Block 5 - High Yield Flashcards
Triple drug regiment for maintenance immunotherapy
- Glucocorticoid
- Anti-proliferative
- Cyclosporin or tacrolimus
AE: Cytokine release syndrome
rATG and Alemtuzumab
This drug is humanized anti-CD52 and actively depletes T cells
Ametuzumab
This drug is a humanized antibody that binds CD25 and inhibits T cell proliferation
Basiliximab
MOA of Azathioprine
Azathioprine -> 6-mercaptopurine -> 6-TIMP (inhibits de novo purine biosynthesis) -> 6-TGTP (inhibits CD28/Rac1 T cell costimulation) -> incorporated into DNA -> apoptosis
Inhibition of lymphocyte proliferation
These drugs interact with azothioprine and increase toxicity
Allopurinol and Febuxostat (gout) -> inhibit xanthine oxidase
MOA of mycophenolate mofetil (MMF)
Converted by plasma esterases to mycophenolic acid, which inhibits IMPDH type II, which is required for the S phase of the cell cycle of de novo purine synthesis
AE: progressive multifocal leukoencephalopathy (and what causes it?)
- Mycophenolate mofetil
- Natalizumab
Reactivation of JC virus
Which anti-proliferative is safe to use in pregnant women?
Azathioprine
MOA of cyclosporine and tacrolimus
Diffuse into cell -> cyclosporin binds to cyclophilin and tacrolimus binds to FKBP -> inhibit calcineurin, preventing it from dephosphorylating NFAT, a TF that allows IL-2 to be produced
Which drugs inhibit signal 1 of T cell activation? Which drugs inhibit signal 2?
Signal 1: cyclosporine/tacrolimus
Signal 2: sirolimus/everolimus
AE: nephrotoxicity and hypertension
Cyclosporine/tacrolimus
MOA of sirolimus and everolimus
Bind FKBP, inhibit mTOR, which normally regulates protein synthesis, cell proliferation, and survival downstream of IL-2 binding to its receptor
What types of transplants are sirolimus and everolimus not recommended for and why?
- Liver transplant (risk of hepatic artery thrombosis)
2. Lung transplant (risk of anastomotic dehiscence)
MOA of Ipilimumab
- Binds to CTLA4
- Prevents CTLA4 from binding to CD 80/86 and from delivering a negative signal
- Leaves CD 28 co-stimulation intact
- Leads to enhanced T cell activation
What is Ipilimumab use to treat?
Late stage melanoma
What are Pembrolizumab and Nivolumab used to treat?
Aggressive metastatic cancers
MOA of Pembrolizumab and Nivolumab
- Bind to PD1 protein on T-cells
- Prevent inhibition of T-cell by PD-L1 (found on tumor cells)
- Maintain T cell activation
AE: bradyarrythmia, AV block, varicella zorster virus infection
Fingolimid
___ have many drug interactions due to being metabolized by CYP3A4.
Calcineurin inhibitors (cyclopsorine and tacrolimus)
Broadest spectrum anti-fungal agent
Amphotericin B
Not active against C. lusitaniae, Pseudallescheria boydii
What is Amphotericin B first-line treatment for?
Life-threatening mycotic infections
MOA of Amphotericin B
Binds to Ergosterol, forms a pore in the membrane, increases permeability, efflux of essential molecules, cell death
How is Amphotericin used?
Initial induction therapy (4 weeks) to reduce fungal burden, replaced azoles for consolidation therapy
What is the only antifungal approved for use in pregnant women?
Amphotericin B
AE of Amphotericin B
- Amphoterrible (fever, chills, spasms, vomiting, headache, hypotension)
- Nephrotoxic
- Hepatotoxic
- Anemia
MOA of Flucytosine
Taken up into cell through a cytosine permease, converted to 5-flurouracil (with cytosine deaminase) -> 5-FUTP (inhibits RNA synthesis) and 5-FdUMP (inhibits thymidylate synthase, which inhibits DNA synthesis)
Fungistatic
What are the 3 fungi Flucytosine can treat?
- C. neoformans
- Cnadida
- Chromoblastomycoses
What combination is used to treat Candidiasis or Cryptococcosis?
Flucytosine + Amphotericin B
What combination is used to treat Chromoblastomycosis?
Flucytosine + Itraconazole
What drug is good for treatment of cryptococcal meningitis?
Flucytosine + Amphotericin B
What is the cause of AE in Flucytosine?
Endogenous gut microflora express cytosine deaminase and can convert the drug to 5-flurouracil, an anti-metabolite
AE: bone marrow toxicity
Flucytosine
List the azoles in order of least to broadest spectrum of activity
Keto < Flu < Itra < Vori < Posa
How are the azoles involved with CYP450?
Inhibitors and substrates
Itra and Vori are most involved
MOA of azoles
Inhibit 14-alpha-sterol demethylase, preventing the synthesis of ergosterol and impairing growth
Itra and Vori should never be given with what drug and why?
Statins - rhabdomyolysis
AE: decreased cortisol and testosterone -> gynecomastia, libido, impotence, menstrual irregularities
Ketoconazole
AE: alopecia with long duration/high dose
Fluconazole
Good for fungal bladder infections?
Fluconazole
Which azole should NOT be used for Crytptococcal meningitis?
Itraconazole