Antifungals, antimycobacterials, antivirals Flashcards
What’s a genus of bacteria that includes many species of pathogens?
mycobacterium
What are the targets of antimycobacterials?
enzymes that mycobacteria use to build their cell walls
How are mycobacteria different than typical bacteria?
easier to control but harder to treat because they replicate slower.
CAN exist in a dormant state which makes them resistant to nearly all abx
What’s the standard treatment in active mycobacterial disease?
- Rifampin
- Isoniazid
- Pyrazinamide
- Ethambutol
Note: takes weeks to get susceptibility results
How does isoniazid work?
- bactericidal
- inhibits mycolic acid synthesis!
- effective against active AND dormant TB
- acts as a weak MAO-I (careful with SSRI/SNRI)
- alters pyridoxine metabolism (give B6 to all patients)
What are the two most important drugs for TB?
- isoniazid
- rifampin
What is isoniazid active against?
M. tuberculosis and M. kansasii
How is isoniazid clinically utilized?
mycobacterial infections
When is isoniazid your DOC?
latent TB, active TB
What are ADRs of isoniazid?
hepatotoxicity, peripheral neuropathy (use pyridoxine), hemolysis in G6PD deficiency
What are examples of rifamycins?
- rifampin
- rifabutin
- rifapentine
- rifaximin
What’s the MOA of rifamycins?
- bactericidal
- Inhibits DNA-dependent RNA polymerase
- very good oral bioavailability
- resistance emerges when drug is used alone
What should you always screen for drug ineractions?
rifamycins – extremely potent CYP450 inducers!!
also, reduced effectiveness of oral contraceptives
What are rifamycins GOOD for?
mycobacteria
What are rifampins moderate for?
staph, acinetobacter, enterobacterciae
What are rifamycins utilized for?
mycobacterial infections – usually in combo w/ deep seeded “typical” bacterial infections (MRSA) or if prosthetic material
When is rifamycin your DOC?
TB = tuberculosis, MAC = mycobacterium avium complex
What are ADRs of rifamycins?
orange-red colored secretions (urine, tears)
Do rifamycins have DIs?
many due to enzyme induction
What’s the MOA of pyrazinamide?
- bacteriostaticuncertain but requires bioactivation via hydrolytic enzymes to form pyrazoic acid
- shortens duration 9m - 6m
NOT pyridoxine
AVOID IN PREGNANCY
When are pyrazinamides clinically active?
M. tuberculosis
When are pyrazinamide clinically utilized and is your DOC?
active TB
What are the ADRs of pyrazinamide?
polyarthralgia (40%), hyperuricemia, mylagia, maculopapular rash, porphyria, photosensitivity
What’s the MOA of ethambutol?
- bacteriostatic
- inhibits formation of arabinoglycan, component of mycobacterial cell wall
- only 1st 2 months of tuberculosis therapy
- **NOT recommended in children <5yo **
When is ethambutol clinically active and utilized?
- M. tuberculosis, M. avium-intracellulare, M. kansaii
- active TB and MAC infections
What are ADRs of ethambutol?
- dose-dependent visual disturbances
- headache
- confusion
- hyperuricemia
- peripheral neuritis
- difficulty deferentiating from red and green
What are the increase of systemic fungal ifnections a consequence of?
medical advancement
What are types of moulds?
aspergillus (a. fumigatus, mucor spp, rhizopus spp)
dermatophytes
What are types of yeasts?
candida (C.albicans)
cryptococcus (C.neoformans, C. gattii)
Malassezia (M. furfur)
What are dimorphic fungi?
histoplasma capsulatum
coccidioides immitis
sporothirix schenkii
blastomyces
Imidazoles: COMET-K
Clotrimazole
Oxiconazole
Miconazole
Econazole
Tioconazole
Ketoconazole
Triazoles: FIT VIP
Fluconazole
Itraconazole
Teraconazole
Voriconazole
Isavuconazole
Posaconazole
Allyamines: TAN
Terbinafine
Amorolfin
Naftifine
Echinocandins: MAC
Micafungin
Anidulafungin
Caspafungin
What are examples of polyenes?
amphotericin B, nystatin
What is the MOA of polyenes?
- fungicidal/fungistatic (dependent)
- binds to ergosterol in fungal cell membranes, forming leaky pores
What’s used to decrease polyene side effects?
lipid formulations and different dosing dependent
What are ADRs of polyenes?
nephrotoxicity, infusion reactions (chills, fever, muscle spasms, hypotension), electrolyte abnormalities (hypokalemia)
When do polyenes have good coverage?
candida and aspergillus, cryptococcus neoformans, dimorphic fungi, molds
When do polyenes have moderate coverage?
zygomycetes
When are polyenes clinically utilized?
unknown fungal infections, use for candidiasis and aspergillosis (less often with newer/safer agents)
When are polyenes your DOC?
cryptococcal meningitis and serious dimorphic fungi and mold infections
What are DIs with polyenes?
nephrotoxic drugs (additive)
What are examples of azoles?
fluconazole, itraconazole, voriconazole, ketoconazole
What’s the MOA of azoles?
