Lecture 6 Antivirals Flashcards
Which viral diseases are babies and toddlers immunised against in Australia?
Hep B, polio, measles, mumps, rubella, varicella.
What is an immunoglobulin?
Protein found in the serum and in the immune cells which functions as an antibody. Inhibits penetration of the host cell by viruses.
Why are newer drugs, such as aciclovir, more selective?
Because they are inactive until phosphorylated by enzymes that are preferentially synthesised by the virus.
Describe antiretroviral drugs.
Used to suppress the replication of HIV virus. Resistance to single drug develops rapidly, so drug combinations are used: 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor.
Known as Highly Active Antiretroviral Therapy.
What is interferon alpha, and how does it act?
Antiviral protein normally produced by leucocytes. Produced by virally-infected cells. Binds to cell surface receptors and stimulates production of enzymes in the host cell that inhibit viral mRNA translation by host ribosomes, thus inhibiting viral replication and augmenting viral clearance.
Describe the administration of interferon alpha, its indications for use, and its adverse effects.
Given by injection in the treatment of chronic persistent Hep B, and in combination with ribavirin in chronic hep C.
Adverse effects include headache, myalgia, chills, fever and rigours, fatigue, anorexia and bone marrow suppression.
What is PEGinterferon, and what are the advantages of pegylation?
Interferon with polyethylene glycol attached. Enhances half life, masks the agent from host immune system, prolongs circulatory time and provides water solubility.
What are some drugs, other than interferon alpha, that are used in the treatment of chronic Hep B? What is their mechanism of action?
Adefovir, entecavir, telbivudine. All prevent viral DNA synthesis.
What is the rationale for drug use in chronic hepatitis?
To prevent or delay disease progression to cirrhosis, liver failure and hepatocellular carcinoma by long term suppression of viral replication and improvement of liver histology.
Describe ribavirin, including mechanism of action, indications for use, dosage form and adverse effects.
Broad spectrum antiviral. Nucleoside analogue that interferes with RNA and DNA synthesis to inhibit protein synthesis and viral replication.
Indicated for use in serious lower respiratory tract infection due to RSV.
Given by inhalation, can cause irritated eyes, nose, throat and rash.
Can precipitate on contact lenses and cause conjunctivitis. has teratogenic effects in pregnancy.
Which antiviral drugs prevent a virus from entering or leaving the host cell?
Amantadine and immunoglobulins prevent entry into host cell. Neuraminidase inhibitors (oseltamivir and zanamivir) prevent release from host cell.
Describe amantadine, including mechanism of action, indications for use and contraindications.
Interferes with the replication of influenza A by inhibiting the transmembrane M2 protein that is essential for uncoating the virus. Has a narrow spectrum, and influenza vaccine is usually preferable.
Contraindicated in pregnancy (teratogenic)
Describe neuraminidase inhibitors, including mechanism of action, dosage form, indications for use.
Reduce influenza virus replication by inhibiting the viral surface enzyme neuraminidase, preventing release of new virus from the cells.
Treatment and prevention of influenza A and B. Starting treatment within 48 hours of symptoms shortens duration by half to 1 day.
Eg oseltamivir (oral) and zanamivir (inhaled).
Zanamivir may exacerbate bronchospasm.
What is palivizumab?
Monoclonal antibody produced by a single clone of cells.
Neutralises and inhibits fusion of respiratory syncitial virus with the host cell, preventing its replication.
Used to prevent lower respiratory tract disease due to infection with RSV in infants at high risk of RSV. It is very expensive.
List the guanine analogues that inhibit nucleic acid synthesis. Include their indications, dosage form.
Aciclovir: herpes simplex, varicella zoster. low bioavailability.
Famciclovir: Tablets. Herpes simplex, varicella zoster, CMV.
Ganciclovir (IV and intravitreal). taken 2-3x daily.
Valaciclovir: tablets. converted to aciclovir in liver.
Valganciclovir: tablets and oral liquid. Converted to ganciclovir in liver and intestinal wall. Used for CMV retinitis and to prevent CMV disease after transplants.
