Pharm Antiviral Drugs Part 1

1. A 74-year-old diabetic woman was brought to the emergency room with fever (102.7° F), shaking chills, cough, headache and malaise. Physical examination showed profound dyspnea and rales were audible on auscultation on both lungs. Chest x-ray showed bilateral infiltrates and blood gas analysis revealed significant hypoxia. A gram stain of the sputum showed no bacteria. Fluorescent antibodies identified influenza A virus on cells of nasal aspirates. An appropriate therapy was started which included a drug that acts by inhibiting viral uncoating. Which of the following drug was most likely prescribed?

Foscarnet

Ganciclovir

Zidovudine

Amantadine

Cidofovir

Indinavir

Learning objective: explain the mechanism of action of amantadine
Answer: D
Amantadine and rimantadine are drugs approved for both prophylaxis and therapy of influenza
A. They act by preventing uncoating of the virus once it is fused to the cell membrane. The
drugs can reduce the severity of symptoms and the duration of the illness and are mainly used
in elderly patients or in those with underlying diseases, like in the present case The drugs have
no effect on influenza B and C viruses or parainfluenza viruses. Unfortunately 92% of the
circulating influenza A viruses are resistant to adamantane derivatives.
A, B, C, E, F) These antiviral drugs are not active against influenza viruses

Explanation

Learning objective: explain the mechanism of action of amantadine
Answer: D
Amantadine and rimantadine are drugs approved for both prophylaxis and therapy of influenza
A. They act by preventing uncoating of the virus once it is fused to the cell membrane. The
drugs can reduce the severity of symptoms and the duration of the illness and are mainly used
in elderly patients or in those with underlying diseases, like in the present case The drugs have
no effect on influenza B and C viruses or parainfluenza viruses. Unfortunately 92% of the
circulating influenza A viruses are resistant to adamantane derivatives.
A, B, C, E, F) These antiviral drugs are not active against influenza viruses

2. A 23-year-old man had recurrent genital herpes which was effectively treated each time by acyclovir. The patient asked his physician why the treatment was not able to prevent recurrence. Which of the following was most likely the answer of the physician?

Acyclovir has a very short duration of action

Recurrence is due to a new contact with infected partners

Antiviral drugs have no effect on the latent state of viral diseases

Recurrence is due to a hypersensitivity reaction to viral proteins

Resistant to acyclovir is the rule after one cycle of therapy

Learning objective: explain why antiviral drugs cannot prevent recurrence if viral diseases.
Answer: C
Herpes viruses replicate in the skin or mucous membrane at the initial site of infection, then
migrate up the neuron and become latent in the sensory ganglion cells. The virus can be
reactivated from the latent state by a variety of factors including sunlight, hormonal changes
trauma, stress an fever at which time it migrates down the neuron and replicates in the skin,
causing lesions. No currently available antiviral drug attacks viruses during latency but acts only
on actively replicating viruses.
A, B, D, E) (see explanation above)

Explanation

Learning objective: explain why antiviral drugs cannot prevent recurrence if viral diseases.
Answer: C
Herpes viruses replicate in the skin or mucous membrane at the initial site of infection, then
migrate up the neuron and become latent in the sensory ganglion cells. The virus can be
reactivated from the latent state by a variety of factors including sunlight, hormonal changes
trauma, stress an fever at which time it migrates down the neuron and replicates in the skin,
causing lesions. No currently available antiviral drug attacks viruses during latency but acts only
on actively replicating viruses.
A, B, D, E) (see explanation above)

3. A 24-year old man visited his physician complaining of painful ulcers on his penis. Upon examination multiple rounded translucent vesicles were seen on the penis gland, intermixed with superficial, circular ulcers which were very painful to the touch. Regional limphoadenopathy was also present. A preliminary diagnosis was made. Which of the following drugs was most likely prescribed for the treatment of the patient's disorder?