- fungicidal and fungistatic (dependent)
- inhibits fungal P450 dependent enzymes blocking ergosterol synthesis
- mainstays of antifungal therapy
What’s the ADRs of azoles?
hepatotoxicity, Qtc prolongation, rash, upset stomach
What DIs do azoles have?
many – inhibits CYP450
Which is the only azole with significant utility in candiduria?
fluconazole
What’s fluconazole have good and moderate clinical activity?
good = candida albicans, candida tropicalis, candida parapsilosis, candida lusitaniae, cryptococcus neoformans, coccidiodes immitis
moderate = candida glabrata
When is fluconazole utilized clinically?
candidiasis, cryptococcal meningitis, cocciodal meningitis
orally or IV
When is fluconazole your DOC?
many susceptible fungal infections, invasive and non invasive candidiasis (NOT candida krusei)
Why are only oral formulations availble of itraconazole?
caps<bioavailability than solution
* caps need to be taken with meal
* solution taken on empty stomach
* absorption drops with agents that lower gastric acidity
When is itraconazole good and moderate clinically?
good = candida albicans, c. parapsilosis, c. tropicalis, c. lusitaniae, cryp. neoformans, aspergillus, dimorphic
moderate = candida glabrata and candida krusei
When is itraconazole clinically utilized?
- dermatomycosis
- histoplasmosis
- blastomycosis
- coccidiomycosis
- sporotrichosis
When is itraconazole your DOC?
histoplasmosis and blastomycosis
What is recommended with voriconazole?
administer 1 hour before or after a meal – 90% oral bioavalability this way.
also, monitor drug levels because of varaible nonlinear elimination
When does voriconazole have good and moderate activity?
good = candida albicans, candida lusitaniae, c. parapsilosis, c. tropicalis, c. krusei, cryptococcus neoformans, aspergillus
moderate = candida glabrata, candida albicans that are flu-resistant, fusarium
When is voriconazole clinically utilized/ yoru DOC?
invasive aspergillus, other molds
What’s important to remember about posaconazole?
Take PO forms with food or soda, and also suspension and tab that have different dosing
When does posaconazole have good or moderate activity?
good = candida albicans, candida lusitaniae, c. parapsilosis, c. tropicalis, c. krusei, aspergillus, zygomycetes, other moulds, dimorphic fungi
moderate = fusarium, c. glabrata
When is posaconazole clinically utilized?
fungal infection prophylaxis, zyomycosis, resistent oropharyngeal candidiasis, fungal infections
When is posaconazole your DOC?
prophylaxis for invasive aspergillosis and candidiasis
What are examples of echinocandins?
caspofungin, micafungin, anidulafungin
all IV only
What’s the MOA of echinocandins?
fungalstatic and fungicidal depending
inhibit glucan syntase, decreasing fungal cell wall synthesis
What are the ADRs of echinocandins?
excellent safety profile – GI distress, flushing from histamine, rare hepatotoxicity
What are DIs of echinocandins?
cyclosporine increase (Caspofungin) and increase sirolimus (micafungin)
When do echinocandins have good or moderate activity?
Good = candida albicans, c. glabrata, c. lusitaniae, c. parapsilosis, c. tropicalis, c. krusei, aspergillus
moderate = candida parapsilosis, dimorphic fungi
When are echinocandins clinically utilized?
invasive candidiasis, esophageal candidiasis, empiric therapy for fungal infections
When are echinocandins your DOC?
invasive candidiasis
What can viruses cause on the host cell?
death, transformation (papillomaviruses), latent infection
Why do antiviral agents have limitations?
limited effectiveness at the point of symptoms
What are antivirals for herpes?
acyclovir (IV/PO/topical), valacyclovir (PO), famciclovir (PO)
val and fam are prodrugs!
What are MOAs for antivirals for herpes?
activated by viral thymidine kinase to forms that inhibit viral DNA polymerase
What are ADrs for antivirals of herpes?
nephrotoxicity (must hydrate and renally dose) , CNS effects
Consider oral forms causing GI issues
How are herpes antivirals good and moderately active for?
good = HSV-1 and HSV -2
moderate = varicella zoster
When are antiviral for herpes your DOC?
severe or difficult to treat HSV infections, severe HSV outbreaks among HIV patients (acyclovir), HSV-2 infections/prevention, VZV
How do you dose acyclovir?
based on ideal body weight
What are examples of neuraminidase inhibitors?
oseltamivir (PO) and zanamivir (inhaled)
What is the MOA of neuraminidase inhibitors?
prevents viral neuraminidase enzymes from releasing new virions from the host cell, preventing replication
most effective starting EARLY
When should neuraminidase inhibitors be started?
within 2 days of symptom onset, decreases ~1 day
What influenzas are neuraminidase inhibitors good for?
A and B
When are neuraminidase inhibitors your DOC?
