Module 6 Section 3 (Antifungals, Antivirals, Antiretrovirals) Flashcards
What is the difference between antifungal and antiviral drugs?
An antifungal drug refers to any medication used to treat a fungal infection, while antivirals treat viral infections.
These drugs exploit the differences between human and fungals cells, and human and viruses, respectively.
- The development of these agents led to vast improvements in the treatment of illnesses such as systemic fungal infections, the flu, and HIV.
True of false: the incidence of serious fungal infections continues to increase, particularly in patients who have HIV or who are required to take immunosuppressive drugs.
True
List 3 antifungals.
1) Amphotericin B
2) Echinocandins
3) Imidazoles
What is Amphotericin B? Discuss the mechanism of action and adverse effects
Amphotericin B is the drug of choice for therapy of severe fungal infections.
- It is poorly absorbed from the GI tract and must therefore be administered intravenously for systemic fungal disease.
Mechanism of action: Amphotericin B binds to ergosterol, a steroid in the outer membrane of susceptible fungi that is not present in mammalian cells.
- Evidence suggests that amphotericin B forms aggregates that sequester ergosterol from the lipid bilayers, thereby resulting in fungal cell death.
Adverse Effects: it causes a variety of adverse effects, with kidney toxicity being the major dose-limiting toxicity.
What are Echinocandins? Discuss the mechanism of action and adverse effects
These antifungals are also only available intravenously for systemic fungal infections.
Mechanism of action: they act by inhibiting 1,3-beta-D-glucan synthesis, an essential component of the fungal cell wall.
- Without 1,3-beta-D-glucan, the fungi loss structural integrity of the cell wall.
Adverse effects: these drugs are well tolerated and adverse effects are minimal.
- They are contraindicated in pregnancy.
What are Imidazoles (Azoles)? Discuss the mechanism of action and adverse effects
The imidazoles (e.g. ketoconazole, fluconazole, etc.) are effective for systemic or topical fungal infections (e.g. ringworm). - A number of these agents (e.g. miconazole) are available as over-the-counter drugs for the treatment of candidiasis (i.e. yeast infections).
Mechanism of action: these antifungals all inhibit a fungal cytochrome P450, thereby inhibiting ergosterols synthesis.
- The selective toxicity of the azoles lies in their higher affinity for the fungal P450 than the human P450s.
Adverse effects: varies depending on the specific imidiazole, however, a concern for all drugs in this class is hepatotoxicity.
What is a virus?
A virus is a small, infectious agent that is only able to multiply within the living cells of other organisms, including animals, plants, and bacteria.
Viruses can be deadly, and for this reason, there is a great need for additional and more effective antiviral drugs.
True or false: viral replication requires several steps. Drugs can act at any of the steps in the viral life cycle.
True
What is influenza?
Influenza, commonly referred to as the flu, is an extremely contagious respiratory illness caused by the influenza virus.
It is one of the top 10 causes of death in Canada.
What are the 2 drugs used to treat the flu?
Amantidine: this drug inhibits the uncoating of viral RNA within infected cells, thereby preventing viral replication. It’s used for prevention of influenza due to the influenza A virus.
- Unfortunately, viral resistance is a problem.
Oseltamivir (Tamiflu): it's a neuraminidase inhibitor, which is an enzyme that allows the spread of the virus from cell to cell. - Drugs of this class prevent neighbouring cells from being infected with the virus.
Infection with the herpes simplex virus (HSV) results in a recurrent infection of the mouth and genitals. What drug is used to treat this? How does it work?
Acyclovir is the drug of choice for treatment of serious HSV infections.
Long-term use of acyclovir by oral administration for prevention will markedly decrease the frequency of recurrence of genital herpes.
Acyclovir is also useful in combating infections due to varicella-zoster virus (VSV), the virus that causes chickenpox and shingles.
Acyclovir is taken up into infected cells, where the virus activates the drug.
- Active acyclovir then inhibits viral DNA replication. Thus, acyclovir is selective for cells that are infected with the virus.
What are retroviruses?
Retroviruses are a group of viruses that replicate through the process of reverse transcription.
What is the life cycle like for retroviruses?
The life cycle of retroviruses is similar to that of ‘normal’ viruses, however in most viruses, the viral DNA is transcribed into RNA, which is then used to make proteins.
1) Retroviruses work differently, in that the viral RNA is reverse-transcribed into DNA, which is then integrated into the host cell’s DNA.
2) The host cell then treats the viral DNA the same as its original DNA, making viral proteins as well as the regular host cell proteins.
- An example of a retrovirus is Human Immunodeficiency Virus (HIV), which is treated using antiretroviral agents.
Antiretroviral drugs are classified based on their mechanisms of action. That is, the site of the retroviral life cycle it blocks. Discuss the 4 different MOA for these drugs.
1) Nucleoside and Nucleotide Reverse Transcriptase Inhibitors: drugs from this class block the transcription of RNA and the synthesis of new DNA.
- These drugs slow the progression of HIV infection and prolong survival.
2) Protease Inhibitors: during the final maturation of the HIV virus, the virus is associated with proteins that become immature budding particles.
- Viral protease cleaves these budding proteins to form the final structural proteins of the mature virus core.
- Inhibiting these viral proteases prevents the mature virus core from forming.
3) Integrase Inhibitors: drugs in this class are inhibitors of viral integrase, which is the enzyme responsible for integrating viral genetic material into the DNA of the host cell.
- Therefore, they prevent the final step in the transfer of the virus into the host DNA.
4) Combination Therapy for the Treatment of HIV: optimal therapy for HIV infection is multiple drug therapy with two nucleoside analogues, a protease inhibitor, and other classes of agents.
- The drugs are used in the following circumstances:
• Patients with HIV infection. The aim is to lower the viral load to near zero. Treatment is for life.
• Prophylactic use when a person has been exposed to the virus and is at risk of contracting the disease.
• Prevent vertical transmission from mother to neonate during pregnancy.
Which one of the drugs listed is commonly used in the treatment of HIV?
a) Protease inhibitor
b) Amantadine
c) Acyclovir
d) Neuraminidase inhibitor
a) Protease inhibitor
