Antiviral Drugs Flashcards
What are the 4 types of antivirals?
- Nucleoside analogs (Nucs)
- Non-nucleosides (Non-nucs)
- Protease Inhibitors
- Entry inhibitors
What virus functions are targeted by antivirals?
- Entry
- Genome replication
- Assembly
- Release from cell
What host cell defenses are targeted by antiviral therapies?
Intrinsic immunity via interferon pathway
What is an issue of the specificity of antiviral drugs?
- Most drugs only target one virus
- Broad spectrum drugs are rare
What type of cytotoxic effects result from antiviral use?
- “Off target” effects can harm cells
- “On target” drugs directed at viral enzymes can be defeated by resistance mutations
What are some issues with duration of antiviral effects?
- They are reversible competitive inhibitors
- Virus replication can resume when drug is cleared
- Tx may need to be lifelong
Describe viral drug resistance
- Resistance mutations often exist before Tx
- Drugs select for resistant virus strains
What characteristics favor emergence of resistant viral variants?
- High rate of virus replication
- High mutation rate (RNA >>> DNA)
- High selective drug pressure (longterm/multiple Tx)
- Immunosuppressed hosts that can’t clear virus-infected cells
What are the strategies to limit drug resistant viral infections?
- Alleviate immunosuppression in the patient (lower doses of anti-T cell drugs)
- Combine drugs with different targets (lower probablility that multiple resistance mutations will be present
- Target host fns (infected cells may have unique targetable profile)
Who should be treated for HSV1, HSV2, VZV?
Neonates (HSV), Patients with frequent recurrence (1/2), Those w/ HSV complications (encephalitis, dissemination, eye infections), Those with zoster
What is the leading drug for HSV infections? What type of drug is it? How effective is it against VZV?
Acyclovir; Guanosine nucleoside analog (NUC); Less effective than for HSV 1/2
What is the mechanism of acyclovir action?
- Viral (HSV) thymidine kinase takes up A and phosphorylates it
- Host kinases (GMPK and NDPK) phosphorylate A
- Viral DNA polymerase incorporates A into viral DNA halting synthesis
What is Ganciclovir used for? What type of drug is it? What are complications of use? Who should be treated?
CMV; Guanosine nucleoside analog (NUC); similar to acyclovir; Highly toxic - BM suppresion, Mutagenic/teratogenic, severe SEs; Bone marrow and organ transplant patients, immunosuppressed people with active CMV, or those with CMV retinitis
What type of drug is Foscarnet? What is its mechanism? What is it effective against? Route of administration?
Trisodium phosphonoformate Broad Spectrum antiviral; Inhibits viral DNA polymerase; All herpes viruses; IV only
What type of drug is Cidofovir? What is it effective against? Route of administration?
Broad spectrum nucleoside analog of cytosine (NUC); DNA viruses: herepesvirus, adenovirus, papillomavirus, poxvirus; IV
What is the major side-effect of broad spectrum antivirals?
renal toxicity
What are the treatment options for HBV? Who should be treated?
PEG-IFN-ALPHA, Entecavir, Tenofovir disoproxil fumarate; People with chronic active HBV, those coinfected with HCV/HIV, and those progressing to cirrhosis, liver failure, or hepatocellular carcinoma
What are the treatments for Influenza virus? Mechanism? Who should be treated?
Zanamivir, Oseltamivir; Both are sialic acid analogs that inhibit viral neuraminidase (sialidase) vausing virions to remain attached to the cell; Severely ill, children < 2 yo, Adults > 65 yo, Pregnant women, Immunosuppressed, ANYONE who has influenza
What is a broad spectrum RNA antiviral? What type of drug is it? Route of administration? Approved uses?
Ribavirin; Nucleoside analog of guanosine (NUC); Oral, IV, Aerosol; HCV, RSV
What is the general Tx for HCV? What are issues with Tx?
PEG-INF-ALPHA and ribavirin; Not all HCV genotypes respond, difficult Tx regimen complicated by bad sideffects
What was the earliest Tx for HIV? What type of drug is it? Why is it no longer in use?
AZT; Nucleoside analog of thymidine (NUC)/Nucleoside Reverse Transcriptase Inhibitor)
What are the 4 methods for HIV treatment?
- Entry inhibition
- Reverse transcriptase inhibitor
- Integrase inhibitor
- Protease inhibitor
What is an example of an anti-HIV entry inhibitor?
Maraviroc
What is an example of an anti-HIV Nucleoside/tide RT inhibitor?
Tenofovir
