ATC Group: N02A Opioids

Buprenorphine is an opioid partial agonist/antagonist which attaches itself to the μ (mu) and κ (kappa) receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible link with the μ receptors which, over a prolonged period, minimises the need of illicit opioids for patients with opioid dependence.

Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic. Butorphanol is most closely structurally related to levorphanol. Butorphanol exhibits partial agonist and antagonist activity at the μ-opioid receptor, as well as partial agonist activity at the κ-opioid receptor (Ki = 2.5 nM; EC50 = 57 nM; Emax = 57%). Stimulation of these receptors on central nervous system neurons causes an intracellular inhibition of adenylate cyclase, closing of influx membrane calcium channels, and opening of membrane potassium channels. This leads to hyperpolarization of the cell membrane potential and suppression of action potential transmission of ascending pain pathways. Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.

The combination of paracetamol with codeine is a well-tolerated and effective analgesic. It consists of complementary active substances with different properties, but with common indication, the relief of pain. A special feature of the combination of paracetamol and codeine is the rapid onset of action after 10-20 minutes and the duration of action for 4-6 hours.

Dextromoramide is a powerful opioid analgesic approximately three times more potent than morphine but shorter acting. The main advantage of this drug is that it has a fast onset of action when taken orally, and has a high bioavailability which means that oral dosing produces almost as much effect as injection. It also has a relatively low tendency to cause constipation which is a common problem with opioid analgesics used for cancer pain relief, and tolerance to the analgesic effects develops relatively slowly compared to most other short-acting opioids.

Propoxyphene, a synthetic opiate agonist, is structurally similar to methadone. Its general pharmacologic properties are those of the opiates as a group. The analgesic effect of propoxyphene is due to the d-isomer, dextropropoxyphene. It binds to the opiate receptors and leads to a decrease of the perception of pain stimuli. Propoxyphene possesses little to no antitussive activity and no antipyretic action.

Dihydrocodeine is a semisynthetic narcotic analgesic with a potency between morphine and codeine. It is also a centrally-acting anti-tussive. Dihydrocodeine works on the cough centre to lessen the incidence and intensity of coughing fits.

The combination of dihydrocodeine and paracetamol is used to treat aches and pains, including headaches, migraines, muscle and joint pain, period pain and toothache.

Fentanyl is a potent µ-opioid analgesic with rapid onset of analgesia and short duration of action. Its primary therapeutic actions are analgesia and sedation and is approximately 100-fold more potent than morphine as an analgesic. Secondary effects of fentanyl on central nervous system (CNS), respiratory and gastro-intestinal function are typical of opioid analgesics and are considered to be class effects.

Hydromorphone is an agonist of mu receptors. The pharmacological actions of hydromorphone and morphine do not differ significantly. Hydromorphone and related opioids produce their major effects on the central nervous system and bowel. Hydromorphone is indicated for the relief of severe pain in cancer.

Ketobemidone is a powerful synthetic opioid painkiller. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted, in part, by its metabolite norketobemidone. This may make it useful for some types of pain that do not respond well to other opioids.

Meptazinol is a centrally acting analgesic belonging to the hexahydroazepine series, which has demonstrated mixed agonist and antagonist activity at opioid receptors. It is used for the short term treatment of moderate pain.

Morphine is a narcotic analgesic obtained from opium. Morphine acts as an agonist at opiate receptors in the CNS particularly Mu and to a lesser extent Kappa receptors. Mu receptors are thought to mediate supraspinal analgesia, respiratory depression and euphoria, and Kappa receptors, spinal analgesia, miosis and sedation.

Nalbuphine is an opioid with kappa-agonistic and mu-antagonistic properties. Beside the essential agonistic (analgesic) effect nalbuphine has antagonistic effects of about a fourth of nalorfine and ten times of pentazocine.

Nicomorphine is the 3,6-dinicotinate ester of morphine. Nicomorphine is a strong opioid agonist analgesic two to three times as potent as morphine with a side effect profile similar to that of dihydromorphine, morphine, and diamorphine. The 3,6-diesters of morphine are drugs with more rapid and complete central nervous system penetration due to increased lipid solubility and other structural considerations.

Opium alkaloids (opioids and isoquinoline derivatives) induce constipation, euphoria, analgesia and sedation dependent on the dose and derivative. The constipating effect is caused by inhibition of the intestines' peristalsis.

Oxycodone is a full opioid agonist with no antagonist properties. It has an affinity for kappa, mu and delta opioid receptors in the brain and spinal cord. Oxycodone is similar to morphine in its action. The therapeutic effect is mainly analgesic, anxiolytic, antitussive and sedative.

Oxycodone and naloxone have an affinity for kappa, mu and delta opiate receptors in the brain, spinal cord and peripheral organs (e.g. intestine). Oxycodone acts as opioid-receptor agonist at these receptors and binds to the endogenous opioid receptors in the CNS. By contrast, naloxone is a pure antagonist acting on all types of opioid receptors. Naloxone counteracts opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut.

Oxycodone and paracetamol combination is used to relieve moderate to severe pain. Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.

Oxymorphone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxymorphone is analgesia. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

Pentazocine is an opioid, benzomorphan derivative analgesic with actions and uses similar to those of morphine. It has weak narcotic antagonist actions.

Pethidine is a synthetic opioid analgesic similar with similar actions to morphine. Like other opioids, pethidine binds to opioid receptors and exerts its principal pharmacological actions on the central nervous system where its analgesic and sedative effects are of particular therapeutic value. Pethidine also causes the release of histamine from mast cells resulting in a number of allergic-type reactions.

Phenazocine is an opioid analgesic drug, which is related to pentazocine and has a similar profile of effects. Effects of phenazocine include analgesia and euphoria, also may include dysphoria and hallucinations at high doses, most likely due to action at κ-opioid and σ receptors. Phenazocine appears to be a much stronger analgesic with fewer side effects than pentazocine, probably due to a more favorable μ/κ binding ratio. Phenazocine is a much more potent analgesic than pentazocine and other drugs in the benzomorphan series, most probably due to the presence of an N-phenethyl substitution, which is known to boost μ-opioid activity in many classes of opioid analgesics. Consequently, phenazocine has four times the potency of morphine as an analgesic. Also it does not cause spasm of the sphincter of Oddi, making it more suitable than morphine for the treatment of biliary or pancreatic pain.

Piritramide is a pure µ-opioid receptor agonist, which has a slightly less analgesic potency than morphine. Analgesia results from activation of the µ-opioid receptors in the spine and the higher pain centres such as the thalamus and cerebral cortex, thereby raising the pain threshold and the sensitivity to pain.

Tapentadol is a strong analgesic with µ-agonistic opioid and additional noradrenaline reuptake inhibition properties. Tapentadol exerts its analgesic effects directly without a pharmacologically active metabolite.

Tilidine is a synthetic opioid painkiller, for the treatment of moderate to severe pain, both acute and chronic. Tilidine itself is only a weak opioid, but is rapidly metabolised in the liver and gut to its active metabolite nortilidine and then to bisnortilidine. It is the (1S,2R)-isomer (dextilidine)¹² that is responsible for its analgesic activity. Nortilidine binds to opiate receptors in the central and peripheral nervous systems and suppresses pain perception and transmission.

Tramadol, a cyclohexanol derivative, is a centrally acting opioid analgesic. It is a non-selective pure agonist at μ, δ and κ opioid receptors with a higher affinity for the μ receptor. Other mechanisms which contribute to its analgesic effect are inhibition of neuronal reuptake of noradrenaline and enhancement of serotonin release.