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51 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Name the various anti-viral drugs, including their classes. |
NRTIs: Zidovudine, Lamivudine NNRTIs: Efavirenz, Nevirapine Protease inhibitors: Ritonavir, Lopinavir Entry/fusion inhibitors: Maraviroc Integrase inhibitors: Raltegravir, dolutegravir DNA polymerase inhibitors: Acyclovir, valacyclovir, ganciclovir, valganciclovir |
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What is the mode of action of zidovudine? |
Inhibits nucleoside reverse transcriptase, by competing with cellular nucleotides for active centre of reverse transcriptase. They are analogues of thymidine nucleotides. Hence prevent HIV from forming pro-viral DNA, by preventing addition of more bases by reverse transcriptase. |
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What is susceptible to the action of zidovudine? |
Retroviruses (HIV) |
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Describe the pharmacokinetics of zidovudine. |
A: Oral or IV administration D: Widely distributed, penetrates well into CSF compared to other anti-HIV drugs (used for meningitis) M: Mainly by glucuronidation in liver E: 20% urinary excretion of unchanged drug |
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What are the clinical uses of zidovudine? |
To treat HIV |
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What are the toxicity effects of zidovudine? |
- Myelosuppresion (macrocytic anemia, neutropenia) - GIT disturbances - CNS related effects (headache, insomnia, anxiety) - Mitochondrial damage-related effects (lactic acidosis, hepatic steatosis) - Increased risk when taken during pregnancy |
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What are the drug interactions of zidovudine? |
CYP enzyme inhibitors (eg isoniazid in treatment of TB) increases plasma zidovudine concentration. Probenecid decreases renal clearance of zidovudine. |
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What is the mode of action of lamivudine? |
Inhibits nucleoside reverse transcriptase, by competing with cellular nucleotides for active centre of reverse transcriptase. They are analogues of cytosine nucleotides. Hence prevent HIV from forming pro-viral DNA, by preventing addition of more bases by reverse transcriptase. |
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What is the spectrum of activity for lamivudine? |
Retroviruses (HIV), DNA viruses with reverse transcriptase (Hep B) |
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Describe the pharmacokinetics of lamivudine? |
A: Good oral bioavailability
D: Widely distributed, penetrates less well into CSF compared to zidovudine M: Minimal metabolism E: Mainly excreted unchanged in urine |
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What are the clinical uses of lamivudine? |
Treat HIV Treat Hep B |
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List the toxicity effects of lamivudine. |
Usually minimal effects, but possible GIT disturbances, CNS related effects, potential lactic acidosis when used with another NRTI during pregnancy. |
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What are the drug interactions of lamivudine? |
Co-trimoxazole (used to treat pneumocystis jiroveci) can increase plasma lamivudine levels due to displacement of lamivudine from plasma protein binding. |
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What is the mode of action of efavirenz? |
Binds to active site of HIV-1 reverse transcriptase enzyme, inhibiting viral DNA formation. |
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What is the spectrum of activity of efavirenz? |
Retroviruses (HIV-1 but not HIV-2)
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Describe the pharmacokinetics of efavirenz. |
A: Orally on empty stomach. (Plasma concentration increases 50% when taken with high-fat meal)
D: Poor entry into CSF due to high degree of protein-binding M: Hydroxylated in liver to inactive metabolites E: Urinary and faecal excretion of unchanged drug |
'No eclairs while eating Efavirenz' (eclairs are fattening!) 'Efavirenz - Empty stomach' |
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What is the clinical use of efavirenz? |
To treat HIV patients
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List the toxicity effects of efavirenz. |
- CNS-realted effects (e.g. dizziness, agitation, confusion)
- Skin allergies (e.g. rash) - Raised liver enzymes - Potential teratogenicity |
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What are the contraindications involved when using efavirenz? |
- Pregnancy
- Patients with liver impairment |
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What are the drug interactions with efavirenz? |
- With CYP inhibitors (e.g. ritonavir, erythromycin, isoniazid, cause increased efavirenz concentration
- Efavirenz a CYP inducer itself, causes fall in drug concentration of itself (and other drugs e.g. warfarin) - Efavirenz a CYP competitive inhibitor, |
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What is the mode of action of nevirapine? |
Binds to active site of HIV-1 reverse transcriptase enzyme, inhibiting viral DNA formation. |
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What is the spectrum of activity of nevirapine? |
Retroviruses (HIV-1 but not HIV-2)
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Describe the pharmacokinetics of nevirapine. |
A: Good oral bioavailability, with or w/o food.
