Antivirals and Antifungals Flashcards
► Large DNA virus spread by direct contact due to viral shedding from saliva or blood
■Infection through broken skin and inoculates nerve tissue.
- remain latent for long periods of time without reproducing and avoid
the immune response.
■ Immune deficiency states, stress, irritating agents reactivate latent virus.
■ Occurs on keratinized tissue.
Herpesvirus
Which HSV is primarily oral?
HSV-1
Which HSV is primarily genital?
HSV-2
Is HSV DNA or RNA?
DNA
The following treat ____:
* Acyclovir, famciclovir, valacyclovir
* Famciclovir and valacyclovir better oral
bioavailability than acyclovir
* Longer half-life, dosed less frequently
* More expensive
* Excellent safety for all three
medications
* Selectively converted to active compounds
within virally infected cells
* Acyclovir is the only intravenous agent
Herp
■Drugs are structural analogs of nucleosides-building blocks of DNA & RNA.
■Good anti-viral drugs- block viral nucleic acid synthesis.
■ Are selectively toxic prodrugs. Only viruses with viral thymidine kinase are affected
DNA NUCLEOSIDE ANALOGS:
RNA retrovirus:
Transforms its RNA into DNA, reversing the
natural process
Requires reverse transcriptase (viral DNA
polymerase)
■ Main target: T-cells (CD4) and
macrophages
● host- where the virus harbors and replicates
■ In the host cell cytoplasm:
1st Step: Viral RNA transcribed into a double-
stranded DNA
2nd Step: Viral DNA incorporated into T-cell’s DNA
HIV
Is HIV DNA or RNA virus?
RNA
ARE NRTIs used alone or paired with another NRTI?
Pairs
- Incorporated into viral RNA stops
transcription to DNA - Interrupt the virus from duplicating
- Nucleoside analogs converted by host
cell thymidine kinase to nucleotides
Nucleoside reverse transcriptase inhibitors
What NRTI is most often utilized?
Lamivudine
► Directly binds/blocks reverse transcriptase enzyme
Disadvantages:
* Highest incidence of resistance ~ 18% * 1 in 5 after first year!
* High cross-resistance in entire class* Requires only a single mutation
* CYPP450 Inducers
Advantages:
* Daily dosing. (Long Half lives)
* No interference with food
* Do not increase TG; less severe side effects vs. PI’s
* Can use in renal disease
Block the infection of new cells by HIV
* Delvaridine (Rescriptor, DLV)
* Efravirenz (Sustiva, EFV)
* Nevirapine (Viramune, NVP)
Non-nucleoside reverse transcriptase inhibitor
- Blocks last stage of virus production – new protein production
- Prevents HIV Assembly
- All are CYP 3A4 substrates
Often “boosted” - Strong inhibitors of CYP3A4 added to
boost levels of PI’s/NNRTI’s - Ritonavir (Norvir) and cobicistat
(Tybost) are strong CYP3A inhibitors
that are added - Less frequent dosing, same efficacy
- Less resistance:
- “Unboosted” resistance ~ 5%/yr
- “Boosted” resistance < 1%/yr
Protease Inhibitors (PIs)
Adverse Effects: - Increase TG, lipodystrophy,
hyperglycemia
Oral adverse effects: - Fosamprenavir (Lexiva) - Perioral
numbness (lips), taste changes - Atazanavir (Reyataz) - Dental
(tooth) pain, taste changes - Ritonavir (Norvir) - Taste changes
Protease Inhibitors (PIs)
What are the main side effects for PIs
Lipodystrophy, increase TG, hyperglycemia
- Bind integrase enzyme; Block viral DNA
integration into host cell DNA - No major side-effects
- Preferred for initial therapy
- High efficacy
- Low adverse effect profile
- Minimal drug interactions
- Raltegravir (Isentress, RAL)
- Dolutegravir (Tivicay, DTG)
- Elvitegravir (Stribild or Genvoya,
EVG) - Bictegravir (Biktarvy)
Integrase Strand Transfer Inhibitors
(INSTIs)
If the drug ends in -navir, what is it?
Protease inhibitors
Obligate Intracellular Parasite
»Replicates inside host
respiratory cells
Two major surface
glycoprotein antigens
* Hemagglutinin (H)
* cell attachment
* Neuraminidase (N)
* maturation and release
Influenza A
- FDA indications: Prophylaxis and treatment of influenza A & B
- Mechanism: Prevent the release of new virions from the cell surface
- Binds the surface antigen neuraminidase, on influenza A & B viruses
preventing release of new viruses. - Neuraminidase releases virus from cell surface
- Oseltamivir (Tamiflu)
- Zanamivir (Relenza)
- Peramivir (Rapivab)
Neuraminidase Inhibitors (NAIs)
Inhibits initiation of mRNA
transcription of viral RNA
Endonuclease inhibitors
How is selective toxicity achieved w/ fungi?
Targeting ergosterol and chitin
Subgroup of molds that live on skin.Normal inhabitants of skin, contagious, spread by contact. Produce keratinases that dissolve keratin Hyphal filaments penetrate into keratin (stratum corneum) Invades hair shafts & nail beds
►(Tinea) infections affect keratinized tissues – skin, nails, hair, etc.
Dermatophyte
»Terbinafine (Lamisil oral or topical)
»Naftifine (Naftin)
* Binds/inhibits squalene epoxidase
* Squalene precursors build up and are also
toxic aiding toxicity
* Requires actively growing fungi
* Fungicidal against Dermatophytes Only.
* Weak fungistatic activity against Candida
* Little drug interaction potential
* Few side-effects
Allylamines
: Most common fungal infection in mouth
Oropharyngeal (Tx: 14-days duration)
* Clotrimazole troches (one 10-mg troche dissolved slowly five times daily) * difficult to adhere, poor choice in xerostomia, contains sucrose, DDIs in HIV, taste alterations
* Miconazole mucoadhesive buccal tabs (50mg 1xdaily apply to mucosal surface
over canine fossa)* Daily dosing, tasteless & sugar free, more expensive, best patient compliance.
* Nystatin swish and swallow (400,000 to 600,000 units four times daily) * not always palatable, contains sucrose, concerning for dental caries over prolonged time periods
* Good in xerostomia, good in HIV, co-dispense lozenge if has appliances
Esophagitis
* Fluconazole - 400 mg as a loading dose and then 200 to 400 mg daily for 14 to 21
days given orally
Candida
: may have Candida
superinfection
* Topical barriers keep moisture out,
prevent reoccurrences.
* Barrier creams (eg, zinc oxide paste) or
petrolatum
* Clotrimazole ointment BID x1-3wks,
if positive fungal
Angular cheilitis
