EXAM FIVE COVERAGE Flashcards
What antivirals are used for Herpes Simplex HSV and Varicella Zoster VZV?
- Acyclovir
- Valacyclovir
- Penciclovir
- Famciclovir
- Docosanol (HSV Only)
What antivirals are used for Cytomegalovirus CMV?
- Ganciclovir
- Valganciclovir
- Foscarnet
- Cidofovir
Acyclovir
- 10x more potent against HSV than VZV
- Requires 3 phosphorylation steps for activation
Valacyclovir
- Prodrug of Acyclovir
- More potent PO valacyclovir = IV acyclovir
Famciclovir
- Renally eliminated
- Inhibits DNA Polymerase
- Has 3 OH Groups
Penciclovir
Topical Agent
1. Prodrug of Famciclovir
Docosanol
Topical Agent
1. Inhibits fusion of HSV
Acyclovir AEs
- Nausea
- HA
- Diarrhea
- Nephrotoxicity
- Neurotoxicity
Famciclovir AEs
- Nausea
- HA
- Diarrhea
Valacyclovir AEs
- Nausea
- HA
- Neurotoxicity
How to avoid Neurotoxicity for Acyclovir?
Infuse slowly, maintain hydration, avoid concomitant nephrotoxic agents
How to avoid Neurotoxicity for Acyclovir and Valacyclovir?
Infuse slowly, monitor in high doses of valacyclovir
Ganciclovir
Acyclic Guanosine Derivative
1. Same MOA as Acyclovir
2. IV
Valganciclovir
- Prodrug of Ganciclovir
- PO = Take with FOOD
Foscarnet
Inorganic pyrophosphate analog
1. Requires NO phosphorylation
2. Blocks pyrophosphate binding site, blocking DNA polymerase binding
Cidofovir
Cytosine Analog
1. Does NOT require activation for phosphorylation
2. Inhibits DNA polymerase
What is a MAJOR AE concern for Ganciclovir and Valganciclovir?
Myelosuppression
All Anti-CMV drugs are really eliminated causing probable nephrotoxicity, what are the possible forms of nephrotoxicity seen with each drug?
Ganciclovir/Valganciclovir: INCREASE SCr
Foscarnet: TUBULAR Damage
Cidofovir: Proximal TUBULE Damage
How do you prevent Nephrotoxicity with Foscarnet?
- Maintain adequate hydration
- Prehydrate with NS
How do you prevent Nephrotoxicity with Cidofovir?
- Pre and Post Hydration with 1L NS
- Probenecid – 3 DOSES on day of cidofovir infusion: it prevents tubule uptake and increase the half life of the drug
What is Letermovir?
Random Anti-CMV Agent
MOA: Maturation Inhibitor
Specifically for Prophylaxis
Baloxavir Marboxil = Xofluza
- Inhibits PA
- Approved for adults and adolescents >12
- Single weight based dose
- CHELATION Interaction
What are the Neuraminidase Inhibitors used in Influenza?
- Oseltamivir
- Zanamivir
- Peramivir
Competitively inhibit neuraminidase activity
Oseltamivir PO = Tamiflu
AE: N/V, HA, take with FOOD
Zanamivir INH = Relenza
AE: Cough, bronchospasm
AVOID if airway disease or allergy with milk
Peramivir IV = Rapivab
AE: Diarrhea, Hyperglycemia, SJS
Influenza Big Picture
- PA Endonuclease or Neuraminidase Inhibition
- MUST initiate within 2 days of symptom onset
- Oseltamivir and Peramivir RENALLY dosed
HBsAg
HBC surface antigen
HBVDNA
Viral Load
Anti-HBc
Antibody to HBV core
Anti-HBs
Antibody to HBV cell surface
Antigen of Surface HBs present greater than 6 months suggests chronic HBV but antibody to surface HBs present suggests what?
Immunity to HBV
Antibody to Core Particle present suggests what?
Past or present infection
What is the disease course for Hepatitis B?
Inflammation –> Fibrosis –> Cirrhosis
What are the FOUR major phases of Hepatitis B?
- Immune Tolerant
- Immune Clearance
- Non-Replication
- Reactivation
What two phases of Hepatitis B are considered active fighting phases and would require treatment?
