Antivirals 2 Flashcards
Treatment of HIV
Combination of drugs aimed at suppressing HIV replication.
Current recommendation: 2 NRTI’s, either a protease inhibitor, NNRTI, or integrase inhibitor.
Goal of tx:
Maximally suppress viral load replication
Restore and preserve immunologic function
Improve quality of life
NRTI MOA:
Analogs of nucleotides that are incorporated into viral DNA to stop synthesis.
Mitochondrial DNA might be susceptible.
Which NRTI is excreted via liver?
Abacavir. All others are secreted by kidney and may cause kidney disease.
Do NRTIs have a lot of drug interactions?
No
Adverse effects of NRTIs
Decrease bone density Kidney disease (except abacavir) GI probs Fatty liver Abnormal distribution of body fat CNS anxiety, depression Lactic acidosis Pancreatitis
Resistance of NRTIs
Do not combine agents of the same class of nucleotides. Ex: Don’t use two thymidine analogs.
NNRTIs MOA
Highly selective inhibitor of HIV1 reverse transcriptase. Drug effects enzyme and inactivates it. Not incorporated into DNA.
Advantage: Doesn’t effect host cells or cross react with NRTIs
NNRTI side effects
Many drug interactions
High incidence of hypersensitivities
Efavirenz
Most effective, long 1/2 life, CNS side effects (vivid dreams)
Nevirapine. When do you use it?
Reserved for advanced diseases due to potential for liver toxicity.
Protease inhibitor MOA
Inhibit HIV protease- responsible for formation of essential enzymes and proteins. Prevents maturation of viral particles. Results in the production of non-infectious irons. Still released, but can’t affect our immune cells.
Protease inhibitor pharmacokinetics
Most have poor bioavailability.
Metabolized by P450 (P450 Inhibitor)
No dosage adjustment needed in patient with renal problems
Limited CNS penetration
Protease inhibitor adverse effects
Paresthesias (numbing of hands and feet)
GI
Changes in glucose and lipid metabolism (monitor diabetic pts)
Chronic use–> fat redistribution, similar to NRTIs
Protease inhibitor drug/drug interactions?
Veryyyy common. Drugs that rely on metabolism for termination of action may accumulate to toxic levels.
When to use ritonavir
Used as enhancer to other protease inhibitors. It’s the only time you can use 2 PI’s! Not used on its own.
Increases the bioavailability of second drug by inhibiting it’s metabolism. CYP450 inhibitor.
