CNS PHARMACOLOGY

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CNS PHARMACOLOGY

• GENERAL PRINCIPLES OF CNS DRUG ACTION
• CNS NEUROTRANSMITTERS
• OPIOIDS AND ANALGESIA
• ANTIDEPRESSANTS

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GENERAL PRINCIPLES

• CNS drugs most frequently used type
• Therapeutic as well as social use
• (?
  well-being)
• BBB - lipid soluble drugs pass through
• Most CNS drugs modify synaptic processes

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ADAPTATION TO DRUG USE

• Neuroadaptation may occur with prolonged drug
  exposure
• a) Therapeutic effects ? - eg antidepressants
• b) Tolerance -to therapeutic and/or side
• 
  effects
• need to progressively ?
  dose to
• produce the original
  effect

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TOLERANCE

• Mechanisms include ? drug metabolism, ? receptor
  numbers or activity (homeostatic)
• May ? physical and possibly psychological
  dependence
• Withdrawal ? rebound activity, eg
• depressant withdrawal
  seizures
• (alcohol, barbiturate)
• stimulant withdrawal
  depression
• (amphetamine)

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CNS NEUROTRANSMITTERS

• Mainly excitatory
• - glutamate (? in epilepsy)
• - ACh (? in AD)
• Mainly inhibitory
• - opioid peptides (? effects for analgesia)
• - GABA (?to treat epilepsy, anxiety,?sleep)
• - dopamine (? for PD, ? for schizophrenia)
• - NA and 5-HT (? to treat depression)

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OPIOID ANALGESICS

• Multiple receptor subtypes (inhibitory)
• Agonist ? ? pain sensation (? substance P)
• ? suffering (limbic cortex)
• Morphine-like agonists include codeine and heroin
• Synthetic agonists - pethidine, fentanyl and
  methadone-like drugs
• Antagonist at all receptor types naloxone

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UNWANTED EFFECTS OF OPIOID ANALGESICS

• ? respiratory centres in medulla
• constipation (GIT), nausea (CTZ)
• pupillary constriction, cough suppression
• morphine ? histamine release ? hypotension,
  bronchoconstriction
• tolerance develops quickly (no cross-tolerance to
  CNS depressants)
• abuse (less with treating pain) ? physical,
  psychol. dependence (abstinence syndrome)
  

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DEPRESSION

• Extremes of mood
• mania (high) depression
  (low)
• - major depression unrelated to life events
• - bipolar disorder manic-depressive illness
• Antidepressant drugs
• Action - ? NA and serotonin (5-HT) in brain
  (monoamine hypothesis of depression)

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ANTIDEPRESSANT DRUGS

• 3 Main drug types
• TCAs - block reuptake of NA 5-HT
• MAO inhibitors - block breakdown of NA and 5-HT
  by enzyme MAO
• Selective 5-HT reuptake blockers (SSRIs)
• eg fluoxetine (Prozac)
• Antidepressant effects take 1-3 weeks
• (? neuroadaptive changes)

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ANTIDEPRESSANTS

• Irreversible MAOIs can cause a hypertensive
  crisis due to NA release by dietary tyramine (in
  cheese, avocados, fermented meats)
• ECT may be used for more rapid treatment effects,
  or where drugs are not successful
• Bipolar disorder - stabilised by lithium
• ( antipsychotic or antidepressant if needed)
• - monitor plasma levels - toxicity