Penicillin G

Doxycycline

Metronidazole

Acyclovir

Ketoconazole

Learning objective: outline the therapeutic uses of acyclovir.
Answer: D
The type of the lesion strongly suggests genital herpes. Other genital diseases are unlikely, as
explained below. Acyclovir is the drug of choice for genital herpes. Oral therapy speed up the
healing and reduces the frequency of reactivation episodes.
A) Penicillin G is effective in case of primary syphilis. The disease causes a red genital papule
that soon erodes to form a ulcer. However the ulcer is painless.
B) Doxycycline is the drug of choice for granuloma inguinale, a disease caused by
Calymmatobacterium granulomatis, a gram-negative rod. The initial lesion of this disease is a
painless nodule that slowly develops into a rounded, elevated granulomatous mass and finally
into a creeping, serpiginous ulcer.
C) Metronidazole is the drug of choice for trichomoniasis. The disease can cause urethritis but
not ulcers on the penis.
E) Topical miconazole is used to treat genital candidiasis. Even if the disease can sometimes
cause vesicles or erosions of the penis it is symptomless in men, in most cases.

Explanation

Learning objective: outline the therapeutic uses of acyclovir.
Answer: D
The type of the lesion strongly suggests genital herpes. Other genital diseases are unlikely, as
explained below. Acyclovir is the drug of choice for genital herpes. Oral therapy speed up the
healing and reduces the frequency of reactivation episodes.
A) Penicillin G is effective in case of primary syphilis. The disease causes a red genital papule
that soon erodes to form a ulcer. However the ulcer is painless.
B) Doxycycline is the drug of choice for granuloma inguinale, a disease caused by
Calymmatobacterium granulomatis, a gram-negative rod. The initial lesion of this disease is a
painless nodule that slowly develops into a rounded, elevated granulomatous mass and finally
into a creeping, serpiginous ulcer.
C) Metronidazole is the drug of choice for trichomoniasis. The disease can cause urethritis but
not ulcers on the penis.
E) Topical miconazole is used to treat genital candidiasis. Even if the disease can sometimes
cause vesicles or erosions of the penis it is symptomless in men, in most cases.

4. The diagram below depicts a simplified pathway of the viral growth cycle: Which of the steps shown in the pathway is most likely inhibited by enfuvirtide?

A

B

C

D

E

F

G

H

I

Answer: B
Enfuvirtide is an antiretroviral agent that most likely acts by preventing the conformational
changes required for the fusion of the viral membrane with the host cell membrane. In this way
the entry of virus into the cell is blocked.

Explanation

Answer: B
Enfuvirtide is an antiretroviral agent that most likely acts by preventing the conformational
changes required for the fusion of the viral membrane with the host cell membrane. In this way
the entry of virus into the cell is blocked.

5. A 43-year-old man with AIDS presented to his physician with a complaint of multiple painful ulcers in tongue and palate. Exfoliative cytology was done which led to the diagnosis of herpes simplex infection, and a therapy with oral acyclovir was initiated. Two weeks later no improvement was seen and the dose of the drug was increased but without success. Which of the following was most likely the cause of failure of acyclovir therapy?

Mutation of aspartate protease

Viral transpeptidase deficiency

Viral thymidine kinase deficiency

Viral neuraminidase deficiency

Mutation of reverse transcriptase

Learning objective: explain the most common reason of failure of acyclovir therapy.
Answer: C
Acyclovir resistance is the most common cause of failure of acyclovir therapy. Acyclovir resistant
strains of HSV and VZV arise chiefly from mutations in the thymidine kinase gene that result in
little or no production of the enzyme. Since viral thymidine kinase is essential for conversion of
acyclovir to active derivatives, resistance to the drug ensues. Resistant strains are most
commonly reported in severely immunocompromised patients receiving extended course of the
drug, like in the present case.
A, B, D, E) All the mentioned enzymes are not involved in the mechanism of action of the drug,
and therefore their deficiency cannot be the cause of resistance to the drug action.

Explanation

Learning objective: explain the most common reason of failure of acyclovir therapy.
Answer: C
Acyclovir resistance is the most common cause of failure of acyclovir therapy. Acyclovir resistant
strains of HSV and VZV arise chiefly from mutations in the thymidine kinase gene that result in
little or no production of the enzyme. Since viral thymidine kinase is essential for conversion of
acyclovir to active derivatives, resistance to the drug ensues. Resistant strains are most
commonly reported in severely immunocompromised patients receiving extended course of the
drug, like in the present case.
A, B, D, E) All the mentioned enzymes are not involved in the mechanism of action of the drug,
and therefore their deficiency cannot be the cause of resistance to the drug action.

