Anaerobic Agents, Influenza, And Antifungals Flashcards
Clindamycin provides coverage for what type of bugs?
Gram + anaerobes
-Gr + S. Aureus, GABHS, CA MRSA
- abscesses, bacterial vaginosis
What is the MOA for Clindamycin?
Inhibits protein synth by binding to 50s ribosome; can compete with Macrolides
Both bacteriostatic and bactericidal
What is a good alternative drug if allergic to PCNs?
Clindamycin
What are the SE of Clindamycin?
C. Diff and diarrhea, fever/rash, minor risk of hepatotoxicity, neutropenia, and preterm birth with cream for bacterial vaginosis
What is the MOA of metronidazole (flagyl)?
Prodrug
With anaerobic bugs, can create free radicals toxic to cell, bind to DNA and cause cell death
- bactericidal
What is metronidazole (Flagyl) prescribed for?
- Gram - anaerobes
-* first line for c diff - *protozoal infections: trichomonas vaginalis, giardia, entamoeba histolytica
- soft tissue infections including acne, intraabdominal infections, colitis, bacterial vaginosis dt gardnerella vaginalis
- H pylori if you need an alternative to amoxicillin
What are the SE of metronidazole (flagyl)?
Metallic taste, neuropathies, seizures, disulfiram like reactions (avoid anything containing ETOH), inhibitor of CVY2C9 (DDI with s-warfarin)
What type of vaccine is Flumist and who should NOT get it?
-live attenuated
- avoid if egg allergy, GBS, immunocompromised, steroids, HIV, CA, asthma, 2nd and 3rd tri pregnancy, peds if taking aspirin
What should pts do if they get FluMist?
Avoid immunocompromised for 7d (book says 7, lecture says 21)
Which Influenza drugs are NOT recommended anymore?
Amantadine and Rimantadine
- dt resistance, no longer recommended, limited to flu A coverage
Which drugs are recommended for flu A and B?
Baloxavir, Oseltamivir (tamiflu), Peramivir, Zanamivir
Essentially, what do Baloxavir, Oseltamivir, Peramivir, and Zanamivir do?
Block viral budding and release via neuraminidase inhibition
Who can get Oseltamivir and what are it’s SE?
Any age group, oral or suspension, ok for NGT
- GI upset, HA
Which flu drug is given as an inhalation?
Zanamivir
- SE broncos pass, avoid with respiratory disease or milk protein allergy
Who should get a neuramidase inhibitor?
Severely ill, + comorbidities, in hospital and around other immunocompromised, even if its post 48h infection
- under 2y and over 65y, women pregnant or postpartum, adults taking long term aspirin, American Indian or AK Native, morbidly obese
Amphotericin is what type of antifungal?
Ergosterol Inhibitor
-fungicidal
- lipophilic drug, binds to ergosterol in cell wall causing lysis
Why can ergosterol inhibitors, like amphotericin, cause nephrotoxicity and electrolyte abnormalities?
Amphotericin creates a pore in cell membranes, but can also affect human cells, particularly in nephrons.
What are the SE of amphotericin?
-infusion reactions (chills, fever, rigors); give with NSAIDs, Benadryl, etc.
- with decreased CrCl if given too fast can cause cardiac dysrythmias dt electrolyte changes
- can increase toxicities of dig and neuromuscular blockers
What do the liposomal products do for amphotericin?
They provide lipid binding to protect against nephrotoxicity
Does amphotericin cross BBB?
No
What is flucytosine used for?
Typically with another drug like amphotericin B or fluconazole for cryptococcal/candidal meningitis, candida peritonitis, candiduria
What is Flucytosine’s MOA?
Related to chemo agent 5-FU, stops fungal cell replication by inhibiting DNA/RNA synthesis
How does flycytosine affect bone marrow?
If the trough is too high it can cause bone marrow suppression
What are flucytosine’s ADEs?
-bone marrow suppression, GI
- caution with other myelosuppressive drugs like clozapine, carbamazepine, AZT
- renal dosing
- fungus can down regulate cytosine deaminase for resistance
What is nystatin’s MOA?
Ergosterol inhibitor, binds to ergosterol in cell wall causing lysis
- no absorption from GI tract or topically, too toxic for IV, only given topical or vaginal tablet
What is nystatin given for?
Cutaneous, mucocutaneous and oral candida infections
What type of drug is Terbinafine?
Antifungal, ergosterol inhibitor, synthetic allylamine
-causes cell lysis
-large Vd
-t1/2 8-16d
What does Terbinafine cover?
Trichophyton, microsporum, candida, epidermiphyton, scopulariosis, dermatophytes (toe nail fungus)
How long is the dosing for Terbinafine for toe nail fungus?
12w
What are the clinical issues for Terbinafine?
SE: GI, malaise, dysgeusia, hepatotoxicity (check LFTs)
- can Rifampin can cause a 100% increase in clearance
- Cimetidine can cause a 33% reduction in clearance
What drugs are included in the ergosterol inhibitors class of Azoles?
[Triangles: Fluconazole, Itraconazole, Voriconazole]
[Imidazoles: Clotrimazole, Ketoconazole, Miconazole]
What is the MOA for Azoles?
