Antifungals Flashcards
Antifungals
- Candidiasis
- Coccidiodomycosis
- Cryptococcosis
- Histoplasmosis
- Pneumocystis
- Blastomycosis
Categories of antifungals
Systemic drugs for systemic infections:
* Amphotericin B
* Flucytosine
* Azoles-> Triazoles and Imidazoles
* Echinocandins
Oral systemic for mucocutaneous infections
* Greiseofulvin
* Terbinafine
Topical drugs for mucocutaneous infections
* Nystatin
* topical azoles->Clotrimazole and Miconazole
* Topical allylamines-> Terbinafine and naftifine
Diagnosis of fungal diseases
- Clinical symptoms
- serologic testing
- histopathologic examination
- culture of clinical specimens
Fungi vs Bacteria
Bacteria: cell wall of peptidoglycan
Fungi:
* cell wall of chitin and other polysaccharides
* Eukaryotic-> ribosomes and dna-> similar to human cells and not a good drug target
* Cell membranes= ergosterol not cholesterol thus a drug target
Overall targets
Amphotericin B
IV
MOA: disrupts cell wall-> electrolyte channel
Activity: most candida, aspergillus, mucorales, endemic mycoses
AE: Infusion, transient Nephrotoxicity, electrolyte abnormalities
ORAL DOC FOR PREGNANCY
USE FOR SERIOUS AND LIFE THREATENING
Flucytosine
MOA: interfering both dna and protein synth-> inside cell wall
USE: COMBO WITH AMPHOTERICIN B BC MONOTHERAPY IS HIGHLY RESTRICTED
avoid in pregnancy
AE: hematologic (high rbc), hepatitis, GI- n/v/d
Azoles
- Imidazoles
* Ketoconazole- topical
* Miconazole- topical
* Clotrimazole-topical - Triazoles (all oral)
* Itraconazole
* Fluconazole
* Voriconazole
* Isavuconazole
* Posaconazole
Azoles general
Moa: cell membrane damage
AE: GI hepatotoxicity
avoid in prego
drug interactions: with CYP450
Imidazoles
- Clotrimazole- Myclex, Lotrimin
- Miconazole
- Ketoconazole
- Butoconazole
- Terconazole
spectrum against candida
Triazoles
- Itraconazole- BLASTOMYCOSIS, HISTOPLASMOSIS, SPOROTHRIX, risk of severe CHF- poor penetration into CSF
- Fluconazole-increased risk of miscarriage, GOOD CSF penetration
- Voriconazole- Primary for INVASIVE ASPERGILLOSIS with statins, cyclosporine, tacrolimus- HEPATOTOXIC, SKIN RASHES, SKIN CANCER SURVEILLANCE
- Isavuconazole- prodrug
- Posaconazole-prophylaxis for those with prolonged neutropenia - against candidiasis and aspergillosis
Drug interactions: Warfarin, oral hypoglycemics, benzodiazepines
NOT FOR PREGO
Imidazoles and triazoles AE
Itraconazole- hepatic failure and death
Fluconazole- Nausea, headache, rash, vomiting, SKELETAL AND CARDIAC DEFORMITIES IN INFANTS FROM PREGNANCY
Voriconazole- teratogenic, hepatotoxic, prolonged QT interval, visual and auditory hallucinations
Echinocandins
- Capsofungin- dissem and mucocut candidal infxn-> febrile neutropenia empiric
- Mycofungin- mucocutan candidiasis, and prophylaxis candida infxn in bm transplant
- Anidulafungin- esophageal candidiasis and invasive candidiasis
MOA: inhibit beta d glucan synth
AE: hepatotoxicity, inj site reactions, renal toxicities, cardiac toxic
Fungicidal
no research on pregnancy
Griseofulvin
MOA: inhibit microtubule fxn-> mitotic spindle
binds to keratin precursor cells-> prolonged resistance to fungal invasion
Narrow antifungal spectrum, low clinical efficacy, prolonged duration
Spectrum: Dermatophytes- microsporum, epidermophyton, trichophyton-> common skin infxn (Tinea corpus, capitus, pedes, unguium, cruris)
AE: Headache, leukopenia, neutropenia, basophilia, monocytosis-> CHECK CBC, efficacy of combination oral contraceptive agents= reduce it
NOT OKAY IN PREGNANCY
FATTY MEAL FOR ABSORPTION
TX HAIR SKIN AND NAILS
Terbinafine
- most commonly used topical drug for cutaneous dermatophyte infxn
- ORAL FOR TINEA UNGUIUM (NAIL)
- AVAILABLE OTC
- MOA: reduce ergosterol biosynth
- AE: LFTS MUST BE MONITORED DURING ORAL TX, rare toxic
Not for prego
Nystatin
MOA: induce membrane permeability-> intracellular leakage and cell death
Spectrum: candida, cryptococcus, histoplasma, coccidioides
AE: n/v/d
Uses: Oral thrush, Topical, Vaginal infxn
Thrush tx
- Nystatin
- Clotrimazole troches
- Fluconazole
1st line tx of fungal diseases
- Histoplasmosis- amphotericin
- Blastomycosis- self limited
- Coccidiodomycosis- extrapulmonary disease- amphotericin b and meningitis is fluconazole
- Crytococcosiss- Amphotericin B with flucytosine
