1997 Clinical pharmacology

By Duy Thai

ANALGESICS II

Codeine
• A naturally occurring opioid anaglesic
• Less potent than morphine
• Lower ceiling
• Limited by the intrinsic efficacy of codeine at the receptor
• Partially metabolised to morphine
• Cannot produce same level of analgesia
• Orally active
• It does not undergo significant first pass metabolism, hence it is equally active when given orally
or intravenously.
• Produces little or no euphoria due to low potency (less potential for abuse)
• Little respiratory depression (lower potency on opioid receptors)
• Safer drug due to lower potency
• Anti tussive at subanalgesic doses
• Codiene is included in cough & cold mixtures at low doses to reduce cough (will not produce
other opioid effects)

Diamorphine (heroin)
• Same action as morphine
• High potency
Diamorphine (diacetyl morphine)
(Inactive)

Monoacetyl morphine
(Active)

Morphine
(Active)
• More lipid soluble than morphine
• Able to penetrate the CNS rapidly
• Hence, rapid euphoria
• Favoured as a recreational drug
• An effective analgesic (not available in Australia though)

Opioid agonists
• Pethidine
• Agonist at µ receptors (similar to morphine)
• Short half life (analgesia lasts for around 3 to 5 hours, which is half the time of morphine)
• Less respiratory effects
• It is the preferred analgesic in labour
• Opioids given to the mother during childbirth often cross into the neonatal circulation and
cause respiratory depression.
• Pethidine causes less respiratory depression in neonates than with morphine
• Orally active
• Given epidurally during labour
• Can also be used for post operative analgesia

• Fentanyl
• Very potent (80 times more than morphine)
• Short half life - the effects wear off quickly
• Given via IV infusion (used to be given as patches on the skin to give continuous administration)
• It gives a high level of anaesthesia
• Used with neuroleptic drugs (neurolep analgesia - particularly for cardiovascular/thoracic
surgery)

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 1997 Clinical pharmacology
By Duy Thai

• The patient is not really unconscious, but they do not feel any pain. The benefit is that
they do not experience cardiovascular depression.

• Methadone
• Drug of choice as a substitute of opioids
• Cross tolerance with heroin
• Used in withdrawal treatment
• Orally active, does not undergo the same liver metabolism as morphine
• Long half life
• Slow rise and fall in plasma levels because it is taken orally (twice daily)
• The withdrawal reaction is less intense but prolonged
• Accumulation in proteins including the brain -> prolonged withdrawal reaction
• Intensity of the withdrawal is proportional to the rate of decline in plasma levels
• Often used in replacement therapy because it can be taken orally, and because of less intense
withdrawal reactions

Partial agonists
• Pentazocine
• Less likely to be abused because there is no euphoric effect (produces dysphoria)
• Abuse potential arises because of the ability of the drug to cause euphoria
• Partial agonist
• Efficacy: κ > µ
• It is an antagonist at µ receptors. Hence it produces κ analgesia
• Dysphoria (affinity for κ, σ)
• Opposes action of full agonists (e.g. morphine)
• Given alone, gives analgesia because of reaction at κ receptors
• If given on top of morphine, can induce a withdrawal response due to antagonistic effects

• Buprenorphine
• Partial agonist (µ)
• Good analgesic if given alone
• Respiratory depression
• Less likely to produce dysphoria because it acts on the µ receptor

Antagonists
• Naloxone
• Pure opioid receptor antagonist
• When given alone, has no agonist effect, hence suggests there is very little basal activity at
opioid receptors.
• Affinity for all opioid receptors (can use to treat any opioid overdose)
• Not orally active due to hepatic metabolism. Is usually given IV, can also be given
subcutaneously
• Will induce severe withdrawal reaction, because of rapid decline in activity of opioids
• Will inhibit the pain relieving effects of acupuncture, indicating that this procedure may be due in
part to the release of endogenous opioids.
• Rapidly reverses respiratory depression , cardiovascular depression
• Has a short half life. Therefore, the actions of the opioids can start working again when the
effects of naloxone wear off.

Therapetutic opioid use

• Analgesia
• Moderate to severe pain
• Surgery, trauma
• Burns
• Chronic pain, e.g. cancer
• Use morphine
• Regular dosing
• It is important to treat the pain properly than to prevent tolerance
• Oral administration (to reduce the development of tolerance)
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 1997 Clinical pharmacology
By Duy Thai

• Slow release tablets

• Alternatives: methadone, fentanyl patch
• Pain from myocardial infarction
• Relives distress from the pain as well as the pain itself
• Level of analgesia produced:
• Codeine < aspirin < aspirin + codeine
• Combination of an opioid and non opioid gives additive effects without the increase in
side effects
• Not all pain responds well to opioids - e.g. bone pain, inflammatory pain
• Therefore, useful to combine with a NSAID
• Antitiussive
• Codeine at subanalgesic doses
• Codeine acts directly on cough receptors
• Dextromethorphan
• D isomer of codeine analogue - no analgesic activity and less GIT effect
• L isomer has analgesic effect
• Diarrhoea
• Codeine and opioids with more selective action on GIT
• Inhibit GIT motility - may cause constipation
• Diphenoxylate - more selective action on GIT, less access to CNS
• Anaesthesia
• Fentanyl IV (short half life, rapid reversal of anaesthesia
• Epidural morphine or pethidine (for labour)

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