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Pharmacotherapeutics I > Antifungal Agents > Flashcards

Flashcards in Antifungal Agents Deck (35):
1

Fungi

Eukaryotic organisms that live as saprophytes or parasites. Resistant to ABX.
Termed Mycoses

2

Types of Fungi

Superficial- skin, nail/hair, mucous membranes
Systemic- deep tissues, organs

3

3 Groups of fungi that cause disease

Molds
True yeast
Yeast-like fungi

4

Fungal pathogenicity results from

Mycotoxin production
Allergenicity/inflammatory reactions
Tissue invasion
Opportunistic fungal infections are important causes of disease in immunosuppressed

5

Route selection for superficial and cutaneous infections

Selection of anti fungal therapy should be based on extent and type of infection
Superficial and cutaneous- usually topical
Follicular, nail, or widespread- systemically

6

Vehicle selection

Ranking the drying effect of formulations
gel>lotion/solutions/cream/ointment
Powders are used only as adjuncts

7

Systemic fungal infections

Tx depends on stage and severity
Choices revolve around the same drugs for all systemic fungal infections
Risk factors include- immunosuppression (HIV, CA chemo, or steroids), diabetes, TPN

8

Antifungal Drugs

Polyene antibiotics
Imidazole antifungals
Triazole antifungals
Other antifungal agents
Tx can last weeks to months and is more effective on the skin than the nails.

9

Amphortericin B

Polyene ABX
Naturally occuring polyene macrolide antibiotic produced by streptomyces nodosus
MOA- Bind to ergosterol in the fungal cell membrane and form pore-> leak "-cidal"
Selective toxicity
Resistance- infrequent due to decreased ergosterols in membrane

10

Nystatin

Polyene ABX
MOA- Bind to ergosterol in the fungal cell membrane and form pore-> leak "-cidal"
Selective toxicity
Active transport mechanism

11

Amphortericin- pharmacokinetics

ROA- IV
Liposomal preps less renal and infusion toxicity

12

Amphortericin indications and ADRS

Broad specturm anti-fungal used in potentially fatal systemic infections
-Candida albicans, histoplamsa capsulatum, cyrptococcus neoformans, coccidoices immites, blastomyces dermatitides, aspergillis
ADRs- HYPOTENSiON, anemia, nephrotoxocity, thrombophlebitis, fever/chills, allergic reactions

13

Nystatin-pharmacokinetics

Topically as a cream
Vaginal troches
Suspension deliver drugs to oral mucosa

14

Nystatin- indications and ADRS

Used to supress candidiasis on the sin and mucous membranes (oral&vaginal)
ADRs- N/V/D

15

Flucytosine (Ancobon)

Polyene ABX
MOA- inhibits synthesis of fungal pyrimidines
ROA- PO
Indications- in combination w/ amphoB to treat systemic candiasis and cryptococcuss meningitis
ADRs- N/V/D, rare hepatotoxicity and seen more often is thrombocytopenia, neutropenia, bone marrow suppression

16

Griseofulvin (Fulvicin)

Polyene ABX
MOA- binds to fungal microtubules disrupting mitotic spindles "-static"
Indications- DOC in kinds for wide spread dermatophyte or intractable dermatophyte infection where topical agents have failed. No longer for dermatophyte infection of nails
ADRs- fever, HA, mental confusion, rashes, GI disturbances.

17

Griseofulvin (Fulvicin)- drug interactions

P450 inducer- barbiturates, OCP, warfarin
High fat meals increase absorption
Potentiates intoxicating effects of ETOH

18

Ketoconazole (nizoral)- MOA

Azoles Imidazoles
MOA- broad spectrum: histoplasma, blastomyces, candida, coccidioides, NO ASPERGILLUS
Predominately fungistatic but can be -cidal depending on dose
Inhbits C-14-alpha-demethylase (P450 enzyme) disruptong the membrane
Also inhibits human steroid synthesis leading to decreased testosterone and cortisol production.

19

Ketoconazole (nizarol)- Pharmacokinetics and ADR

PO-requires gastric acid for dissolution
Penetration into tissues limites, effective in tx of histoplasmosis in lung, bone, skin, soft tissue
Doesn't enter CNS
ADRs- N/V, anorexia, endocrine effects such as gynecomastia, impotence, irreg menses, teratogenic due to endocrine effects

20

Ketoconazole (nizarol)- Drug interactions and resistance

P450 INHIBITOR
Resistance- mutation of p450 enzyme leasts to decreased azole binding
Ability to pump azole out of the cell.

