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17. Clinical Pharmacology and Therapeutics > 8. Antiviral Agents > Flashcards

8. Antiviral Agents Flashcards

1
Q

What is a virus?

A

An obligate intracellular parasite with no cell wall/membrane that is capable of causing disease in the infected host.

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2
Q

What is the range of size for viruses?

A

25-400 nanometres.

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3
Q

What do viral genomes consist of?

A

DNA or RNA.

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4
Q

How do viruses replicate?

A

Using host metabolic machinery, hide within host cell.

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5
Q

Why are there not many successful antivirals?

A

Because the virus is in the host cell so can’t prevent replication unless the host is injured too.

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6
Q

What are the 6 stages of viral replication?

A

Attachment, penetration, uncoating, replication/protein synthesis, assembly, release.

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7
Q

Name two antivirals used to treat influenza A and B.

A

Oseltamivir (tamiflu), zanamivir.

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8
Q

What is the route of administration for flu drugs oseltamivir and zanamivir?

A

Oseltamivir - oral, zanamivir - inhaled/intranasal.

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9
Q

What is the mechanism of action of flu drugs oseltamivir and zanamivir?

A

Neuraminidase inhibitors, blocks release of newly assembled influenza virions from the host cell.

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10
Q

How can resistance to flu drugs oseltamivir and zanamivir develop?

A

Mutation of neuraminidase so it doesn’t allow the drugs to bind well.

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11
Q

Why are flu drugs oseltamivir and zanamivir still used despite resistance?

A

The mutations causing resistance form less fit viruses whereby the virus is ineffective in its job of infecting so less severe disease state.

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12
Q

When are flu drugs oseltamivir and zanamivir administered to exert therapeutic effects?

A

Prophylactically to prevent infection or within 48 hours of infection to reduce intensity and duration of symptoms.

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13
Q

Which diseases are herpes viruses associated with?

A

Cold sores, encephalitis, genital infections.

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14
Q

Which antiviral is directed at herpes viruses?

A

Aciclovir (‘zovirax’).

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15
Q

What are the routes of administration for the herpes antiviral drug aciclovir?

A

IV, oral, or topical cream.

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16
Q

What is the mechanism of action for herpes antiviral drug aciclovir?

A

Purine/pyramidine analogues which are phosphorylated by viral thymidine kinase (activates) to inhibit viral DNA synthesis.

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17
Q

How does resistance develop against herpes antiviral drug aciclovir?

A

Thymidine kinase enzyme mutation in virus which prevents binding to acyclovir so it can’t act as a false substrate in DNA replication.

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18
Q

When is herpes antiviral drug aciclovir active?

A

In acute phase of viral infection where patient is symptomatic, not in latent phase as prevention of outbreak.

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19
Q

Which antiviral treats cytomegalovirus?

A

Ganciclovir.

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20
Q

What is the route of administration for CMV antiviral drug ganciclovir?

A

IV to cross BBB.

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21
Q

When is CMV antiviral drug ganciclovir used?

A

For CMV retinitis in immunocompromised patient and CMV prophylaxis in transplant patients.

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22
Q

What is the mechanism of action of CMV antiviral drug ganciclovir?

A

Analogue of acyclovir with greater affinity for CMV, phosphorylates using a different enzyme, inhibits viral DNA synthesis.

23
Q

What are the ADRs of CMV antiviral drug ganciclovir?

A

Myelosuppressive, carcinogenic/teratogenic.

24
Q

Why is renal failure a contraindication for ganciclovir antiviral therapy in CMV?

A

It’s renal cleared so accumulates in renal failure.

25
Q

Name three antivirals used to treat HBV/HCV.

A

Lamivudine, sofosbuvir, interferon alpha.

26
Q

What is lamivudine used for and what is its route of administration?

A

For HIV and hepatitis B, oral route.

27
Q

What is the mechanism of action of HIV/HBV antiviral drug lamivudine?

A

Reverse transcriptase inhibitor - acts as false substrate and chain terminator of reverse transcriptase enzyme in viral replication.

