Antivirals and Antifungals

Question 1

► 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.

Answer 1

Herpesvirus

Question 2

Which HSV is primarily oral?

Answer 2

HSV-1

Question 3

Which HSV is primarily genital?

Answer 3

HSV-2

Question 4

Is HSV DNA or RNA?

Answer 4

DNA

Question 5

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

Answer 5

Herp

Question 6

■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

Answer 6

DNA NUCLEOSIDE ANALOGS:

Question 7

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

Answer 7

HIV

Question 8

Is HIV DNA or RNA virus?

Answer 8

RNA

Question 9

ARE NRTIs used alone or paired with another NRTI?

Answer 9

Pairs

Question 10

• Incorporated into viral RNA stops
  transcription to DNA
• Interrupt the virus from duplicating
• Nucleoside analogs converted by host
  cell thymidine kinase to nucleotides

Answer 10

Nucleoside reverse transcriptase inhibitors

Question 11

What NRTI is most often utilized?

Answer 11

Lamivudine

Question 12

► 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)

Answer 12

Non-nucleoside reverse transcriptase inhibitor

Question 13

• 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

Answer 13

Protease Inhibitors (PIs)

Question 14

What are the main side effects for PIs

Answer 14

Lipodystrophy, increase TG, hyperglycemia

Question 15

• 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)

Answer 15

Integrase Strand Transfer Inhibitors
(INSTIs)

Question 16

If the drug ends in -navir, what is it?

Answer 16

Protease inhibitors

Question 17

Obligate Intracellular Parasite
»Replicates inside host
respiratory cells
Two major surface
glycoprotein antigens
* Hemagglutinin (H)
* cell attachment
* Neuraminidase (N)
* maturation and release

Answer 17

Influenza A

Question 18

• 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)

Answer 18

Neuraminidase Inhibitors (NAIs)

Question 19

Inhibits initiation of mRNA
transcription of viral RNA

Answer 19

Endonuclease inhibitors

Question 20

How is selective toxicity achieved w/ fungi?

Answer 20

Targeting ergosterol and chitin

Question 21

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.

Answer 21

Dermatophyte

Question 22

»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

Answer 22

Allylamines

Question 23

: 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

Answer 23

Candida

Question 24

: 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

Answer 24

Angular cheilitis

Question 25

MOA: Inhibit cytochrome P450 14-alpha-demethylase to inhibit lanosterol from being made into ergosterol

Answer 25

Azoles

Question 26

: 50 mg (1 tablet) applied to upper gum once daily
for 7-14 days
* Apply in morning after brushing. Alternate sides of mouth with
each application; do not crush, chew, or swallow. Avoid chewing
gum while in place.
* If the tablet does not adhere to gum or falls off within 6 hours
of application, same tablet should be repositioned immediately.
* Exposure time important: goal entirety of waking hours.

Answer 26

Miconazole (Oravig)

Question 27

10mg (1 troche) dissolved slowly 5 times daily for 7-14 days
* Metabolized in liver – 3A4. Contraindicated in liver disease.
* Avoid in combination with benzodiazapines; HIV
* Oral Troche for management of oral candidiasis
* Patient Education: 5 times daily. Swallow the saliva. No eating or drinking for 30min
following medication
* Dissolves over 30 minutes and remains in saliva for up to 3 hours

Answer 27

Clotrimazole (Mycelex):

Question 28

• First Line Drugs for systemic fungal infections
• Fewer drug-drug interactions and expanded spectrum
• Still metabolized via the cytochrome P450 enzyme system
• All azole agents are both metabolized by and slow hepatic cytochrome P450
• Safer side-effect profiles than Amphotericin B or ketoconazole for systemic use
• Hepatotoxicity

Answer 28

Triazoles: Fluconazole

Question 29

• High absorption after oral administration with high distribution into all tissues
• Long half-life (approx. 24hrs) allows for once-daily dosing
• Significant excretion via kidney – dose adjustment when administered to renal impairment
• Strong inhibitor of CYP2C19 and a moderate inhibitor of CYP2C9 and CYP3A4
• Caution: benzodiazepines; warfarin
• Pregnancy Category C – drug also excreted in breast milk
• Avoid in breastfeeding and pregnancy.
  Dentistry: Esophogeal candidiasis or refractory, resistant oral candidiasis.
  Fluconazole
  Rx: 200mg PO daily x 14days

Answer 29

Fluconazole (Diflucan)

Question 30

Binds to ergosterol in fungal membranes. Fungicidal
Polyenes not effective against dermatophytes.

Answer 30

Polyenes

Question 31

: Same chemistry, mode of action, and spectrum of activity:
 Topical only for mucocutaneous candidiasis.
 No GI absorption - entirely excreted in feces – Preg Cat B.
 Alternative to Clotrimazole / Pts w/liver disease.
► Binds to ergosterol in fungal membranes. Fungicidal
Polyenes not effective against dermatophytes.
Suspension (sucrose),
Topical Use Only: Length of contact important:
Troches/pastilles last ~ 20 mins.
Rinses hold for 2mins.
Patient Counseling:
Swish in mouth then,
Hold in mouth for as long as possible then,
No eating or drinking for 30mins

Answer 31

Nystatin (Mycostatin)

Question 32

• Common Indications:
• Apthous stomatitis
• Recurrent aphthous ulcers (RAU)
• Chemo-induced oral mucositis

Answer 32

Magic mouthwash

Question 33

What are the most common 3 ingredients in magic mouthwash?

Answer 33

Diphenhydramine
Lidocaine
Maalox

Question 34

• Antihistamine / reduce inflammatory process
• Limit pain sensation
• Reduce swelling, erythema
• May be useful for trauma, food allergens, or infections

Answer 34

Diphenhydramine

Question 35

• Topical anesthetic
• Relieves pain associated with irritated oral/pharyngeal mucous
  membranes
• IMPORTANT: ingesting too much can lead to arrhythmias
• Use minimal amounts
• Swish and SPIT

Answer 35

Viscous lidocaine

Question 36

• Primarily used as vehicle to enhance coating of other ingredients
  within the mouth

Answer 36

Maalox

Question 37

Side effects of ______;
* taste disturbances (49%)
* burning and/or tingling in the oral cavity (29%)
* drowsiness or any central nervous system adverse effects (11%)
* gastrointestinal symptoms - constipation, diarrhea and nausea (11%)

Answer 37

Magic mouthwash