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By Duy Thai
ANALGESICS 1
Definition
• Drugs which are used to decrease pain
• There are 3 main classes of analgesics:
1. NSAIDs
2. Paracetamol
3. Opiods
NSAIDs
• Mechanism of action is via inhibition of cyclo oxygenase
• This prevents the production of prostaglandins from arachidonic acid
• Since there is no prostaglandin synthesis, the unused arachidonic acid gets converted to leukotrienes via
lipoxygenase.
• Have analgesic, antipyretic and anti inflammatory actions (Aspirin is often used as an antithrombotic agent because
the levels required are low, so there are no other effects which occur at higher doses)
• The analgesic action results from 2 mechanisms:
1. Peripheral mechanisms:
• Inhibition of prostaglandins (particularly PGE2 at peripheral pain receptors.
• PGE2 is a hyperalgesic. This means that it does not cause pain directly, instead, it
enhances the pain receptor’s sensitivity to algesic (pain producing) substances such as
bradykinin and substance P
2. Central mechanisms
• Prostaglandins act in the spinal cord and higher centers to promote the transmission of
pain signals to the brain.
• Level of analgesia produced by NSAIDs:
• Effective for mild to moderate pain associated with inflammation
• NSAIDs reduce the cause of the pain (inflammatory mediators) as well as the sensation of pain
• Effective for headache
• Headaches may be caused by cerebral vasodilation due to prostaglandins. Therefore, inhibition of
prostaglandins can relieve the vascular pain
• Surgical and cancer pain (if combined with opioids)
Paracetamol
• Analgesic and antipyretic, but it is NOT anti inflammatory
• Its mechanism of action is similar to that of NSAIDs
• It inhibits COX, but it only works in the CNS
• It does not inhibit peripheral COX. Why?
• There are various peroxides produced in inflammatory states. The presence of these peroxides
inhibits the action of paracetamol. However, peroxides are not produced in the CNS and so
paracetamol only works centrally to relieve pain and fever
• Therapeutic uses of paracetamol:
1. Analgesic
• Does not act on the peripheral nociceptors like NSAIDs do
• It inhibits spinal or supraspinal pain pathways
• It can be used to treat mild to moderate pain, but not pain due to inflammation (e.g. arthritic pain).
It does not attack the cause, only the symptoms.
2. Anti pyretic
• Inhibits PGE2 synthesis in the hypothalamus
Increase cAMP
• Paracetamol is recommended for use in children with fever. Aspirin should never be used when a young child has
fever:
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1997 Clinical pharmacology
By Duy Thai
OPIOID ANALGESICS
• Have a different mechanism of actions to NSAIDs or paracetamol (It does not inhibit COX)
• The term opioids, encompasses:
1. Natural analgesic substances
• Obtained from the opium poppy - morphine, codeine
• These are called opiates
2. Synthetic analgesic substances
• Pethidine
• Fentanyl
3. Endogenous analgesic substances
• Encephalins
• Endorphins
Ouch!!!
Primary afferent fibre
* * Denotes where opioids act to
presynaptically inhibit the fibre
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1997 Clinical pharmacology
By Duy Thai
Opioid receptors
• There are 4 receptor types: µ, δ, κ, σ
• µ and δ are functionally identical
• They cause hyperpolarisation of a nerve terminal by opening K+ channels
• µ receptors are highly concentrated in brain areas involved in nociception and it is the receptor
which morphine predominantly interacts with
• The κ receptor inhibits membrane Ca2+ channels
• The σ receptor is no longer considered to be a true opioid receptor because it is not blocked by
naloxone, which is an antagonist at all other opioid receptors.
Respiratory depression ++ + -
Pupil Constriction - Dilation
GI motility Reduced - -
Smooth muscle spasm ++ - -
(affects sphincter tone)
Behaviour/affect Euphoria ++ Dysphoria + Dysphoria +
Sedation ++ Sedation + Psychotomimetic
Physical dependence ++ + -
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1997 Clinical pharmacology
By Duy Thai
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