Pulm: Drugs used to Treat Fungal Infections Flashcards
Polyene fungal drug
Amphotericin B
Azole drugs for Pulm infections
Fluconazole
Itraconazole
Voriconazole
Echiocandin Drugs for Pulm Infections
Caspofungin
Micafungin
Andidudlafungin
MOA of Amphotericin B
Bind to ergosterol of fungal cells
but also cholesterol in human cells!
What organ is amphotericin specifically toxic for?
Nephrotoxic
-BB warning
Adverse effects of amphotericin?
CNS-headache, fever, chills Renal-toxic GI-dyspepsia, pain, cramping CV-hypotension Resp-tachypnea
What should you do when first prescribing amphotericin?
Prevent overdose–>cardiopulm arrest
-tell patients to verify name and dosage before administration
Monitor Closely!
-look for N/V, chills, rigors
Indications for amphotericin?
Those with life threatening fungal infections, NOT noninvasive forms such as thrush or candidiasis
MOA of the azoles?
Interrupt the conversion of lanosterol to ergosterol by binding fungal CYP450
What make voriconazole different than the other azoles?
Newer, so they have more activity against strains of Candida resistant to fluconazole
Should you give terfenadine with fluconazole?
No, contraindicated
What drugs should you not proscribe with fluconazole?
Those that prolong QT interval
-Class Ia and III antiarrythmics, erythromycin, etc
Is fluconazole safe in pregnancy?
No, has not been established
If a patient has QT prolongation or hypokalemia, is fluconazole appropriate?
Nope
-he has this like 4 times (important?)
The azole antifungals inhibit what CYP?
CYP3A4
-therefore increase the concentrations of a variety of drugs (CCBs, immunosuppressants, chemo, macrolides, SSRIs) etc
What can be done to increase absorption of Itraconazole?
Take with food and a high acidic beverage (OJ)
-increases absorption
When is itraconazole contraindicated?
Pregnancy, Left ventricular dysfunction, and HF (BB warning)
What are some adverse effects of intraconazole?
Hepatic damage
-jaundice, dark urine, N/V
MOA of voriconazole (slightly different than other azoles?)
Inhibits CYP450 mediated 14 alpha-lanosterol dimethylation
If a patient has QT prolongation or hypokalemia, is voriconazole appropriate?
Nope, can also prolong QT
What should you monitor before starting and during voriconazole therapy?
Hepatic liver tests
Which CYP does Voriconazole have the highest affinity for?
CYP2C19
Should you alter dosage of voriconazole in renal impairment?
Oral does NOT need an adjustment, but parenteral does
MOA of the echinocandins?
inhibit B(1-3)-D-glucan synthesis, so block the cell wall synthesis
Indications for the echinocandins?
IV use of systemic candida infection
Which anti-fungal can cause red-man syndrome?
The echinocandins (-fungins) -mast cell histamine release
Which echinocandin has had life threatening hypotension and bradycardia associated with it?
Anidulafungin
BB warnings of the echinocandins?
Hepatic malignancy (shown in rats) -monitor LFTs!!
MOA of flucytosine?
Prodrug of 5-fluorodeoxyuridulic acid, which interferes with DNA synthesis
What is flucytosine mainly used for now?
Combined with liposomal amphotericin for cryptococcal meningitis
can also be used in life threatening candidiasis
BB warning for flucystosine?
Renal and Hepatic impairment
-monitor closely
Also bone marrow toxicity
Is flucystosine okay during pregnancy? what about breastfeeding?
No and No
