UI - 000170

AU - Hoskin PJ

AU - Hanks GW

TI - Opioid agonist-antagonist drugs in acute and chronic pain states. [Review]

AB - The agonist-antagonist opioid analgesics are a heterogeneous group of drugs with moderate to strong

analgesic activity comparable to that of the pure agonist opioids such as codeine and morphine but with a

limited effective dose range. The group includes drugs which act as an agonist or partial agonist at one

receptor and an antagonist at another (pentazocine, butorphanol, nalbuphine, dezocine) and drugs acting as a

partial agonist at a single receptor (buprenorphine). These drugs can be classified as nalorphine-like or

morphine-like. Meptazinol does not fit into either classification and occupies a separate category.

Pentazocine, butorphanol and nalbuphine are weak mu-antagonists and kappa-partial-agonists. All three

drugs are strong analgesics when given by injection: pentazocine is one-sixth to one-third as potent as

morphine, nalbuphine is slightly less potent than morphine, and butorphanol is 3.5 to 7 times as potent. The

duration of analgesia is similar to that of morphine (3 to 4 hours). Oral pentazocine is closer in analgesic

efficacy to aspirin and paracetamol (acetaminophen) than the weak opioid analgesics such as codeine.

Neither nalbuphine nor butorphanol is available as an oral

formulation. At usual therapeutic doses nalbuphine and butorphanol have respiratory depressant effects

equivalent to that of morphine (though the duration of such effects with butorphanol may be longer). Unlike

morphine there appears to be a ceiling to both the respiratory depression and the analgesic action. All of

these 3 drugs have a lower abuse potential than the pure agonist opioid analgesics such as morphine.

However, all have been subject to abuse and misuse, and pentazocine (but not the others) is subject to

Controlled Drug restrictions. Buprenorphine is a potent partial agonist at the mu-receptor, and by

intramuscular injection is 30 times as potent as morphine. A ceiling to the analgesic effect of buprenorphine

has been demonstrated in animals and it is also claimed in humans. However, there are no reliable data

available to define the maximal dose of buprenorphine in humans. A practical ceiling exists for sublingual use

in that the only available formulation is a 2 micrograms tablet and few patients will accept more than 3 or 4

of these in a single dose. The duration of analgesia is longer than that of morphine, at 6 to 9 hours. There

have been suggestions that buprenorphine causes less respiratory depression than morphine, but viewed

overall it appears that in equianalgesic doses the 2 drugs have similar respiratory depressant

effects.(ABSTRACT TRUNCATED AT 400 WORDS) [References: 118]

SO - Drugs 1991;41:326-34