Influenza prophylaxis and influenza infection w/ symptoms <2 days
What are ADRs of neuraminidase inhibitors?
oseltamivir: GI symptoms, HA and fatigue can also occur when drug is given for a longer period
zanamivir: pulmonary adverse effects, avoid w/ asthma
How does HIV infect the body?
infects lymphocytes and macrophages and results in progressive decline of CD4 T-cells – leads to opportunistic infections
How is HIV transmitted?
sexually, perinatally, breastfeeding, IV drugs
What are the 3 phases of HIV disease?
- Acute seroconversion – fever, flu-like illness, lymphadenopathy, rash, several weeks
- asymptomatic HIV – few or no signs/symptoms but CD4 T cell count declines…may last a few years to a decade
- AIDS – immune system damaged enough for significant opportunistic infections, <200 CD4 T cell count
What was the first antiretroviral drug for HIV?
zidovudine (AZT) in 1987
What is ART or HAART?
- current treatment regimen with 3-4 drugs
- suppress viral replication and restore number of CD4 cells
- ART recommended for all HIV infected indviduals
- significantly decreases morbidity and mortality
What should you always do with HIV treatment?
- combo therapy = reduces likelihood of drug resistance, slows disease progression
- individualized treatment
- always check for DIs
What are some NRTIs (nucleotide reverse transcriptase inhibitors)?
abacavir, emtricitabine, lamivudine, tenofovir, zidovudine
What’s the MOA of NRTIs?
inhibit HIV reverse transcriptase after phosphorylation by cell enzymes
What are ADRs of NRTIs?
- peripheral neuropathy
- GI effects
- bone marrow suppression
- hypersensitivity (abacavir)
- lactic acidosis, hepatic steatosis, pancreatitis
- nephrotoxicity
What is generally the backbone of most ART regimens?
2 NRTIs – renally dosed
What else can NRTIs be used for?
Hep B virus (tenofovir, emtricitabine, lamivudine)
What are examples of NNRTIs (non-nucleotide)?
efavirenz, nevirapine, etravirine, rilpiverine
What’s the MOA of NNRTIs?
inhibit same enzyme as NRTIs but different mechanism
What are ADRs of NNRTIs?
- Cns problems - EFV
- rashes
- hepatotoxicity - NVP
- hypersensitivity w/ flu like sxs, fever, juandice, ab pain
- lipohypertrophy “buffalo hump”
- hyperlipidemia - EFV and NVP
- EFV + pregnancy category D
Why is it essential to stick to your HIV regimen?
easily can develop resistance
What are some protease inhibitors?
atazanavir, ritonavir (boosting), ritonavir (full dose), lopinavir
What’s the MOA of protease inhibitors?
Inhibit viral protein processing by binding to site of protease activity on HIV
What are ADRs of protease inhibitors?
- cardiovascular (MIs and strokes)
- severe GI: take w/ food
- hepatotoxicity
- liphypertrophy
- nephrotoxicity
What are DIs with protease inhibitors?
MANY - strong CYP450 inhibitors
Protease inhibitors are ____ resilient to development of resistance
more
Protease inhibitors did what with highly active antiretroviral therapy
began the era – major impact on prolonging life span
True or false: only ATV of protease inhibitors is used w/o booster
true
What are examples of integrase inhibitors?
raltegravir, elvtegravir, dolutegravir
What’s the MOA of integrase inhibitors?
block integration of proviral gene into human DNA
newest class of ART and regarded as 1st line therapy
What are ADRs/ DIs of integrase inhibitors?
pretty well tolerated – increases creatine kinase, LFT, GI…minimal DIs
What’s a CCR5 inhibitor?
maraviroc
Whats the MOA of CCR5 inhibitors?
inhibits CCR5 receptors on cell membrane preventing entry of HIV into cell
What are ADRs of CCR5 inhibitors?
hepatotoxicity – black box warning
muscle and joint pain
diarrhea
What are DIs of CCR5 inhibitors?
metabolized by CYP450 – dosage adjustments are required
True or false: you do not need genetic testing to start Maraviroc
false
What do you need to test for Maraviroc?
HIV tropism w/ trofile test
What must you be to use maraviroc?
CCR5-positive
do not use with dual/mixed or CXCR-4 tropic HIV-1
What is paxlovid?
Drug for COVID-19 that’s combo but in separate tablets (Nirmatreivir and ritonavir)
reduces symptoms by 2-3 days
What’s the MOA of nirmatreivir and ritonavir (paxlovid)?
protease inhibitor binding to enzyme preventing replication
Are there any DIs with paxlovid?
Yes - a lot.
What is remdesivir?
- inpatient or outpatient IV
- for covid or ebola
- RNA polymerase inhibitor
- may interact w/ hydroxychloroquine
- can cause elevated liver enzymes, PT increase, renal impairments
What is malnupiravir?
- oral COVID med
- within 5 days of symptoms
- acts as ribonucleoside analog for viral RNA polymerase increasing mutations
- diarrhea, nausea, dizziness
Can antiviral medications treat viral hepatitis?
yes – NRTIs, NPIs, interferons, nucleoside analogues
What’s a serious potential side effect of isoniazid?
peripheral neuropathy from lack of B6
