Drug allergy pathophysiology: Difference between revisions
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*'''[[Reactive metabolites]]'''- Some drugs may not be reactive with macromolecules in their original state, however may form reactive particles after undergoing [[metabolism]] by [[CYP450]] enzymes. As part of drug metabolism by [[hepatocytes]], some drugs may not undergo correct detoxification and bind to or haptenate [[intracellular]] proteins. <ref name="pmid7798534">{{cite journal |author=Meekins CV, Sullivan TJ, Gruchalla RS |title=Immunochemical analysis of sulfonamide drug allergy: identification of sulfamethoxazole-substituted human serum proteins |journal=J. Allergy Clin. Immunol. |volume=94 |issue=6 Pt 1 |pages=1017–24 |year=1994 |month=December |pmid=7798534 |doi= |url=}}</ref> | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Revision as of 18:26, 14 August 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2]
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Drug Allergy |
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Diagnosis |
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Treatment |
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Case Studies |
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Drug allergy pathophysiology On the Web |
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Risk calculators and risk factors for Drug allergy pathophysiology |
Overview
Medications can cause allergic reactions through various mechanisms. The drug can either act as a direct antigenic particle, or it can cause activation of immune cells by the direct interaction with immune cell receptors.
Pathophysiology
Drugs Acting as Antigens
Most drugs do not act as antigenic particles in their mature form. This is because they are usually small, and therefore not recognized by immune receptors enough to actually activate T cells or B cells. However, drugs can act as antigens if they are presented to lymphocytes by antigen presenting cells such as dendrites. This response specific to the drug can be solely T-cell mediated, antibody mediated, or can have components of both.
- Stimulation of the antibody response- In general, antigens are processed by antigen presenting cells and presented to T-cells. This leads to t-cell activation and produces cytokines which then activate B cells. B cells then recognize the antigen through its IgG receptor, and becomes activated subsequently producing antigen-specific immunoglobulins. Modern pharmaceuticals that are proteins or resemble proteins, can stimulate antibody and T cell responses similar to other protein antigens. Examples of drugs that cause this type of reaction are:
- insulin
- enzymes
- antisera
- recombinant proteins (monoclonal antibodies)
- vaccines
Some of these compounds can induce antibody formation without any T cell interaction.
- Drugs as haptens or pro-haptens- Small drugs can become immunogenic by binding covalently to larger macromolecules such as host proteins on cell surfaces or in plasma. The drug is then called a hapten, and the antigenic compound is then called a hapten-carrier complex. These complexes can also induce a a T cell and antibody response. Drugs that give rise to metabolites that can act as haptens are called pro-haptens. For example, penecillin often acts as a hapten when the beta-lactam ring breaks open and reacts with lysine to form a hapten-carrier complex called penecilloyl determinant, which is capable of stimulating T-cells and antibodies [1] [2]. A few drugs which have this capability are
- penecillin and other beta-lactam antibiotics
- penecillamine
- gold and other heavy metals
- Reactive metabolites- Some drugs may not be reactive with macromolecules in their original state, however may form reactive particles after undergoing metabolism by CYP450 enzymes. As part of drug metabolism by hepatocytes, some drugs may not undergo correct detoxification and bind to or haptenate intracellular proteins. [3]
References
- ↑ Lafaye P, Lapresle C (1988). "Fixation of penicilloyl groups to albumin and appearance of anti-penicilloyl antibodies in penicillin-treated patients". J. Clin. Invest. 82 (1): 7–12. doi:10.1172/JCI113603. PMC 303468. PMID 3392217. Unknown parameter
|month=ignored (help) - ↑ Padovan E (1998). "T-cell response in penicillin allergy". Clin. Exp. Allergy. 28 Suppl 4: 33–6. PMID 9761028. Unknown parameter
|month=ignored (help) - ↑ Meekins CV, Sullivan TJ, Gruchalla RS (1994). "Immunochemical analysis of sulfonamide drug allergy: identification of sulfamethoxazole-substituted human serum proteins". J. Allergy Clin. Immunol. 94 (6 Pt 1): 1017–24. PMID 7798534. Unknown parameter
|month=ignored (help)