Fungi RX Flashcards
Hazen and Brown ASKED what question? “the good idea”
Is there a bacterium that produces a chemical that kills mold?
No funal b4 1954
Most systemic fungal infx had 50-100% mortaility
Streptomyces noursei bacterium, the source of the world’s first antifungal drug
Nystatin. 1950, FDA approved 1954
Too toxic for systemic administration used as a topical
What are the structural differences btwn Nystatin and amphotericin B?
1) Structure- NY STATE IN- 6 double bonds
AMP- one extra double bond, 7 total
Made from streptomyces nodosus, G+, non water soluble, Amphoteric polyene macrolide
(2) MOA- bind to ergosterol fungi cell wall. Open pores, Leak K+
(3) P’kin-NYstatin, topical and oral, t1/2 15d, NO Adj
AMP B- IV only!
(4) Orgs-Broad, yeast, CANDIDEMIA, cryptococus neoformans
(5) Clinical uses DOC: mycotic infx, cryptococcus, histoplasma, blastomyces, coccidioides, aspergillus
(6) Major ADRs -nephrotoxicity-baseline serum creatinine; hepatotoxicity, additive w/ other renal toxic drugs. LOW TW, Hypertension, phlebitis IV site
(7) Resistance-Dec drug affinity/binding to ergosterol,
dec concentration of ergosterol
Why was Amphotericin reformulated into lipid emulsions?
in order to reduce human toxicity
Mr. Jones, this fungi will treat your cryptococcus neoformans. Its is similar to pyrimidine and cystosine, thus affecting DNA, RNA. This drug is activated by phorphylation, and flora l/t antineoplastic drug that is toxic. We will need to adj due to your renal dz. Lastly we will add Amp B, for more bang!
FLUTICOSINE
1) Structure-water soluble synthetic pyrimidine. Similar to cytosine.
(2) MOA- convert drug to phosphorylated
active compound. inhibits DNA, RNA synthesis. Human dont phosphorylate flucytosine. Synergistic w/ amphotericin
(3) P’kin-ORAL.CSF, adjustment for renal failure. Cp levels to avoid toxicity and ensure efficacy.
(4) Orgs- narrow range
(5) Clinical uses- Cryptococcus neoformans and chromoblastomycosis, some candida species only.
(6) Major ADRs -Intestinal flora may biotransform drug to toxic antineoplastic drug, fluorouracil. Bone marrow toxicity/MYELOSUPPRESSION with amphotericin B.
Measure Cp.
(7) Resistance-reduced metabolism phosphorylation
Ms. Dowd, this drug will help your treat and prevent fungi MENGINITIS. This drug works with a CYP450 enzyme. But this enzyme affects other drugs, but has wide TW. So safe, but not if your are PREG.
FLUCONAZOLE
1) Structure-synthetic imidazoles or triazoles
(2) MOA-dec ergesterol by INHIB fungi CYP450 enzymes. NOT topical d/t affinity
(3) P’kin - RENAL. ORAL, higher water solubility, CSF penetration. PO, IV
(4) Orgs.- TX and Prophlaxis, cryptococcal meningitis, ICU candidemia, echinocandons, mucocutaneous candidiasis. VJ.
(5) Clinical uses
(6) Major ADRs -least drug interactions, d/t CYP450. widest therapeutic index. PREG D
(7) Resistance- mutations of CYP450 enzyme, dec binding
MR. PETER, this PILL will help your treat BROAD CANDIDA, not your skin. This drug works with a CYP450 enzyme so many drug affect this. We will need to monitor LIVER. This also may upset your stomach. Are your on RIF, RIFbut, Rifa? Maybe let not use this drug.
ITRACONAOLE-BROADER- NO CNS
KETOCONAZOLE
1) Structure-synthetic imidazoles or triazoles
(2) MOA- dec ergesterol by INHIB fungi CYP450 enzymes AND HUMANS. NOT topical d/t affinity
(3) P’kin -HEPATIC, Poor CNS
(4) Orgs. -BROAD
(5) Clinical uses -CANDIDA, endemic, mycoses, dermatophytes, and aspergillus. NOT for skin or nail
(6) Major ADRs - CYP450 drug-drug interactions, GI, LIVER, Adrenal
(7) Resistance- mutations of CYP450 enzyme, dec binding
MR. GLUE
HI, We are inserting this IV for your ASPERGILOSIS, bc Amp B not working. You may have stomachache, redness, and adj for your LIVER dz. This blocks an enzyme called GLlUCAN, which destroys the fungi cell wall.