Immune Clearance and Reactivation
Immune Clearance and Reactivation phases both have HIGH ALT and ACTIVE Inflammation, but how do they differ in terms of HBVDNA?
Immune Clearance = HIGH
Reactivation = Intermediate-High
What are the 3 main options for HBV Treatment?
- Tenofovir AF and DF
- Entecavir
- Peglated Interferon Alfa 2a
Tenofovir Disproxil Fumarate TDF
- Adenosine nucleotide analog
- KNOWN for nephrotoxicity and osteotoxicity (decrease in mineral density)
- TDF best data in pregnant women
Tenofovir Alafenamid TAF
- Adenoside nucleotide analog
- NOT nephrotoxic or osteotoxic
- TAF is safer and has some data in pregnant women
What are AEs that are seen in TDF and TAF?
- Lactic acidosis
Entecavir
- Guanosine Nucleoside Analog
- Take on EMPTY STOMACH
- Renal dose adjustment
What are the 3 main sites of activity for Entecavir, even thought it does NOT make it more potent that TDF/TAF?
- Base Priming
- Reverse Transcriptase
- Synthesis of new HBVDNA
Pegylated Interferon Alfa 2a
- Inhibits cellular growth, surface antigen expression, etc. multiple MOAs
- WEEKLY INJECTION: same day around the same time
What are the AEs of Pegylated Interferon Alfa 2a
- Fatigue, HA, Insomnia, Depression, Dizziness
- Alopecia
- N/V/D, Anorexia
- Weakness, myalgia
- Fever, increased bacterial infections
- Cytopenias, hypo/hyperthyroidism, increased LFTs
HBV Big Picture
- NO cure
- Only start therapy in those with active inflammation, high HBVDNA, and high ALT
Monitoring for patient with HBV and NO treatment
- HBVDNA
- ALT
- Biopsy every 6-12 months
Monitoring for patient with HBV and ON treatment
- HBVDNA at 12 and 24 weeks after initiation and can extend to every 3-6 months
- Monitor drug toxicities
An increase in HBVDNA can most often be explained by what?
Nonadherence to medication
What element of pathophysiology in HCV causes for the requirement of multiple medications for treatment?
RNA-Dependent RNA Polymerase that is prone to error leading to mutations
What are the goals of treatment for HCV?
- Reduce all cause mortality
- Reduce liver-related complications
- Achieve SVR12 = Cure
What are the NS5A Inhibitors used in HCV?
- Ledipasvir
- Pibrentasvir
- Velpatasvir
- Elbasvir
+ASVIR
What are the NS5B Inhibitors used in HCV?
- Sofosbuvir
+BUVIR
What are the NS3/4A Inhibitors used in HCV?
- Glecaprevir
- Voxilaprevir
+PREVIR
In the treatment of HCV, you MUST ALWAYS use >2 agents from different classes, therefore what are the 3 first line regimens for treatment NAIVE?
- Ledipasvir/Sofosbuvir = HARVONI
- Velpatasvir/Sofosbuvir = EPCLUSA
- Glecaprevir/Pibrentasvir = MAVYRET
HARVONI is considered what type of coverage?
NARROW = covers only GT1
EPCLUSA and MAVYRET are considered what type of coverage?
BROAD = covers GT1-GT2-GT3
What is the dose and duration of HARVONI and EPCLUSA for GT1 treatment?
1 tablet
Duration 12 weeks no matter if cirrhosis is present or not
What is the dose and duration of MAVYRET for GT1 Treatment?
3 tablet
Duration 8 weeks no matter if cirrhosis is present or not
What is the duration of MAVYRET for GT2 and GT3 Treatment?
8 weeks
What is the duration of EPCLUSA for GT2 and GT3 Treatment?
12 weeks
If cirrhosis =MUST check for resistance prior to starting
Harvoni, Epclusa, and Mavyret are all affected by strong CYP3A4 Inducers but what does Amiodarone do to them?
Sofosbuvir + any other direct acting antiviral = BRADYCARDIA
AKA only MAVYRET not affected
What two ingredients and drugs are affected by ACID Suppressants?
