Drug-related hypersensitivity due to Abacavir induced ADR

In the previous article Drug related hypersensitivity, prevalence, diagnosis and therapeutic considerations, we discussed about how different drugs lead to different allergic responses. However, it is important that mechanism of different drug is studied which leads to ADR. In the present article Abacavir, a drug which is used for the treatment and prevention of Human Immuno Deficiency Virus (HIV) (Hewitt et al., 2002) is being discussed. Abacavir is a synthetic carbocyclic nucleoside which is categorised under the class of Nucleoside Reverse Transcriptase Inhibitors.

The molecular weight of the drug causes hypersensitivity reaction which activates the immune response faster by covalently binding to the self-protein producing a haptenated molecule which is then presented to the adaptive immune system to induce an immune response.

Mode of Action in HIV infected Patients

Abacavir acts by incorporating itself into the DNA of the virus which stops the building process of transcription from RNA to DNA. The resulting DNA is incomplete which causes reverse transcriptase process thus halting the virus development process. The carbovir triphosphate lacks a 3’ –OH group and thus blocks the HIV replication and blocks the HIV formation and stops the formation of new cells (De Clercq, 2009) (See Figure 2 below).

It is rapidly absorbed in the form of oral dosage. Maximum concentration of the drug reached in about 0.8 hours after dosing. About 98% of drug goes under extensive hepatic transformation via the alcohol dehydrogenase and glucuronyl transferase enzymes to inactive metabolites. About 50% of the drug Abacavir bounds to the plasma proteins. Symptoms of the hypersensitivity reaction caused by the abacavir are fever, rash on skin, gastrointestinal including nausea, vomiting, diarrhea, abdominal pain, constitutional including generalized malaise, fatigue and ache, changes in the body fat, respiratory including cough, pharyngitis. Abacavir commonly causes anaphylaxis, liver failure. Sometimes it causes mouth ulceration, lymphadenopathy.

Hypersensitivity due to Abacavir allergy

Furthermore, the world statistics, although Abacavir is a well tolerated drug, however hypersensitivity due to the drug is found among 5-8% of the total world population mostly mediated by activation of HLA-B*5701 due to MHC-I presentation of derivative Abacavir leading to disruption of normal activity (Chessman et al 2008, Zhang, et al, 2012). This ultimately leads to hypersensitivity and is detected within 6 weeks of treatment through symptoms like fever, rashes, GI tract sensitivity, and respiratory problems (Hetherington, et al, 2001). Among the case countries, maximum incidence is found in European population i.e. 5%, followed by 1% prevalence in Asian population and less than 1% in African population. Among treatment options, low fat diet and aerobic exercises are suggested. Further, drugs like, Thiazolidiones and Metformin  have been found to improve immune response to sensitivity and Gemfibrozil and atorvastatin helps in lowering the lipids (Marfatia & Makrandi Smita, 2005).

Reference

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