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