Velpatasvir = EPCLUSA
Ledipasvir = HARVONI
What DDI affects Harvoni, Epclusa, and Mavyret and must require dose adjustments?
Statins
What are the 3 MOST COMMON AEs of DAA?
- HA
- Fatigue
- Nausea
What are characteristics that make patients with HCV more difficult to treat?
- Presence of Cirrhosis
- Previous treatment failure
- GT1a over GT1b
- Presence of resistance mutations
What is Ribavirin?
MOA: Inhibit initiation and elongation of viral fragments through RNA polymerase
1. TAKE WITH FOOD
2. ANEMIA AE MAJOR
3. AVOID IN PREGNANCY and 6 MONTHS post
Old Agent
Monitoring for HCV Pre-Treatment HBV Reactivation
- HCV has suppressive activity against HBV
- Pre-Screen before starting HCV treatment
Monitoring for HCV During Treatment
- LFTs
- CBC if on RIBAVIRIN
Monitoring for HCV POST Treatment
- SVR12 - 12 weeks after treatment completed - sustained virology response 12 weeks after
What are the Replicative Enzymes in HIV?
- Reverse Transcriptase = replication
- Integrase = permanent infection
- Protease = cleaves polybprotein making it infectious
HIV binds to 1 or 2 coreceptors on the CD4 cell, what are those 2 sites?
- CXCR4
- CCR5
After binding to the CD4 cell, attachment and fusion occurs how?
Attach via gp120 subunit on HIV envelope attaches to CD4
Fusion via HIV envelope subunit gp41 fuses to CD4 cell
After attachment and fusion, reverse transcriptase does what?
Convert HIVRNA to HIVDNA
HIVDNA then travels to the nucleus of CD4 where ___ integrates HIVDNA into human DNA
Integrase
Replication and Assembly of new HIVRNA move to the cell surface which is non-infectious, however, immature HIV buds off the CD4 cell and HIV releases ____ that cleaves the long protein chains making it mature and infectious?
Protease
What are the drug targets in HIV treatment?
- Entry Inhibition
- Reverse Transcriptase and Nucleosides
- Integrase
- Protease
What are the specific targets that fall under Entry Inhibition targets?
- CCR5 on CD4 cell
- gp120 on HIV cell
- Domain 2 on the CD4 cell
- gp41 on the HIV cell
List the drugs that are classified as Entry Inhibitors
- Maraviroc
- Fostemsavir
- Ibalizumab
- Enfuirtide
Maraviroc
CCR5 Antagonist
1. ONLY drug to work on CD4 Cell
2. Salvage Therapy
3.BID
AE: Orthostatic Hypotension
Fostemsavir
Attachment Inhibitor
1. Hydrolyzed to Temsavir - Prodrug
2. PO BID
AE: QT Prolongation
Ibalizumab
Post Attachment Inhibitor
1. Causes conformational change prevents HIV binding to CD4
2. Salvage Therapy
3. IV
AE: Infusion Related
Enfuvirtide
Infusion Inhibitor
1. Prevents the fusion of HIV envelope and the CD4 cell
2. SQ BID
AE: Nodules at Injection Site
Would you use entry inhibitors as initiation therapy for HIV?
NO they are SALVAGE therapy and ALL can be taken without regard to food
List the drugs that are classified as Nucleoside Reverse Transcriptase
- Abacavir
- Emtricitabine
- Lamivudine
- Tenofovir AF
- Tenofovir DF
- Zidovudine
What is the class adverse effect for Nucleoside Reverse Transcriptase NRT?
MITOCHONDRIAL toxicity
Lactic Acidosis most common
What is the AE of Abacavir and what should be tested before initiating therapy?
AE: Hypersensitivity, fever
TEST HLAB5701 REQUIRED
What are the AEs of Emtricitabine and Lamivudine?
NONE, well tolerated
What are the AEs of Tenofovir AF and Zidovudine?
TAF: Increased LDL
Zidovudine: Anemia, neutropenia
How often should NRTs be dosed?
QD or BID
TAF/TDF are QD
Zidovudine is BID
the rest are either
List the drugs that are Non-Nucleoside Reverse Transcriptase
- Doravirine
- Ertavirine
- Efavirenz
- Rilpivirine
NNRTs work by causing conformational change and inactivating RT, but how do NRTs differ?
