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Pharmacology > GYN/Final: Anti-fungals > Flashcards

GYN/Final: Anti-fungals Flashcards

1
Q

fungal cell walls are made of

A

chitin

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2
Q

fungal cell membranes made of

A

ergosterol

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3
Q

two main fungi that cause dz in humans

A

yeasts

molds

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4
Q

which group of drugs alter cell membrane permeability (3)

A
  • azoles
  • polyenes (amphotericin B and nystatin)
  • terbinafine
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5
Q

which group of anti fungals block beta-glucan synthesis

A

echinocandins aka caspofungin

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6
Q

which group of drugs block nucleic acid synthesis

A

flucytosine

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7
Q

which group of drugs disrupt microtubule functions

A

griseofulvin

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8
Q

Amphotericin B

  • drug class
  • MOA
  • DOC for?
  • coverage

-kinetics: routes of admin, absorption, bound to?, distiburtion, metabolism, exxcretion, t/12

A

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
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9
Q

Amphotericin B adv rxn (5)

-how to get rid of some of them too?

A

“AMPHOterible”

  1. Nephrotoxicity****
    - dose dep
    - decrs GFR, Renal tubular function, Mg and K wasting,
    * **    liposomal formulas are assoc with less nephrotoxicity
  2. Anemia
  3. Fever/chills— long infusion times recc to avoid this
  4. Hypotension (severe) with hypokalemia
  5. Thrombophlebitis
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10
Q

what do you monitor for patients on Amphotericin B

A
  1. infusion related rxns
  2. renal function—b4 and during tx
  3. electrolytes
  4. CBC to monitor for anemia
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11
Q

how can you avoid thromboplebitis with Amphotericin B admin?

how can you avoid chills/fever assoc with infusion?

A

adding heparin to the infusion

avoid fever/chills rxn by doing a SLOW infusion

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12
Q

Nystatin

  • drug class
  • MOA
  • indications
  • routes
  • absorption
  • SE
A

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****

  1. contact dermatitis
  2. SJS
  3. hypersensitivity
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13
Q

how are azoles categorized

  • list the drugs in each category
  • difference b/w each category
A

Imidazoles: TOPICALLY for CUTANEOUS infections

  • clotrimazole
  • ketoconazole
  • miconazole

Triazoles: SYSTEMIC ADMIN for tx and prophylaxis systemic and cutaneous mycoses

  • fluconazole
  • itraconazole
  • voriconazole
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14
Q

azoles

  • MOA
  • pregnancy
  • resistance
A

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

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15
Q

Azoles are ____ to CYP__

A

inhibitors of CYP450 34A

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16
Q

Fluconazole

  • indications/spectrum
  • for the inds, list two big ones it covers
  • routes
  • abs–food or no food?
  • distribution
  • t1/2
  • SE
  • pregnancy
A
  • 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

17
Q

Itraconazole

  • spectrum
  • DOC
  • bioavail?
  • met
  • forms avail in
  • abs for each route
  • t 1/2
  • SE
  • avoid in?
A 
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
18
Q

what can impair the absoprtion of itraconazole capsule

A

PPIs

19
Q

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?
A

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*

20
Q

Clotrimazole

  • MOA
  • inds
A

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
21
Q

Miconazole

  • indications
  • routes of admin
A

localized tx for vaginal and PO candidiasis and DOC tinea

  • buccal
  • cream
  • vag suppository
22
Q

SE for clotrimazole and Miconazole

A

Contact dermatitis
Burning sensation
Vaginal discharge

PO uses:

  • Local discomfort of oral cavity
  • nasea
  • HA
  • diarrhea
23
Q

Efinaconazole

  • indicaitons
  • duration of tx?
A

Topical use for tx of

  1. Trichophyton rubrum
  2. Trichophyton mentagrphytes
  3. Candida albicans

duration of tx=48 weeks

24
Q

Terbinafine

  • class
  • indications + duration of tx
  • kinetics: bioavail, bound, deposition, half life, CYP?,
  • avoid in?
  • SE (3)
A

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
25
Q

List the one echinocandin we need to know

A

Caspofungin*** know this one

26
Q

Caspofungin

  • moa
  • routes
  • uses, DOC for?
  • kinetics: bioavail, any dose adjustments, metabolized, drug-drugs
  • SE
A

interfere with synthesis of fungal cell wall by inhibiting synthesis of beta-D-glycans–>cell lysis–>cell death

IV ONLY*** for all echinocandins

Indications:
*fungistatic for Aspergillus– SEC LINE

  • fungicidal for Candida (glabrata and krusei esp)
  • DOC for INVASICE candidasis and esophageal candidiasis esp in immmno comp

PO bioavail is poor- why its admin IV *** and IV only bc its for serious infections

YES for hepatic dysfunction

Metabolized CYP450
DRUG-DRUG: DO NOT GIVE WITH CYCLOSPORIN bc it causes transaminitis *****

SE: as a class, the echoinocandins are very wel tolerated + safe*** bc of the MOA (better tolerated than amphotericin)

  • nausea
  • fever + rash
  • phelbitis
  • flushing (slow infusing rates decrs risk)
  • asympto transaminitis
27
Q

what drug to not adminsiter with caspofungin and why

A

cyclosporin

causes transaminitis

28
Q

why are echoinocandins so well tolerated as a class?

A

because mamalian cells do not have beta-d-glycan

29
Q

Flucytosine (5-FC)

-uses

A

USES:

  • mc in combo***** with other anti-fungals for tx of:
    1. Cryptococcus
  • ->meningitis*****
30
Q

SE for 5-FC (6)

A
  1. Neutropenia (low WBC)
  2. Thrombocytopenia (low plats)
  3. Dose-related bone marrow suppression
    * FIRST THREE ARE REVERSIBLE
  4. hepatic dysfunction
  5. N/V/D
  6. Enterocolitis
31
Q

Griseofluvin

  • uses/routes
  • duration of treatmnt
  • kinetics: abs (incrs with?), not effective what route?, [ ]s where, metabolized,
  • contras
A

PO

INDS=Dermatophytosis of scalp + hair (tinea capitis)***
tx: 6-12MO (esp with onychomycosis) *****

Kinetics:

  • incrs w/ high fat meals
  • not effective topically
  • [ ] in hair, skin, nails, adipose tissue
  • CYP450 inducer

Contra in pregnancy

32
Q

Ciclopirox

-uses and routes

A

shampoo–seborrheic dermatitis

*creams, gels suspension–tinea pedis, corporis, cruris, cutaneous candida, tinea versicolor

33
Q

Tavaborole

  • uses and routes
  • moa
A

Toenail onychomycosis TOPICAL

tinea pedis
tinea cruris
tinea corporis

MOA: inhibits fungal protein synthesis

Pharmacology (28 decks)

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