Exam 5 real one. Flashcards
Oral Trush TX:
Fluconazole 200 mg LD then 100 mg 7-14 days
QTC
Esophageal Trush TX:
Flucanzole 200 mg PO LD, followed by 100-200 14-21 days
Vulvovaginal Candidiasis tx:
Fluconazole 150 PO
can also do topical azoles
Ibrexafungerp
Severe: Fluconzole 100-200 mg PO daily
Topical azoles
Recurrent: Osteseconazole or Fluconazole
Refractory: Boric Acid
Cryptococcal Meningitis TX:
3 stages:
Amp B + Flucytosine
tjhen Fluconazole 800 mg for 8 wekks
then fluconazole 200 mg for year
Releat LP
Histoplasmosis TX:
Mild/Moderate: Itraconazole 200 mg PO TID x 3 days then 200 mg PO BID for 12 momths
Severe: Itra + Amp B
MAC TX:
Clarithromycin 500 mg PO BID + Etham
Azithro + Ethambutol
If severe add Rifabutin 300 mg PO QD
If really bad <50 CD4: Add Levo, moxi, amikacin, streptomycin
PJP TX;
TMP-SMX 15-20 mg/kg/day -21 sdays
Renal
Alt: Primaquine or pentamidine
Add Prednisome if PO<70
Toxoplasmosis TX:
Pyrimethamine 200 mg PO by weight.
pyramethamine + sulfa+ Leucovorin
or TMP SMX 5/mg/kg IV- 6 weeks
Trush/Esopagitis and vaginisit Prevention:
Use ART
Not recommended unless frequent severe recurrents:
Fluconazole
Cryptococcal Meningitits Prophylaxis
Recommened only after completion of therapy for acute: Secondary
Fluconazole 200 mg PO daily for 12 monthjs
<100 restart
MAC Prohylaxis
Yes!
Primary: <50 and not on ART
Not recommended if just started ART
Secondary: 12 months
Drugs: azithro or clarithromycin
PJP Prophylaxis:
CD4- 100-200
Must give TMP-SMX PO daily
Stop >200 for 3 months
Toxoplasma Propyhlaxis:
IgG + with <100 :
Required: Bactrim. Stop at >200 or Dapsone
Secondary:Clindamycin + Pyrimethamine+leucovorin
Histoplasma Prophylaxis
<150 CD4 at high risk.
Itraconazole
Risk factors for Neutropenia
Immunocomprosmied.
<10000 cells
Common Neutropenia Bacteria, Fungi, Viruses
S. aureus, strepto, P.aero
Candida, Aspergillus,
HSV, VZV, CMV
Neutropenia clinal Presentation
38.3> (101> or oral temp >38 for 1 hour or longer.
Cultures: blood, cbc, BMP
Neutropenia High vs low risk.
Low: <7 days
stable
Inpatient our outpatient
High: >7 and ANC <100 cells
Neutropenia TX: Low risk.
Ciprofloxacin+Augmetin
or Levo
or Cipro+Clinda
Neutropenia TX: High risk.
Cefepime
Zosyn
Ceftazidime (no gram+)
Imipenem
Meropenem
Indications for adding Vanco in neutropenia:
Pneumonia, G+, Line port,SSTI,
Septic shock
Managing therapy for neutropenia and targeted.
2-3 days re-evaluate empiric therapy.
Pathogen directed=
MRSA- Vanco
VRE- Dapto/linzeolid
ESBL- Carbapenem
KRP- Meropenem
NDM/IMP/VIM- Cefiderocol
Fungal Neutropenia TX:
Amp B
Azoles
Echinocandins(-Fungins)
2 weeks in absense
Neutropenia TX for PNC Allergy
Ciprofloxacin+aztreonam+vanco
Duration of Neutropenia TX:
ANC >500 x 2 days = Stop
ANC <500 by day 7 & Afebrile = stop if low risk, continue if high risk
Still on fever: >500 ANC = Reaccess
<500= continue for 2 weeks
When to use CSF in neutropenia
ANC <500 in uncontrolled dieases, IFI, hypo
last thing too.
Neutropenia Prophylaxis
Cipro or levo.
Dont use these for empiric if used and breakthru occurs.