D: Penetrates CSF better than efavirenz due to lipid solubility. Crosses placenta, secreted in breast milk M: Hydroxylated extensively in liver E: Urinary excretion of metabolites |
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What are the clinical uses of nevirapine? |
To treat HIV |
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What are the toxic effects of nevirapine? |
- Fever, sleepiness, nausea, headache - Skin rashes (allergy) - severe hepatitis |
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What measures can you take to prevent serious skin rashes while on nevirapine? |
Slowly increasing the dose over 2 weeks. |
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What are the impt drug interactions with nevirapine |
- Nevirapine itself is CYP inducer-> decreases plasma concentration of other drugs - interacts with other CYP inducers (e.g. rifampicin, phenytoin) and CYP inhibitors (e.g. ciprofloxacin, isoniazid, ritonavir) -> influences nevirapine concentration |
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What is the mode of action of ritonavir/lopinavir/darunavir etc? |
Binds to active site of HIV protease so as to block the cleaving action on HIV polyproteins |
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What is the spectrum of activity for ritonavir/lopinavir? |
Retroviruses. (HIV) |
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Describe the pharmacokinetics of ritonavir/lopinavir. |
A: Orally (better absorbed with food) D: Widely distributed, doesn't penetrate into CSF M: Extensive first-pass metabolism |
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What are the toxic effects of ritonavir/lopinavir? |
- Hyperglycemia - Hyperlipidemia - Maldistribution of fat - Increased bleeding risk in haemophiliacs - Osteomalacia (reduced bone density) - Hepatic injury (raised bilirubin, transaminases) |
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What is the precaution to take note of when dealing with hyperlipidemia due to saquinavir? |
Do not give lovastatin or simvastatin in managing cholesterol levels, as their plasma drug concentration can rise to toxic levels due to use of saquinavir (a CYP inhibitor) |
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What should a patient avoid eating while on saquinavir? |
Garlic. |
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What are the significant drug interactions with protease inhibitors (PIs)? |
- Interaction with CYP inducers (rifampicin, phenobarbitone, carbamazepine) - Interaction with CYP inhibitors (grapefruit, macrolides) - PIs themselves are CYP inhibitors -> cause increased drug concentration for other drugs e.g. lovastatin, simvastatin |
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What is the mode of action of maraviroc? |
Antagonist of CCR5 receptor on T cells, preventing HIV from binding via Gp120. (For HIV strain that binds to CCR5) |
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Describe the pharmacokinetics of maraviroc. |
A: Rapidly absorbed via oral route M: Metabolised extensively by liver E: Metabolites excreted mainly in stools Unchanged form excreted in urine |
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What is the clinical use of maraviroc? |
Used in combination with other anti-HIV drugs to reduce viral load. |
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What are the toxicity effects when using maraviroc? |
- Hepatotoxicity - Skin allergic rash - Cardiotoxicity |
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What are the contraindications of maraviroc? |
Can only be used in HIV strains that bind to CCR5, not those that bind to e.g. CXCR4. |
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What is the mechanism of action for dolutegravir/raltegravir? |
They are integrase inhibitors. |
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What are the toxic effects of using dolutegravir/raltegravir? |
Generally well-tolerated, may cause hepatitis, allergic rash |
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What is the mode of action for acyclovir/valacyclovir/ganciclovir/valganciclovir? |
They are DNA polymerase inhibitors. - Initial phosphorylation by viral thymidine kinase (to monophosphate form) - Further phosphorylation by host kinases (to triphosphate form) - Triphosphate form inhibits viral DNA polymerase, terminating DNA chain formation |
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In what ways can viruses become resistant to acyclovir/ganciclovir? |
1. Mutations in viral DNA polymerase (gene coding for it) 2. Mutations in viral thymidine kinase (gene coding for it) |
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What is the spectrum of activity for acyclovir/valacyclovir? |
Herpes viruses. HSV > VZV > EBV > CMV |
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Describe the pharmacokinetics of acyclovir/valacyclovir. |
A: Poor oral bioavailability (acyclovir) Better oral bioavailability (valacyclovir) Can be given by IV Can be given topically (eye drops/cream) D: Wide distribution, enters CSF well M: Acyclovir triphosphate metabolised by cellular phosphatases E: 100% excreted in urine! |
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What are the clinical uses of acyclovir/valacyclovir? |
- Herpes simplex virus -> mucocutaneous, genitalia, encephalitis - Varicella zoster virus-> to reduce risk of dissemination. Given orally in immunocompetent, IV in immunosuppressed - Prophylaxis 1. For immunosuppressed pt (e.g. organ transplant) to prevent reactivation of latent VZV 2. For pt with frequent genital infections from HSV |
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What are the toxic effects of acyclovir/valacyclovir? |
- GI disturbances (nausea, diarrhea) - Thrombophlebitis (if given IV) - Renal dysfunction when drug infused too rapidly due to drug deposits on renal tubules - Haemolytic uraemic syndrome - CNS effects (headaches, tremors) |
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Describe the pharmacokinetics of ganciclovir/valganciclovir. |
A: Poor oral bioavailability (ganciclovir) Better oral bioavailability (valganciclovir) Can be given by IV/topical (eye drops) D: Wide distribution, enters CSF well M: Metabolised by cellular phosphatases E: Renal excretion mainly |
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What are the clinical uses of ganciclovir/valganciclovir? |
Mainly used for CMV infections. Oral -> to control CMV retinitis Eye drops -> CMV retinitis IV -> life-threatening CMV infections in HIV pt |
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What are the toxic effects of using ganciclovir/valganciclovir? |
- TERRATOGENIC! - CNS effects (headache) - GIT disturbances (nausea, diarrhea) - Myelosuppression (neutropenia mainly) - Potential carcinogenicity |
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What is the spectrum of activity for ganciclovir/valganciclovir? |
CMV > HSV > VZV > EBV |
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