6. A 34-year-old woman with AIDS was found to have a CD4 lymphocyte count of 45 cell/mm at the last control visit. The patient had an extensive hi 3 story of treatment with a variety of antiretroviral drugs and had been currently taking zidovudine, lamivudine and ritonavir. A tropism test showed that the HIV of the patient used the CCR5 receptor to enter the host cells. A therapy with a drug that prevents entry was started. Which of the following drugs was most likely given?

Ribavirin

Enfuvirtide

Didanosine

Maraviroc

Indinavir

Saquinavir

Learning objective: explain the mechanism of action of maraviroc.
Answer: D
Maraviroc binds to a specific CCR5 receptor on the viral envelope and blocks the fusion of viral
and cellular membrane so preventing viral entry. It has been shown that about 50% of patients
in whom at least two antiviral regimens had failed were infected with R5 HIV-1. Since maraviroc
is active against HIV that use CCR5 exclusively, but not against other HIV strains, tropism
testing should be performed before starting a treatment with this drug, like in the present case.
A) Ribavirin is not an antiretroviral agent.
B) Enfuvirtide is an entry inhibitor, but target a gp41 subunit of the viral envelope.
C) Didanosine is a reverse transcriptase inhibitor.
E, F) Indinavir and saquinavir are protease inhibitors.

Explanation

Learning objective: explain the mechanism of action of maraviroc.
Answer: D
Maraviroc binds to a specific CCR5 receptor on the viral envelope and blocks the fusion of viral
and cellular membrane so preventing viral entry. It has been shown that about 50% of patients
in whom at least two antiviral regimens had failed were infected with R5 HIV-1. Since maraviroc
is active against HIV that use CCR5 exclusively, but not against other HIV strains, tropism
testing should be performed before starting a treatment with this drug, like in the present case.
A) Ribavirin is not an antiretroviral agent.
B) Enfuvirtide is an entry inhibitor, but target a gp41 subunit of the viral envelope.
C) Didanosine is a reverse transcriptase inhibitor.
E, F) Indinavir and saquinavir are protease inhibitors.

7. A 12-day-old, premature baby boy developed a poor feeding pattern, irritability and respiratory distress. His mother, who suffered several episodes of genital herpes, was admitted to labor with premature ruptures of the membranes. Physical examination of the baby revealed several small vesicular skin lesions located on the scalp and a dendritic keratitis was present on both eyes. Which of the following drugs was most likely included in the therapeutic treatment of this baby?

Saquinavir

Acyclovir

Zidovudine

Pentamidine

Fluconazole

Metronidazole

Learning objective: outline the therapeutic uses of acyclovir.
Answer: B
The history of the mother (several episodes of genital herpes) and the signs of the patient
(prematurity, respiratory distress, cutaneous vesicles) suggest that the baby was suffering from
congenital herpes, a disease that affects about 1 in 3000 live births and is acquired, in most
cases, during the passage through the birth canal. The diagnosis is confirmed by the finding of
dendritic keratitis, which is pathognomonic of herpetic keratocongiuntivitis. Antiherpes drugs
include acyclovir, several acyclovir congeners, foscarnet, ganciclovir, cidofovir and trifluridine.
Acyclovir is still the drug of choice for systemic treatment. Foscarnet and cidofovir can be used
for acyclovir resistant strains. Trifluridine can be used topically to managed the keratitis.
A, C) Saquinavir and zidovudine are antiretroviral drugs used only in HIV infection.
D, E, F) These drugs are not antiviral agents.

Explanation

Learning objective: outline the therapeutic uses of acyclovir.
Answer: B
The history of the mother (several episodes of genital herpes) and the signs of the patient
(prematurity, respiratory distress, cutaneous vesicles) suggest that the baby was suffering from
congenital herpes, a disease that affects about 1 in 3000 live births and is acquired, in most
cases, during the passage through the birth canal. The diagnosis is confirmed by the finding of
dendritic keratitis, which is pathognomonic of herpetic keratocongiuntivitis. Antiherpes drugs
include acyclovir, several acyclovir congeners, foscarnet, ganciclovir, cidofovir and trifluridine.
Acyclovir is still the drug of choice for systemic treatment. Foscarnet and cidofovir can be used
for acyclovir resistant strains. Trifluridine can be used topically to managed the keratitis.
A, C) Saquinavir and zidovudine are antiretroviral drugs used only in HIV infection.
D, E, F) These drugs are not antiviral agents.