NRTs stops chain elongation and blocking HIVDNA creation
What is the class adverse effect of NNRTs?
RASH
What is the AE and dosing of Doravirine?
PO QD
Sleep Disturbance
What is the AE and dosing of Efavirenz?
PO QD HS
Sleep disturbance, vivid dreams, hungover feeling
What is the AE and dosing of Ertavirine?
PO BID
Severe Rash
What is the AE and dosing of Rilpivirine?
PO QD with 400 CALORIES
Sleep disturbance, vivid dreams
List the drugs that are Integrase Inhibitors
- Bictegravir
- Cabotegravir
- Dolutegravir
- Elvitegravir
- Raltegravir
What is the MOA of Integrase Inhibitors?
Bind to Mg or Mn cofactor on integrase enzyme and inhibits the activity of the enzyme
Bictegravir
PO QD
AE: False Increase in SCr
FIRST LINE
Cabotegravir
IM q4wks
AE: Injection site
Dolutegravir
PO QD
AE: HA, insomnia, false increase in SCr
Elvitegravir
PO QD with FOOD
HIGHEST risk of resistance, least used
Raltegravir
PO QD or BID
AE: myopathy
List the drugs that are Protease Inhibitors
- Atazanavir
- Darunavir
What is the MOA of Protease Inhibitors?
Bind near active site of protease enzyme and inhibits cleavage of proteins aka inhibits maturation and infective quality
Protease Inhibitors as a class cause N/V/D but how should the drugs be administered?
WITH FOOD
Atazanavir
PO W/MEAL w/ or w/o PKN booster
AE: HYPERbilirubinemia, lipid sparing if unboosted
Darunavir
PO QD/BID W/FOOD and MUST BE BOOSTED
AE: Sulfa rash
List the drugs that are PKN Boosters
- Cobicistat
- Ritonavir
Both are strong CYP450 inhibitors
Cobicistat
With Protease Inhibitor or Elvitegravir
AE: false increase in SCr
Ritonavir
PO with FOOD and Protease Inhibitor
AE: GI, dyslipidemia
Atazanavir DDI Acid Suppressants
Protease Inhibitor
Antacids: take them 2hrs before or 1 hr after
H2RAs: take at the same time or 10hrs after
PPIs: AVOID
Rilpivirine DDI Acid Suppressants
NNRT
Antacids: take 2 hrs before or 4 hrs after
H2RAs: take 12hrs before or 4 hrs after
PPIs: AVOID
What drug class interactions via Chelation and should be separates with Mg, Al, Fe, Ca, Zn 2 hrs before or 6 hrs after administration?
INSTs = Integrase Inhibitors
NNRTs interact with what type of CYP3A4?
ALL of them interact with 3A4 substrates
Efavirenz and Etravirine interact with 3A4 inducers
INSTIs interact with what type of CYP3A4?
Bictegravir, Folutegravir, and Elvitegravir interact with 3A4 substrates
Protease Inhibitors interact with what type of CYP3A4?
ALL of them interact with 3A4 Substrates and Inhibitors
Entry Inhibitors interact with what type of CYP3A4?
Maraviroc and Fostemsavir interact with 3A4 substrates
PKN Boosters interact with what type of CYP3A4?
Cobicistat and Ritonavir interact with 3A4 inhibitors
What are 3A4 inducers that we worry about?
Rifamycins, carbamezepine, oxcarbazepine, anti-epileptics, and St. Johns wort
Statin metabolism is inhibited by Protease Inhibitors and PKN Boosters, what statins can be used in and which ones are CI’d?
Atorvastatin and Rosuvastatin = Preferred
Lovastatin and Simvastatin = CI
Corticosteroid metabolism is inhibited by Protease Inhibitors and PKN Boosters, which ones can be used while the rest should be avoided?
Beclomethasone and Flunisolide
Warfarin has interactions with what two drugs?
Efavirenz and Ritonavir
In terms of Cobicstat and Ritonavir, what DOACs should be AVOIDED and NEVER used with them?
Dabigatran = AVOID w/ Cobicstat
NEVER USE RIVAROXABAN
For NRTs when should you renally dose adjust?
