Antiviral Agents
Characteristics of Viruses
Viruses cause a variety of conditions in living organisms.
Each virus consists of a single virus particle containing either DNA or RNA enclosed in a protein coat.
To replicate and carry on metabolic processes, a virus must enter a host cell.
The replication process of a virus occurs within the host cell, leading to the death of the host cell and the release of new virus particles into the body.
Developing effective antiviral drugs poses challenges because they must destroy the virus without harming the human host’s cells.
Interferons are proteins released by the host that act to prevent viral replication, providing a defense mechanism against infections.
Stages of Virus Replication
Step A: Virus Adherence
A virus adheres to the surface of the host cell.
Step B: Virus Entry
The virus enters the host cell through a process known as pinocytosis.
Step C: Coat Shedding
The virus sheds its protein coat once inside the cell.
Step D: Replication of Viral Nucleic Acids
The viral nucleic acids (either DNA or RNA) are replicated inside the host cell.
Step E: Synthesis of Viral Proteins and Capsid
Viral proteins, including those that will form the capsid, are synthesized.
Step F: Assembly of New Virions
New virus particles (virions) are assembled.
Step G: Release
The new virions are released from the host cell, often causing the cell to die.
Antivirals Across the Lifespan
Children
Children are very sensitive to the effects of most antiviral drugs.
Many antiviral medications have not been proven safe and effective for pediatric use.
Adults
It is crucial to understand that antivirals are specifically used for treating viral infections.
Antiviral drugs can have significant adverse effects on fetal development.
Older Adults
Older adults may be more susceptible to the adverse effects of antivirals.
Caution is needed when administering antivirals to patients with hepatic or renal dysfunction.
Agents for Influenza A and Respiratory Viruses
Prevention through vaccination is deemed the best option.
Some antiviral drug therapies are available for treating infections.
Action of Antivirals
They inhibit viral enzymes, slow the spread of the virus, or induce viral death.
Pharmacokinetics
The pharmacokinetics vary depending on the specific drug used.
Contraindications and Cautions
Oseltamivir: Use with caution in individuals with renal dysfunction.
Antiviral use during pregnancy or breastfeeding requires careful consideration.
Adverse Effects
Adverse effects may arise, linked to effects on dopamine levels in the body.
Drug–Drug Interactions
Caution should be observed with nasal influenza vaccines in combination with neuraminidase inhibitors.
Question #1
Statement: Treatment of a viral infection is difficult without serious toxic effects for the host.
True/False: True
Rationale: Since a virus must enter human cells to survive, treating viral infections often leads to serious toxic effects for the host.
Agents for Herpes and Cytomegalovirus
Action
These agents inhibit viral DNA replication by competing with viral substrates, forming shorter and ineffective DNA chains.
Pharmacokinetics
Pharmacokinetics varies with specific drugs used.
Contraindications and Cautions
Some antiviral drugs are highly toxic; extreme caution is required for patients who are pregnant or lactating.
Known allergies, renal disease, and CNS disorders are significant cautions.
Adverse Effects
Common adverse effects include nausea, vomiting, headache, depression, paresthesia, neuropathy, rash, and hair loss; renal dysfunction is also a concern.
Drug–Drug Interactions
Be cautious when prescribing nephrotoxic drugs and zidovudine concurrently with herpes antivirals.
Agents for HIV and AIDS
Antiretroviral Agents
Include various classes:
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Nucleoside reverse transcriptase inhibitors (NRTIs)
Protease inhibitors
Fusion inhibitors
CCR5 coreceptor antagonists
Integrase strand transfer inhibitors
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Action
They bind directly to HIV reverse transcriptase, blocking both RNA- and DNA-dependent DNA polymerase activities.
Pharmacokinetics
Rapidly absorbed from the gastrointestinal (GI) tract, metabolized in the liver, and excreted in urine and/or feces.
Contraindications and Cautions
Caution is exercised during pregnancy and lactation.
Adverse Effects
These medications have gastrointestinal effects, and may cause dizziness, blurred vision, headache, or flu-like syndrome which may relate to the underlying disease.
Drug–Drug Interactions
Notable interactions include:
Delavirdine with antiarrhythmics, clarithromycin, anti-TB drugs, and other medications.
Efavirenz interactions with midazolam and rifabutin, among others.
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Action
Compete with naturally occurring nucleosides that viruses utilize to build DNA chains.
Pharmacokinetics
Generally rapidly absorbed from the GI tract, metabolized by the liver, and excreted mainly via the urine.
Contraindications and Cautions
Cautions include pregnancy, breastfeeding, hepatic dysfunction, and potential for bone marrow suppression.
Adverse Effects
Include hypersensitivity reactions, pancreatitis, hepatomegaly, neurological issues, and bone marrow suppression.
Protease Inhibitors
Action
Protease inhibitors block the activity of protease, which is essential for HIV to fuse with host cells and inject itself.
Pharmacokinetics
Varies by drug but generally, these agents have different absorption and metabolism profiles.
