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Chapter 8:
Antifungal and Antiviral Agents
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Outline
• Antifungals
• Antiviral: Herpes
• Antiviral: HIV
• Antiviral: Chronic Hepatitis
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Antifungals
Nystatin(Mycostatin)
Imidazoles
Amphotericin B
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Antifungal Agents
• Caused by molds, yeasts, fungi
• Candida
▫ Normal flora of mouth & other areas of body
▫ Over-growth caused by Superinfection or
immunocompromised patients (HIV)
• Fungal infections (mycosis) classified into 3 groups
1. Systemic (common in HIV)
2. Superficial or mucocutaneous: dental

TX: topical (most common), systemic (severe cases)
3. Subcutaneous
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Antifungal Agents Nystatin(Mycostatin)
• Usual: oral suspension liquid rinse, lozenge, cream
• Mechanism of action: binds to sterols in the fungal
cell membrane & causes lysis
▫ Bacteria do not contain sterols in their cell membrane
 Reason nystatin is not effective against bacteria
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Antifungal Agents : Imidazoles
Used in dentistry
1) Clotrimazole(Mycelex)
• Lozenge for oral use (contains sugar)
• Do NOT use in pt with HIGH caries risk
Drug Interactions
2) Ketoconazole(Nizoral)
Warfarin
 Systemic fungal infections, used after
CCB
oral meds not worked
Erythromycin
3) Fluconazole(Diflucan)
 Severe, extensive oropharyngeal candida
 Can be used as preventive in HIV
patients
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Antifungal Agents: Amphotericin B
• Used in the tx of many serious systemic fungal
infections
• Nickname: “amphoterrible” due to side effects
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NBQ
Which of the following drugs interacts with
systemic fluconazole(Diflucan)?
a.
b.
c.
d.
Erythromycin
Penicillin
Acetaminophen
Ibuprofen
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs interacts with
systemic fluconazole(Diflucan)?
a.
b.
c.
d.
Erythromycin
Penicillin
Acetaminophen
Ibuprofen
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs is the treatment of
choice in the therapy of oral candidiasis?
a.
b.
c.
d.
Nystatin rinse
Ketoconazole tablets
Fluconazole tablets
Miconazole ointment
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs is the treatment of
choice in the therapy of oral candidiasis?
a.
b.
c.
d.
Nystatin rinse
Ketoconazole tablets
Fluconazole tablets
Miconazole ointment
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Antiviral Agents
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Antiviral Agents
Tx of viral infections extremely difficult
▫ They are obligate intracellular organisms that require
cooperation from the host
▫ To kill virus = also kill host
▫ Viruses are smaller then bacteria, fungus, protozoa
▫ All virus’s have genetic info: RNA or DNA, surrounded
by protected PRO coat
▫ Virus invades host cell-injected its genetic material
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Antiviral Agent Outline
Herpes simplex
ANTIHERPETIC DRUGS
Acyclovir sodium(Zovirax)
Docosanol cream(Abreva)
Penciclovir(Denavir)
Famciclovir(Famvir)
Valacyclovir(Valtrex)
Acquired immunodeficiency syndrome (AIDS)
ANTIRETROVIRAL DRUGS
Nucleoside reverse transcriptase inhibitors (NRTIs)
Nonnucleoside reverse transcriptase inhibitors (NNRTI)
Protease inhibitors(PIs)
Fusion (Entry) Inhibitors
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Herpes Simplex
ANTIHERPETIC DRUGS
Notations
Acyclovir sodium(Zovirax)
Inhibit DNA synthesis
Penciclovir(Denavir)
Inhibit DNA synthesis
Docosanol cream(Abreva)
Inhibit fusion of virus to cells
Famciclovir(Famvir)
Ganciclovir injectable(Cytovene)
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Herpes Simplex
•
•
•
•
HSV-1: oropharyngeal, lips, vermillion border
HSV-2: genital
Primary herpectic gingivostomatitis: 1st exposure
Early tx with Zovirax or Famvir can shorten
duration
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Herpes Simplex: ACYCLOVIR (ZOVIRAX)
• Spectrum
▫ HSV 1 & 2
▫ Varicella zoster: herpes 3
▫ Epstein-Barr: herpes 4
• Application