HIV Target Cell
Gp120 binds to CD4 on T cells, macrophages, and dendritic cells.
CD4 T Helper.
Route of transmisson for aids/hiv
- Mucouse membranes * most comoon
Blood stream
Mother to Child
Who to screen HIV on?
Patients aged 13-64 in any health care setting (repeat annual in high risk)
All pregnant women. repeat 3rd trimester
All TB patients
All STD patients
Rapid Testing For HIV at home things to know.
OraQuick
+ = see medical
- = counsel on seroconversion window (3 months for the OraQuick) repeat testing
CD4 Counts for stages.
> 500 stage 1
200-499 stage 2
<200 or OI diagnosis (Aids) stage 3
NRTIs MOA and AE:
Synthetic purine and pyrimidine analogn- elongation termination
AE: Mitochondrial toxicity and lactic acidosi
Renal
NNRTIs: MOA and AE
Allosteric site of reverse transciptase reducing function
AE: Rash
Hepatic. DI
-virine
PIs: MOA and AE
Inhibit action of viral protease preventing aseembly, maturation and realse of new virions
AE: GI Intolerence, Insulin Resistance, Lipodystrophy
-navir
the “Boosting” HIV drugs.
Ritonavir with Cobicistat = potent CYP3A4
INSTIs: MOA and AE
Inhibit HIV integrase, prevent the provial DNA integration
Metal Ions
AE: Weight Gain
-gravir
Attachment Inhibitor MOA
binds to gp120 on surfance of HIB, blocking attachment to CD4
Temsavir
Post-attachment Inhibitor MOA
Binds to domain of D2 of the CD4 T -cell . Required for entry interruption.
CCR5 MOA
Binds to CCR5 on the CD4 cell surfance, blocks binding of gp120.
Need tropism assay
Capsid Inhibitor MOA
Binds to P24 subunit. Interferes with viral lfiecycle.
long HL: Cyp3a4. MDR drug
What to start for HIV treatment?
Two NRTIs plus a INSTI or NNRTI or PI
Dolutegravir plus lamivudine also good.
FDA dose of Dolutegravir
50 mg daily (INSTI-naïve)
50 mg BID (INSTI-experienced)*
*This dosing regimen required when co-administered with UGT1A/CYP3A
inducers (efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or
rifampin)
ART classes that require renal adjustment
NRTIs expect abacavir
Fluconazole has renal (antifungal)
Labs required prior to Abacavir and maraviroc
HLA-B*5701 - Abacavir
Tropism Assay - Maraviroc
Minor vs Major Resistance Mutation HIV
Major- Amino acid subsistituion
Minor- accessory muitation
HIV: Resistance testing
At entry of care. or when ART starts.
or when failure occuring.
HIV Pregancy: TX
Max ART. If not genotype
Dolutegravir Plus (TDF or TAF) + (Emtricitabine or lamivudine)
DTE*
Dolutegravir/abacavir/lamivudine
only if HLB - and wihtout heb B
HIV Pregnancy Viral Loads.
> 1000 VL or unknown = C-section + IV Zidovudine
<50 - no IV Zidovudine needed
If 50-1000= IV Zidovudine
Postpartum considerations HIV
Zidovudine for 2-6 weeks
Neonatal HIV Detection
NATs used
Birth, 14-21 days, 1-2 months, and 4-6 months
Two positive for diagnosis of HIV
Presumptive:
2 NATs negative at >2 or >4 = negative
1 NAT at >8 weeks
1 negative Ab test at >6 months
Definitive:
2 neg NAts at 1 & 4 months (2-6 weeks after dc ARV)
2 negaties Ab at >6 months
HIV RNA neeed to prevent transmission of HIV
<200
HIV: PrEP CIs
If HIV + or <77 dont use
TDF <60
<30 TAF
Within 72 hours
HIV Prep : Oral Daily
Use: Emtricitabine + TDF or Emtricitabine + TAF for men and transgenders
HIV PrEP: on-demand
Emtricitabine +TDF 200 mg
2 tabs 2-24 hours before sex
1 tab 24 hours later
then 1 next day
HIV PrEP: IV
Cabotegravir 600 mg
HIV: PrEP labs
HIV 1 week before PrEP
HIV RNA
STI
HIV: PEP TX
occupational or sexual assult.
