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xS1B5 - Pharmacology > S1B5 - Antiviral Drugs > Flashcards

S1B5 - Antiviral Drugs Flashcards

1
Q

What treatment option should be considered only for severe RSV infection?

A

Ribavirin is approved for the treatment of RSV infection, however the routine use of nebulized ribavirin in infants and children with RSV lower respiratory tract infection is not recommended. Ribavirin should be reserved for immunosuppressed patients with severe RSV infection.

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2
Q

What drug is foscarnet contraindicated with because of the associated hypocalcemia with foscarnet use?

A

Foscarnet is contraindicated with pentamidine (IV administration for Pneumocystis jirovecii pneumonia) because of hypocalcemia.

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3
Q

Describe the mechanism of action of amantadine in the context of influenza.

A

Amantadine inhibits the M2 protein of Influenza A, which normally acidifies viral particles to allow uncoating and escape from endosomes. Adsorption and penetration of the virus is normal, however viral uncoating is prevented and transcription by viral RNA polymerase cannot occur.

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4
Q

A medical student recommends to you, his attending, that a chronic hepatitis C patient go on ribavirin monotherapy. Is this treatment regimen appropriate for the patient?

A

Oral ribavirin is used in conjunction with interferon alfa-2b for chronic hepatitis C and should not be used as monotherapy for the treatment of hepatitis C.

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5
Q

What is the prevalence of amantadine resistance in influenza viruses?

A

Resistance to amantadine is very high, with 92-100% of strains being resistant via M2 mutations. For this reason, amantadine is rarely prescribed.

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6
Q

Acyclovir is effective when used to treat infections with which viruses?

A

Acyclovir, famciclovir, and valacyclovir are guanosine analogs used to treat active HSV and VZV (not latent forms).

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7
Q

What is the mechanism of acyclovir? Does it need to be activated?

A

Mechanism of action of acyclovir is a prodrug guanosine analogue that is phosphorylated by viral thymidine kinase. Triphosphate is formed by cellular enzymes and acts to preferentially inhibit viral DNA polymerase by chain termination.

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8
Q

An anti-influenza medication is found to inhibit the uncoating of the virus after the virus particles have been endocytosed. Which viral protein is targeted by this medication?

A) gp120

B) gp21

C) Hemagglutinin

D) Neuraminidase

E) M2 protein

A

M2 protein

Answer Explanation

Amantadine targets the M2 protein in viruses. The purpose of the M2 protein is to acidify the viral particle after it is endocytosed, allowing it to escape the endosome and initiate replication.

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9
Q

What is the mechanism of action of cidofovir?

A

Cidofovir mechanism of action is by acting to preferentially inhibit viral DNA polymerase. It does not require phosphorylation by viral kinase.

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10
Q

What are four drugs that are indicated to treat CMV?

A

Drugs to treat CMV include

  • Ganciclovir and valganciclovir (increased oral bioavailability relative to ganciclovir)
  • Foscarnet
  • Cidofovir
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11
Q

Which antiviral was indicated in the treatment of influenza A but not influenza B?

A

Amantadine was originally used as prophylaxis/treatment of influenza A (not influenza B).

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12
Q

Describe 2 mechanisms of viral resistance to ganciclovir.

A

Mechanisms of viral resistance include DNA polymerase mutations and mutations to viral kinase (gene UL97).

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13
Q

What activity does acyclovir have against EBV? CMV?

A

Acyclovir, famciclovir, and valacyclovir have weak activity against EBV and no activity against CMV.

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14
Q

Mutation of which enzyme leads to acyclovir resistance?

A

Mechanism of resistance includes mutated viral thymidine kinase.

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15
Q

What are toxicities associated with amantadine usage?

A

Toxicity to amantadine include:

  • CNS depression (ataxia, depression)
  • Livedo reticularis (mottled discolouration of the skin)
  • Anticholinergic symptoms such as dry mouth, constipation, urinary retention, blurry vision (due to mydriasis and cycloplegia)
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16
Q

A guanosine analogue is prescribed for CMV. Which medication was most likely prescribed?

A) Ganciclovir

B) Enfuviride

C) Didanosine

D) Acyclovir

E) Foscarnet

A

Ganciclovir

Answer Explanation

Ganciclovir and valganciclovir are guanosine analogues used in the treatment and prophylaxis of CMV.

Acyclovir is also a guanosine analogue but has limited efficacy against CMV. Acyclovir is a prodrug that gets converted into acyclo-GMP by viral thymidine kinase. CMV does not express a thymidine kinase.

Foscarnet is a phosphonic acid derivative that may be used in the treatment of drug-resistant CMV.

