BASIC PRINCIPLES OF PERIPHERAL NERVOUS SYSTEM PHARMACOLOGY

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BASIC PRINCIPLES OF PERIPHERAL NERVOUS SYSTEM
PHARMACOLOGY

• Synaptic neurotransmission target of drugs
• PNS somatic and autonomic divisions
• Differences in neurotransmitters and receptors in
  the ANS

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CHOLINERGIC DRUGS

• ANS - parasympathetic cholinergic (muscarinic)
  synapses
• effects of muscarinic agonists and antagonists
• antimuscarinic side effects of some drugs
• effects of anticholinesterase (cholinesterase
  inhibitor) drugs

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CHOLINERGIC DRUGS

• Drug action at the neuromuscular junction
  (nicotinic receptors)
• muscle relaxation for surgery and ECT nicotinic
  receptor blockade
• reversal of this neuromuscular blockade
  anticholinesterase drugs

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ADRENERGIC DRUGS

• ANS sympathetic division adrenergic synapses
• receptor selectivity of adrenergic drugs
• clinical use of adrenergic agonists and
  antagonists

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LOCAL AND GENERAL ANAESTHESIA

• 1. Local anestheticsa) classification and
  therapeutic usesb) adverse effects/ toxicityc)
  application topically injection (nerve block,
  IV regional anesthesia, epidural spinal
  anesthesia)

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LOCAL AND GENERAL ANAESTHESIA

• 2. General anesthetics a) types (i) inhalation
  agents (halothane, nitrous oxide) (ii)
  intravenous agents (barbiturates,
  benzodiazepines, opioid analgesics)b)
  stages of anesthesiac) basic pharmacologyd)
  adverse effects
• e) adjuncts to anesthesia (preanesthetic
  medication, anticholinergic drugs, neuromuscular
  blocking agents, postanesthetic medications)

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THE NERVOUS SYSTEM A REVIEW

• Overall Functions - integration and homeostasis
• Divisions - CNS PNS, PNS - somatic motor
  autonomic NS, ANS - parasympathetic sympathetic

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PNS somatic and autonomic divisions

• SOMATIC
• comprises single neurone btw CNS effector
• innervates skeletal muscle
• always leads to muscle excitation

• AUTONOMIC
• two neurone chain btw CNS effector
• innervates smooth cardiac muscle, glands and GI
  neurones
• inhibition / excitation of effector cells

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AUTONOMIC NERVOUS SYSTEM REVISITED

• Functions of the ANS - regulation of heart,
  secretory glands (salivary, gastric, sweat),
  smooth muscle (bronchi, blood vessels,
  urogenital, GIT)
• Effector Organs
• Structure

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COMPARISON OF SYMPATHETIC PARASYMPATHETIC NS

• PARASYMPATHETIC NS
• slow heart rate
• increase gastricsecretion
• emptying of bowel
• emptying of bladder
• accomodation
• pupil constriction

• SYMPATHETIC NS
• regulation of the CV system
• regulation of body temperature
• fight or flight (fright) response

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Synaptic Neurotransmission Target of Drugs

• Neural synapses, initiation of action potentials
• Neuropharmacology
• Transmitter synthesis (increase, decrease)
• Transmitter storage (deplete vesicles of
  transmitter, decrease receptor stimulation)
• Transmitter release (promote, inhibit)
• Receptor binding (agonist, antagonist)
• Termination of transmitter action (block uptake,
  inhibit breakdown of transmitter)

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Differences in neurotransmitters and receptors in
the ANS

• NEUROTRANSMITTERS
• RECEPTORS
• ACETYLCHOLINE
• NORADRENALINE
• NICOTINIC, MUSCARINIC, alpha, beta receptor
  subtypes

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CHOLINERGIC DRUGS

• Effects of muscarinic agonists
• Bethanecol (urinary retention and intestinal
  paralysis)
• Effects of muscarinic antagonists
• Atropine (preparation for anaesthesia, ophthalmic
  examination, bradycardia, biliary colic,
  intestinal hypermotility and muscarinic poisoning