28
Q

What is the mechanism of action of HCV antiviral drug sofosbuvir?

A

Blocks action of HCV viral polymerase to prevent production of new virus.

29
Q

What is interferon alpha used for and what is its route of administration?

A

Treatment of hepatitis B/C, IM injection.

30
Q

What is the mechanism of action of HBV/HCV drug interferon alpha?

A

Immunomodulatory effect, stimulates proteins to enhance cellular resistance to viral infection.

31
Q

What are the ADRs of interferon alpha treatment for HBV/HCV?

A

Flu-like illness, fever, chills, headaches, malaise, myalgia, arthralgia, nausea, vomiting, diarrhoea in first few hours-days.

32
Q

What is ribavirin use to treat?

A

Chronic hepatitis C and infants with severe respiratory syncytial virus.

33
Q

What is the route of administration for chronic HCV and infant RSV drug ribavirin?

A

Oral or IV.

34
Q

What is the mechanism of action of chronic HCV and infant RSV drug ribavirin?

A

Guanosine analogue - inhibits guanosine triphosphate formation to prevent viral messenger RNA capping. Presents assembly of viral genome/DNA.

35
Q

What are the ADRs of chronic HCV and infant RSV drug ribavirin?

A

Transient anaemia, teratogenic.

36
Q

What is the prevalence of resistance to chronic HCV and infant RSV drug ribavirin?

A

Rare, hardly any reports.

37
Q

What are the groups of antivirals used to treat HIV?

A

Nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors. New therapies - integrase inhibitors, and receptor inhibitors.

38
Q

What is the mechanism of action for HIV nucleoside reverse transcriptase inhibitor drugs?

A

Inhibit DNA polymerase so CNA can’t replicate.

39
Q

Name one nucleoside reverse transcriptase inhibitor.

A

Zidovudine.

40
Q

What are some ADRs of HIV nucleoside reverse transcriptase inhibitor drugs?

A

Hyperlactataemia, lactic acidosis, hepatomegaly and steatosis.

41
Q

Name on non-nucleoside reverse transcriptase inhibitor for HIV treatment.

A

Nevirapine.

42
Q

What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors used for HIV treatment?

A

Active without future phosphorylation, non-competitive inhibitors of HIV reverse transcriptase so it binds at different site to the NRTI but same effect.

43
Q

Which HIV strand do non-nucleoside reverse transcriptase inhibitors work on?

A

HIV-1, not HIV-2.

44
Q

Name on protease inhibitor used in HIV therapy.

A

Ritonavir.

45
Q

What is the mechanism of action of protease inhibitors used in HIV treatment?

A

Blocks cleavage of viral polyproteins by HIV protease enzymes, preventing the production of viral proteins for the formation of final mature virions.

46
Q

Name one fusion inhibitor used in HIV therapy.

A

Enfuviritide.

47
Q

When are fusion inhibitors used in HIV therapy?

A

As salvage drug if all else haven’t worked.

48
Q

What is the route of administration of fusion inhibitors in HIV therapy?

A

Subcutaneous (only HIV therapy).

49
Q

Name one integrase inhibitor used in HIV therapy.

A

Raltegravir.

50
Q

What is the mechanism of action of integrase inhibitors used in HIV therapy?

A

Prevent integration of HIV DNA provirus into host cell genome.

51
Q

Why should antiviral drug resistance be tested for?

A

To optimise clinical outcomes, quality of life, longevity of the patient; save costs and adverse effects of ineffective therapy; reduce pool of drug resistant viruses in population that may transmit between individuals, reducing effectiveness of standard therapy.

52
Q

When is antiviral drug resistance tested?

A

With evidence of therapeutic failure, due to resistance, poor compliance.

53
Q

How is antiviral drug resistance tested?

A

Phenotypic characterisation linked to genetic mutations: incubate suspected drug resistant virus with varying concentrations of drug of interest in culture, look for graded response compared to a wild-type virus, look at specific sequencing/genotype of the mutation.

17. Clinical Pharmacology and Therapeutics (25 decks)

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