Anaphylactoid reactions histamine release

The mechanism of induction of histamine release by alphaxalone and alphadolone shown by the leucocyte test in susceptible individuals is not clear at present, but it appears to be like Cremophor EL. This means that it could be due either to an anaphylactic or anaphylactoid (direct histamine release) reaction. We did not find histamine release with these agents from the leucocytes of normal volunteers. We were unable to elicit a positive Prausnitz-Kiistner reaction in two patients in whom a reaction occurred after a second exposure to Althesin, and in whom the vehicle did not produce any response, either in the direct skin test or in the leucocyte test. 

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. 

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. 

Histamine release and anaphylactoid reactions occur with alcuronium (10-12). The precise incidence is not clear. Erythema is said to occur much less frequently than after D-tubocurarine (3). A retrospective study in Australia (13) showed that 37% of serious anaphylactoid reactions reported there were associated with alcuronium alcuronium, however, at that time accounted for almost 50% of the total muscle relaxant consumption in Australia, and if this is taken into account the likelihood of a serious reaction is less than with D-tubocurarine, as others have also concluded (14). Chnical features reported range from erythema to severe hypotension and tachycardia (15) and bronchospasm (16,17). In a large prospective surveillance study (SEDA-15,125) (SED-12,473) involving over 1400 patients given alcuronium (initial dose 0.25 + 0.09 mg/kg), there were adverse reactions in almost 18% of the patients, with moderate hypotension (20-50% fall) in 13%, severe hypotension in 0.8%, and bronchospasm in 0.1%. 

Anaphylactoid reactions can occur after the intravenous administration of Cremophor (SEDA-22, 526) when it is used as a diluent of alfadolone/afaxolone (SED-11,211) (2), ciclosporin (3), paclitaxel (4), propanidid (SED-11, 211) (5,6), teniposide (7), and vitamin K (8,9). Cardiorespiratory arrest after intravenous miconazole has been attributed to the histamine-releasing properties of Cremophor (10). 

The authors noted that many opioids are potent histamine releasers and most reactions to opioids are anaphylactoid rather than IgE-mediated. It was of particnlar interest that the patient was able to tolerate the opioids hydrocodone and codeine. 

Assem ES. Characteristics of basophil histamine release by neuromuscular blocking drugs in patients with anaphylactoid reactions. Agents Actions 1984 14(3 ) 435-40. 

Anaphylactoid reactions have been documented, and signs suggestive of histamine release are not uncommon. These are mostly mild such as flushing of the skin. Occasionally bronchospasm and/or hypotension can lead to circulatory arrest. Suxamethonium is the relaxant most commonly associated with the syndrome of malignant hyperthermia. 

Fatalities from normal doses and overdoses of intravenous NAC have not been reported. This is most probably due to the fact that the body produces this compound naturally and can rapidly metabolize it in the liver. Toxicity is usually limited to anaphylactoid reactions and nausea/vomiting. The average time for the onset of adverse effects following commencement of the infusion of NAC was 30 min (range, 5-70 min). In vivo and in vitro tests indicate that NAC is an inhibitor of allergen tachyphylaxis by inhibition of prostaglandin E synthesis. Adverse reactions are anaphylactoid in type and have been attributed to cause histamine release. 

The use of surfactants in parenteral products is limited by their potent side-effects. All surfactants, especially those that are ionic may cause hemolysis. Anaphylactoid reactions have been noted, particularly in association with the destruction of lymphocytes, resulting in histamine release. Phospholipids are generally well-tolerated, and are frequently used in the preparation of emulsions. Nonionic surfactants such as Cremophor EL and polysorbate 80 (Tween 80) are known to cause hypersensitivity reactions (Eschalier et al., 1988 Mounier et al., 1995 Theis et al., 1995 Munoz et al., 1998 Volcheck and Van Dellen, 1998), including hypotension, largely via histamine release mechanisms. Because of potential side-effects, it is now traditional to pretreat the patient with an antihistamine and possibly a corticosteroid (e.g., prednisone) before administration of formulations that contain Cremophor EL. 

