Protease Inhibitors
Examples
- Atazanavir
- Lopinavir
- Ritonavir
- Darunavir
- Ritonavir
Indications
- HIV 1 and HIV 2
Contraindications
Contraindications
- Acute porphyria
- Breast-feeding
- Diabetes mellitus (associated with hyperglycaemia)
- Hepatitis B and Hepatitis C
- Hepatic Insufficiency
- Renal insufficiency
- Patient with cardiac disorders (including conduction disorders, structural heart disease, drugs that prolong QR interval)
- Pregnancy
Mechanism
mRNA transcribed from the provirus is translated into two biochemically inert polyproteins. A virus-specific protease then converts the polyproteins into various structural and functional proteins by cleavage at the appropriate positions. HIV-specific protease inhibitors then bind to the site where cleavage occurs preventing viral propagation. As this step does not occur in host biology, this is a useful target for chemotherapeutic intervention.
Administration
Oral (for all drugs)
Adverse Reactions
- Diarrhoea
- Lipodystrophy
- Abnormalities of lipid metabolism - Hyperlipidaemia
- Insulin resistance and worsening of diabetic control
Interactions
Protease inhibitors act as inhibitors of hepatic cytochrome P450 3A4 and thereby can increase the effect of opioids, TCAs, SSRIs, triptans, antifungal drugs and some antipsychotic drugs
Increased metabolism of oral contraceptive - additional methods should be used
Increased metabolism of oral contraceptive - additional methods should be used
Education
Treatment regimes for HIV are no longer as complex as they once were, however patient education about compliance is still important.
Additional contraceptive methods are advised with the oral contraceptive pill.
Additional contraceptive methods are advised with the oral contraceptive pill.
Pharmacokinetics
Administration is oral, with varying first pass metabolism and absorption is pH dependent; high fat meals and a higher pH in the gastric environment may facilitate absorption. Metabolism is primarily by the hepatic p450 mechanism and excretion is faecal.
