Immunopharm Flashcards
immunophilin inhibition: MOA, indications, toxicities
- inhibition of IL-2/3 via cyclophilin/FKBP inhibiting calcineurin or FKBP-12 inhibiting mTOR
- normal anti immuno uses; Drug eluding stents (sirolimus/tacrolimus)
- renal dysfunction, HTN, neurotoxicity. All things Hyper-liver functiony + normal 3
Corticosteroids: MOA, Indications, Toxicities
- MOA: inhibits receptor/HSP90 activated gene txn
- indication: general anti inflammatory agent, immunosuppressant (GVHD, organ transplants) hemo cancers. Generally part of cocktail.
- toxicity: Adrenal suppression (must wean off) Na retention (-> HTN, edema et al), increased glycogenolysis, glucogenesis, and lipolysis, developmental/structural issues (muscle wasting, osteoporosis et al)
Antimetabolites: 4
Azathioprine
Mycophenolate mofetil
Methotrexate
Leflunomide
Azathioprine: MOA, Indications, Interactions, toxicities
Think of old WoW player (Azeroth), IBD (nerd)and arthritis and is going bald (RA, alopecia) stays at his PC so he has gout,
- MOA: prodrug -> mercaptopurine (via glutathione) (inosine analog); inhibits de novo purine synthesis.
- small scope of use: transplant, IBD, RA
- interactions: allopurinol, ACE other myelosupressives
- alopecia, pancreatitis/hepatitis + normal 3
Mycophenolate mofetil: MOA, indications, interactions, toxicity
- MOA: inosine analog - inhibits de novo purine synthesis
- indications: transplantation, steroid GVHD, Lupus nephritis, RA derm disorders refractory to topical trt.
- interactions; immunophilins, EH circulation, tubular secretions
- toxicity: Normal 3
Leflunomide
- MOA: anti-metabolite, inhibits dihydroorate dehydrogenase for pyrimidine synthesis
- indications: RA, Wegeners syndrome, SLE, MG
- interactions: EH recirculating
- toxicities: BLACKBOX: hepatotoxic teratogenic; reversible alopecia and normal 3
Lune-moon-tide-reversible alopecia; don’t bang under a full moon, because your liver with die and you’ll have a deformed kid. (Blackbox-hepatotoxic and teratogenic)
Methotrexate
- MOA: antimetabolite; DHFR inhibition-> also increases adenosine (which is anti inflammatory)
- indications: psoriasis, neoplasms, RA, GVHD
- interactions: tubular secretion, reduced renal flow, nephrotoxicity, organic acids
- toxicities: teratogenic, pneumonitis, hepatic fibrosis + normal 3
Cyclophosphamide: MOA, Indications, Interactions, toxicities
- MOA: screws with txn 4 ways; X-linking, ring cleavage, mismatching, guanine excision
- indications: pre-trt BMT, cancer, childhood nephrotic syndrome, severe SLE
- interactions: myelosupression, nephrotoxicity
Toxicities: LOTS; normal + cardio, alopecia, reproductive toxicity, mutagenic, SiADH, hemorrhagic cystitis (acrolein)
Calcineurin inhibitors: MOA, interactions
- MOA: cyclosporine -> cyclophilin -> calcineurin -> calmodulin -> active NFAT -> IL-2
Tacrolimus -> FKBP -> calcineurin et al. - indication: lots - uveitis and bechets
- interactions: CYP3A4 (hence lots) and sirolimus/methotrexate
- toxicities: normal + Hirsutism, gum hyperplasia, lots of kidney issues. (Cyclosporine sp.)
The tacky psycho made fun of the blind (uveitis) French guy (bechets) who turned out to be a chick with a beard (hirautism) and bad gums (gum hyperplasia) He gets in fights (drug interactions) especially with serious (sirolimus) meth heads (methotrexate)
Calcineurin inhibitors: rolimus, indications, interactions, Toxicities
Tacrolimus/pimecrolimus
- MOA: FKBP inhibitor
- indications: transplantation, atopic eczema
- interactions: CYP3A4
- toxic: black box cancer risk, renal and neurotoxic
mTOR inhibitors:
- sirolimus/everolimus
- MOA: -> FKBP - 12 -> inhibits mTOR -> inhibits p70s6 kinase/PHAS-1 -> inhibits IL-2 expression
- indications: many- drug eluting stents
- interactions: CYP3A4, P-GPTN, cyclosporine
- lymphocele, delayed wound healing et al.
Motorsports are forever serious. (mTOR, sirolimus/everolimus) At 76 (p706S kinase) mph you hit phase 1 and break your tire seal and Cee Your People (CYP interactions) cycling past. (Cyclosporine interaxn)
TNF-a inhibitors: (6) eat a cig and die of malignant heart failure
Etanercept Inflixumab Adalimumab Certolizumab Golimumab Thalidomide
TNF-a inhibitors: (6) MOA
Etanercept: binds both TNF-a/B (intercepts both)
Infliximab: binds TNFa with high affinity (IV)
Adalimumab(golimumab): same as inflixumab (+ crohns) (subQ: gollum gets under frodos skin)
Certolizumab pegol: pegged, binds TNFa with high affinity
TNF-a inhibitor toxicities: eat a cig and die of malignant heart failure
Malignancy
Heart failure exacerbation
Demyelinating disease
IL-1 inhibitor
- anakinra:MOA- binds IL-1 and prevents binding
- indications: RA (with bony erosions) and CAPS (muckle wells syndrome, Hibernian fever)
- toxicity: HA, allergy, GI distress
Anakin was a and ill one (IL-1) got his bones eroded by lava and had to put on a cap. Then as vader he was a real headache and pain in the ass.
IL-6 inhibitor: (top of clock - 6)
- Tocilizumab
- MOA: humanized IgG Ab against IL-6 receptor
- indications: RA (better with methotrexate)
- toxicities: increased cholesterol, demyelination, no anti-DNA Abs
Our patient at the top of the hour, had high cholesterol and was on methotrexate for years for his RA.
Antithymocyte globulin
- anti-serum from animals
- MOA: recognizes multiple epitopes on human T cells -> Mac clearance
- indications: transplants (first you transplant, then you transplant)
- toxicity: cytokine release syndrome + normal
