• Like
  • Save
Antifungal Treatment
Upcoming SlideShare
Loading in...5
×

Antifungal Treatment

  • 6,027 views
Uploaded on

Antifungal Treatment

Antifungal Treatment

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
  • Fioricet is often prescribed for tension headaches caused by contractions of the muscles in the neck and shoulder area. Buy now from http://www.fioricetsupply.com and make a deal for you.
    Are you sure you want to
    Your message goes here
No Downloads

Views

Total Views
6,027
On Slideshare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
126
Comments
1
Likes
1

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide

Transcript

  • 1. Antifungal Treatment
  • 2. Fungi for generalists
    • Superficial (skin, nails, oral, vaginal)
      • Very common in otherwise healthy people
      • Frequent episodes suggest interference with immune defenses as in diabetes, antibiotic Rx
    • Systemic
      • rare except in severely immune- compromised
  • 3. Antifungals Lamisil Terbinafine Allylamine Triazoles Imidazoles SUBCLASS Griseofulvin Fluconazole Itraconazole Ketoconazole GENERIC Grisactin Fulvicin Gris-PEG Griseofulvin Diflucan Sporanox Nizoral Azoles TRADE CLASS
  • 4. General Indications
    • Ketaconazole
      • Systemic fungal infections (candidiasis, blastomycosis, coccidioidomycosis, histoplasmosis)
      • Severe recalcitrant dermatophyte infections unresponsive to topical
    • Fluconazole
      • Candidiasis, including vaginal
      • Cryptococcal meningitis
    • Itraconazole
      • Blastomycosis, histoplasmosis, apergillosis
      • Onychomycosis
    • Terbinafine
      • Onychomycosis
    • Griseofulvin
      • Tinea infections of skin, hair, nails unresponsive to topical
      • NOT candidiasis, blastomycosis, coccidioidomycosis, histoplasmosis
  • 5. Azoles: Patient Variables
    • Geriatrics
      • More susceptible to hepatotoxicity
      • Require lower dosing in reduced renal function
    • Pediatrics
      • S&E NOT established
    • Pregnancy
      • Category C: Benefit > risk to fetus
    • Lactation
      • Excreted in breast milk. Do NOT use in nursing women.
  • 6. Azoles: Monitoring
    • Assess LFTs prior to initiating Tx and periodically (baseline & Q2wk x 2 mo, then Q1-2 mo)
    • Assess for s/s of hepatitis
      • Fatigue, anorexia, N/V, jaundice, dark urine, pale stools
    • Assess for interference with steroidgenesis
      • High-dose ketoconazole: adrenal suppression
      • High-dose itraconazole: hypokalemia & secondary V-fib
    • Assess response to Tx with repeat cultures
  • 7. Azoles: Patient Education
    • Food enhances absorption of itraconazole, variably affects ketoconazole, no effect on fluconazole
    • Administer antacids, H2-blockers, proton pump inhibitors, or anticholinergics at least 2 hours after ketoconazole or itraconazole
    • Immediately report any s/s of hepatitis
      • Fatigue, anorexia, N/V, jaundice, dark urine, pale stools
    • Take as prescribed. Inadequate treatment  poor response or early recurrence of symptoms
    • Women of childbearing age: USE CONTRACEPTION OR ABSTINENCE
  • 8. Ketoconazole
    • Contraindications
      • Hypersensitivity
      • Fungal meningitis (poor CNS penetration)
      • Use with Propulsid  serious cardiac arrhythmias
    • Warnings / Precautions
      • Hepatic toxicity: clinically significant / fatal hepatitis  D/C immediately if s/s, effects usually reversible may take weeks to months
      • Steroidgenesis: directly inhibit adrenal cortisol and testosterone synthesis  low sperm counts, decreased libido, impotence, gynecomastia, menstrual irregularities
      • Hypersensitivity & anaphylaxis
      • Weak bases require gastric acidity for dissolution/absorption  do NOT take with antacids, anticholinergics, or H2-blockers
  • 9. Ketoconazole: Pharmacokinetics
    • Bioavailability varies depending on gastric pH
    • Ketoconazole absorption variable with food
    • Itraconazole 2-3 x greater bioavailability with food esp lipids
    • Hypochlohydria in AIDS  decreased bioavailability
  • 10. Ketoconazole
    • Adverse Effects
      • Mild / transient – don’t require D/C
      • Most common: N/V
    • Drug Interactions
      • Least favorable toxicity profile
      • Inhibits P450 3A4, also inhibits 1A2, 2C, 3A4
      • Propulsid  serious cardiac arrhythmias
      • Do NOT take with antacids, anticholinergics, or H2-blockers  decreases bioavailability
  • 11. Triazole
    • Indications
      • Oropharyngeal & esophogeal candidiasis
      • Single dose Tx of vulvovaginal candidiasis
    • Contraindications
      • Hypersensitivity
    • Warnings / Precautions
      • Hepatotoxicity
      • Allergic / Dermatologic reaction – anaphylaxis & exfoliative dermatitis (rare)
      • Dose reduction for renal dysfunction
      • Use care in use with elderly
  • 12. Triazoles: Pharmacokinetics
    • Absorption & bioavailability NOT affected by food or gastric pH
    • Excreted renally with therapeutic concentrations achieved in urine
    • UNIQUE among azoles in that it crosses the blood-brain barrier & has good CSF penetration
