Tinea and onchomycosis Flashcards
Tx of infections; MOA; Elim and dose mod in dysfxn; drugs producing hepatic or CV dysfxn; CYP interactions; teratogenic actions; immune suppression
For widespread tinea infections, what can be used?
terbinafine; itraconazole; fluconazole;
localized tinea infection Tx
Azoles; terbinafine; naftifine; ciclopirox
Tx for onychomycosis
terbinafine; itraconazole; fluconazole
Tx for onchomysis topical
ciclopirox; amorolfine
What is the MOA for ciclopirox?
blocks fungal transmembrane transport and depletes essential substrates thus interfering with DNA/RNA synthesis (high [ ] cause intracellular leakage)
does Ciclopriox have effects on the fungal cell wall?
NO=> does not inhibit synthesis or cause lysis
What are significant toxicities with systemic Azole admin?
organ dysfxn; contraindication in concurrent disease or drug (CYP) interactions
What are the advantages and disadvantages of topical tx of azoles?
Tx occurs w/o significant systemic toxicity but not suitable for all infections
Ketoconazole use is limited for what reasons?
Hepatoxicity; adrenal insuffiency; DDI with CYP
What is a DDI of fluconazole, posaconazole and voriconazole?
CYP 3A4 interactions
Which drugs affect 2C9 and 2C19?
fluconazole; voriconazole
Posaconazole affects what type of activity?
P-gp activity
What are ADEs associated with fluco, posacon and voricon -azoles?
QT prolongation and dysrhythmias; hepatotoxicity; elevated LFTs
What are specific ADEs of voriconazole?
visual disturbances (optic neuritis: color change, photophobia); photosensitizes the skin in SCC and melanoma
Can flucon, posacon and voricon reach the CSF?
yes (dep on molec weight and P-gp affinity):
Flucon > voricon > itracon
What is significant for administration with posaconazole?
MUST be with full meal or acidic carbonated drink for adequate bioavailability
What is the effect of flucon, posacon and voricon in pregnancy?
contraindicated in pregnancy (Cat C)
What is the elimination of fluconazole?
renal
Dose adjustment with fluconazole?
yes with organ dysfxn
Metabolism of flucon, posacon and voricon
extensie hepatic metab
Terbinafine metabolism
hepatic (long half life)
terbinafine elimination
renal
What ADEs are associated w/ oral terbinafine usage
lymphopenia and neutropenia
What patients should avoid taking terbinafine?
immunosuppressed => cause opportunistic infections
admin of amorolfine
topical only with limited absorption
Terbinafine use in pregnancy
category B so risk is very little
MOA for naftifine?
anti-inflam via inhibition of inflam mediators such as PG, LTs and histamines => causes vasoconstriction
Naftifine static or cidal
locally cidal against G+ and G-
Metabolism of naftifine (topical)
hepatic
elimination of naftifine (topical)
renal
Contraindications for naftifine use
Hx of hypersensitivity to drug or co-formulated materials
What should naftifine not be used with?
topical azoles
Why cant topical azoles and naftifine be used together?
pharmacodynamic interference=> inhibits sterol production at earlier points so will diminish effectiveness
DDI with naftifine
no systemic DDI
Ciclopirox admin
topical only but limited absorption
Possible ADE with ciclopirox or amorolfine
hypersensitivity/allergy to drug or co-formulation materials; irritate if on skin abrasions
MOA of amorolfine
inhibits ergosterol synthesis
What are BBW with itraconazole?
heart failure; ventricular dysfunction; co-admin w/ drugs
MOA of itraconazole?
negative inotropic action (decrease force of heart contraction)
Metabolism of itraconazole
extensive hepatic
elimination of itraconazole
renal
Contraindications of itraconazole
concurrent drugs with CYP interaction;
liver dysfxn/hepatic toxicity => monitor LFTs;
post-partum
Pregnancy and itraconazole
Cat C but congenital deformities present
Post-partum and itraconazole
distributed in breast milk