5x/day for 4 days
• Uses


HIV: HSV1&2
Immune competent: HSV2 ONLY
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Herpes Simplex: Penciclovir(Denavir)
• Topical
• Use during prodromal stage
• Immuno-competent patients
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Herpes Simplex : Docosanol(Abreva)
• OTC (combo petroleum + cocoa butter)
• Topical applied 5x/day
• Inhibits fusion virus to cell membranes – blocks
more viral replication
• ↓healing time by ½ day
• Have to start med w/in 12 hours of prodromal
symptoms
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Review Question
Which of the following antiherpetic drugs is
recommended for herpes labialis?
a.
b.
c.
d.
Ganciclovir
Famciclovir
Valacyclovir
Penciclovir
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following antiherpetic drugs is
recommended for herpes labialis?
a.
b.
c.
d.
Ganciclovir
Famciclovir
Valacyclovir
Penciclovir
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs is contraindicated for
the treatment of herpes labialis?
a.
b.
c.
d.
Penicillin
Docosanol
Acyclovir
Penciclovir
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs is contraindicated for
the treatment of herpes labialis?
a.
b.
c.
d.
Penicillin
Docosanol
Acyclovir
Penciclovir
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs is available OTC for the
treatment of herpes labialis?
a.
b.
c.
d.
Valacyclovir
Docosanol
Acyclovir
Penciclovir
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs is available OTC for the
treatment of herpes labialis?
a.
b.
c.
d.
Valacyclovir
Docosanol
Acyclovir
Penciclovir
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
AIDS
ANTIRETROVIRAL DRUGS
Nucleoside reverse transcriptase inhibitors (NRTIs)
Nonnucleoside reverse transcriptase inhibitors (NNRTI)
Protease inhibitors(PIs)
Fusion (Entry) Inhibitors
Integrase inhibitors
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
HIV General Info
 HIV type 1: RNA retrovirus
 HIV type 2: Western Africa, rare to USA
 Single strand RNA virus that converts to a
double-stranded DNA to make more retroviruses
through a specific enzyme: reverse transcriptase
 Newly produced viral DNA enters the host cell
nuclei and is incorporated into the host
chromosome through a special HIV enzyme:
integrase
 Now only new virus cell replication occurs
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
HIV TX
 Objective antiretroviral therapy is to reduce viral
load = improve survival
 Decision for start of drug therapy
o CD4 count = 500mm3
o Viral load = 30,000 copies per mL blood
plasma
 HAART therapy (Highly Active AntiRetroviral
Therapy)
o Preferred initial regime
o Uses 3-4 drugs to suppress viral replication,
prevent opportunistic infections
o 20 drugs approved in US
o 78% patient become resistant to @ least 1 drug
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HIV TX
HAART TX COMBO
2 NRTI + NNRTI + PI
Preferred method
2 NRTI + NNRTI
Alternative
2 NRTI + PI
Alternative
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
AIDS
Nucleoside reverse transcriptase inhibitors (NRTIs)
Abacavir(Ziagen)
Didansosine(Videx)
Emtricitabine(Emtriva)
Lamivudine(Epivir)
Stavudine zidovudine(Retrovir)
Tenofovir disoproxil fumarate(Viread)
Zalcitabine-HIVID
1st drugs on the market in USA in 1980s
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NRTI
• Embed themselves into viral DNA
↓
• Inhibit conversion of RNA to DNA by binding to
reverse transcriptase enzyme
↓
• Virus replication decreased
• Many adverse effects
• Enlarged liver
• Life-threatening lactic acidosis
• Neuropathy
• Oral: xerostomia, oral ulcers, stomatitis
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
AIDS
Nonnucleoside reverse transcriptase inhibitors (NNRTI)
Efavirenz(Sustiva)
Nevirapine(Viramune)
Delavirdine(Rescriptor)
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NNRTI
• Same action as NRTIs on virus (just a different
receptor)
• When used alone = resistance quickly occurs
• Adverse effects
• Fatal liver damage
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
AIDS
Protease inhibitors(PIs) ~avir ending for all!
Amprevavir(Agenerase)
Atazanavir(Reyataz)
Fosamprenavir(Lexiva)
Indinavir(Crixivan)
Lopinavir+Ritonavir(Kaletra)
Nelfinavir(Viracept)
Ritonavir(Norvir)
Saquinavir(Fortovase, formerly Invirase)
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Protease Inhibitors (PI)
• MOST POTENT of all HIV drugs!
• Action
▫ Prevent breakdown of PRO produced by virus
into infectious mature viruses
▫ Advantage: new viruses cannot be released to
infect more cells
• Only class metabolized by P450 liver enzymes:
many drug interactions
• Side effects
▫ Oral paresthesia, dental pain, taste changes,
metallic taste in mouth, taste impairment
▫ Liver damage
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
AIDS
Fusion (Entry) Inhibitors
Enfuvirtide(Fuzeon)
Integrase Inhibitors
Raltegravir(Isentress)
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Fusion (Entry) Inhibitors
• Interfere with entry of HIV-1 into host cells
• Inhibit fusion of the virus and cell membrane
Integrase Inhibitors
• Inhibit action of integrase
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
All of the following drugs are nucleoside reverse
transcriptase inhibitors used to treat AIDS EXCEPT
one. Which one is the EXCEPTION?
a.
b.
c.
d.
e.
Didanosine
Zidovudine
Ritonavir
Abacavir
Lamivudine
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
All of the following drugs are nucleoside reverse
transcriptase inhibitors used to treat AIDS EXCEPT
one. Which one is the EXCEPTION?
a.
b.
c.
d.
e.
Didanosine
Zidovudine
Ritonavir
Abacavir
Lamivudine
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs could cause metallic
taste in mouth?
a.
b.
c.
d.
Didanososine(Videx)
Delavirdine(Rescriptor)
Indinavir(Crixivan)
Enfuvirtide(Fuzeon)
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
NBQ
Which of the following drugs could cause metallic
taste in mouth?
a.
b.
c.
d.
Didanososine(Videx)
Delavirdine(Rescriptor)
Indinavir(Crixivan)
Enfuvirtide(Fuzeon)
NRTI
NNRTI
PI
Fusion Inhibitor
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Chronic Hepatitis B & C
• Inteferons: inhibit cell growth & expression
• Protease Inhibitors
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