- Candida- depends on location
- Aspergillosis- Voriconazole
Yeast infection
OTC: gyne-lotrimin, monistat
uncomp: Fluconazole
Complicated: Fluconazole, Nystatin, Amophotericin B or Flucytosine
Prego: imidazole vaginally
Combination topicals
fungal infxn with inflamm dermatitis
Ex: Lotrisone= clotrimazole and betathasone or Mycolog 2- nystatin and traimcinolone
Malaria Plasmodium overall
- immigrants or people from endemic countries
1. Chloroquine drug of choice, resistance growing but prophylax for Caribbean/CA
2. Quinin/quinidine- kills schizonts-> increasing resistance seen
Plasmodium species
- P. falciparum
- P. Vivax
- P. Malariae
- P. Ovale
Prophylaxis for malaria
Chloroquine- for susceptible
Doxycycline
Metronidazole (Flagyl)
Antibiotic, antiprotozoal, antiparasitic- broad spectrum
some anaerobic coverage
MOA: loss of helical dna-> breakage
Contraind: PREGNANCY AND USE OF DISULFRAM WITHIN PAST 2 WKS
Care with anticoags and dilantin
Metronidazole indications
Flagyl
- Amebiasis
- BVaginosis due to Gardnerella
- Diverticulitis
- gyn assoc pelvic infxn
- trichomoniasis
- CDiff assoc diarrhea
- Giardiasis
- Surgical site infxn
Bacterial vaginosis
Itchy, redness, gray white or yellow discharge, fishy smell, vaginal bleeding after sex
Metronidazole
if allergic: Clindamycin cream
Strawberry red cervix
Trichomonas infxn
Diarrhea, abdominal pain-> Giardia
- Tinidazole
- Metronidazole used off label
untreated water/pools in kids
Metronidazole/tinidazole patient education
- metallic taste
- ALCOHOL WILL MAKE YOU SICK
- MC nausea
- avoid propylene glycol products-> soft drinks, sweet tea, artificial sweeteners, marinades and dressings, frosting, food colorings, baked goods
SE of anti parasitics
- GI
- peripheral neuropathies
- flushing
- headache
- hematuria
- hypotension
- myelosuppression
Helminthes
- Cysticerscosis
- Neurocysticercosis
Uncooked pork
Caused by tapeworm Taenia solium
complication: invasions in CNS
TX:
1. Neurocystercosis 1st with surgery
2. Helminth second + Albendazole
Albendazole
Antihelminthic
MOA: degeneration of cytoplasmic microtubules in intestinal cells of helminths
warning: Bone marrow suppression and transaminase elevates
NOT FOR PREGNANCY IN 1ST TRIMESTER
SE: INCREASED INTRACRANIAL PRESSURE, alopecia, nausea, fever
Followup mri every 6 months for cystic lesions resolution
Pinworms
Mebendazole
2nd line: Albendazole- safe, minimal SE
DOC for ascariasis, enterobius
PT ed: shower, clena laundry
* keep fingernails short, children wash their hands
1st line: Pyrantel pamoate (Pin-X)- otc
Ectoparasites
Pediculosis (lice) and scabies
insecticides
scabies- intense itching in fingerwebs and feet, burrow underskin and channel
1. Permethrin cream- kids over 2 months- kills scabies mite and eggs (DOC FOR SCABIES)
2. Oral ivermectin- over 30% of body area
3. crotamiton lotion- adults
4. sulfur ointment- children under 2 months
5. Lindane lotion- toxic to nervous system- only for tx failures
Scabies and adjunctive measures
- tx rec for all household members at the same time
- bedding adn clothing during 3 days b4 tx should be washed and dried
- or store in closed plastic bag for several days to a week
- can return to work, child care, school, work the day after tx
Lice infestation
Pediculosis and Pthiriasis
- Launder all used in last 2 days in hot water
- plastic bag for 2 weeks
- vacuum
- rinse all pediculicides from hair over a sink
Pediculosis and pubic lice OTC
- Pyrethrins with piperonyl butoxid-> kills only live lice not unhatched eggs- 2 yrs and older
- Permethrin lotion 1%- kill live not eggs (nits), 2 months and older
lice prescription tx
- Benzyl alcohol lotion 5%- kills lice but not eggs $$$
- Ivermectin lotion 0.5%-prevents new hatched lice from surviving
- Malathion lotion 0.5%- kills lice and partially ovicidal
- Spinosad 0.9% topical suspension- kills lice and eggs $$$$$
Pneumocystis Jirovecii (carinii) Pneumonia (PJP)
MC OI in pts with AIDS
80% will have pjp at some point
Fungus with protozoan characteristics
SXS: fever, dyspnea, tachypnea, rales/rhonchi, nonproductive cough
DX: identification of organism in induced sputum or specimen
untreated= dead
TX: Trimethoprim-sulfamethoxazole (cotrimoxazole)
