Dr Sharon Rees @reesprescribe
Day 1: Seven days of nucleoside reverse transcriptase inhibitors (NRTIs), inspired by #ItsASin. The first HIV/AIDs drug #AZT (zidovudine) was discovered from unusual RNA/DNA elements found in marine sponges in the 1950s. Such analogues drew attention as anticancer drugs, because of the ability to disrupt cell function.
Dr Sharon Rees @reesprescribe
(cont) Abandoned as ineffective for cancer, #AZT was rediscovered during the frantic search for an HIV/AIDs treatment and was licensed by the FDA in 1987. #AZT was given in high doses, causing some toxicity. Resistance also became problematic. However, it did prolong life.
Dr Sharon Rees @reesprescribe
Day 2: It took a further decade to develop the combination drugs now standard therapy, as effective suppressors of HIV replication and also contain drug resistance. Newer versions of NRTIs eg #abacavir are the focus of this series.
Dr Sharon Rees @reesprescribe
Day 3: #abacavir kinetics: good oral bioavailability and tissue penetration eg into the CNS. Hepatic metabolism by alcohol dehydrogenase and glucuronidation, but no significant CYP450 activity. Avoid in moderate-severe liver impairment. Mostly renal excretion of metabolites, dosage reduction end stage renal failure. t½ ~ 1.5 hours.
Dr Sharon Rees @reesprescribe
Day 4: Once inside the cell, HIV makes self-copies via the reverse transcriptase enzyme allowing DNA production and reproduction, taking over even more cells. #abacavir pretends to be a DNA component, but is deliberately defective, preventing creation of viral DNA. Effective against HIV-1and 2.
Dr Sharon Rees @reesprescribe
Day 5: ADRs #abacavir; Common; GI effects and decreased appetite, dizziness, fatigue, fever, rash. Severe include osteonecrosis, pancreatitis, lactic acidosis, SJS (not exhaustive). Much in literature re cardiovascular risks with HIV drugs, but none listed in BNF/SPC for #abacavir. Can cause weight gain.
Dr Sharon Rees @reesprescribe
(cont) Resistance is thought to have emerged slowly to #abacavir; however, some HIV strains are now resistant and some are also multi-resistant to more than one NRTI, including #abacavir.
Dr Sharon Rees @reesprescribe
Day 6: Only a low number of drug-drug interactions (DDIs). There are six listed in BNF and the HIV drug tipranavir is the only ‘severe’ interaction. The remainder of DDIs are ‘moderate’ and are all anticonvulsants.
Dr Sharon Rees @reesprescribe
Interesting fact; there are now over 25 HIV drugs licensed in UK, with many fixed dose combinations, supporting medical needs, lifestyle and compliance. The new regimens mean HIV/AIDs is a manageable long-term condition and can produce a level of remission, but a cure is elusive #BeMoreJill #ItsASin
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Further reading on #AZT #abacavir
- HIV infection: https://bnf.nice.org.uk/treatment-summary/hiv-infection.html
- Abacavir: https://bnf.nice.org.uk/drug/abacavir.html#indicationsAndDoses
- Zidovudine: https://bnf.nice.org.uk/drug/zidovudine.htmll
- Electronic Medicines Compendium: https://www.medicines.org.uk/emc/product/5518/smpc#gref
Both AZT (zidovudine) and abacavir belong to the same group of HIV drugs, the NRTIs
TRUE or FALSE?
Abacavir is a nucleoside analogue
TRUE or FALSE?
There is no resistance to abacavir
TRUE or FALSE?
Abacavir is usually taken alone
TRUE or FALSE?
Which of the following is TRUE?
- Abacavir should be avoided at all stages of renal impairment
- There is little/no phase 1 liver CYP450 breakdown
- Excretion is mainly faecal
- Abacavir has a long half-life
There are multiple severe drug-drug interactions
TRUE or FALSE?
Which best describes the mechanism of action for abacavir
- Once in the body, abacavir prevents viral entry into the body's immune cells
- Abacavir enhances the intra-cellular killing capacity of lymphocytes so they can destroy the virus
- Abacavir inhibits the ability of the reverse transcriptase enzyme to make true DNA copies
- Abacavir prevents the virus from being released from infected cells
Which of the following is a common adverse drug reaction?
- Fatigue
- Lactic acidosis
- Pancreatitis
- Stevens-Johnson syndrome
Abacavir can be combined with dolutegravir and lamivudine
TRUE or FALSE?
With all the new drug combinations, HIV/AIDs can now be cured
TRUE or FALSE?