What is known about allergy to morphine?/nThe question relates to a patient with self-reported alle

Fråga: What is known about allergy to morphine? The question relates to a patient with self-reported allergy to morphine, symptoms unknown.

Sammanfattning: Hypersensitivity reactions after morphine administration have been reported. These reactions are rare and include anaphylactic reactions, asthma, urticaria, and edema. Many adverse reactions to morphine, e.g. administration site reactions, may be due to pharmacological histamine release, although severe reactions have been associated with Ig-antibodies against morphine.

Svar: A question about morphine and allergy has been answered previously in Drugline (1).

Hypersensitivity reactions to morphine and other opiates are documented, but rare. Anaphylactic reactions, asthma, urticaria, and edema have been reported (2). Ig-E antibodies against morphine and codeine have been found in subjects who have had life-threatening anaphylactic reactions (1).

However, morphine can also stimulate histamine release directly form mast cells, without prior sensitisation. This is considered a pharmacological effect, and cannot be classified as a hypersensitivity reaction (3). Histamine release may be connected with flushing, heat sensitivity, pruritus, and headache, all of which are common side effects following morphine administration. It has also been proposed that histamine release can be associated with vasodilatation and decreased blood pressure, leading to increased concentrations of plasma epinephrine (5). Histamine release may also contribute to bronchoconstriction, and morphine should therefore be avoided in patients with asthma (3).

Histamine release following morphine administration has been measured in several studies. Highly increased histamine levels have been reported (5), but there have also been studies where no significant increase in plasma histamine levels has been detected (6). The opioid antagonist naloxone does not alter the release of histamine or inhibit release after morphine administration (7). Codeine, with lower affinity for opioid receptors, is more potent than morphine in releasing histamine (2). This suggests that histamine release is not mediated by opioid receptors.

In the files of SADRAC (The Swedish Adverse Drug Reactions Advisory Committee) there are 107 reports of adverse reactions possibly related to morphine treatment. Seventy-two (67%) of these are classified as skin disorders, and nearly half of them are application site reactions that might be due to histamine release. There are 17 cases of pruritus and nine of urticaria. One anaphylactic reaction, and one case each of asthma, edema and swollen throat have also been reported (4).

Morphine and codeine produced skin reactions in 47 opiate-tolerant subjects tested by skin prick test. Skin prick tests with sensitive subjects compared to opiate-tolerant subjects showed no difference in sensitivity and therefore skin prick testing is not useful as diagnosis for morphine sensitivity (7).