Week 7- Antifungal and Antiviral Agents (Ch 8)

Infections with _______ affect the skin and produce athlete's foot, "jock itch" and ringworm treated with OTC products.

tinea

Patients taking sanquinavir should avoid _________.

sunlight

Bacteria do not contain _____ in their cell wall membranes, so nystatin is not active against them.

sterols

AIDS: Nucleoside Reverse Transcriptase Inhibitors- CNS Effects

- headache, agitation, and insomnia -Nausea occurs in 50% of patients -Oral manifestations: taste perversions, edema of the tongue, bleeding gums, and mouth ulcers -Adverse reactions sometimes limit treatment with AZT.

Antiviral Agents: Ganciclovir

-(Cytovene, Cytovene IV and DHPG) -Inhibits replication of most herpes viruses -Prevention and treatment of cytomegalovirus (CMV) in persons with AIDS.

Antiviral Agents: Docosanol

-Abreva -OTC for HSV-1 -Shortens healing time by a half day -Must be applied within 12 hours of prodromal symptoms

Antifungal Agents: Imidazoles- Clotrimazole

-Clotrimazole- For Oropharyngeal candidiasis -OTC cream for topical application or vaginal cream -Lozenges dissolve in 15-20 minutes orally -Patients with xerostomia may have a difficult time dissolving lozenges -Adverse reactions are GI, can cause elevated liver enzyme levels in 15% of patients -Systemic clotrimazole is embryotoxic

Antifungal Agents:Imidazoles- Fluconazole

-Diflucan -Used for treatment of oropharyngeal and esophgeal candidiasis and serious systemic candidal infections. One-tablet fluconazole is used to treat vaginal candidiasis or to treat candidiasis that has not responded to conventional therapy.

Antifungal Agents: Nystatin (as medication)

-For oral treatment, nystatin is available in a containing 50% sucrose -The patient is told to swish (2 minutes), and spit or swallow 4 times daily -For children and infants, a dropper is used and the finger is rubbed over the oral cavity

Antifungal Agents:Imidazoles- Ketaconazoles - Adverse Reactions

-GI. Most serious side effect: hepatotoxicity: occasionally is fatal. Patients taking other hepatotoxic drugs must be watched closely. -In higher doses, it inhibits the secretion of the corticosteroids and lowers the secretion of the serum levels of testosterone, leading to gynecomastia and impotence. -FDA category C -Embryotoxic -Many drug interactions -Increases blood levels of: cyclosporine, warfarin, cortecosteroids, phenytoin, digoxin, lovastatin, and simvastatin -Isoniasid, phenytoinm and theophylline can decrease ketaconazole serum levels

Antiviral Agents: Acyclovir (Zovirax)

-Herpes simplex-1 --- "Cold sores" "fever blisters" Most antiviral agents inhibit viral DNA synthesis. -Spectrum includes herpes simplex- 1, varicella zoster (chicken pox and shingles), Epstein-Barr, Herpesvirus simae and cytomegalovirus -Several mechanisms of resistance have been found

Antiviral Agents: Acyclovir (Zovirax)- Oral Uses

-Initial HSV-2 and management of recurrent HSV-2 infections in both immunopompromised and healthy patients. -Used for prophylaxis of recurrent HSV-2 infections in both groups

Antiviral Agents: Acyclovir (Zovirax)- Other uses

-Injectible: Used for severe initial HSV-2 infections in the healthy patient -Other uses include herpes zoster (shingles) and varicella zoster (chicken pox) treatment.

Other Antifungal Agents: Griseofulvin

-Interupts cell mitosis. -Spectrum includes tineas (ringworm) -Tightly bound and deposited in diseased keratin precursors (hair, skin, nails) but does not include Candida organisms. -Adverse reactions: Headache, GI, overgrowth of Candida, depression of hematopoietic functions and increase in carcinogenicity

AIDS: Protease Inhibitors (more gen)

-Ketaconazole greatly increases the levels of sanquinavir -Pts taking sanquinavir should avoid sunlight -Its development has hade a substantial difference in the mortality and morbidity of AIDS patients.

Other Antifungal Agents: Amphotercin B- Adverse Rxn

-Many serious adverse reactions: Hypokalemia (too little serum potassium), headache, chills, muscle and joint pain, chills, fever, malaise, GI complaints, and nephrotoxicity -Many serious drug interactions

AIDS: NONnucleoside Reverse Transcriptase Inhibitors

-Nevirapine (VP, Viramune) Combined with the nucleoside analogues and the protease inhibitors -When used alone, resistance occurs quickly

Antifungal Agents:Imidazoles- Ketaconazoles

-Nizoral -oral and pharyngeal candidiasis -High rate of adverse reactions -Used as a last resort -Mechanism of action: alters cell membrane permeability

Antifungal Agents: Nystatin (vaginal medication)

-Nystatin is available in vaginal tablets for use in vaginal infections. The tablets can be used orally. It can be dissolved in the oral cavity 4 times a day. Unflavored. -Some immunocompromised patients may require long-term prophylactic antifungal agents to control candidiasis

