Drugs for Fungal Infections and Influenza (Staudinger) Flashcards
Fungal Infection Drugs
What drugs are found in these families:
- Echinocandin (C/M/A)
- Azole Drugs (F/I/V)
- Polyenes (AB)
- Flucytosine
- caspofungin, micafungin, anidulafungin
- “-fungin”
- fluconazole, itraconazole, voriconazole
- Amphotericin B
- Flucytosine
Amphotericin B
What is its MOA, what does it affect in mammalian cells and what does it lead it, and what 4 fungal infections is it indicated for (A/C/CN/BD)?
MOA: binds to sterol component of cell membrane leading to alterations in cell permeability/integrity and death (binds ergosterol in in fungal cell wall)
- standard treatment of severe, invasive fungal infec.
- reserved for pts. unable to tolerate other agents
- binds to CHOLESTEROL in mammalian cells = CYTOTOXICITY (very NEPHROTOXIC)
I: Cryptococcus neoformans, Blastomyces dermatitidis, aspergillus, candida
- NOT for NON-INVASIVE fungal infections
Amphotericin B
Why should use be cautioned and what can improper use lead to?
- want to prevent inadvertent overdose = fatal cardiac/cardiopulmonary arrest
- make sure to verify product name and dosage pre-administration, especially if dose is over 1.5 mg/kg
- anaphylaxis has also been reported along with nausea, vomiting, chills, and rigors (more common with IV administration)
Which form of Amphotericin B, deoxycholate or liposomal AmBisome formulation), is significantly more nephrotoxic?
Amphotericin B deoxycholate
Fluconazole
What is its MOA, what are two contraindications of use (T/QTP), and how does it affect pregnant pts?
MOA: interruption of conversion of lanosterol to ergosterol by binding to fungal cytochrome P450 and subsequent disruption of fungal membranes
CI: terfenadine and drugs known to prolong QT interval/metabolized via CYP3A4
P: could cause SERIOUS/specific BIRTH DEFECTS
Fluconazole
How does it affect the QT interval, which pts should be cautioned when taking Fluconazole (HK/CF), what drug should it NOT be used with, and how is it metabolized?
- associated with prolongation of the QT interval on ECG by inhibiting the Rectifier Potassium Channel current
- causes Torsade de pointes
- caution use in pts. with hypokalemia and advanced cardiac failure
- do NOT give Fluconazole with erythromycin (inc. risk of cardiotoxicity and sudden death)
M: both substrates and INHIBITORS of CYP3A4 (inc. lvls of other drugs metabolized by CYP3A4, such as CCBs, chemotherapeutics, SSRIs, macrolides, etc)
Itraconazole
What is its MOA, what is a potential harmful effect of use (LD), what is its major Black Box Warning, and how is it metabolized?
MOA: interruption of conversion of lanosterol to ergosterol by binding to fungal P450 and subsequent disruption of fungal membranes
- rarely causes liver disease (N/V that won’t stop, jaundice, dark urine, abdominal pain)
BB: heart failure (inotropic effects that can exacerbate)
M: CYP3A4
Voriconazole
What is its MOA, what 3 pts should NOT take this drug (HGI/LLD/GGM), and how is it metabolized?
MOA: interruption of conversion of lanosterol to ergosterol by binding to fungal P450 and subsequent disruption of fungal membranes
CI: pts with Hereditary Galactose Intolerance, Lapp Lactase Deficiency, Glucose-Galactose Malabsorption
- voriconazole contains LACTOSE
M: CYP2C19 (also CYP2C9 and CYP3A4)
- oral administered can be used in renal failure
- parenteral can NOT be used in renal failure
Echinocandins
What is this families MOA, what infection is Micafungin used for mainly, what is an adverse effect of these drugs (RMS), and what is their major Black Box Warning?
MOA: inhibit Beta(1,3)-D-glucan synthase, a key enzyme for integrity of the fungal cell wall that forms glucan (major component of cell wall)
- damages fungal cell walls
- can be given IV for systemic Candida infections (especially in patients undergoing hematopoietic stem cell transplantation)
AE: “Red Man” syndrome
BB: for Micafungin in European Medicine Agency but not US FDA due to development of foci of altered hepatocytes and tumors after >3 month treatment period in rats
Fluctyosine
What is its MOA, what 4 drugs has it been used in combination with (K/F/I/AB), what are its 4 Black Box Warnings (RI/P/BF/BMD), and how is it metabolized?
MOA: pyrimidine analogue that has activity against fungal species that interferes with purine/pyrimidine metabolism
- used in combo with ketoconazole, fluconazole, itraconazole, and liposomal amphotericin B (CRYPTOCOCCAL MENINGITIS)
BB: renal impairment, pregnancy, breastfeeding, and bone marrow depression (irreversible in immunocompromised pts)
M: minimal hepatic, 96% eliminated via renal (URINE)
What are the 3 families of Influenza drugs (NI/A/B) and what are the 3 drugs in the Neuraminidase Inhibitor family (O/P/Z)?
- neuraminidase inhibitors, amantadine, baloxavir
NI: oseltamivir (ORAL), peramavir (IV), zanamivir (INHALED)
Neuraminidase Inhibitors
What is their MOA and what does it cleave, what is the indication of Oseltamivir, and what are two warnings of use (BI/AV)?
MOA: competitively inhibit viral neuraminidase enzymes and prevent viral reproduction by budding from host cell (cleaves SIALIC ACID in glycoproteins on surface of human cells)
OI: influenza A and B in pts. within 48 hrs (acute, uncomplicated illness)
W: serious bacterial infections may begin and do NOT give live vaccine (intranasal) 2 wks before or 48 hrs after oseltamivir is given (interfere with vaccine effectiveness)
Oseltamivir is NOT substitute for early flu vaccine
Peramivir (Intravenous Neuraminidase Inhibitor)
What is its indication?
I: treatment of acute uncomplicated influenza in pts 18+ who have been symptomatic for no more than 2 days
Baloxavir
What is its MOA and what 2 enzymes is it metabolized by?
MOA: inhibits virus mRNA replication = NO TRANSCRIPTION
M: UGT1A3 and CYP3A4
Amantadine
What is its MOA, what other disease can it be used for, and what are 3 major warnings of use (NMS/RD/LD)?
How is it metabolized?
MOA: not clearly understood, but may interfere with function of transmembrane domain of the viral M2 protein (Influenza A); also used for PARKINSONS (inc. dopamine and does NOT possess anticholinergic activity)
W: Neuroleptic Malignant Syndrome (due to dose reduction or withdrawal), renal disease, liver disease
- early diagnosis is IMPORTANT
M: not metabolized by P450s or UGT enzymes
- half-lives range from 10-14 hrs
- renal impairment inc. this to 7-10 days
