Farmakologi antivirus 1 (Kuliah 8)

Summary

This lecture covers antiviral drugs and their mechanisms of action against various viruses like herpes, HIV, influenza, and hepatitis. It explains how viruses are intracellular parasites and rely on the host's metabolism for replication. The lecture discusses specific antiviral drugs such as acyclovir, ganciclovir, and interferons, highlighting their role in inhibiting viral replication at different stages, from attachment to release. Emphasis is placed on drugs for treating herpes simplex, HIV, and CMV infections, including their pharmacokinetics, side effects, and resistance patterns.

Takeaways

• 😀 Antivirus medications were developed in the 1950s and have evolved over the past 60-70 years.
• 😀 Viruses are obligate intracellular parasites, meaning they require a host cell to replicate.
• 😀 Antivirus medications work by inhibiting different stages of viral replication within the host cell.
• 😀 HIV, herpes, and influenza are among the viruses treated with antiviral medications, with specific drugs targeting each virus type.
• 😀 For herpes simplex and varicella-zoster, antiviral drugs like acyclovir, valacyclovir, and famciclovir are used to block viral replication.
• 😀 Acyclovir is a guanosine analog that needs activation through phosphorylation to become effective in inhibiting viral DNA synthesis.
• 😀 Resistance to acyclovir can occur due to deficiencies in the host’s viral enzymes like thymidine kinase or DNA polymerase.
• 😀 Ganciclovir is used to treat cytomegalovirus (CMV) infections, especially in immunocompromised patients, and is available in both IV and intraocular forms.
• 😀 Foscarnet, a non-nucleoside antiviral, inhibits viral polymerase and is used for herpes and CMV infections but can cause nephrotoxicity.
• 😀 Trifluridine is a topical antiviral for treating eye infections caused by herpes simplex virus (HSV) and is toxic for systemic use.

Q & A

What is the primary characteristic of a virus, as explained in the script?

A virus is described as an obligate intracellular parasite, meaning it must live inside a host cell to replicate and survive. It relies on the host's metabolism to reproduce.

What are some examples of antiviral drugs mentioned for treating herpes simplex and varicella-zoster?

The antiviral drugs mentioned for herpes simplex and varicella-zoster are acyclovir, valacyclovir, famciclovir, ganciclovir, and foscarnet.

How do antiviral drugs function in inhibiting the replication of viruses?

Antiviral drugs block various stages of viral replication, such as attachment to the host cell, entry, uncoating, synthesis of nucleic acids, protein synthesis, and virus release.

What is the mechanism of action of acyclovir?

Acyclovir is a guanosine analog that requires activation through phosphorylation by viral and host cell enzymes. It inhibits viral DNA synthesis by competing with deoxyguanosine and incorporating into the DNA, halting chain elongation.

What are the potential side effects of acyclovir when used orally?

Oral acyclovir can cause gastrointestinal disturbances such as diarrhea, nausea, and vomiting. It may also lead to headaches and renal issues, especially in high doses or in dehydrated patients.

What is the role of protease inhibitors in HIV treatment?

Protease inhibitors work by blocking the viral enzyme protease, which is essential for the maturation of new viral particles. This inhibits the formation of functional viruses.

Why is it important to adjust the dosage of acyclovir in patients with kidney failure?

Since acyclovir is eliminated via the kidneys, impaired renal function can lead to drug accumulation and increased risk of toxicity. Therefore, the dosage must be adjusted in patients with kidney failure.

What is the significance of valacyclovir in comparison to acyclovir?

Valacyclovir is an ester prodrug of acyclovir. It has better bioavailability, meaning it is absorbed more effectively in the body, and is converted to acyclovir in the liver.

What are the indications for the use of ganciclovir in antiviral therapy?

Ganciclovir is used primarily for cytomegalovirus (CMV) infections, including retinitis, colitis, esophagitis, and infections in immunocompromised patients, such as those undergoing organ transplantation.

What are the side effects associated with foscarnet?

Foscarnet can cause nephrotoxicity (kidney damage), electrolyte imbalances (such as low calcium), and central nervous system effects like headaches and seizures.