Antiviral Agents: Pencyclovir

-Pencyclovir -Helps the pain and the healing time on the lips and face

AIDS: Protease Inhibitors (gen)

-Saquinavir (Saquin'avir) prevents the maturation of the HIV-infected cells -Adverse reactions: rash, hyperglycemia, and parasthesias, -GI: pain, diarrhea, and vomiting. -Oral adverse reactions: buccal mucosa ulceration

Other Antifungal Agents: Amphotercin B (gen)

-Serious systemic fungal infections -Used IV -Alters cell membrane permeability, allowing for loss of potassium and other cellular contents -Kills may fungi

Antifungal Agents:Imidazoles- Ketaconazoles- warnings

-Should not be used with rifampin (TB agent) because rifampin renders its blood level undetectable. ***Ketaconazole may decrease the effect of oral contraceptives: an alternative method of birth control should be suggested.*** -Can cause hepatotoxicity if alcohol is used

Antiviral Agents: Acyclovir (Zovirax)- General Uses

-Topical: Initial herpes genitalis (HSV-2) and limited non-life threatening initial and recurrent mucocutaneous herpes simplex HSV-1 and HSV-2 in imunocompromized patients. -Has not been effective in the treatment of recurrent HSV-1 and HSV-2 in healthy patients -It does not prevent the transmission of infection, and it does not prevent recurrence. -Although available literature does not support the use topical acyclovir for management of HSV-1 in dentistry, it is used extensively. -No acyclovir products are approved for the treatment of recurrent HSV-1 in the healthy patient.

Antiviral Agents: Acyclovir (Zovirax)- Side Effects

-Topical: stinging, burning, or mild pain -Headache, vertigo, dizziness, fatigue, irritability, insomnia, GI, acne, hair loss, arthralgia, lymphadenopathy, menstrual irregularities

Other Antiviral Agents: Amantadine (Aman'tadine)

-Used for Influenza A virus -Inhibits the penetration of the virus into host cells or inhibits the uncoating of the virus -Side effects: nausea, dizziness, lightheadedness, and insomnia -Can be used prophylactically for prevention of the influenza A viral infection or for treatment to reduce the symptoms of the infection. -Has been used in institutionalized patients to prevent the spread of infection.

Antiviral Agents- Famcyclovir

-Used for recurrent episodes of HSV-2

Antifungal Agents: Nystatin (uses)

-Used for the treatment and prevention of oral candidiasis in susceptible cases -Although C. albicans is a frequent inhabitant of the oral cavity, only under unusual conditions does it produce disease. -Often patients are immunocompromised

Antifungal Agents: Nystatin (gen)

-a polyene macrolide antibiotic -Causes increase in membrane permeability allowing leakage of potassium and other essential cellular constituents. -Bacteria do not contain sterols in their cell wall membranes, so nystatin is not active against them. -Not absorbed via the intact skin -Poorly absorbed from GI tract -Side effects: mild and infrequent with topical or oral doses Larger doses may cause nausea, vomiting and diarrhea

Other Antiviral Agents: Interferons

-have anti viral, cytotoxic and immunomudulating action. -Uses for acute hepatitis, chronic hepatitis B and C, leukemia, AIDS- related Kaposi's Sarcoma, and Multiple Sclerosis

Antifungal Agents: Nystatin (pastilles)

-licorice-flavored rubbery sugar containing drops that dissolve in the mouth over a period of 15 minutes. -The sugar content must be taken into account and patients with xerostomia could develop decay rapidly.

AIDS: Nucleoside Reverse Transcriptase Inhibitors

-zidovudine (AZT, Retrovir) -Blocks viral replication and conversion into a form that can get into an uninfected host cell. -Has no effect on cells already containing HIV. -Well absorbed orally, distributed to most body tissue, including cerebrospinal fluid -Metabolized in the liver and excreted by the kidneys -Reduces the morbidity and mortality from AIDS and AIDS-related complex -Opportunistic infections are reduced in both number and frequency. -Toxicity is related to bone marrow toxicity. Transfusions are often required.

AIDS: Nucleoside Reverse Transcriptase Inhibitors- Drug Interactions

Acetaminophen, indomethacin and aspirin and AZT can potentiate each other's effects.

Oral lesions caused by __________ are managed with prescription of nystatin, clotrimazole, ketaconazole, or fluconazole.

C. albicans

AIDS Cocktails (3 types of drugs)

The groups of drugs used are: 1-Nucleoside reverse transcriptase inhibitors 2-Nonnucleoside reverse transcriptase inhibitors and 3-Protease inhibitors "Cocktail" has all three

Ganciclovir can be used for prevention and treatment of __________ in persons with AIDS.

cytomegalovirus (CMV)

Ganciclovir inhibits replication of most ______ viruses

herpes

Antiviral Agents: Famcyclovir- Adverse Effects

many: fever, coma, chills, confusion, abnormal thoughts, dizziness, bizarre dreams, headaches, psychosis, tremors, parasthesia, dysrhythmia, hypertension, hypotension, hemorrhage, anorexia, blood dyscrasias

Nystatin causes increase in ________ permeability allowing leakage of potassium and other essential cellular constituents.

membrane