PTN - Antivirals (Mehta) Flashcards
If the triphosphate version of acyclovir (ACV) and zidovudine (AZT) are the actual pharmacological inhibitors, why are the drugs not administered as the triphosphate?
A. Not stable in circulation
B. No mechanism to enter cell
C. Too expensive to synthesize
D. All of the above
D. All of the above
What are the 3 mechanisms that lead to acyclovir resistance?
- Impaired production of viral thymidine kinase (most common)
- Altered thymidine kinase substrate specificity
- Altered viral DNA polymerase (rare)
How do the cyclovir drugs (acyclovir, famcyclovir, etc.) exhibit selective toxicity to virally-infected cells over human cells?
Human thymidine kinase will not phosphorylate the drug, and human DNA polymerase is not inhibited by the triphosphate.
What drug is used to treat cytomegalovirus?
Gancyclovir
One of the main side effects of treating with the drug gancyclovir is that it causes myelosuppression (neutropenia and thrombocytopenia). What drug can be co-administered to prevent this from happening?
A G-CSF analog (Filgrastim) will increae production of neutrophils
What is the drug acyclovir used to treat?
Herpesvirus infections
Specifically, HSV-1 and 2 and VZV
High concentrations can be used to treat VZV and CMV, but gancyclovir works best for CMV
What is the mechanism of action of foscarnet?
Non-competitive inhibition of viral DNA polymerase
Foscarnet reversibly blocks the pyrophosphate binding site of viral polymerase to inhibit cleavage of pyrophosphate from dNTPs
What are the two major dose-limiting toxicities of foscarnet?
- Nephrotoxicity
- Hypocalcemia
What are the 5 classes of current anti-retrovirals?
- Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTIs)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Protease inhibitors (PIs)
- Integrase Strand Transfer Inhibitors (INSTIs)
- Early inhibitors
How does drug resistance to anti-retroviral therapy occur in HIV patients who faithfully take their medications?
HAART suppresses viral load to undetectable levels, but often there is a latent viral reservoir that is not affected by HAART.
This reservoir replenishes during resistance or interruption of drug therapy.
How does highly-active antiretroviral therapy (HAART) help to limit the emergence of resistant virus?
HAART is a combination therapy and uses multiple types of antiretroviral drugs to try to inhibit as many types of HIV virus and to prevent resistance to individual drug therapies.
True or False: Single agent drug resistance to HIV therapy is present in every individual infected with HIV.
True
This is the reason that HAART is more effective than a single drug at diminishing the effects of HIV.
Patient’s HIV genotypes are also determined to provide the therapy that each patient will best respond to.
What are the 2 toxicities specific to all nucleoside reverse transcriptase inhibitors (NRTIs)?
- Lactic acidosis
- Hepatic steatosis
What prototype drug is considered to be a nucleoside reverse transcriptase inhibitor (NRTI)?
Zidovudine (AZT)
What is the clinical manifestation of Stevens-Johnson Syndrome?
A. Polyp-like skin lesions
B. Erectile dysfunction
C. Dermis separates form epidermis
D. A henway
C. Dermis separates from epidermis
Stevens-Johnson Syndrome is a consequence of non-nucleoside reverse transcriptase inhibitors (NNRTIs). It begins as a fever and rash that spreads to the mucous membranes and other parts of the skin. Eventually, the epidermis separates from the dermis, leading to blistering and sloughing off of the epidermal layer of skin.