TDF = CrCl <50
Others = CrCl <15
PDE5 Inhibitor metabolism is inhibited by Protease Inhibitors and PKN Boosters, what is the max dose that can be used?
Sildenafil = 25 mg q48hrs
Tadalafil = 10 mg q72hrs
Vardenafil = 2.5 mg q72hrs
What is the Gold Standard Test for HIV?
Antigen/Antibody Test
HIV Pathophysiology is infected CD4 cells resulting in a decline in immune function, what amount of CD4 is indicative of AIDS?
<200
Anti-Retroviral Therapy ART is consisted of what?
2 NRT backbone + 3rd agent from a different class (NNRT/PI/INSTI)
What are the first line regimens of ART for HIV?
- Biktarvy =TAF+Emtricitabine+Bictegravir
- Descovy + (Trivicay) = TAF+Emtricitabine + (Dolutegravir)
- Triumeq = Abacavir+Lamivudine+Dolutegravir
- Dovato = Lamivudine+Dolutegravir
Biktarvy Considerations
Single Tablet Regimen
MOST USED
Descovy + Tivicay Considerations
2 TINY tablets
MUST be taken TOGETHER
Triumeq Considerations
Very large single tablet regimen
MUST ASSESS HLA before
Dovato Consideration
DUAL THERAPY
Single tablet regimen
Do NOT USE if HIVRNA >500,000 copies/mL
What are the APPROVED DUAL therapy options for HIV?
- Dovato = approved for naive patients only
- Juluca (Dolutegravir/Rilpivirine) = approved for experienced patients only
- Cabreuva (Cabotegravir/Rilpivirine) = IM
What is the most important factor in maintain suppression?
ADHERENCE
What should you AVOID for HIV THERAPY?
- Two agents from classes that is not NRT
- Dual therapy that is not approved
- 3 NRTs = resistance
- 2 PKN boosters = ONLY need ONE
- Lamivudine + Emtricitabine = both are cytosine analogs aka antagonistic
What are monitoring considerations for HIV therapy?
HIV RNA
CD4
CMP
CBC
STIs
Pre-Exposure Prophylaxis PrEP Regimen Options
- Truvada = at risk through sex or IV drug use
- Descovy = at risk through sex excluding receptive vaginal sex
1 TAB PO QD
Adults and Adolescents >35 kg
How often do you have to re-test for HIV?
EVERY 3 MONTHS
Post Exposure Prophylaxis PEP
Best if initiated within 72 hrs of exposure
TDF/Emtricitabine + Either Raltegravir or Dolutegravir x 28 days
What are the recommended regimens for infants born to mothers with HIV?
PAIR 2 NRTs + 3rd Agent
2 NRT:
1. TDF + Emtricitabine - nephrotoxicity possible
2. Abacavir + Lamivudine - test HLA
3rd Agent:
1. Raltegravir = BID
2. Dolutegravir = CNS AE, teratogen?
3. Atazanavir + Ritonavir =interaction with acid suppressant
4. Darunavir + Ritonavir = BID
When is Intrapartum Zidovudine recommended?
HIVRNA>1,000 C-Section delivery
Postpartum, must start ART ASAP what are the two regimens?
- HIVRNA <50 copies/mL = Zidovudine PO BID x 4 WEEKS
- HIVRNA >50 copies/mL = Zidovudine + Lamivudine + Raltegravir or Neirapine BID x 6 WEEKS
How many tests can safely exclude HIV for infants?
2 Negative Tests
Mycobacterim Avium Complex MAC Manifestations
Fever, night sweats, weight loss
Greatest risk CD4 <50
MAC Primary Prophylaxis
- Initiate ART
- If unable to start ART =
Azithromycin 1200 mg weekly = preferred
Clarithromycin 500 mg BID
MAC Treatment
- Macrolide (Azithro or Clarithro) + Ethambutol
- Rifamycin considered as 3rd agent is needed
Duration = 12 months
Toxoplasmic Encephalitis Manifestation
Toxoplasma Gondii - Protozoan Parasite
Encephalitis most common
Most Common with CD4 <100
Toxoplasmic Encephalitis Primary Prophylaxis
Indicated in those with positive IgG and CD4 <100
1. Bactrim PO Daily - DC once CD4 >200
Toxoplasmic Encephalitis Treatment
Acute 6 WEEKS = Sulfadiazine + Pyrimethamine + Leucovorin
Chronic >6 Months = LOW dose Sulfadiazine + Pyrimethamine + Leucovorin
- DC when CD4 >200 and asymptomatic for 6 MONTHS
What is the AE of Dapsone?
