Anaphylactic reactions drugs involved

Bermejo, N. et al., Platelet serotonin is a mediator potentially involved in anaphylactic reaction to neuromuscular blocking drugs, Br. J. Anaesth., 70, 322, 1993. 

These are adverse reactions resembling the effects of histamine liberation Chistaminoid ) and unrelated to the mode of action of the drug itself. Histamine release appears to be the main factor involved in all types of hypersensitivity reactions and its release explains most of the manifestations. The term anaphylactoid may equally be used to describe these reactions, meaning simply that they resemble anaphylactic reactions, while the term anaphylactic is used specifically for immune-mediated phenomena involving previous sensitisation of the patient. It is often difficult to determine the true nature and cause of the reaction. 

There are really two factors to be considered. First, the capability of a particular drug to cause the event which I just described, and secondly the capability of a drug administered to a person in which this process has taken place to be immediately recognized as antigenic and to elicit an anaphylactic reaction. A number of different chemical reactions have been associated with this phenomenon. One of them is simple acylation of protein by the / -lactam. Inasmuch as the mechanism of action of both the penicillins and cephalosporins is also thought to involve acylation by the -lactam, I think that it is very unlikely that there will ever be a -lactam antibiotic which is active and which will not in some patients form antigenic material by this same mechanism. It is my impression that cephalosporins have a lesser tendency to sensitize than some penicillins and that not all penicillin-sensitive people react to a given cephalosporin. The differences are probably quantitative and will never be qualitative. 

In severe anaphylactic reactions, the life-threatening events commonly involve airway obstruction, laryngeal edema, and vascular collapse due to peripheral vasodilation and reduction in blood volume. Hypoxemia can contribute to cardiac events, including arrhythmias and myocardial infarction. Drugs used to treat anaphylaxis mainly target the receptors used by neurotransmitters of the sympathetic nervous system. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

L-Tyrosine metabolism and catecholamine biosynthesis occur laigely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andUpid metabolism. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bile acids and the detoxification process of aromatic drugs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabolism related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Co-administration of beta-blockers has been associated with an increased risk of severe allergic drug reactions and reduces the effect of adrenaline in the immediate treatment of anaphylactic shock. The mechanism involves changes in the regulation of anaphylactic mediators (281). 

The main systems affected by adverse effects of the quinolones are the skin, liver, and nervous system. The best-known adverse effect is phototoxicity, the risk of which varies markedly among the quinolones lomefloxacin and sparfloxacin carry a particularly high risk. The development of phototoxicity is based on an interaction between hght and the drug. Neurotoxicity also occurs, with marked variation of incidence between the various compounds. Hypersensitivity reactions to quinolones are rare, and include anaphylactic shock and anaphylactoid reactions. Organ-specific reactions attributed to hypersensitivity involve the liver and kidneys. If hypersensitivity reactions occur, switching from one qui-nolone compound to another is probably not advisable, since there is cross-reactivity. 

In another survey conducted by the clinical section of the British Pharmacological Society over a one-year period from 1986 to 1987, 8163 healthy volunteers received drugs for research purposes.Potentially life-threatening adverse effects were reported in 0-04% and moderately severe adverse effects in 0-55%, with no lasting sequelae. The three severe reactions were skin irritation and rash requiring hospitalisation, anaphylactic shock after an oral vaccine, and perforation of a duodenal ulcer after multiple-dose non-steroidal anti-inflammatory drug all made a complete recovery. The results were similar to those reported in the earlier ABPI survey and the authors concluded that the risk involved in these studies is very small... 

Table 2. Drugs and compounds most frequently involved in anaphylactic and anaphylactoid reactions. (Adapted from van Arsdel 1978)...

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