Inhibit ergosterol synthesis by inhibiting an enzyme dependent on CYP450, inhibiting creation of ergosterol, inhibiting cell synthesis
- can also cross over and effect human cells (adrenal and gonadal steroid hormone formation)
Fluconazole is used for what?
Oral, esophageal, UTI, vaginal candida, cryptococcal meningitis dt good CNS penetration
Is fluconazole affected by food or gastric acidity?
No
Is fluconazole subject to renal dosing?
Yes, dt long half life
What drug to drug interactions should you watch out for with fluconazole?
Warfarin, as fluconazole is a CYP2C8/9 inhibitor
What is Itraconazole used for?
Aspergillosis, Blastomycosis, and Histoplasmosis mainly
- also onychomycosis, oral and esophageal candida
Does Itraconazole require food or gastric acidity to be absorbed?
Yes, but only with capsule. Caution with H2RA, PPI agents. Can take with a coke
What should you watch out for with Itraconazole?
Rising LFTs with long term use, and drug to drug interaction (strong CYP450 3A4 inhibitor
What is Isavuconazonium used for?
Invasive Aspergillosis and Mucormycosis
What should you watch out for with Isavuconazonium?
- drug:drug - major CYP450 3A4, OCT2, P-gp inhibitor
- monitor LFTs, renal dose
- can cause hypokalemia, edema, HA, N/V
What is Voriconazole given for?
Mostly Invasive aspergillosis and candidemia
- also esophageal candidiasis, scedosporiosis, fusariosis
What are the major drug:drug interactions with Voriconazole?
- need to increase maintenance dose of Voriconazole if on Dilantin
- will need to increase dose of efavirenz if on it
-2C19, 2C9 and 3A4 inhibitor
What are the SE of Voriconazole?
QT prolongation, melanoma, hallucinations, vision changes, liver tox, anaphylaxis w CKD
- absorption not dependent on gastric acidity, but take one hour before or after meal
- renal dosing recommended
-Preg D
What is Posaconazole used for?
Invasive Aspergillosis, candida infections, cryptococcal infections, mucormycosis
What are the SE of Posaconazole?
-fever, HA, fatigue, most at risk for QT prolong, electrolyte changes, n/v/d
- only renal dose when CrCl below 20
- strong 3A4 inhibitor
- take with meals, avoid PPI, H2RA
What antifungal is a pregnancy category D?
Voriconazole
Ketoconazole is given for what?
Fungal infections (candida, blastomycosis, histoplasmosis, paracoccidiomycosis)
*Seborrheic dermatitis
Tinea Versicolor
What forms do Ketoconazole come in?
Tablet, topical, shampoo
What other use is Ketoconazole used for besides fungal infections?
Prostate CA, dt inhibition of androgen synthesis via CYP450 inhibition of testosterone production
Does Ketoconazole penetrate into CNS?
No
Does Ketoconazole require gastric acidity?
Yes, avoid antacids, drink a coke
What is clotrimazole (Lotrimin) used for?
Cutaneous candidiasis and vulvovaginal candidiasis
What is Miconazole (Monistat) used for?
Tinea corporis (ring worm) or pedis (athlete’s foot) or cruris (jock itch)
Vulvovaginal candidiasis
What is Terconazole used for?
Vulvovaginal candidiasis
What is Luliconazole used for?
Tenia pedis, Tinea cruris or corporis
What is oxiconazole (oxistat) used for?
Tinea corporis, cruris, pedis, and versicolor
What is Sulconazole used for?
Tinea infection
What is Efinaconazole used for and why is it a pain in the ass?
Onychomycosis (toe nail infection), requires you to paint your toes with it qd x 48 weeks
Echinocandins are which drugs?
Anidulafungin, caspofungin, micafungin
What is the MOA for echinocandins?
Inhibits formation of 1,3 beta D glucan, a component of candida cell walls, resulting in lysis
What form are echinocandins given?
IV
What are echinocandins given for?
Candidemia, aspergillosis (caspofungin), and prophylaxis for stem cell transplants (micafungin)
What are the SE for anidulafungin?
Itching. no renal dosing. No known drug interactions
What are the SE for caspofungin?
Hypotension, edema, tachycardia, fever/chills, HA, hypokalemia, N/V/D, increased LFTs, phlebitis
- no renal dosing but decrease with hepatic impairment
- up dose for CYP450 inducers (rifampin, carbamazepine, phenytoin, efavirenz, nevirapine)
- avoid with cyclosporine dt hepatic tox
What are the SE for Micafungin?
hypokalemia, hypomag, fever, HA, N/V/D, thrombocytopenia, insomnia, phlebitis, BP changes
- no renal or hepatic dosing
What is Griseofulvin used for?
Ringworm of scalp, body, or foot caused by trichophyton, microsporum, epidermophyton
What is Griseofulvin’s MOA?
Fungistatic. Targets new skin where it binds to keratin, preventing new fungal infections. Treatment takes a long time
What is the pregnancy category for Griseofulvin?
Category D/X