Emtricitabine + TDF for 28 days. + INSTI for 28 days
ASAP within 72 hours.
Test for HIV before repeat at 4-6 weeks
Antifungals: Allylamines
Terbinafine
MOA: Inhibits squalene epoxidase
More selective to fungal.
Antifungal drugs: polyenes
MOA
Amp B: binds ergosterol
Targets egrosterol of fungal olnly.
leakage of intraccellular cations
Main Difference Between Fungal and Human Cell Membranes:
Fungal cells contain ergosterol in their cell membranes.
Human cells contain cholesterol instead.
Antifungal drugs: Azoles
MOA: Inhibit 14a-demethylase
Selective fungal CYP inhibitor
Inhibits lanosterol to ergosterol using iron.
Antifungal Drugs: Echinocandins
Micafungin, caspofungin- all IV
Cyclin long side chains.
Inhibits B 1,3 D-glucan cell wall synthsis
Antifungal: Flucytosine MOA: also dosing
MOA; Antimetabolite
Inhibits Thymidylate synthase and protein synthesis.
5-FU deaminated by cytosine deaminase
25mg/kg/dose po q6h
Antifungal: Tavaborole
MOA: Inhibits Leucyl transfer RNA (LeuRS) uses Boron
Topical
Be able to explain the toxicity of amphotericin B. How does this relate to flucytosine
therapy?
Be able to describe why amphotericin B and flucytosine are often used in combination.
Renal Tox.- lipid formations reduce this for Amp B
Used together to treat Cryptococcal meningitis
Synergistic mechanism:
Amphotericin B disrupts membrane, increasing flucytosine uptake
Flucytosine inhibits DNA and RNA synthesis (via 5-FU)
Combo= lower AMP B dose.
Monitor: Flucyotosine narrow window.
Be able to explain how the metabolism of flucytosine in fungal cells differs from that in
animal cells..
Fungal Cells:
Take up flucytosine via cytosine permease
Convert it to 5-fluorouracil (5-FU) via cytosine deaminase (only fungi have this)
5-FU → 5-FdUMP (inhibits DNA synthesis) & 5-FUTP (disrupts RNA)
Animal (Human) Cells:
Lack cytosine deaminase → can’t convert flucytosine to 5-FU
No toxic metabolites form → selective tox
Be able to explain the reaction that is catalyzed by thymidylate synthase, and how flucytosine
inhibits the reaction
Flucytosine inhibits thymidylate synthase by generating 5-FdUMP, a suicide inhibitor, that traps the enzyme in an inactive complex, blocking DNA synthesis in fungi.
Thymidylate Synthase Reaction:
Catalyzes the conversion of dUMP → dTMP (deoxyuridine → deoxythymidine)
Requires N⁵,N¹⁰-methylene tetrahydrofolate as a methyl donor
Essential for DNA synthesis (thymidine is a DNA base)
Isoniazid TB: MOA, Resistance
INH
Activated by KatG: inhibits mycolic acids
resistance in InhA gene
Weakens cell wall.
Rifampin (RIF) MOA, Resistance,etc
MOA: Binds to RNA polyermease to block RNA
orange piss.
Pyrazinamide (PZA) : MOA, Resistance, etc
Uses PncA for activation
reduces pH. interferes with funciton ability.
PncA gene
contribution: kills
panD
Ethambutal (EMB) MOA, Resistance, etc
Inhibits arabinosyl transferases. Arabinogalactan. Weakens cell well.
Resistance: emB
Synergisitc with Rifampin. Not used alone/
FQs in TB: MOA, etc
Moxi: inhibits DNA gyrase and top 4.
Resistance: hyra A and PanC.
Bedaquiline MOA in TB
ATP synthase inhibitor
discrupts energy supply.
MDR drug.
Pretomanid in TB; MOA, etc
Activated by nitroreductase (Dnd)
ATP depletion.
TB Drug susceptible treatment.
RIPE - 6 months
RIMP - 4 months
there is continuation phase R I. - 18 weeks.