  • 13. Triazoles
    • Pediatrics
      • S&E NOT established
    • Adverse Effects
      • Most Common (single dose): headache, nausea, abdominal pain, diarrhea, dyspepsia, dizziness
      • Most Common (multidose): nausea, headache, skin rash, vomiting, abdominal pain, diarrhea
      • SERIOUS: seizures, exfoliative skin disorders, leukopenia, thrombocytopenia, serious hepatic reactions
  • 14. Triazoles
    • Drug Interactions
      • P450 2C and 3A4 inhibitor
      • Decreases blood levels of OCPs
    • Overdose
      • Gastric lavage & hemodialysis
  • 15. Itraconazole (Sporonox)
    • Indications
      • Wide spectrum of antifungal activity
    • Contraindications
      • Coadministration with propulsid & halcion
      • Use with caution in patients with hypersensitivity to to other azoles
    • Warnings / Precautions
      • Obtain culture prior to Tx
      • Hepatitis – monitor hepatic enzymes
      • HIV – decreased absorption of drug
      • Absorption decreased with decreased gastric acidity
  • 16. Itraconazole (Sporonox)
    • Pharmacokinetics
      • Reduced absorption with decreased stomach acidity
      • Therapeutic concentrations may persist in fingernails & toenails for up to 6 mo after D/C
    • Adverse Effects
      • Greater specificity for P450 3A4 enzyme system
    • Overdose
      • NOT removed by dialysis
      • Gastric lavage & sodium bicarbonate
  • 17. Terbinafine
    • Contraindications
      • Hypersensitivity
    • Warnings
      • Hepatic failure: worse in Hx of liver disease Assess liver function BEFORE prescribing
      • Ophthalmic: changes in ocular lens & retina
      • Neutropenia: reversible if D/C’d
      • Dermatologic: SJS, toxic epidermal necrolysis
      • Renal: do not use with significant renal impairment
  • 18. Griseofulvin
    • Indications
      • Tinea infections of skin, hair, nails
    • Contraindications
      • Hypersensitivity (5-7%)
      • Hepatocellular failure
      • Porphyria
  • 19. Griseofulvin: Warnings/Precautions
    • Hypersensitivity (5-7%)
      • Skin rash, urticaria, angioneurotic edema  D/C
    • Prophylaxis
      • S&E NOT established
    • Prolonged therapy
      • Monitor renal, hepatic, hematopietic function periodically
    • PCN cross sensitivity
      • Derived from PCN
    • Lupus erythematosus
      • Exacerbation or lupuslike syndromes
    • Photosensitivity
      • Use sunblock & protective clothing
  • 20. Griseofulvin
    • Pharmacokinetics
      • Better absorption when taken with meals high in fat content
      • Variable GI absorption
      • Peak: 4 hrs
    • Pediatrics
      • May produce estrogen-like effects in children: enlarged breasts, hyperpigmentation of areola, nipple & external genitalia
    • Pregnancy
      • Category C: embryotoxic & teratogenic
    • Monitor
      • Baseline & periodic: renal, liver, hematopoietic function
  • 21. Griseofulvin
    • Adverse Effects
      • Common: hypersensitivity – skin rashes, urticaria, angioneurotic edema (rare)
      • Oral thrush, N/V, epigastric distress, diarrhea, headache, fatigue, dizziness, insomnia, mental confusion, impairment of performance of routine acitivities
      • High dose or prolonged Tx: interference with porphyrin metabolism, proteinuria, leukopenia, hepatic toxicity, GI bleed, menstrual irregularities, paresthesias of hands and feet, granulocytopenia
    • Drug Interactions
      • NOT metabolized by P450
      • Decreases activity of OCPs & anticoagulants
  • 22. Griseofulvin: Pt Education
    • Bioavailability improves when given with food
    • Headaches disappear with continued Tx or taken with food
    • Continue for entire course of Tx – effects not immediately noticeable
    • Photosensitivity – avoid prolonged exposure to sunlight or sunlamps; use sun block and protective clothing
    • Notify provider of rash or sore throat
    • May potentiate effects of alcohol
  • 23. Fungi Morphology
    • Yeast
      • Unicellular fungi
      • Typically round or oval
      • Reproduce by budding
      • May form pseudohyphae (long chains)
    • Molds
      • Multicellular colonies composed of tubular structures (hyphae)
      • Grow by branching & longitudinal extension
    • Dimorphism
      • Fungi may be yeast or mold depending on env conditions
  • 24. Mycosis
    • Presence of parasitic fungi in or on the body
    • Most pathogenic fungi are yeast, are nonmotile, and are nontransmissible
    • May be superficial, subcutaneous, or deeply invasive
    • Fungi are eukaryocytes like mammalian cells
      • Key difference b/w is the sterol used to make the cell membrane
      • Fungi: ergosterol VS. Mammals: cholesterol
    • Mechanism of action = interaction with / inhibition of ergosterol synthesis
  • 25. Mechanisms of Action
    • Azoles
      • Fungistatic (vs. fungicidal)
      • Inhibition of ergosterol synthesis  cell membranes becomes more permeable & leak cell contents  inhibits cell growth & replication
    • Griseofulvin
      • Deposited in keratin of diseased tissue making it resistant to fungal infection
      • Diseased tissue gradually exfoliated & replaced with healthy tissue