21

Azoles Imidazoles

Clotrimazole (Lortimin, mycelex)
Miconazole (Monostat, desenex)
Terconazole (terazol)
Butoconazole (Femstat3)
Topical only; severe toxicity when used IV
MOA and spectrum same as ketoconazole
Topical use w/ contact dermititis, vulvar irritation, edema
TOPICAL MICONAZOLE IS A POTENT INHIBITOR OF WARFARIN METABOLISM

22

Fluconazole (diflucan)- MOA

Azoles Triazoles
Inhibits synthesis of fungal membrane ergosterol
Lacks endocrine side effects
Penetrates CSF of normal and inflammed meninges

23

Fluconozole (diflucan)- uses, ROA and ADRs

DOC- cryptococcuss neoformans, candidemia and coccidioidomycosis, effective against all forms of mucocutaneous candidiasis; used prophylactically in immunocompromised pts
ROA- Oral or IV
ADRs- N/V and rash

24

Fluconazole (diflucan)- drug interactions

Moderate inhibitor of CYP3A4 (cyclosporin, lovastatin) and strong inhibitor of CYP2C9
Tetratogenic

25

Itraconazole (Sporanox)

Azoles triazoles
MOA- inhibits synthesis of fungal membrane ergosterol lacks endocrine side effects; -static
DOC- blastomycosis, aspergillis, sporotrichosis, paracoccidiodomycosis, histoplasmosis

26

Itraconazole (sporanoz)- pharmacokinetics and ADRs

PO- requires acid for dissolution
Extensively protein bound and distributes throughout most tissues including bone and adipose, but not CSF
Biologically an active metabolite
P450 INHIBITOR
Avoid in pregnancy
ADRs- N/V, rash, hypokalemia, HTN, edema, HA

27

Itraconazole (sporanox)- contraindications

Strong inhibitor and substrate of CYP34A, contraindicated w/ lovastatin, simvastatin, midazolam, triazolam. May decrease OCP effectiveness, and increased digoxin levels

28

Voriconazole (vfend)

Azole triazoles
PO or IV
Invasive aspergillosis and serious infections caused by scedosproium apiospermum and fusarium species
Penetrates tissues and CSF
ADRs- similar to other azoles; transient visual disturbance occurring shortly after dose

29

Voriconazole (vfend)- Contraindictations

Inhibitor of CYP2C18, 2C9, 3A4. Contraindicated in patients taking rifampin, phenobarital, carbamasepine. Dose adjustments may be required w/ statins, benzodiazepines, and warfarin

30

Posaconazole

Azole triazoles (new antigungal)
Only available as oral suspension and must be taken with high fat meal for adequate absorption
Spectrum similar to itraconazole, w/ additional effect on Zygomycetes such as mucor
More effective than other azoles in treating fungal infections in immunosuppressed patients (myelogenous leukemia, stem cell transplantation, refractory esophageal candidiasis)
Inhibits CYP3A4

31

Terbinafine (Lamisil)

Allylamines
MOA- prevents ergosterol synthesis by inhibiting the enzyme squalene oxidase; -cidal
PK- lipophillic- penetrates superficial tissues including the nails
Administered orally- fingernail and toenail regimens differ, 40% bioavailability due to 1st pass metabolism, therapy is 3 months.

32

Terbinafine (lamisil)- indications and ADRS

Active against dermatophytes and candida albicans
ADR- mild- HA, N/Dm rash, taste and visual disturbance
Rare but serious effects- cholestatic jaundice, blood dyscrasias, steven-johnson syndrome
Baseline LFTs and CBC (repeat q 4-6wks)

33

Onychomycosis (nail infection) treatments

Terbinafine- 1st line agent (not candida)
Itraconazole- alternative 1st line therapy (preferred for candida infections)
These drugs have REPLACED grseofulvin and ketoconazole for this type of infection

34

Caspofungin (Cancidas)

Echinocandins
2nd line therapy for those who failed amphoB or itraconazole (expensive)
Interferes w/ synthesis of fungal wall
Limited to aspergillus and candida species
ADRs- fever, rash, nausea, phlebitis, and flushing rxn.

35

Micafungin (Mycamine)

Echinocandins
Esophageal candidas
Prophylaxis of invasive candida infections in pts undergoing hematopietic stem cell transplantation
ADRs- fever, rash, nausea, phlebitis, and flushing rxn.