OPIOID ANALGESICS: CLASSIFICATIONS AND EQUIANALGESIC DOSES OF OPIOID ANALGESICS
The opioid analgesics are defined as drugs having morphine-like effects.
Mechanism of action : the opioid receptors
The opioid analgesics exert their effects and side effects by interaction with opioid receptors in the brain and spinal cord. These receptors normally interact with a range of endogenous opioid substances including the endorphins and enkephalins. There are a number of different types of opioid receptor including mu, delta and kappa. Analgesia is primarily mediated by the mu receptor which is also responsible for the side effects of respiratory depression, reduced gastrointestinal motility, miosis, euphoria and physical dependence. The kappa receptor mediates some analgesia as well as the dysphoric and psychotomimetic side effects.
Classifications-The opioid analgesics can be classified by strength, whether they are natural or synthetic, and by their agonist or antagonist action at the opioid receptor.
Strong and weak opioids-The 'weak' opioids, as might be used in Step 2 of the WHO Analgesic Ladder, are better termed 'opioids for mild to moderate pain'. Codeine is the prototype 'weak' opioid; oxycodone is an alternative. Morphine is the strong opioid of choice; methadone is a suitable alternative for patients intolerant of morphine.
Agonists and antagonists-An agonist drug binds to a receptor and produces a physiological effect. The prototype agonist is morphine which binds to the mu receptor to produce analgesia.
An antagonist drug binds to a receptor without producing a physiological effect and can prevent binding of an agonist to, or displace it from, the receptor. The prototype antagonist is naloxone which prevents or reverses the effect of morphine at the mu receptor.
A partial agonist has less intrinsic activity at the receptor site than a full agonist. It will produce less effect than the full agonist and will exhibit a ceiling effect above which increasing doses produce no extra effect. If the partial agonist has greater affinity for the receptors than the full agonist, it may displace the full agonist. Buprenorphine is the partial agonist used in clinical practice. Given alone, it has an agonist action; given in low dose with an agonist it will have no adverse effect, but given in higher dose it will act as an antagonist and may precipitate pain and withdrawal symptoms.
A mixed agonist-antagonist has agonist effects when given alone but acts as an antagonist when given with or after another agonist. Pentazocine is a mixed agonist-antagonist. Given alone, it will have an agonist action; given with another agonist it will act as an antagonist and may precipitate pain and withdrawal symptoms.
Knowledge of the actions of these partial agonist and mixed agonist-antagonist drugs is important as their inadvertent use may lead to unanticipated complications.
Equianalgesic doses of opioid analgesics-The approximate equianalgesic doses of different opioid drugs. These conversion factors are approximate and do not take into account individual patient variation. In some cases they are derived from studies of single doses rather than continued therapy.
• Each drug must be titrated against pain and side effects for each individual patient.
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