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22 Cards in this Set

  • Front
  • Back
Antifungal Agents include:
1.
2.
3.
4.
5.
6.
Antifungal Agents include:
1. Amphotericin B*
2. Fluconazole
3. Ketoconazole
4. Itraconazole
5. Voriconazole (Vfend)
6. Non-Systemic Preparations
Amphotericin B
method of action:
Amphotericin B
method of action: binds to STEROLS present in fungal cell membranes:increases permeability of membrane causing LEAKAGE
Amphotericin B
pharmacotherapy:
Amphotericin B
pharmacotherapy: Clinically used IV for a wide variety of systemic fungal infections caused by candida, Cryptococcus, Aspergillus, Histoplasma, Blastomyces, Mucor; as a bladder irrigation for urinary tract infections with Candida spp; as topical and oral preparations
Amphotericin B
safety profile:
Amphotericin B
safety profile:
a. adverse effects frequently encountered with infusing include: shaking chills, fever, nausea/vomiting, headache, myalgia/arthralgias
*May premedicate with acetaminophen, diphenhydramine, NSAIDS or corticosteroids prior to the infusion; meperidine may shorten the duration of rigors

b. Nephrotoxicity: COMMON (renal tubular acidosis)
1. manifests as ELEVATED SERUM CREATININE
2. May necessitate interruption in therapy or dose reduction
3. LIPOSOMAL preparations may be less nephrotoxic

c. Hypokalemia/hypomagnesemia: may require supplementation
d. Phlebitis

e. Anemia: usually milk

f. Anaphylaxis associated with LIPID preparation
Amphotericin B
administration:
Amphotericin B
administration:
a. Intravenous (STANDARD FORMULATION)
1. Use only DEXTROSE as a diluent; precipitation may result if mixed with IV solutions containing electrolytes
2. Concentration should not exceed 0.1 mg/ml for peripheral administration
3. 1 mg test doese; do not premedicate
4. Maintenance dose 0.5-1.5 mg/kg/day
5. Infuse over 4-6 hours
6. Total dose dependent on type of infection - duration of therapy usually several weeks to months

b. Intravenous (liposomal preparation)
1. DEXTROSE only for diluent
2. Final concentration 1mg-2mg/ml
3. Dose 5mg/kg once daily
4. Infuse over 2 hours

c. Bladder Irrigation
1. Use STERILE WATER for irrigation; 50mg/liter
2. Irrigate with 1 liter/day continuously over 3-5 days
Fluconazole
method of action:
Fluconazole
method of action: inhibition of ERGOSTEROL SYNTHESIS; increases membrane permeability causing LEAKAGE
Fluconazole
pharmacokinetics:
Fluconazole
pharmacokinetics:
a. Rapidly absorbed, good bioavailability, NOT affected by gastric pH
b. Excellent penetration of body fluids, including CSF
c. Renally excreted
Fluconazole
pharmacotherapy:
Fluconazole
pharmacotherapy:
a. Oropharyngeal, esophageal and vaginal candidasis
b. Serious systemic candidal infections including UTI, peritonitis, and pneumonia
c. Cryptococcal meningitis
d. Prophylaxis in AIDS patients
Fluconazole
safety profile:
Fluconazole
safety profile:
a. Well tolerated
b. GI: n/v/d, abdominal pain
c. Rash, headache
d. Hepatotoxicity
e. Drug interactions: see Ketoconazole
*somewhat wearker inhibitor of hepatic drug metabolizing enzymes than ketoconazole, itraconazole
Ketoconazole
method of action:
Ketoconazole
method of action: Similar to fluconazole- inhibition of ERGOSTEROL SYNTHESIS; increases membrane permeability causing LEAKAGE
Ketoconazole
pharmacokinetics:
Ketoconazole
pharmacokinetics:
a. Absorption: Requires an ACIDIC environment; avoid concomitant antacids or drugs that INCREASE gastric pH
b. Elimination: Hepatic metabolism, biliary excretion
Ketoconazole
pharmacotherapy:
Ketoconazole
pharmacotherapy:
a. Superficial and invasive candidal infections (e.g. oral thrush, candida, esophagitis)
b. ALTERNATIVE agent to amphotericin B in the treatment of mild to moderate systemic histoplasmosis, coccidioidomycosis, and blastomycosis
c. Dermatophytoses (e.g. ringworm infections-tineas)
Ketoconazole
safety profile:
Ketoconazole
safety profile:
a. GI: dose related n/v
b. Hepatotoxicity - rare
c. Adrenal insufficiency: inhibition of cortisol sythesis
d. Gynecomastia - inhibits steroidogenesis
e. Pruritus
f. Drug interactoins:
1. Drugs that INCREASE gastric pH (antacids, H2 antagonists, omeprazole, didanosine); impaierd ketoconazole absorption
Itraconazole
method of action:
Itraconazole
method of action: similar to FLUCONAZOLE:- inhibition of ERGOSTEROL SYNTHESIS; increases membrane permeability causing leakage
Itraconazole
pharmacokinetics:
Itraconazole
pharmacokinetics:
a. Absorption similar to KETOCONAZOLE; requires ACIDIC environment, best when taken with food
b. Good penetration into most body fluids
c. Elimination: hepatic metabolism with some "first pass" effect; biliary excretion
Itraconazole
pharmacotherapy:
Itraconazole
pharmacotherapy:
a. Very active in vitro against many fungi including Blastomyces spp, Histoplasma, Aspergillus, Candida spp
b. Effective in treatment of superficial and systemic mycoses
c. May be useful in treatment of FLUCONAZOLE-resistant thrush in AIDS
d. Onychomycosis (fungal nail infection)
Itraconazole
safety profile:
Itraconazole
safety profile:
a. ADRs similar to fluconazole
b. Hypokalemia
c. Hypertriglyceridemia
d. Drug Interactions: similar to ketoconazole
Voriconazole (Vfend)
mechanism of action:
Voriconazole (Vfend):
mechanism of action: azole antifungal that inhibits ergosterol synthesis
*very effective for EVASIVE ASPERGILLOSIS
*inhibits hepatic enzymes (CYP 2C9, CYP 3A4), so has many drug interactions
*adverse effects include visual disturbances, rash, hepatotoxicity
Non-Systemic Preparations include:
Non-Systemic Preparations include:
Clotrimazole (Lotrimin), econazole, miconazole (Monistat), nystatin, terbinafine, terconazole, others
Non-Systemic Preparations dosage forms:
Non-Systemic Preparations dosage forms:
a. topical creams, ointments, solutions, powders
b. vaginal creams, suppositories
c. oral suspensions, lozenges
Non-Systemic Preparations
pharmacotherapy:
Non-Systemic Preparations
pharmacotherapy:
a. Used topically in the treatment of fungal infections of skin, mucus membranes, oral cavity, and vagina.
Non-Systemic Preparations
safety profile:
Non-Systemic Preparations
safety profile:
a. local burning and itching
b. hypersensitivity reactions: usually associated with preservatives in the formulations