In addition to causing their pulmonary sequestration, C5a can Induce release of oxygen radicals from neutrophils (45). Further, both C3a and C5a stimulate mast cells to release histamine. These substances can cause injury to the pulmonary endothelium. Increased vascular permeability and smooth muscle contraction. Such processes have been assoeiated with the severe anaphylactoid reactions reported to occur on rare occasions with the clinical use of membrane devices (46). A connection between complement activation and such reactions has been suggested but not proven. In addition, the sequelae of complement activation may produce the hypoxemia observed during hemodialysis (4 ) and the pulmonary hypertension described in an animal model of extracorporeal circulation (48). 

Many compounds, including a large number of therapeutic agents, stimulate the release of histamine from mast cells directly and without prior sensitization. Responses of this sort are most likely to occur following intravenous injections of certain substances. Tubocurarine, succinyl-choline, morphine, some antibiotics, radiocontrast media, and certain carbohydrate plasma expanders may elicit the response. The phenomenon may account for unexpected anaphylactoid reactions. Vancomycin-induced red-man syndrome involving upper body and facial flushing and hypotension may be mediated through histamine release. 

Anaphyla. is is a type I reaction in which the drug ( ) interacts with IgE lixed to mast cells contrast media) can produce an anaphylaxis-like (anaphylactoid) reaction on first exposure. 

The leucocyte histamine release test (referred to in greater detail in Chaps. 1-7) is one of the in vitro correlates of immediate allergy which may find useful application in investigating reactions to local anaesthetics. It is of some value in detecting acute reactions, whether they are truly anaphylactic or due to direct (non-immune) histamine release (anaphylactoid). It is also more accurate (quantitative), more reliable and more predictive than skin tests, and above all it is free from risk. 

Lorenz W, Doenicke A (1978) Anaphylactoid reactions and histamine release by intravenous drugs used in surgery and anaesthesia. In Watkins J, Ward AM (eds) Adverse response to intravenous drugs. Academic Press, London Grune Stratton, New York, pp 83-112... 

Lorenz W, Doenicke A, Reimann HJ, Schmal A, Schwarz B, Dorman P (1978) Anaphylactoid reactions and histamine release by plasma substitutes a randomized controlled trial in human subjects and in dogs. Agents Actions 8 397-399 Liiben G, Quast U, Geiger H (1981) Prekallikrein activator levels and side effects with human albumin preparations. Dev Biol Stand 48 123-127 Lund N (1973) Anaphylactic reactions induced by infusion of haemaccel. Br J Anaesth 45 929... 

Properties Water-sol. m.w. 15,000-200,000 Toxicology Histamine-releasing props. may cause anaphylactoid reactions questionable carcinogen experimental tumorigen, teratogen, reproductive effects TSCA listed Precaution Combustible Hazardous Decomp. Prods. Heated to decomp., emits acrid smoke and fumes Storage Hygroscopic... 

Moneret-Vautrin (1979, 1983) has suggested that exogenous histamine and histamine releasers may lead to anaphylactoid reactions when there is functional impairment of the mucosa, either in early childhood before maturation of exclusion mechanisms or later due to intrinsic disease of the gut or to the action of pharmaco-active agents. However, the relevant foods (cheese, egg white, shellfish, nuts) are also those to which evidence of IgE-mediated sensitization is found commonly, and as we have seen, absence of demonstrable specific IgE antibody in the serum does not prove the non-allergic nature of the reaction. This remains an area of potentially useful future research. 

Other evidence shows that histamine is not the main mediator in the anaphylactoid reaction. For example, the injection of histamine itself does not elicit all the symptoms which are typical of an anaphylactoid response [171]. Moreover, egg-white and dextran elicit a full anaphylactoid oedema in rats whose skin histamine has been reduced to about 9% of the control values by compound 48/80 pretreatment [371]. Depletion studies with the antibiotic polymyxin B sulphate indicate that a maximum release of skin histamine, with little change of the tissue 5-hydroxytryptamine, does not modify the egg-white or dextran reactions [485]. Not all antihistamines inhibit the anaphylactoid reaction [90, 187, 248, 463, 464, 487, 530], and it is possible that the antihistamines found by earlier workers to inhibit the reaction possessed non-specific effects and especially anti-5-hydroxytryptamine activity [61,137, 203, 489]. 

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