Hemolytic Anemia
Check G6PD FIRST
What is the AE of Atovaquone?
GI, disgusting flavor
What is the AE of Sulfadiazine?
Rash, sulfa
What is the AE of Pyrimethamine?
Pantocytopenia
Cytomegalovirus Manifestations
Retinitis most common followed by colitis
Highest risk in CD4 <50
What is the primary prophylaxis for Cytomegalovirus?
ART
What is the treatment of Cytomegalovirus Retinitis?
Induction: 2 wks IV ganciclovir or PO valganciclovir BID
Maintenance: PO valganciclovir QD
Duration = 3 MONTHS until CD4 <100
What is the treatment of Cytomegalovirus Colitis?
IV ganciclovir
3-6 weeks
Pneumocystis Pneumonia Manifestation
Pneumocystic Jiroveci PJP
Highest Risk CD4 <200
Pneumonia symptoms
What is the primary/secondary prophylaxis for Pneumocystis Pneumonia?
Bactrim PO QD - continue until CD4 >200 for 3 months
What is the treatment for Pneumocystis Pneumonia?
Mild-Mod = Bactrim PO TID
Severe = Bactrim IV TID + CORTICOSTEROIDS
Duration 21 DAYS REGARDLESS OF SEVERITY
Oropharyngeal/Esophageal Candidiasis Manifestation
C. Albicans
Creamy white plaques
What is the primary prophylaxis of Oropharyngeal/Esophageal Candidiasis?
NOT recommended
What is the treatment of Oropharyngeal/Esophageal Candidiasis?
PO FLUCONAZOLE
Oropharyngeal = 1-2 weeks
Esophageal = 2-3 weeks
Cryptococcal Meningitis Manifestations
Cryptococcus Neoformans or C.Gatti
Highest risk CD4 <100
What is the primary prophylaxis for Cryptococcal Meningitis?
NOT recommended
What is the treatment for Cryptococcal Meningitis?
Induction = 2 weeks IV Liposomal Amphotericin B + Flucytosine
Consolidation = 8 weeks Fluconazole 800 PO QD
Maintenance = 1 year Fluconazole 200 PO QD
When can you DC Cryptococcal Meningitis therapy?
> 1 yr since anti fungal infection
Asymptomatic
CD4 >100
On effective ART
Disseminated Histoplasmosis Manifestations
Histoplasma Capsultaum
Greatest Risk CD4 <150
What is primary prophylaxis of Disseminated Histoplasmosis?
None
What is the treatment of Disseminated Histoplasmosis?
Induction: Liposomal Amphotericin B >2 weeks
Maintenance: Itraconazole for <12 months
When can you DC Disseminated Histoplasmosis therapy?
Azoles x 1 year
Negative fungal blood culture
Absent serum or urine histo antigen
Not Detectable HIVRNA
CD4 >150
Immune Reconstitution Inflammatory Syndrome IRIS
Hyper-Inflammatory Response to Infection
Can occur with rapid change from high HIVRNA/low CD4 to lowHIVRNA/high CD4
IRIS is most often seen with what and what therapy is recommended?
MAC and supportive care
In Fungal infections, drugs that target cell wall synthesis have what specific target?
(B1,3)-D-Glucan synthase
In Fungal infections, drugs that target cell membrane synthesis have what specific target?
Squalene Epoxidase or Lanosterol Demethylase
Squalene –> ___ –> Erogsterol
Lanosterol
List the drugs that are Cell Wall Inhibitors in Fungal Infections
- Caspofungin
- Micafungin
- Anidulafungin
What is the MOA of Cell Wall Inhibitors in Fungal infections?