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CHOLINERGIC DRUGS

• Antimuscarinic side effects of some drugs
• - dry mouth, blurred vision photophobia,
  elevation of IOP, urinary retention,
  constipation, ansence of sweating, tachycardia,
  asthma (drying of bronchial secretions)
• Effects of anticholinesterase (cholinesterase
  inhibitor) drugs
• Neostigmine Physostigmine
• muscarinic effects, myasthenia gravis

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CHOLINERGIC DRUGS

• Drug action at the neuromuscular junction
  (nicotinic receptors)
• succinylcholine (depolarising)
• binds to nicotinic receptors but does not
  immediately dissociate
• muscle relaxation (preceded by tansient
  contractions and paralysis is shorter in
  duration)
• tubocurarine (non-depolarising)
• competes with Ach for nicotinic binding sites
• muscle relaxation, hypotension, CNS (nil)
• reversal of this neuromuscular blockade
  anticholinesterase drugs

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ADRENERGIC DRUGS

• Sympathomimetics
• Mechanisms of receptor stimulation (direct,
  promote NA release, inhibit reuptake, inhibit NA
  metabolism, receptor selectivity)
• Consequences of alpha and beta stimulation

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Adrenergic Agonists ADRENALINE ISOPRENALINE

• Clinical uses
• delay absorption of local anaesthetic
• control superficial bleeding
• produce nasal congestion
• elevate BP
• mydriasis
• AV heart block
• myocardial arrest
• shock
• asthma (not routine)

• Adverse effects
• hypertensive crisis
• arrythmias
• angina
• necrosis
• hyperglycaemia

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Adrenergic Antagonists Propranolol
Phentolamine

• Adverse Effects
• ALPHA BLOCKADE
• postural hypotension
• reflex tachycardia
• nasal congestion
• inhibition of ejaculation
• BETA BLOCKADE
• bradycardia
• reduce CO
• CHF
• AV heart block
• bronchial constriction

• Clinical Uses
• ALPHA BLOCKADE
• hypertension
• reversal of xs alpha stimulation
• phaechromocytoma
• BETA BLOCKADE
• hypertension
• angina pectoris
• cardiac arrhythmias

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Local Anesthetics

• MECHANISM OF ACTION
• blockade of axonal conduction (block Na
  channels), nonselective, temporal sequence (pain,
  cold, warmth, touch, deep pressure)
• CLASSIFICATION
• esters vs amide types
• THERAPEUTIC USES
• Localised loss of sensation
• Use with vasoconstrictors

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Local Anesthetics

• ADVERSE EFFECTS / TOXICITY
• CNS stimulation then depression
• CVS vasodilation cardiac depression
• allergy, hypersensitivity reactions (esters)
• depress uterine contractions, bradycardia, CNS
  depression in neonate
• APPLICATION- topical (surface skin mucous
  membranes) lignocaine, cocaine - by injection
  (nerve block, IV regional, epidural, spinal (SA)
  - hypotension

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General Anesthetics

• Types(i) inhalation agents (halothane, NO2)
• suppression of neuronal activity of brain and
  spinal cord, not receptor mediated
• index of potency MAC (low MAC high potency)
• (ii) intravenous agents (barbiturates,
  benzodiazepines, opioid analgesics)
• used alone or as adjunct to IH A
• Thiopental, Diazepam,

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Stages of Anesthesia

• Stage of analgesia
• Stage of delirium
• Stage of surgical anesthesia
• Stage of medullary paralysis

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Basic Pharmacology

• Neuronal effect
• anesthetic disrupt membrane structure of nerves
• interferes in action potential generation
• is not a receptor-mediated process

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Adverse Effects

• INHALATIONAL ANESTHESIA
• respiratory cardiac depression
• sensitisation of the heart to catecholamines
  (halothane)
• malignant hyperthermia (rare)
• aspiration of gastric contents (loss of reflexes)
• INTRAVENOUS ANESTHESIAextravasation can cause
  tissue damage, 24-hr hangover, cv respiratory
  depression, cv respiratory depression,
  unpleasant psychological reactions

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Adjuncts to Anesthesia (preanesthetic medication)

• Anticholinergic drugs (decrease secretions)
• Anxiolytic agents (reduce anxiety)
• Opioids or NO2 (analgesia)
• Antiemetics
• Neuromuscular blocking agents (muscle
  relaxation)
• Post-anesthetic medications