8. The diagram below depicts a simplified pathway of the viral growth cycle: Which of the steps shown in the pathway is most likely inhibited by ritonavir?

A

B

C

D

E

F

G

H

I

Answer: G
Saquinavir belong to the group of protease inhibitors. These drugs inhibit HIV protease, an
aspartic endopeptidase that cleaves viral polypeptide products to form structural proteins of the
virion core and essential viral enzymes (i.e reverse transcriptase, integrase, etc.)

Explanation

Answer: G
Saquinavir belong to the group of protease inhibitors. These drugs inhibit HIV protease, an
aspartic endopeptidase that cleaves viral polypeptide products to form structural proteins of the
virion core and essential viral enzymes (i.e reverse transcriptase, integrase, etc.)

9. A 5 year-old girl was admitted to the emergency room because of fever (102 F°) and disorientation in time and space. Soon after the admission the patient had a seizure. Ceftriaxone and dexamethasone were initiated but the next day the patient became lethargic and lapsed into a coma. Examination of the cerebrospinal fluid was normal and a CT scan of the brain revealed a decrease density in a small area of the right parietal lobe. Acyclovir IV was started and after 5 days of therapy the patient was alert, responsive and actively moving. The patient was most likely suffering from which of the following diseases?

Neisseria meningitis

Toxoplasma encephalitis

Cryptococcal meningitis

Cytomegalovirus encephalitis

Herpes encephalitis

Learning objective: outline the therapeutic uses of acyclovir.
Answer: E
The signs and symptoms of the patient suggested the presumptive diagnosis of bacterial
meningitis but the lack of efficacy of antibiotic therapy and the normal CSF rose the suspicion of
herpes simplex virus encephalitis, which is the most common sporadic viral infection of the
CNS. Acyclovir is the drug of first choice and the efficacy of the therapy confirms that the patient
was suffering from herpes encephalitis.
A) (see explanation above)
B, C) These diseases are quite rare in patients without HIV, and cannot be cured with antiviral
drugs.
D) Cytomegalovirus infection occur mainly in immunocompromised patients or is congenital,
and acyclovir is not active against CMV.

Explanation

Learning objective: outline the therapeutic uses of acyclovir.
Answer: E
The signs and symptoms of the patient suggested the presumptive diagnosis of bacterial
meningitis but the lack of efficacy of antibiotic therapy and the normal CSF rose the suspicion of
herpes simplex virus encephalitis, which is the most common sporadic viral infection of the
CNS. Acyclovir is the drug of first choice and the efficacy of the therapy confirms that the patient
was suffering from herpes encephalitis.
A) (see explanation above)
B, C) These diseases are quite rare in patients without HIV, and cannot be cured with antiviral
drugs.
D) Cytomegalovirus infection occur mainly in immunocompromised patients or is congenital,
and acyclovir is not active against CMV.

10. A 31-year-old man with AIDS was recently diagnosed with cytomegalovirus pneumonia. The patient's current medications included zidovudine, didanosine and saquinavir. An IV therapy with ganciclovir was started. Which of the following adverse effects could be most likely predicted from the concurrent administration of ganciclovir and the antiretroviral drugs?

Anemia and neutropenia

Retinal detachment

Cataract

Sexual dysfunction

Hyperglycemia

Lactic acidosis

Learning objective: describe the adverse effects of ganciclovir.
Answer: A
Ganciclovir is a drug of choice for CMV infections. The dose-limiting toxicity of both zidovudine
and ganciclovir is bone marrow suppression and therefore anemia and neutropenia can be
predicted from the concurrent administration of ganciclovir and zidovudine.
B, C) Retinal detachment and cataract are adverse effects of ganciclovir that can occur following
intravitreal administration of the drug for CMV retinitis. They do not occur when the drug is
administered IV for systemic anti-CMV therapy..
D) Sexual dysfunction is not an adverse effect of the drugs the patient has been receiving.
E) Hyperglycemia can occur after prolonged administration of protease inhibitors (i.e.
saquinavir) but does not occur with ganciclovir.
F) Lactic acidosis has been reported with the use of nucleoside reverse transcriptase inhibitors,
but it is does not occur with ganciclovir.

