Pharm - AntiVirals Flashcards
- Explain why “selective toxicity” is more difficult with viruses than with bacteria.
Viruses replicate by co-opting the host cell’s metabolic machinery. As a result, there are fewer differences between viruses and their human hosts to exploit for drug development than between bacteria and humans.
- Explain the difficulties in developing drugs against viruses
It is difficult to develop anti-viral drugs because there is such a wide spectrum of heterogeneous agents.Another difficulty is that, due to the heterogeneous nature of viruses mentioned above, antiviral drugs are often effective against only a few viruses while most antibacterial drugs target multiple bacterial species.
- Give three indications for acyclovir
HSV, VZV, EBV
For HSV:
– Mucocutaneous herpetic lesions
– Genital herpes lesions
– Prophylaxis in AIDS and other immunocompromised patients.
- List two blood-related adverse effects of ganciclovir
- Leukopenia (low levels of leukocytes in blood)
2. Thrombocytopenia (low #’s of platelets in blood)
- Apply what could be monitored to determine the duration of foscarnet action to a clinically-relevant case scenario.
Clearance primarily by the kidney and is directly proportionate to creatinine clearance.
Drug Monitoring
Daily creatinine and BUN(blood urine nitrogen) during induction*
Calcium, magnesium, and phosphorus*
Check Hgb/Hct monthly*
Electrolyte disturbances, sometimes severe, can develop even after therapy is discontinued.*
If maintenance therapy is used, check creatinine, BUN, and ions weekly.
Major toxicity of zanamavir and for what population it should not be prescribed
Zanamavir is a Neuraminidase inhbitor
Bronchospasm, decline in respiratory function
Not recommended in patients with underlying airway disease (COPD, asthma)
If benefit > risk, use short acting bronchodialator prior to administration, monitor after use
- Draw a diagram of antivirals working through viral versus host cell kinases, include the sites of action of four specific drugs.
Acyclovir: Phosphorylation by TK (thymidine kinase)
Ganciclovir: Phosphorylation by CMV protein kinase (UL97)
Zidovudine, Idoxuridine, Cytarabine, Vidarabine are activated by host cell kinases
- Explain why acyclovir is more selectively toxic than other antivirals.
The increased selectivity is partly a result of acyclovir’s initial phosphorylation by a viral TK that is absent in uninfected cells.
More selectively toxic than the drugs that require phosphorylation only by the host enzymes.
Acyclovir: Phosphorylation by TK (thymidine kinase)
- List three viruses that acyclovir can be used against
Herpes simplex virus
Epstein-Barr virus
Varicella-zoster
- List two indications for valacyclovir.
Recurrent genital herpes
Varicella-Zoster infections.
- List two indications for famciclovir.
For the management of acute herpes zoster
- Suppression of recurrent genital herpes
- Apply the early symptoms and DOC for herpes encephalitis to a clinically-relevant case scenario.
Seizure, headache, decreased consciousness, fever, lethargy and disoriented. Left temporal lobe decreased density, lack of bacteria in CSF (+ red blood cells)
Acyclovir 10 mg/kg IV Q 8 hr
- Explain how ganciclovir is metabolized to an active form inside host cells.
For CMV
• Acts as an antimetabolite, which is phosphorylated first by viral (monophosphorylation) and then by cellular kinases (di –and tri phosphorylation) to form a nucleotide that inhibits DNA polymerase of CMV.
- Explain how cidofovir has selective toxicity.
– Cidofovir is activated by intracellular enzymes to form an inhibitor of DNA polymerases.
– 1000-fold more effective against the DNA polymerases of viruses such as herpes virus than against the DNA polymerase of the host cell.
- Explain what is unique about the metabolism requirement of foscarnet.
Inhibits (in vitro) viral DNA polymerase, RNA polymerase, or HIV RT directly, without requirement for activation by phosphorylation.