Didanosine and enfuvirtide are anti-HIV drugs.

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17
Q

Name at least 2 of the common side effects of ganciclovir.

A

Common side effects of ganciclovir:

  • Hematologic: anemia; neutropenia in AIDS patients, thrombocytopenia
  • GI: diarrhea; anorexia, and vomiting
  • Renal toxicity
  • General: fever
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18
Q

Describe the mechanism of action of ganciclovir.

A

Ganciclovir mechanism of action is by acting as a 2’-deoxyguanosine analogue that first gets phosphorylated by CMV to form ganciclovir monophosphate, then undergoes intracellular conversion to form ganciclovir triphosphate (a dGTP analogue). This inhibits viral DNA synthesis and replication via competitive inhibition of viral DNA polymerases, and incorporation into viral DNA, ultimately causing chain termination.

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19
Q

Which of the following is a relative contraindication to the use of foscarnet?

A) Renal insufficiency

B) Cirrhosis

C) History of right upper lobectomy

D) History of rhabdomyolysis

E) Nonalcoholic steatohepatitis

A

Renal insufficiency

Answer Explanation

Foscarnet’s primary toxicity is nephrotoxicity.

20
Q

What is ribavirin and what is it effective in treating?

A

Ribavirin is a nucleoside analog, which has a broad spectrum of antiviral activity that can be used against RSV, hepatitis C, and influenza A and B.

21
Q

Name the primary toxicity of foscarnet.

A

Toxicities associated with foscarnet includes nephrotoxic and electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia).

22
Q

Besides being used to treat HBV and HCV infections, what are other indications for interferon alpha?

A

IFN-α (interferon-α) indications can be remembered by the mnemonic “CCHHARM”

  • Chronic HBV & HCV infections
  • ​Condyloma acuminatum (HPV 6 and 11)
  • Hairy cell leukemia
  • HHV-8 - Kaposi sarcoma
  • Alpha-interferon
  • Renal cell carcinoma
  • Malignant melanoma
23
Q

What antiviral drug can be used as an alternative to (val)acyclovir to treat herpes zoster because of a better oral bioavailability?

A

Famciclovir also has a better bioavailability than acyclovir and can be used for herpes zoster.

24
Q

What antiviral is used to treat Parkinson disease and drug induced EPS?

A

Secondary use of amantadine is the treatment of Parkinsonism and extra-pyramidal symptoms (e.g. drug-induced).

25
Q

Name 2 primary toxicities of interferon therapy.

A

Toxicities of interferons include flu-like syndrome and neutropenia.

26
Q

True or False: Acyclovir is effective against latent infections.

A

Acyclovir, famciclovir, and valacyclovir are guanosine analogs used to treat active HSV and VZV (not latent forms).

27
Q

When a patient is administered the common regimen for hepatitis C (IFN-α and ribavirin) what side effect should be closely monitored that could affect the patient’s well-being?

A

Neuropsychiatric side effects have been associated with IFN-α plus ribavirin for treatment of HCV.

28
Q

What are the indications for acyclovir?

A

Acyclovir is used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis.

29
Q

What infection are neuraminidase inhibitors used to treat? What are some examples of neuraminidase inhibitors?

A

Neuraminidase inhibitors include oseltamivir and zanamivir are used as prophylaxis and treatment of influenza A and B.

30
Q

What antiviral medication acts to inhibit DNA and RNA polymerase along with reverse transcriptase without the need for activation by viral kinase?

A

Mechanism for foscarnet is a pyrophosphate analogue that preferentially inhibits viral DNA and RNA polymerase in addition to reverse transcriptase.

31
Q

A patient who has been treated with prochlorperazine for nausea develops repetitive, involuntary, purposeless movements of her lips and face. Which medication may improve her symptoms?

A) Neosynephrine

B) Haloperidol

C) Thioridazine

D) Amantadine

A

Amantadine

Answer Explanation

This patient has akathisia, an extrapyramidal disorder, likely as a result of the prochlorperazine. Extrapyramidal symptoms can be difficult to treat; possible therapies include decreasing the dose of the offending medication, switching to another medication, starting beta blockers, or prescribing anti-Parkinsonism drugs. Amantadine, while primarily developed for treatment of influenza, also increases the release of dopamine and is therefore a treatment for Parkinsonism and extrapyramidal symptoms. Because the prochlorperazine was prescribed for nausea, prescribing thioridazine and haloperidol, neither of which have anti-nausea effects, is not appropriate.

32
Q

Which antiviral is most effective against RNA-based viruses?