Explanation

Learning objective: describe the adverse effects of ganciclovir.
Answer: A
Ganciclovir is a drug of choice for CMV infections. The dose-limiting toxicity of both zidovudine
and ganciclovir is bone marrow suppression and therefore anemia and neutropenia can be
predicted from the concurrent administration of ganciclovir and zidovudine.
B, C) Retinal detachment and cataract are adverse effects of ganciclovir that can occur following
intravitreal administration of the drug for CMV retinitis. They do not occur when the drug is
administered IV for systemic anti-CMV therapy..
D) Sexual dysfunction is not an adverse effect of the drugs the patient has been receiving.
E) Hyperglycemia can occur after prolonged administration of protease inhibitors (i.e.
saquinavir) but does not occur with ganciclovir.
F) Lactic acidosis has been reported with the use of nucleoside reverse transcriptase inhibitors,
but it is does not occur with ganciclovir.

11. A 23-year-old, heroin addicted man presented to the hospital complaining of severe fatigue and scleral icterus. Physical examination showed hepatomegaly and mild ascites. Significant laboratory findings were: total bilirubin 4.4 ng/mL, ALT 380 U/L, AST 320 U/L. Serologic tests were positive for hepatitis C virus infection. Which of the following pairs of drugs would be appropriate for this patient?

Interferon-alpha and foscarnet

Ribavirin and saquinavir

Interferon-alpha and ribavirin

Saquinavir and foscarnet

Zidovudine and ganciclovir

Ganciclovir and foscarnet

Learning objective: outline the pharmacological therapy of hepatitis C.
Answer: C
The signs and symptoms of the patient suggest the diagnosis of viral hepatitis and the serologic
tests confirmed the presence of a HCV infection. Both HBV and HCV are transmitted
parenterally so both infections are likely in intravenous drug users. In fact the incidence of HCV
infection can be as high as 90% among these users. Interferons are the drug of choice for both
hepatitis B and C, but recently the combined therapy with interferon alpha and ribavirin has
been shown to be superior than interferon alone and the combination has been approved by
FDA for this purpose. Monotherapy with ribavirin alone is not effective.
A, B, D, E, F) All these drug combinations include at least one drug that is useless against
HCV.

Explanation

Learning objective: outline the pharmacological therapy of hepatitis C.
Answer: C
The signs and symptoms of the patient suggest the diagnosis of viral hepatitis and the serologic
tests confirmed the presence of a HCV infection. Both HBV and HCV are transmitted
parenterally so both infections are likely in intravenous drug users. In fact the incidence of HCV
infection can be as high as 90% among these users. Interferons are the drug of choice for both
hepatitis B and C, but recently the combined therapy with interferon alpha and ribavirin has
been shown to be superior than interferon alone and the combination has been approved by
FDA for this purpose. Monotherapy with ribavirin alone is not effective.
A, B, D, E, F) All these drug combinations include at least one drug that is useless against
HCV.

12. The diagram below depicts a simplified pathway of the viral growth cycle: Which of the steps shown in the pathway is most likely inhibited by amantadine?

A

B

C

D

E

F

G

H

I

Answer: C
.Amantadine most likely acts by preventing uncoating, that is the separation of the viral core
from the outer structural components, that takes place after the fusion process.

Explanation

Answer: C
.Amantadine most likely acts by preventing uncoating, that is the separation of the viral core
from the outer structural components, that takes place after the fusion process.

13. A 33-year-old woman with AIDS was recently diagnosed with cytomegalovirus retinitis. The ophthalmologist prescribed a drug that must be phosphorylated first by virusspecific enzymes, and then by host's cell enzymes to become active. Which of the following drugs was most likely given?