Amp B AE:
Nephrotoxicity
Electrolyte Abnormalities (HypoKalemia, Hpyomagnesmia)
Flucytosine AEs
Hematologic: Bone marrow suppression
Monitor: CBC, platelets, Scr, BUN
Itraconazole AEs and Metabolized
P450 3A4 Inhibitor
Active metabolite=hydroitraconazole
Clearnce decreasse with dose
Depends on gastric acidity- oral
not affected by fasting/acidity=oral solution
Blastomycosis and Histo
Hepatotox, QTC prolong. Serum trough >0.5-1
Voriconazole AEs and Metabolism
P450 2c19, 2C9, 3A4
Avoid if CrCL <50 in IV not in oral
For invasive aspergillosis.
Visual disturbance, liver function increase, QTC, diffuse painful
Echinocandins SOA
C. glabrata, C. krusei, C. Lusitaniae, C. Auris
GALK
1st line.
Caspofungin Adverse Effects
Histamine rash, Fever, Phlebitis
N/V/headache
Micafungin AEs
Hyperbilirubinemia, Nausea, diarrhea, eosinophillia, rash
Lice Treatemnt options OTC &Prescription
Pyrethrins
Spinosads
Pinworm Entrobiasis (tape worm) Treatment
Benzimidazoles
Albendazole
Benzimidazole MOA
Binds to tubulin. inhibits form the minus end.
Not in prego.
Malaria Lifecycle d
1) infected mosquito injects Sporozoites
2) sporozoites migrate to liver
3) merozoites form and released into blood
4) in blood the merozoites become trophozoite
5) multiply in blood.
6) mero become gametoctes
7) female mosiqotes eats gameotyes
SMTG. suck my tits g
Artemisinin MOA
Sesquiterpene lactone endoperoxxideActivated in heme-iron.
In Blood stage, short HL
May inhibit PfPl3K
Mutation: Kelch 13. Delays.
4-aminoquinolines MOA and drugs (Chloroquine)
Stop heme from being broken down, the parasite eats. Chloroquine inhibits heme polymerization
Mutation in PfCRT1
8-aminoquinolone:MOA and drugs
liver stage drugs for P.vivax and P. ovale. Usually in combo
Free radicals
Primaquine- hydroxylation OH-PQM then spontanous oxidation H202
***G6PD Deficiency must test
Chemoprophylaxis for Malaria.
Atovaquone/proguanil (Malarone) 1-2 days before 7 after: <crCl 50, expensive
Chloroquine: 1-2 weeks before; 4 weeks after
Doxycycline: 1-2 days beforel 4 weeks after: Wear sunscreen. not in prego or kids <8
Mefloquine: 2 weeks before, 4weeks after: mental issues: can in prego
Primaquine: 1-2 days before; 7days after; Need G6PD testing; no preg
Tafenoquine: 3 days before; 1 week after: G6PD;mental avoid
Severe Malaria Criteria
Have 1>
Coma
Hemo<7
AKI
ARDS
Shock
Acidosis
Parasite density of >5%
TX of Malaria with Chloroquine resistance or unknown
Artemether-lumefantrine * preffered
Atovaquone-proguanil
Quinine sulfate + doxy (qtc)
TX of uncomplicated Malaria with Chloroquine resistance, no mefloquine resistance
Mefloquine* last line (seizures)
Do arthemether
TX of uncomplicated Malaria Chloroquine sensitive
Chloroquine or HydroChloroquine
TX for Anti-relapse Malaria P. vivax and P. ovale
Primaquine G6PD
Tafenoquine: G6PD- avoid in psycho
TX for Malaria P.Falciparum
*Artemether-lumefantrine prefeered if chlorquine resistant
Chlorquine preferred if no resistance.
TX of P.Ovale or P.Vivax malaria with chlorquine resistance
Artemether-lumefantrine PLUS after G6PD testing Primaquine
TX of P.Ovale or P.Vivax malaria with NO chlorquine resistance
Chloroquine + Primaquine or Tafenoquine (G6PD)
TX of Severe Malaria
Do a blood smear ever 12-24 hours until negative
IV artesunate = treat until parasite density <7 up to 7 days.
After finish do oral Artemether-lumefantrine
