GYN/Final: Anti-fungals Flashcards
fungal cell walls are made of
chitin
fungal cell membranes made of
ergosterol
two main fungi that cause dz in humans
yeasts
molds
which group of drugs alter cell membrane permeability (3)
- azoles
- polyenes (amphotericin B and nystatin)
- terbinafine
which group of anti fungals block beta-glucan synthesis
echinocandins aka caspofungin
which group of drugs block nucleic acid synthesis
flucytosine
which group of drugs disrupt microtubule functions
griseofulvin
Amphotericin B
- drug class
- MOA
- DOC for?
- coverage
-kinetics: routes of admin, absorption, bound to?, distiburtion, metabolism, exxcretion, t/12
class: polyene anti-fungal/anti-abx
MOA:
- binds to ergosterol in fungal cell membrane–>makes it more permeable–>creating pores–> things leak out–>cell death
- fungicidal mainly
DOC: systemic mycoses for SEVERE LIFE THREATENING invasive infection
Coverage: wide rangemainly know it can cover a lot
- Aspergillus
- Blastomycese
- Candida Albicans
- Cryptococcus
- Histoplasma
- Mucor
Pharmkinetics:
- only injectable formulas: can be modified for direct insertion (intrathecal or bladder)
- SLOW IV INFUSION
- poor GI absorption*
- formulated with lipids to make it less nephrotoxic
- very bound to plasma proteins
- good distribution–> EXCEPT CNS***, eye, peritoneal fluid and synovial fluid
- 2 week T1/2
- hepatic metabolism
- small amt excretion in urine
Amphotericin B adv rxn (5)
-how to get rid of some of them too?
“AMPHOterible”
- Nephrotoxicity****
- dose dep
- decrs GFR, Renal tubular function, Mg and K wasting,
* **liposomal formulas are assoc with less nephrotoxicity - Anemia
- Fever/chills— long infusion times recc to avoid this
- Hypotension (severe) with hypokalemia
- Thrombophlebitis
what do you monitor for patients on Amphotericin B
- infusion related rxns
- renal function—b4 and during tx
- electrolytes
- CBC to monitor for anemia
how can you avoid thromboplebitis with Amphotericin B admin?
how can you avoid chills/fever assoc with infusion?
adding heparin to the infusion
avoid fever/chills rxn by doing a SLOW infusion
Nystatin
- drug class
- MOA
- indications
- routes
- absorption
- SE
Polyene anti-fungal
MOA: same as amphotericin
Routes:
PO—swish/swalllow or spit
Topically: lotions, creams, gels, etc
Indications: *Localized tx* for oral, esophageal and cutaneous CANDIDIASIS ****swish and swallow ****swish and spit
- cream
- oral suspension (oral and esophageal)
- cream, ointment and powder (cutaneous or vulvovaginal)
- IV USE LIMITED DUE TO TOXICITY
*Poor GI Absorption
SE: Oral suspension 1. diarrhea 2. nausea 3. stomach pain 4. vomiting 5. hypersensitivity
Topical****
- contact dermatitis
- SJS
- hypersensitivity
how are azoles categorized
- list the drugs in each category
- difference b/w each category
Imidazoles: TOPICALLY for CUTANEOUS infections
- clotrimazole
- ketoconazole
- miconazole
Triazoles: SYSTEMIC ADMIN for tx and prophylaxis systemic and cutaneous mycoses
- fluconazole
- itraconazole
- voriconazole
azoles
- MOA
- pregnancy
- resistance
block cytochrome CYP450 –>interferes w/ ergosterol synthesis–>disrupts cell mem–>cell lysis + death
Fungicidal
*but fungistatic against Candida
Contra in pregnancy bc teratogenic
Resistance is increasing–esp with immunocomp PT
Azoles are ____ to CYP__
inhibitors of CYP450 34A
Fluconazole
- indications/spectrum
- for the inds, list two big ones it covers
- routes
- abs–food or no food?
- distribution
- t1/2
- SE
- pregnancy
- candida Albicans* esp for candidemia–> NOT Krusei or Glabrata
- cryptococcus: suppression and tx after Amphotericin and 5-FC
- Coccoides
- Leishmaniasis
TWO BIG ONES IT COVERS: candidemia and cryptococcus meningitis
PO or IV
- very good PO abs–over 90% bioavailability with or without food or pH
- distribution= single dose widely distributed including urine, prostatic fluid and CNS*****
T1/2= 24 hours
SE:
- n/v
- HA
- skin rashes
- AST/ALT change
*gen not used in pregnancy
Itraconazole
- spectrum
- DOC
- bioavail?
- met
- forms avail in
- abs for each route
- t 1/2
- SE
- avoid in?
Broad spectrum DOC: ****Blastomycosis *****Histoplasmosis AKA fungal lung infections
*asperigillus–NOT DOC tho
*High bioavailability–esp in lungs
CAPSULE OR SOLUTION
Capsule: abs is best with food and low pH
Solution: abs is best on empty stomach with acidic beverage
t 1/2: long
met by liver
Distribution: lungs** and all over
SE:
- n/v
- rash
- triad: hypoK, HTN and edema
- ***AVOID in ventricular dysfunction due to its negative inotropic effect
what can impair the absoprtion of itraconazole capsule
PPIs
Vorionazole
- routes
- similar to what drug
- spectrum/DOC
- bioavail…. w or w/o food
- drug interactions
- what happens if you increse dose
- SE— MC one?
IV, PO
*sim to Ketoconazole
Spectrum:
- Aspergillus DOC
- DOC: Candida glabrata and C. krusei
> 90% bioavail PO
***best on empty stomach
widely distributed– YES CNS
Inhibits CYP450 so many drug-drug interactions ****
increase the dose by 50%=can lead to 150% increase in [serum]=non-lineaer pharmacokinetics
SE:
- Vision changes
- visual and auditory hallucinations
*RASH in 7% ** MC— worry about this one
- periostitis with prolonged use
- cardiac toxicity: tosades, QTc», sudden death)
- Alopecia
- nail changes
MONITOR LEVELS IS VERY IMP*
Clotrimazole
- MOA
- inds
MOA: alerts permeability of fungal cell wall–>cell death
INDS: Candida and DOC Tinea
- topical tx for oral, cutaneous and vaginal
- troche=PO/dissolves in mouth
- **cream=cutaneous and vaginal
Miconazole
- indications
- routes of admin
localized tx for vaginal and PO candidiasis and DOC tinea
- buccal
- cream
- vag suppository
SE for clotrimazole and Miconazole
Contact dermatitis
Burning sensation
Vaginal discharge
PO uses:
- Local discomfort of oral cavity
- nasea
- HA
- diarrhea
Efinaconazole
- indicaitons
- duration of tx?
Topical use for tx of
- Trichophyton rubrum
- Trichophyton mentagrphytes
- Candida albicans
duration of tx=48 weeks
Terbinafine
- class
- indications + duration of tx
- kinetics: bioavail, bound, deposition, half life, CYP?,
- avoid in?
- SE (3)
Squalene epoxidase inhibitors
MOA: ergosterol biosynthesis
Uses:
*PO: DOC for dermatophyte onychomycoses, Trichophyton X3MO, tinea capitis
Topical: tinea pedis, capitis, cruis, versicolor
Kinetics:
- bioavail: limited due to first pass met (40%)
- HIGHLY protein bound–depositing skin, nails, adipose tissue
- T 1/2: 200-400 hours… very slow release from tissues
CYP450 inhibitor
AVOID in mod-severe renal impairment
SE:
- GI
- taste disturbances/lose taste
- elevated transaminases