Contraindications and Cautions
Caution is warranted in those with hepatic dysfunction or those being treated with antidiabetic agents.
Adverse Effects
Can cause gastrointestinal effects, changes in liver function, increased cholesterol and triglyceride levels, fat redistribution, and Stevens-Johnson syndrome.
Fusion Inhibitor
Action
Prevents the fusion of the HIV virus with the human cell membrane.
Pharmacokinetics
Administered subcutaneously, metabolized in the liver, and not primarily excreted.
Contraindications and Cautions
Hypersensitivity, pregnancy, or breast feeding, and individuals with lung disease.
Adverse Effects
May experience insomnia, depression, peripheral neuropathy, nausea, diarrhea, pneumonia, and site reaction from injections.
CCR5 Coreceptor Antagonist
Action
Blocks the receptor site on host cell membranes that HIV requires for entry.
Pharmacokinetics
Rapidly absorbed from the GI tract, metabolized in the liver, and primarily excreted through feces.
Contraindications and Cautions
Known drug allergies, breastfeeding, liver disease.
Adverse Effects
May cause severe hepatotoxicity, CNS effects, and upper respiratory infections (URIs).
Drug–Drug Interactions
Can alter serum levels and increase toxicity when interacting with cytochrome P-450 inhibitors and inducers as well as St. John’s wort.
Integrase Strand Transfer Inhibitors
Action
Inhibit the activity of the integrase enzyme needed for viral replication.
Pharmacokinetics
Rapidly absorbed from the GI tract, metabolized by the liver, and excreted in urine and feces.
Contraindications and Cautions
Known hypersensitivities; risks associated with rhabdomyolysis, myopathy, and pregnancy.
Adverse Effects
Potential liver failure, renal impairment, suicidal ideation, headaches, dizziness, insomnia, and weight gain.
Drug–Drug Interactions
Serum levels may decrease if taken in conjunction with rifampin or St. John’s wort.
Question #2
Scenario: A patient with herpes simplex is prescribed an antiviral medication.
Teaching Points:
Use absorbent pads when applying the drug topically to reduce exposure risk.
Expect GI upset, nausea, and vomiting as potential adverse effects.
Start taking the medication promptly for improved effectiveness of antiviral action.
Adhere to dosing protocols to enhance antiviral efficacy.
Answer to Question #2
Correct Answer: C. Start taking the medicine as soon as possible to improve effectiveness of antiviral activity.
Rationale: Rapid administration of the drug following diagnosis is crucial for maximizing antiviral effectiveness.
Question #3
Scenario: A patient with HIV reports pain at the injection site. What type of drug is likely being used?
Options:
Integrase inhibitor
Fusion inhibitor
Reverse transcriptase inhibitor
Protease inhibitor
Answer to Question #3
Correct Answer: A. Fusion inhibitor
Rationale: Fusion inhibitors like enfuvirtide (Fuzeon) are administered subcutaneously, which can lead to injection site reactions, while other drug classes are taken orally.
Anti-Hepatitis B Agents
Action
These agents inhibit reverse transcriptase in hepatitis B, leading to DNA chain termination.
Pharmacokinetics
Rapid absorption from the GI tract, liver metabolism, and urinary excretion.
Contraindications and Cautions
Known allergies, renal impairment, severe liver disease, pregnancy, and HIV infection with tenofovir alafenamide.
Adverse Effects
Side effects can include headache, dizziness, nausea, diarrhea, elevated liver enzymes, hepatomegaly with steatosis, and renal impairment.
Drug–Drug Interactions
Heightened risk of renal toxicity if taken with other nephrotoxic drugs.
Anti-Hepatitis C Agents
Action
The mechanism of action varies significantly between agents.
Pharmacokinetics
These agents are readily absorbed from the GI tract, metabolically processed in the liver, and subsequently excreted via urine and/or feces.
Contraindications and Cautions
Known allergies, severe liver disease, pregnancy, and coinfection of HIV and HCV.
Adverse Effects
Common adverse effects include headache, fatigue, nausea, diarrhea, rash, and severe skin reactions.
Drug–Drug Interactions
Toxic effects or therapeutic loss may occur with other protease inhibitors or if combined with St. John’s wort.
Locally Active Antiviral Agents
Actions
Function by interfering with normal viral replication and metabolic processes at a local infection site.
Indications
Specifically prescribed for local viral infections.
Contraindications and Cautions
Not absorbed systemically; caution is needed with known allergies to topical drugs, and avoidance of application on open wounds.
Adverse Effects
Local burning, stinging, and discomfort may occur with topical applications.
Question #4
Question: Which antiviral drugs are not absorbed systemically?
Options:
Anti-hepatitis B agents
Locally active antiviral agents
Nucleoside agents
Fusion inhibitors
Answer to Question #4
Correct Answer: B. Locally active antiviral agents
Rationale: Locally active antiviral medications do not get absorbed systemically, necessitating caution in patients with known sensitivities to topical drugs.