,
  urinary excretion, 60 unchanged
• Actions
• Eye
• Mydriasis due to block of muscarinic receptors in
  constrictor papillae muscle (passive mydriasis)
• Loss of reaction to light (light reflex loss)
• Relaxation of ciliary muscle (cycloplegia--- Loss
  of accommodation for near vision)
• Impaired aq. Humor drainage (?IOP)
• Decrease lacrimation (local application- effects
  last for 7-10 days)
• Secretions Decreases saliva, bronchial, gastric
  and sweat secretions
• Bronchi Bronchodilatation, dryness of secretions
• CVS ? HR, ?AV conduction due to vagal block. Low
  doses produce bradycardia followed by tachycardia
• BV no effect at therapeutic doses (Most BVs
  have no parasymp supply). Blocks VD induced by
  muscarinic agonists. Toxic doses cause cutaneous
  VD in upper part of body esp. face (Atropine
  flush)
• GIT ? motility and secretions
• Urinary tract Relaxes detrusor muscle and
  contract sphincters
• CNS Mainly excitatory, antiemetic and
  antiparkinsonian effect

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Atropine- Therapeutic uses

• Preanesthetic medication to
• Decrease salivary and bronchial secretions
• Antagonize RC depressants
• Protect heart from bradycardia induced by general
  anesthetics
• Prevent vomiting
• Fundus examination (derivatives are better)
• Heart block, marked bradycardia and carotid
  sinus syndrome
• Bronchial asthma (secretions become vicid, better
  to use ipratropium)
• Colics, gut hypermotility and duodenal ulcers
• Nocturnal enuresis and urinary urgency to reduce
  bladder motility
• Parkinsonism
• Motion sickness but Hyoscine is better
• Hyperhidrosis (excessive sweating)
• In cholinergic poisoning to antagonize muscarinic
  effects as in organophospate poisoning or
  physostigmine poisoning
• Adverse effects
• Dry mouth, blurred vision, tachycardia,
  constipation, urine retention, glaucoma, flush,
  agitation, delirium and hyperthermia (esp. in
  children).
• Treatment of toxicity (symptomatic)
• Care for respiration and stomach wash
• Cold foamentation to reduce hyperthermia

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Hyoscine

• Given orally, also absorbed by skin, Shorter
  duration of action with potent effects on eye and
  secretions, Less effects on heart
• Tertiary amine like atropine, stimulates RC and
  CIC, inhibits vomiting centre and basal ganglia.
  Produces more marked CNS effects (Sedation,
  drowsiness and amnesia). Toxic doses produce
  excitation, agitation, hallucination, coma
• Uses
• Used like atropine and preferred in preanesthetic
  medication of cardiac and thyrotoxic patients
• In motion sickness (Hyosine patch on skin)
• In Menieres disease to prevent vertigo
• Antispasmodic

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Synthetic atropine substitutes

• Mydriatic group Homatropine
• Antisecretory antispasmodic group These show
  muscarinic effects on GIt, insignificant central
  effects (Quaternary amine) eg. Hyoscine butyl
  bromide (Buscopan)
• Ipratropium (Atrovent) is muscarinic blocker,
  produces bronchodilatation without dryness of
  secretions. Quaternary amine, by inhalation in
  bronchial asthma

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ANS

• As mydriatics
• Cyclopentolate eye drops long acting
• Tropicamide eye drops -- short acting
• As Antispasmodic / Anti-ulcer
• Glycopyrrolate, Dicyclomine
• For Overactive Bladder
• Tolterodine.

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DRUGS AFFECTING GANGLIA

• Ganglion blockers
• Classified as
• Depolarizing ganglion blockers
• Produce initial stimulation then block (Nicotine
  large dose)
• Competitive ganglion blocker
• Quaternary amines, Hexametonium and
  chlorisondamine
• Secondary amine (Mecamylamine)
• Trimetaphan short acting histamine liberator,
  by I.V., No CNS effects
• Actions
• Effects like atropine
• Postural hypotension
• Impotence
• USES
• Trimetaphan used in hypertensive emergency, to
  induce controlled hypotension in surgery

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Act by blocking effects of ACh at the skeletal NMJ

• Competitive non depolarizing agents
• (Gallamine, Pancuronium)
• Compete with ACh for nicotinic receptors at the
  NMJ. ?EPP, depolarization threshold is not
  reached
• USES
• Promote sk muscle relaxation
• Promote endotracheal intubation
• Adjunct to surgical anesthesia
• Limit trauma due to Electroconvulsive shock
• Adverse effects
• Respiratory paralysis
• Histamine release
• Bronchospasm
• hypotension

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Act by blocking effects of ACh at the skeletal NMJ

• Non-competitive depolarizing agents
• (succinylcholine, decamethonium)
• Desensitize the nicotinic receptors at NMJ, ?
  receptor sensitivity
• USES
• Promote sk muscle relaxation
• Promote endotracheal intubation
• Adjunct to surgical anesthesia
• Limit trauma due to Electroconvulsive shock
• Adverse effects
• Respiratory paralysis
• Muscle facciculation and pain
• Increased IOP
• Bradycardia (muscarinic effect)

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Autonomic nervous system
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Autonomic nervous system
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Good Bye to PANS

• References
• Pharmacology by Rang and Dale
• Katzung Pharmacology