Antiviral Drugs

Question 1

Gamma Globulin (IgG)

Answer 1

It is assumed that it blocks the attachment of the virus particles to the host cell
Primarily to prevent infections

Question 2

Amantadine and rimantadine

Answer 2

Synthetic antiviral compound.
Amantadine can concentrate in the lysosomes and prevent acidification of the vesicle thus inhibits uncoating of the virus. Targets M2 protein
Clinical use:
Given orally for prevention and treatment of early infection of influenza A virus. Because it blocks an early event during the viral replication cycle, amantadine
must be given before exposure to the virus or within 24-48 hours of onset of symptoms.

Question 3

Neuraminidase inhibitors

Answer 3

Inhibit neurominidase (sialidase) of influenza A and B. Influenza virus neuraminidase is a surface glycoprotein that catalyzes the cleavage of the linkage between a terminal sialic acid and adjacent sugar residue, which promotes the spread of virus in the respiratory tract. Should be given within 48 hr of the onset of flu symptoms

Question 4

Acyclovir (Zovirax)

Answer 4

A prodrug. It requires Herpes viral thymidine kinase for activation. Acyclovir triphosphate inhibits herpes virus DNA replication in two ways.

1. It competitively inhibits viral DNA polymerase, thus inhibits the incorporation of deoxynucleotide triphosphate into viral DNA.
2. Any acyclovir that is incorporated into the viral DNA chain will terminate further DNA chain elongation.

Question 5

Foscarnet (phosphonoformic acid; Foscavir)

Answer 5

Foscarnet selectively inhibits the viral-specific DNA polymerase and reverse transcriptase at the pyrophosphate-binding site. Unlike acyclovir or ganciclovir, intracellular phosphorylation is not required for foscarnet activity, which makes it effective against herpes simplex virus strains that are deficient in thymidine kinase.
Clinical use: Foscarnet is currently used for the treatment of cytomegalovirus retinitis in patients with AIDS. It is also used for the treatment of acyclovir-resistant mucocutaneous herpes simplex.

Question 6

Ribavirin (Virazole, Rebetol)

Answer 6

Clinical use:
Ribavirin is used in the United States as an aerosol in the treatment of severe lower respiratory tract infections due to respiratory syncytial virus.
1998, FDA approved Ribavirin oral capsules in combination with interferon a for the treatment of chronic hepatitis C.

Question 7

Zidovudine (AZT; Retrovir)

Answer 7

Zidovudine or Azidothymidine or AZT was the first drug

licensed for use in HIV treatment (1987 by FDA).

Question 8

Saquinavir (Invirase), ritonavir (Norvir), indinavir (Crixivan),
nelfinavir (Viracept)

Answer 8

These drugs bind and inhibit viral protease, thus preventing cleavage of viral protein precursors to form capsids and viral enzymes for final assembly of viral particles. Given orally.

Question 9

Drug regimens for treating HIV infection

Answer 9

Preferred drug regiments:Two nucleoside reverse tanscriptase inhibitors (NRTIs) plus one protease inhibitor. Or: two NRTIs with a NNRTI

Question 10

Newest anti-HIV agent: Fuzeon (enfuvirtide)

Answer 10

Binds the gp41 subunit of the viral envelope glycoprotein and interferes with the entry of HIV-1 into cells.
Inhibits fusion of viral and cellular membranes.

Question 11

Fungal infections: MYCOSES

Answer 11

Superfical infections affecting skin, nails, scalp or mucous membranes.
- Caused by dermatophytes or yeast (Candida albicans)
Systemic infections affecting deeper tissues and organs.

Question 12

Amphotericin B Basics

Answer 12

Broad-spectrum antifungal agent.
A polyene antibiotic produced by the actinomycete Streptomyces nodusus.
Large ring structure with both hydrophobic and hydrophilic regions.
Binds to sterols (ergosterol) in the fungal
membrane, leading to channel formation
and the loss of intracellular constituents

Question 13

Amphotericin B Selectivity:

Answer 13

High affinity to ergosterol (fungal membrane sterol)

Low affinity to cholesterol (human cell membrane sterol)

Question 14

Amphotericin B Clinical use

Answer 14

The premier drug used to treat the most severe systemic mycoses (e.g. blastomycosis, histoplasmosis, cryptococcal meningitis).
Poorly absorbed: Given orally for fungal superinfection of the GI
Slow i.v. for serious systemic mycosis Intrathecally for meningitis

Question 15

Amphotericin B = amphoterrible

Answer 15

Side effects: Numerous and often serious
renal toxicity (80%)
General toxicity: chills, fever, headache, nausea and vomiting.
Long-term toxicity: amphotericin B nephropathy

Question 16

Griseofulvin

Antibiotic produced by Penicillium griseofulvin

Answer 16

It binds to microtubules, causes interference

with mitotic spindle formation in dividing cells, and blocks mitosis.

Question 17

Griseofulvin

Answer 17

Clinical use: Narrow-spectrum, against dermatophytes.

The drug of choice for extensive and intractable fungal infections of the skin, including athlete’s foot.

Question 18

Azoles

Answer 18

Imidazoles: The 5-membered azole nucleus contains 2 nitrogen: Ketoconazole, miconazole, and clotrimazole
Triazoles: The 5-membered azole ring contains 3 nitrogen: Fluconazole and itraconazole
Mechanism: Inhibits ergosterol synthesis, leading to damaged and leaky cell membrane.

Question 19

Fluconazole (generic, Diflucan): Triazole

Answer 19

Broad-spectrum drug approved by FDA in 1990.
Effective in the treatment of infections with most candida species.
Equal or superior to ketoconazole and clotrimazole in various candidiasis.
Single oral dose approved for the treatment of vaginal cadidiasis in 1994.
For treating fungal meningitis and follow-up therapy (cryptococcal megingitis)
Reaches high concentrations in CNS.

Question 20

Voriconazole, a derivative of fluconazole

Answer 20

2002: approved in the US; Active against molds, such as aspergillus.
Used as primary treatment of invasive aspergillosis

Question 21

Itraconazole (Sporanox) Triazole

Answer 21

Oral, broad-spectrum antifungal agent.
Hydrophobic, requires a low gastric pH for absorption.
Effective alternative to amphotericin B for certain systemic mycoses.

Question 22

Ketoconazole: Imidazole

Answer 22

Broad-spectrum effective against fungi causing systemic and superficial infections
Given orally for chronic mycosis. Requires low gastric pH for absorption.
Not useful for treating fungal meningitis

Question 23

5-Flucytosine

Answer 23

Clinical uses: Given orally. Active against a limited range of systemic fungal infections. Used in combination with
amphotericin B for serious systemic mycosis, such as
cryptococcal menigitis.
Side effects: Bone marrow suppression and GI distress.

Question 24

Caspofungin (Cancidas)

Glucan synthase inhibitors: The echinocandins

Answer 24

Mechanism of action: Inhibits the synthesis of a major fungal cell wall component, beta (1,3)-D-glucan (not present in mammalian cells).
Clinical uses:
For the treatment of invasive aspergillosis in refractory patients (FDA in 2001)
For the treatment of esophageal candidiasis (FDA in 2002)
Slow intravenous infusion