ECHINOCANDINS
CASPOFUNGIN
1) Structure- synthetic cyclic peptides
(2) MOA- inhibition BETA (1-3) GLUCAN destroys cell
walls
(3) P’kin -IV. RENAL excretion
(4) Orgs. - fungal CANDIDA, ASPERGILOSIS
(5) Clinical uses - WHEN amphotericin B has failed
(6) Major ADRs- GI. HEPATIC dz adj dose.
(7) Resistance- NONE
MRS. Grizly,
Good news you are not PREG, so we can treat this systemic dermatophytosis kerion on your head. This is LONG TERM pill is best w/ HIGH fat food. This binds to keratin protein new skin blocking microtubule and is made from PCN.
GRISEOFULVIN
1) Structure-penicillium mold
(2) MOA-binds to keratin in new skin, inhibition of fungal mitosis by blocking microtubule. LTC
(3) P’kin - ORal w/ high fat food
(4) Orgs. (5) Clinical uses -systemic dematophytosis
(6) Major ADRs -allergic syndrome, serum sickness, serious skin rxn w/ warfarin and phenobarbital. PREG D, anticoagulants, Porphyria
replaced by terbinafine.
Mrs. Vanity,
This ointment will help you VJ yeast, and is safe PREG B. DO NOT EAT bc will affect your anticoagulation meds.
1) Structure-imidazole, monistat
(2) MOA- dec ergesterol by INHIB fungi CYP450 enzymes. NOT topical d/t affinity
(3) P’kin
(4) Orgs. (5) Clinical uses - oral thrush, diaper, yeast VJ, tinea corporis, SCD
(6) Major ADRs -Drug interactions,CYP3A4, anticoag, pheytoin. LFTs PREG B-small amounts. weak condomes
(7) Resistance-mutations of CYP450 enzyme, dec binding
Topical Azoles: miconazole ,
1) Structure-imidazole , monistat
(2) MOA- dec ergesterol by INHIB fungi CYP450 enzymes. NOT topical d/t affinity
(3) P’kin
(4) Orgs. (5) Clinical uses – tineas, VJ yeast,
(6) Major ADRs -Drug interactions, anticoag, pheytoin
(7) Resistance-mutations of CYP450 enzyme, dec binding
Mr. Ally Tinea
Lets try this PILL onycho infx on your feet and toes. This may affect TASTe and eyes, but little drug interaction. This detrosy fungi by inhibits squalene epoxidase. Good news is no interactions.
TERBAFINE
1) Structure- allylamine
(2) MOA-inhibits
squalene epoxidase. Fungicidal.
Squalene is toxic
to fungi.
(3) P’kin - Oral, RENAL urine
(4) Orgs. (5)onychomycosis, dermatophytoses, tinea cruris (jock itch crura) and tinea corporis (ringworm legs and arms, tinea pedis, tina capitis
(6) Major ADRs -preg B, hepatotoxicity, in breast milk. Taste and vision. Little CYP450 drug
(7) squalene mutation
Mr. Nas
This drug is a ally structure if you care to know. But many this will help you jock itch, ringworm, and athlete foot from that wrestling match. Will check you vision.
NAFTIDINE
1) Structure-allylamine
2) MOA-inhibits
squalene epoxidase. Fungicidal.
Squalene is toxic
to fungi.
(3) P’kin - topical. RENAL urine
(4) Orgs. (5) Clinical uses tinea cruris (jock itch crura) and tinea corporis (ringworm legs and arms, tinea pedis. (foot)
(6) Major ADRs -preg B, hepatotoxicity, in breast milk. Taste and vision. Little CYP450 drug
(7) Resistance- squalene mutation
What does Polyenes (amphotericin B) target?
ergosterol in fungal cell walls
What enzyme does Azoles (ketoconazole etc.)target?
fungal CYP450
Echinocandins blocks what?
D-glucan synthesis in fungi
RX-caspofungin