A) Acyclovir

B) Amantadine

C) Ribavirin

D) Foscarnet

E) Interferon-β

A

Ribavirin

Answer Explanation

Ribavirin is primarily an anti-RNA virus medication, although it has anti-DNA activity as well.

Acyclovir is used against herpesviruses, which are double-stranded, linear DNA viruses.

Foscarnet inhibits viral DNA polymerase.

Amantadine is used against influenza A, which is an RNA virus. However, the rate of resistance to amantadine is 90%-97%.

33
Q

A recent liver transplant recipient is prescribed valganciclovir. What is the indication for this medication?

A) Treatment for Hepatitis C infection

B) To induce immunosuppression

C) Treatment of Epstein-Barr virus infection

D) Cytomegalovirus prophylaxis

A

Cytomegalovirus prophylaxis

Answer Explanation

Valganciclovir is primarily indicated in active CMV retinitis, or in CMV prophylaxis in immunosuppressed patients, such as recent organ transplant recipients. It does not induce immunosuppression, and there is no reason to assume the patient has EBV or HCV infections.

34
Q

Which antiviral is indicated in ganciclovir-resistant CMV infections?

A

Foscarnet does not require activation by viral kinases, so it may be used in ganciclovir-resistant CMV strains.

35
Q

What are the other mechanisms of Amantadine besides its action on the M2 protein of Influenza A?

A

Secondary mechanisms include:

  • Blockage of muscarinic receptors
  • Increased dopamine release
  • Low-affinity noncompetitive NMDA receptor inhibitor
36
Q

What is the toxicity associated with cidofovir? How can this be reduced?

A

Toxicity of cidofovir include nephrotoxicity, which can be reduced by co-administration of probenecid (reduces the accumulation of drug concentration in the proximal tubule by blocking the anion transport system responsible for active tubular secretion) and IV saline.

37
Q

Name a prodrug purine nucleoside analogue associated with crystalline nephropathy. Can you name a couple other medications associated with crystal nephropathy?

A

Toxicities of acyclovir is obstructive crystalline nephropathy and acute renal failure if not adequately hydrated. Other drugs associated with crystal-induced kidney injury can be remembered be mnemonic SOMATIC

  • Sulfasalazine
  • Orlistat
  • Methotrexate
  • Acyclovir
  • Triamterene
  • Indinavir (and other protease inhibitors)
  • Ciprofloxacin
38
Q

How do neuraminidase inhibitors work in the treatment of influenza?

A

Neuraminidase inhibitors function to inhibit neuraminidase, which cleaves cell membrane structures to enable viral progeny release from infected cells.

39
Q

What is the mechanism of action of ribavirin?

A

Mechanism of ribavirin acts by inhibiting synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.

40
Q

Name 2 indications for foscarnet administration.

A

Foscarnet is used in acyclovir-resistant HSV and CMV retinitis if ganciclovir fails.

41
Q

What two guanosine analogs can be given for HSV prophylaxis in immunocompromised patients?

A

Prophylaxis of acyclovir or valacyclovir, a prodrug of acyclovir that has better oral bioavailability, can be given to immunocompromised patients.

42
Q

Name 4 major adverse effects of ribavirin.

A

Toxicities of ribavirin include:

  • Ribavirin has recently been shown to cause respiratory deterioration in infants being treated for RSV infection.
  • Teratogenic
  • Hepatotoxicity in hepatitis C patients.
  • Hemolytic anemia/leukopenia/thrombocytopenia via non-immune immediate extravascular hemolysis by depleting intracellular stores of adenosine triphosphate.
43
Q

In immunocompromized patients, the better choice for treatment of HSV infections would be

A) Valacyclovir

B) Acyclovir

A

acyclovir

44
Q

Acyclovir is contraindicated or used with caution in combination with other dugs that

A) are hepatotoxic

B) are nephrotoxic

C) cause diarrhea

D) cause hypotension

A

are nephrotoxic

45
Q

Antisense drugs inhibit

A) DNA synthesis

B) RNA synthesis (transcription)

C) protein synthesis (translation)

A

Antisense drugs inhibit protein synthesis (translation).

46
Q

CMV can be treated with

A) Valgancyclovir

B) Acyclovir

C) Trifluridine

D) Docasanol

A

Valgancyclovir

47
Q

The better choice for empirical treatment of influenza in asthma patients is

A) Ostelmavir

B) Zanamavir

C) Amantadine

D) Rimantadine

A

ostelmavir

The neuraminidase inhibitors are more effective than amantadine and rimantadine. Ostelmavir is oral, zanamavir is inhaled.

xS1B5 - Pharmacology (8 decks)

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