Foscarnet

Ribavirin

Ganciclovir

Acyclovir

Vidarabine

Zidovudine

Learning objective: explain the mechanism of action of gancyclovir.
Answer: C
Ganciclovir and acyclovir are nucleoside analogs that must be phosphorylated first by virusspecific
enzymes. Both drugs are phosphorylated by a viral thymidine kinase in HSV infected
cells. Ganciclovir is also phosphorylated by a viral phosphotransferase in CMV infected cells.
This explains why both drugs are active against HSV by only ganciclovir is effective against
CMV.
A) This drug is used in cytomegalovirus retinitis, but it does not require activation by
phosphorylation.
D) Acyclovir has no activity against CMV infections.
E, F) These drugs are nucleoside analogs that must be phosphorylated to become active.
However phosphorylation is done, in these cases, by host’s cell enzymes only, and these drugs
are not effective against cytomegalovirus.

Explanation

Learning objective: explain the mechanism of action of gancyclovir.
Answer: C
Ganciclovir and acyclovir are nucleoside analogs that must be phosphorylated first by virusspecific
enzymes. Both drugs are phosphorylated by a viral thymidine kinase in HSV infected
cells. Ganciclovir is also phosphorylated by a viral phosphotransferase in CMV infected cells.
This explains why both drugs are active against HSV by only ganciclovir is effective against
CMV.
A) This drug is used in cytomegalovirus retinitis, but it does not require activation by
phosphorylation.
D) Acyclovir has no activity against CMV infections.
E, F) These drugs are nucleoside analogs that must be phosphorylated to become active.
However phosphorylation is done, in these cases, by host’s cell enzymes only, and these drugs
are not effective against cytomegalovirus.

14. A 75-year-old patient was brought to the emergency room from a nursing home with chief complains of fever (102.8° F), cough, headache, malaise, anorexia and photophobia. Conventional antibiotic therapy was ineffective and three days later influenza virus was isolated from the sputum. Over the next week, three other nursing home patients developed similar symptoms. Vaccination and chemoprophylaxis were planned for all nursing home residents and staff. Which of the following drugs was most likely administered as a prophylactic measure?

Acyclovir

Foscarnet

Ribavirin

Ganciclovir

Oseltamivir

Zidovudine

Learning objective: outline the prophylactic use of neuraminidase inhibitors.
Answer: E
Vaccination plus chemoprophylaxis against influenza is advisable for residents of nursing
homes or other chronic care facilities and personnel who have extensive contacts with high risk
patients, like in the present case. Oseltamivir and zanamivir are inhibitors of neuraminidases
produced by influenza A an B viruses. These enzymes cleave sialic acid residues from cell
surface so promoting the release of newly formed virus from the surface of infected cells. Both
drugs cause a significant reduction of the symptoms of influenza A and B and are therefore
preferable to amantadine which is effective only against influenza A. Resistance to
neuraminidase inhibitors was quite uncommon till recently, but now rates of resistance to
oseltamivir among H1N1 virus (a subtype of influenza A) have risen abruptly and dramatically.
A, B, C, D, F) These drugs are not effective against influenza viruses.

Explanation

Learning objective: outline the prophylactic use of neuraminidase inhibitors.
Answer: E
Vaccination plus chemoprophylaxis against influenza is advisable for residents of nursing
homes or other chronic care facilities and personnel who have extensive contacts with high risk
patients, like in the present case. Oseltamivir and zanamivir are inhibitors of neuraminidases
produced by influenza A an B viruses. These enzymes cleave sialic acid residues from cell
surface so promoting the release of newly formed virus from the surface of infected cells. Both
drugs cause a significant reduction of the symptoms of influenza A and B and are therefore
preferable to amantadine which is effective only against influenza A. Resistance to
neuraminidase inhibitors was quite uncommon till recently, but now rates of resistance to
oseltamivir among H1N1 virus (a subtype of influenza A) have risen abruptly and dramatically.
A, B, C, D, F) These drugs are not effective against influenza viruses.

15. A 71-year-old man was brought to the emergency room because of fever (103.2° F), chills, dyspnea, and generalized aches in the back and legs. Social history of the patient was significant for an outbreak of flu in the community. A clinical diagnosis of influenza was made and a treatment with oseltamivir was started. Which of the following actions most likely mediated the therapeutic effect of the drug in the patient?