Inhibition of B(1,3)-D-Glucan Synthase
Weakens cell wall, prevents growth
List the drugs that are Allylamine/Benzylamines
- Terbinafine
- Butenadine
- Naftifine
What is the MOA of Allylamine/Benzylamines?
Squalene Epoxidase Inhibitor
Call membrane cannot be maintained, buildup of squalene is toxic to fungal organism
Allylamine/Benzylamines are administered how?
ONLY Systemically/Superficially to treat dermatophytosis
List the drugs that are Imidazole Azoles
- Ketoconazole
- Miconazole
- Clotrimazole
SUPERFICIAL ONLY
List the drugs that are Triazole Azoles
- Fluconazole
- Voriconazole
- Itraconazole
- Posaconazole
- Isavuconazonium
What is the MOA of Azoles?
Inhibit lanosterol demethylase, stopping progression to ergosterol
Cell Dies
Lanosterol Demethylase is a CYP450 enzyme and therefore,
Imidazole affect human CYP450 more than triazoles and are only used topically
List the drugs that are Polyenes
- Amphotericin B
- Nystatin
What is the MOA of Polyenes?
Binds to ergosterol and forms pores causing intracellular contents to leak out
CAN also bind to human cholesterol cells
Flucytosine
Activity in fungal cell nucleus
Competes with RNA synthesis
Griseofulvin
Inhibits mitotic spindle formation and cell division
Echinocandins AE
Infusion Related Reactions
Ibrexafungerp is a Major 3A4 substrate
AVOID inducers
Allylamines/Benxylamine Systemic Terbinafine can cause increased what?
Increased LFTs Monitor at 4 weeks
Triazoles are teratogenic and have what AE as a class?
QT Interval Changes
Fluconazole Pearls/AEs
100mg for oropharyngeal candidasis
800 mg for cryptococcal meningitis
QT PROLONGATION
Good diffusion into CNS
Voriconazole AEs
- VISUAL DISTURBANCES
- Photoxicity, rash
- QT Prolongation
Itraconazole Capsule vs Solution
Capsule = ADMIN WITH FOOD
Solution = ADMIN ON EMPTY STOMACH
What are the AEs of Itraconazole?
- CHF
- QT PROLONGATION
Posaconazole AEs/PEARLS
ADMINISTER W/HIGH FAT meal
1. Hyperaldosteronism
2. QT PROLONGATOIN
Isavuconazonium AE MUST KNOW
QT SHORTENING
Amphotericin AEs
- INFUSION REACTION
- RENAL IMPAIRMENT: irreversible tubular damage
Dose and Nephrotoxicity of CONVENTIONAL Amphotericin
1 mg/kg/day
MOST SEVERE
Dose and Nephrotoxicity of LIPOSOMAL Amphotericin
3-5 mg/kg/day
Less severe
Dose and Nephrotoxicity of LIPID COMPLEX Amphotericin
5 mg/kg/day
Less severe
Flucytosine AE/Pearl
BONE MARROW TOXICITY
PO, Q6hr, weight based
NEVER use as monotherapy
Griseofulvin AE
HEPTATOXICITY
Echinocandins do not have coverage on what organisms?
- Histo. capsulatum
- Crypto. neoformans
- Coccidioides
- Blastomyces
Itraconazole does not have coverage on what organisms?
Candidas glabrata
Fluconazole does not have coverage on what organisms?
- Candidas glabrata
- Aspergillus fumigatus
Flucytosine does not have coverage on what organisms?
- Aspergillus fumigatus
- Histo. capsulatum
- Coccidioides
- Blastomyces
Candida Species most common site of infection?
BLOOD
What is the first line treatment for Candida Species?
Echinocandins
What is the first line treatment for Aspergillus Species?
Voriconazole for 6-12 weeks
What is first line treatment for Blastomyces?
Pulmonary: Itraconazole and Amphotericin B
CNS: Fluconazole
What is first line treatment for Coccidiodomycoses?
Pulmonary: Itraconzole or Fluconazole
CNS: Fluconazole
What is first line treatment for Cryptococcus?
CNS: Amphotericin B + Flucytosine followed by Fluconazole
Pulmonary: Fluconazole
What is first line treatment for Histoplasmosis?
Pulmonary: Itraconazole or Amphotericin B