Antivirals Flashcards
What increased the rate of development of antivirals
HIV crisis, transplant related infections increasing, new pandemics (Covid)
Antiviral Agents Considerations
Viruses are intracellullar, viral latency (viruses targeted when replicating), no culture systems, virus pathogenesis uncertainty and emerging resistance
Antiviral Mechanisms of Action
Virucides (intact virus inactivation), augmentation/modification of host response and viral replication
Virucides Examples
Detergents (soap), UV light, cryotherapy, laser therapy and salicylic acid
Detergent Mechanism of Action
Envelope and membrane disruption
UV Mechanism of Action
Damage to RNA/DNA
Host Response Augmentation Mechanisms of Action
Replace deficient host immune response. Eg Immunoglobulins (antibodies developed outside of the body) and interferons (permeate membranes)
Interferons Outline
Cytokine produced in response to a wide variety of antigens. Bind to target human cells and trigger antiviral response. Don’t last long and don’t trigger adaptive immunity (no memeory)
Pegylated Interferons Outline
Lasts longer in body. Reduced frequency of administration
Interferon Adverse Effects Outline
Flu-like symptoms, leukopenia, thrombopenia, nephrotoxixity, hepatotoxicity, alopecia and thyroiditis
Monoclonal Antibodies Outline
Laborataory made proteins that mimic antibodies (bind to pathogen’s receptors to prevent host cell entry). Can also modulate host immune response by acting as pro-inflammatory antagonist
Agents that inhibit viral replication (anti-herpes)
Aciclovir, Valaciclovir, Ganciclovir, Valganciclovir, Forsacarnet and cidofovir
What is Aciclovir Used To treat
Herpes Simplex Virus 1 (facial legions), HSV 2 (gentitalia legions) and Varicella Zoster Virus (herpes - shingles/chicken pox)
Aciclovir Mechanism of action
Guanine analogue - replaces Guanine (impeding transcription) and inhibits DNA polymerase stopping DNA synthesis. Administered as prodrug ,thymidine kinase inside cell phosphorylates, activating drug (not present in uninfected cells)
Aciclovir Use Clinically
HSV encephalitis, neonatal HSV, disseminated HSV, Disseminated VZV, severe varicella pnuemonia, Immunocompromised HSV prophylaxis. Limited toxicity, risk of nephrotoxicity
Valciclovir Outline
Aciclovir prodrug rapid GIT absorption. Is phosphorylated to aciclovir. Can interact with drugs (eg ibuprofen). Used mainly for genital herpes suppression (doesn’t act sustemicallY0
Ganciclovir Outline
Aciclovir Derivative. Has same mechanism of action (phosphorylation, inhibits DNA polymerase) Mainly targets cytomegalovirus, HSV1 and HSV 2 (IV admin). Used in immunosupressed (AIDS, organ transplants)
Ganciclovir Clinical Use
Prophylaxis for immunosuppressed against cytomegalovirus. Fights pneumonia, GI disease (eg colitis), encephalitis and retinitis
Ganciclovir Side Effects
Neutropenia, thrombocytopenia, headache and confusion
Valganciclovir Outline
Valyl ester prodrug. Taken orally in HIV/AIDs patients. Don’t take with ganciclovir
Foscarnet Outline
Pyrophosphate analogue that binds to DNA polymerase inactivating it. Has acyivity against herpes viruses, hepatitis B and HIV
Clinical Uses of Forscarnet
Used to treat CMV when ganciclovir can’t be administered and when aciclovir ressistant. This wouldn’t have ressistance built against as doesn’t require intracellular phosphorylation
Oseltamivir (TamiFlu) Outline
Neuraminidase inhibitor (prevents budding = replication), specific for influenza A and B. Oral formulation administered 48 hrs after symptoms onset. Reduces symptoms severity and duration. 1st line
Zanamivir Outline
Neuraminidase inhibitor, sepcific to influenza A and B (2nd line). Not used in asthma and COPD due to brochospasms
Remdesivir (veklury) Outline
Inhibits RNA dependent RNA polymerase of coronavirus by being incorporated into RNA chain (nucleoside analogue).
Remdesivir Side Effects
nausea, allergy and liver toxicity
Why treat chronic hepatitis B
Reduce viral load (minimise transfer risk), prevent progression to liver disease/carcinoma. Viral load in blood dictates treatment course. Treatment efficacy monitored by PCR
Lamivudine Outline
Nucleoside analogue, phosphorylated to active form icorperates into DNA terminating it. Used in interferon non-responsiveses. Prophylaxis prevents HBV reoccurence. Administerd orally
Lamivudine Side Effects
Usually well tolerated. pacreatitis and liver acidosis
Ribavirin Outline
Guanine analogue, nucleoside inhibitor. Co-administered with alpha interferion to treat hepatitis C
HIV Antiretroviral Medicines
Administered regardles of patient symptoms (if HIV is detected). Include 2 cucleoside/nuclode reverse transcriptase inhibitors