Prevention of virus release from infected cells

Blockade of fusion of the virus with the host cell

Inhibition of viral transcription

Inhibition of viral proteolytic cleavage

Inhibition of viral protein synthesis

Learning objective: explain the mechanism of action of oseltamivir.
Answer: A
Oseltamivir and zanamivir are inhibitors of neuraminidase an enzyme produced by influenza A
an B viruses. The enzyme cleaves sialic acid residues from cell surface so promoting the
release of newly formed virus from the surface of infected cells. By blocking the enzyme these
drugs inhibit virus release from the infected cells.
B, C, D, E) (see explanation above)

Explanation

Learning objective: explain the mechanism of action of oseltamivir.
Answer: A
Oseltamivir and zanamivir are inhibitors of neuraminidase an enzyme produced by influenza A
an B viruses. The enzyme cleaves sialic acid residues from cell surface so promoting the
release of newly formed virus from the surface of infected cells. By blocking the enzyme these
drugs inhibit virus release from the infected cells.
B, C, D, E) (see explanation above)

16. A 34-year-man with AIDS was recently diagnosed with cytomegalovirus retinitis and a therapy with gancyclovir was started. Two weeks later the disease was not much improved and the ophthalmologist decided to add another drug that, unlike gancyclovir, can inhibit DNA polymerase directly without requiring activation by phosphorylation. Which of the following drugs was most likely prescribed?

Acyclovir

Lopinavir

Ribavirin

Foscarnet

Trifluridine

Nevirapine

Learning objective: explain the mechanism of action of foscarnet.
Answer: D
Foscarnet is an inorganic pyrophosphate analog that inhibits viral DNA polymerase, RNA
polymerase and HIV reverse transcriptase directly, without requiring activation by
phosphorylation. It is effective in the treatment of CMV retinitis and it is often given together with
gancyclovir since it has been shown that the combination is superior to either agent alone in
delaying the progression of retinitis.
A, B, C, E, F) All these drug are not effective in CMV retinitis.

Explanation

Learning objective: explain the mechanism of action of foscarnet.
Answer: D
Foscarnet is an inorganic pyrophosphate analog that inhibits viral DNA polymerase, RNA
polymerase and HIV reverse transcriptase directly, without requiring activation by
phosphorylation. It is effective in the treatment of CMV retinitis and it is often given together with
gancyclovir since it has been shown that the combination is superior to either agent alone in
delaying the progression of retinitis.
A, B, C, E, F) All these drug are not effective in CMV retinitis.

17. A 34-year-old woman reported to her physician a two-day history of genital burning pain that was worse during urination and accompanied by fever and malaise. Physical examination revealed multiple blisters and ulcerative lesions in the vaginal area. A presumptive diagnosis of herpes genitalis was made and an oral drug was prescribed. Which of the following steps of viral growth cycle was most likely inhibited by the prescribed drug?

Attachment to the host cell

Uncoating

Penetration

Transcription

MRNA and protein synthesis

Proteolytic cleavage

Learning objective: identify which step of viral growth cycle is inhibited by acyclovir
Answer: D
The prescribed drug was most likely acyclovir, the drug of choice for herpes genitalis. Oral
therapy speed up the healing and reduces the frequency of reactivation episodes. By inhibiting
the viral DNA polymerase the drug block DNA synthesis. Transcription is therefore inhibited.
A, B, C, E, F) (see explanation above)

Explanation

Learning objective: identify which step of viral growth cycle is inhibited by acyclovir
Answer: D
The prescribed drug was most likely acyclovir, the drug of choice for herpes genitalis. Oral
therapy speed up the healing and reduces the frequency of reactivation episodes. By inhibiting
the viral DNA polymerase the drug block DNA synthesis. Transcription is therefore inhibited.
A, B, C, E, F) (see explanation above)

18. A 34-year-old man with AIDS presented to the hospital because of fever (103.4 °F), malaise, myalgias, nausea, and diarrhea. The patient had started an highly active antiretroviral therapy three weeks previously. He states that the symptoms were most prominent several hours after each dose and that they seemed to be getting progressively worse with each dose. Physical examination disclosed a fine maculopapular rash over his face, trunk and arms. Which of the following drugs most likely caused the patient's syndrome?

