Immunopharm

Question 0

immunophilin inhibition: MOA, indications, toxicities

Answer 0

• 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

Question 1

Corticosteroids: MOA, Indications, Toxicities

Answer 1

• 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)

Question 2

Antimetabolites: 4

Answer 2

Azathioprine
Mycophenolate mofetil
Methotrexate
Leflunomide

Question 3

Azathioprine: MOA, Indications, Interactions, toxicities

Answer 3

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

Question 4

Mycophenolate mofetil: MOA, indications, interactions, toxicity

Answer 4

• 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

Question 5

Leflunomide

Answer 5

• 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)

Question 6

Methotrexate

Answer 6

• 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

Question 7

Cyclophosphamide: MOA, Indications, Interactions, toxicities

Answer 7

• 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)

Question 8

Calcineurin inhibitors: MOA, interactions

Answer 8

• 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)

Question 9

Calcineurin inhibitors: rolimus, indications, interactions, Toxicities

Answer 9

Tacrolimus/pimecrolimus

• MOA: FKBP inhibitor
• indications: transplantation, atopic eczema
• interactions: CYP3A4
• toxic: black box cancer risk, renal and neurotoxic

Question 10

mTOR inhibitors:

Answer 10

• 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)

Question 11

TNF-a inhibitors: (6) eat a cig and die of malignant heart failure

Answer 11

Etanercept
Inflixumab
Adalimumab
Certolizumab
Golimumab
Thalidomide

Question 12

TNF-a inhibitors: (6) MOA

Answer 12

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

Question 13

TNF-a inhibitor toxicities: eat a cig and die of malignant heart failure

Answer 13

Malignancy
Heart failure exacerbation
Demyelinating disease

Question 14

IL-1 inhibitor

Answer 14

• 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.

Question 15

IL-6 inhibitor: (top of clock - 6)

Answer 15

• 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.

Question 16

Antithymocyte globulin

Answer 16

• 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

Question 17

IVIG

Answer 17

Polyclonal human Ig

• MOA: no specific Ag is targeted; normalizes pt. system.
• indications: Autoimmune disorder, Immunodeficiency diseases

Question 18

Rhogam

Answer 18

Duhhhhh.

Question 19

OKT3

Answer 19

Polyclonal mouse Anti CD3 IgG Ab

• MOA: Binds pan T-cell marker; Fixes compliment and clears
• Indications: Acute renal transplant rejection, Second line drug
• Toxicity: Hypersensitivity and anaphylaxis, Rapid clearance,

Question 20

Daclizumab and basilixumab

Answer 20

Daclizumab- humanized
Basiliximab- chimeric
- Binds alpha subunits on IL-2 receptor (cd25: the basilisk was 25 feet long)
- Indications: Acute renal transplant Rejection

Question 21

Ritixumab

Answer 21

Chimeric Anti-CD 20 antibody (B-cells signal transducer) Induces complement mediated lysis
(Riddick (ritixumab) takes down Bs (Bcells))
- toxicity: Severe mucocutaneous reaction
- indications: Non-Hodgkin’s lymphoma (riddick and hodge fought together)

Question 22

Alemtuzumab

Answer 22

Humanized Anti-CD 52 (t cell signal transducer) antibody

- Indications: B-cell leukemia

Question 23

Abatacept

Answer 23

Chimeric anti-B7 Ab
- binds B7-1/2 and inhibits costimulation (like intercept but with a B)
Indications: Transplantation therapy and RA

Question 24

Balatacept

Answer 24

Same as Abaracept except higher affinity for B7-1/2

Question 25

Belimumab

Answer 25

Human anti-BLyS (Bcells activator) - Indications: SLE and RA - Toxicities: G.I. effects

Question 26

Natalizumab

Answer 26

Human anti-Alpha 4 integrin Ab - Indications: Relapsing and remitting multiple sclerosis - toxicities: Progressive multifocal leukoencephalopathy NATA (No Alpha ATtachment)

Question 27

Fingolimod

Answer 27

Sphingosine 1-phosphate receptor agonist - expressed on B/T cells - inhibits lymphocyte homing - Indications: Multiple sclerosis - ECG recommended for patients on antiarrhythmics (The MS dwarf has his gold, but can't get home cause he has a bad heart)

Question 28

Criteria for anaphylaxis

Answer 28

Highly likely: if any of these appear within minutes to hours - Acute onset of Generalized hives, Pruritus, Itching or flushing In skin or mucosal tissue and: 1. Respiratory compromise or 2. Hypotension

Question 29

Immunosupression: hemorrhagic cystitis

Answer 29

Cyclophosphamide | - which also causes alopecia

Question 30

Immunosupression: hemorrhagic cystitis

Answer 30

Cyclophosphamide | - which also causes SIADH

Question 31

Etanercept

Answer 31

Affinity For TNF alpha 1 and TNF alpha 2

Question 32

Cytokine release syndrome

Answer 32

Antithymocyte Ab

Question 33

Progressive multifocal leukoencephalopathy

Answer 33

Potential side effect of natalizumab | - alpha 4 integrin inhibitor

Question 34

Alefacept

Answer 34

LFA-3 costimulatory inhibition | aLeFAcEpt

Question 35

Azathiopine vs. allopurinol

Answer 35

Compete for action of xanthine oxidase

Question 36

Inhibition of dihydroorate

Answer 36

Lefloonamide

Question 37

Reactivation of malignant TB

Answer 37

Risk with administration of TNF-a inhibitor

Question 38

Golimumab

Answer 38

Longer 1/2 life (gollum had unnatural long life).

Question 39

CAPS

Answer 39

Cryopyrin associated periodic fever: treat with IL-1 inhibitor anakinra. - muckle-wells syndrome - Hibernian fever

Question 40

Prophylaxis for P. jirovecii

Answer 40

Almetzumab

Question 41

Meth heads have bad skin and bad joints

Answer 41

RA and psoriasis are indications for methotrexate

Question 42

Eculizumab

Answer 42

Inhibits compliment