Week 3- Antivirals, vaccines, antiretrovirals Flashcards
Describe viral replication.
i) A virus cannot replicate on its own ii) “Obligate intracellular parasites” iii) It must attach to and enter a host cell iv) It then uses the host cell’s energy to synthesize protein, DNA, and RNA v) Viral replication peaks at or before clinical symptoms appear
Why are viruses difficult to kill?
- Viruses are difficult to kill because they live inside our cells
- Any drug that kills a virus may also kill our cells
Describe viral replication steps.
- Adsorption to and penetration into susceptible cells
- Uncoating of viral nucleic acid
- Synthesis of early regulatory proteins
- Synthesis of RNA or DNA
- Synthesis of late structural proteins
- Assembly of viral particles
- Release from the cell
Describe key characteristics of antiviral drugs.
- Able to enter the cells infected with virus
- Interfere with viral nucleic acid synthesis and/or regulation
- Some agents interfere with ability of virus
- to bind to cells
- Some agents stimulate the body’s immune system
Antiviral Medication Agents- antiviral and antiretroviral
- Antiviral agents
- Used to treat infections caused by viruses containing DNA / RNA
- Nucleoside Analogues
- Other antivirals for influenza
- Antiretroviral agents
- Used to treat infections caused by retroviruses e.g. HIV, the virus that causes AIDS
- Have RNA uses reverse transcriptase, integrase, and protease to make DNA
Nucleoside Analogues
-Pharmacodynamics
- Used mainly to treat herpes infection
- ALL result in inhibition of DNA synthesis
Nucleoside Analogues
-Different drugs
- Acyclovir (Zovirax)
- Requires activation by thymidine kinase – selectively activated in infected cells
- Valcyclovir (Valtrex)
- Converted to acyclovir after oral administration
- Famciclovir (Famvir)
- Converted to active penciclovir which is activated by thymidine kinase in infected cells
- Ribavirin (Virazole)
- Active against a wide range of DNA and RNA viruses (Influenza A & B, parmyxoviruses, HCV, and HIV
- Key role when combined with Interferon for treatment of HCV
Nucleoside Analogues
-Pharmacokinetics
- Absorption
- Acyclovir poorly orally absorbed (15 – 20%)
- Famciclovir is absorbed in the intestine for conversion to active form penciclovir
- Valacyclovir is a prodrug and is 54% as bioavailable as acyclovir
- Metabolism and Excretion
- Acyclovir, famciclovir, valacyclovir 90% in urine as unchanged drug
- Liver metabolizes the remaining 10%
Nuceloside Analogues
-Pharmacotherapeutics: Precautions and Contraindications
- Precautions and contraindications
- Adjust to Cr Cl if renal impairment
- Acyclovir, Valacyclovir, Famciclovir can be used during pregnancy
- Acyclovir and Valacyclovir are preferred as most is known
- Some acyclovir is excreted in breast milk but low risk
- Acyclovir approved for children over 2 years
Nuceloside Analogues
-Pharmacotherapeutics: ADRs
- Acyclovir: n & v, headache, skin rash, diarrhea – similar for valcylovir but more common
- Can cause renal dysfunction – more common in older or renal dysfunction
- Famciclovir: headache, dizziness, somnolence, paresthesia
- Drug interactions - minimal
- Clinical use and dosing – RENAL FUNCTION
Amount of dosages each day
- Acyclovir
- Famciclovir
- Valacyclovir
- Acyclovir – 3 – 5 times daily
- Famciclovir – 2 – 4 times daily
- Valacyclovir – 1-2 times daily
Nucleoside Analogues
-Patient Education
- Food does not alter absorption
- Take with a full glass of water
Considerations for Nucleoside Analogues in Primary Care.
- Don’t cure but shorten the duration, decrease the severity, and reduce incidence of sequelae
- HSV – Genital herpes
- Herpes zoster (shingles)
- Within 3 days
- Varicella (chicken pox)
- 20 years and older or immunocompromised (24 hours)
- Gingivostomatitis in children
- Selection is based on cost and convenience
Describe influenza. Type A compared to Type B.
- Serious respiratory tract infection
- Major cause of morbidity and mortality worldwide
- 3 – 11% of the population in the US is affected.
- Caused by influenza viruses, which are highly variable and undergo constant evolution (mutation)
- Type A – more infectious than B
- Type B
What are classifications of anti-virals used for influenza?
- Adamantanes
- Neuraminidase Inhibitors
- Cap-dependent endonuclease inhibitors
Antivirals for Influenza
-Adamantanes
- Adamantanes
- Amantadine and rimantadine effective against Influenza A – HIGH levels of resistance (99%)
Antivirals for Influenza
-Neuraminidase Inhibitors
- Oseltamivir (Tamiflu)
- Zanamivir (Relenza)
- Peramivir (Rapivab) (2014)
- Active against both A and B
Neuraminidase Inhibitors
-Pharmacodynamics/MOA
- Prevent viral replication by interfering with neuraminidase, an enzyme needed for enabling a virus to leave the infected host cell.
- Prevents viral spread across respiratory track mucous membranes.
Neuraminidase Inhibitors
-Oseltamivir, zanamivir, baloxavir, and peramivir
- Should be started within 48 hours of onset of symptoms
- Can be used for prophylaxis (osteltamivir and zanamivir)
- CDC - Seasonal Influenza (Flu) - Antiviral Medications: Summary for Clinicians
- Know guidelines for treatment and prophylaxis
- Know guidelines for who are recommended for antiviral treatment
- Shorten the duration of illness (1-2 days)
- Mitigate severity
- Decrease viral shedding and spread
Antivirals for influenza
-Cap-dependent endonuclease inhibitor
- Cap-dependent endonuclease inhibitor
- Interferes with viral RNA transcription and blocks virus replication
- Baloxavir (Xofluza) A & B (2018)
Differentiate between vaccination and immunization.
- Vaccination: act of administering a vaccine
- Immunization: development of immunity to a pathogen
What is a vaccine?
- Suspension with antigenic molecules derived from a microorganism given to stimulate an immune response to an infectious disease
Describe 4 different types of vaccines.
- Weakened or killed microbe
- Inactivated toxins
- Toxoids derived from microbes
- Immunologically active surface markers extracted or copied from microbes