Zidovudine

Ribavirin

Foscarnet

Abacavir

Lamivudine

Oseltamivir

Learning objective: describe the main adverse effects of abacavir.
Answer: D
The patient was most likely suffering from a hypersensitivity reaction to abacavir. This is a multiorgan
systemic illness that occurs in approximately 5-8% of HIV-infected patients who initiate
therapy with abacavir. The abacavir hypersensitivity reaction resembles a delayed
hypersensitivity reaction and it can cause life threatening complications if abacavir is continued
despite progressive symptoms. In addition, among persons who have experienced the abacavir
hypersensitivity reaction, subsequent rechallenge with abacavir following discontinuation can
cause an immediate and potentially fatal reaction.
A, E) These drugs can cause very rarely hypersensitivity reactions.
B, C, F) these drugs are not active against HIV.

Explanation

Learning objective: describe the main adverse effects of abacavir.
Answer: D
The patient was most likely suffering from a hypersensitivity reaction to abacavir. This is a multiorgan
systemic illness that occurs in approximately 5-8% of HIV-infected patients who initiate
therapy with abacavir. The abacavir hypersensitivity reaction resembles a delayed
hypersensitivity reaction and it can cause life threatening complications if abacavir is continued
despite progressive symptoms. In addition, among persons who have experienced the abacavir
hypersensitivity reaction, subsequent rechallenge with abacavir following discontinuation can
cause an immediate and potentially fatal reaction.
A, E) These drugs can cause very rarely hypersensitivity reactions.
B, C, F) these drugs are not active against HIV.

19. A 34-year-old woman with AIDS had been following an antiretroviral therapy which includes zalcitabine and stavudine. Which of the following adverse effects could be most likely predicted since it was shared by both drugs?

Nephrolithiasis

Myelosuppression

Hallucinations

Peripheral neuropathy

Altered body fat distribution

Learning objective: describe the adverse effects common to zalcitabine and stavudine.
Answer: D
Peripheral neuropathy is a dose-limiting adverse effect of both zalcitabine and stavudine, that
can occur in up to 30% of patients. It is slowly reversible upon the prompt discontinuation of the
drug.
A) Nephrolithiasis is a potential adverse effect of indinavir, not of zalcitabine and stavudine.
B) Myelosuppression is a typical adverse effect of zidovudine. Zalcitabine and stavudine very
rarely cause myelosuppression.
C) Zalcitabine and stavudine easily enter the CNS, but hallucinations are not reported.
E) Altered body fat distribution is a typical adverse effect of protease inhibitors. Zalcitabine and
stavudine do not cause this effect.

Explanation

Learning objective: describe the adverse effects common to zalcitabine and stavudine.
Answer: D
Peripheral neuropathy is a dose-limiting adverse effect of both zalcitabine and stavudine, that
can occur in up to 30% of patients. It is slowly reversible upon the prompt discontinuation of the
drug.
A) Nephrolithiasis is a potential adverse effect of indinavir, not of zalcitabine and stavudine.
B) Myelosuppression is a typical adverse effect of zidovudine. Zalcitabine and stavudine very
rarely cause myelosuppression.
C) Zalcitabine and stavudine easily enter the CNS, but hallucinations are not reported.
E) Altered body fat distribution is a typical adverse effect of protease inhibitors. Zalcitabine and
stavudine do not cause this effect.

20. The diagram below depicts a simplified pathway of the viral growth cycle: Which of the steps shown in the pathway is most likely inhibited by fomivirsen?

A

B

C

D

E

F

G

H

I

Answer: D
Fomivirsen is an antisense oligonucleotide that binds to viral mRNA that encodes a gene
regulatory protein for CMV. The binding disrupts mRNA function, so inhibiting early protein
synthesis of CMV.

Explanation

Answer: D
Fomivirsen is an antisense oligonucleotide that binds to viral mRNA that encodes a gene
regulatory protein for CMV. The binding disrupts mRNA function, so inhibiting early protein
synthesis of CMV.