Joint Pharm

Question 1

Uricosuric

Answer 1

Uricosuric agents increase the rate of excretion of uric acid. Reabsorption of urate mediated by URAT1. Uricosuric drugs compete with urate for transporter–> inhibit reabsoption. Salicylates may increase or decrease excretion of uric acid. Low dose= decrease excretion. High dose= increased excretion.

Question 2

Allopurinol

Answer 2

Mechanism: inhibits xanthine oxidase (prevents synthesis of urate from hypoxanthine and xanthine
Oxypurinol (active metabolite) inhibits the reduced form of XO
Kinetics: metabolized to active metabolite (oxypurinol half life= 18-30; allopurinol half life= 1-2 hours)
SE: induces drowsiness, increase in gout flares after initiation d/t mobilization of urate from tissues
Use: primary and secondary gout

Question 3

Colchicine

Answer 3

Mechanism: antimitotic, arrests cell in G1 by interferring with microtubule and spindle formation
Kinetics: CYP 3A4 metabolism
SE: GI tract toxicity–> N/V/D and abd pain
Contraindicated in pts with concomitant therapy w/ CYP3A4 or PGP inhibitors
Use: acute gout

Question 4

Febuxostat

Answer 4

Mechanism: Non-purine xanthine oxidase inhibitor (compleses w/ both reduced and oxidized form of XO)
Kinetics: CYP metabolism–> active metabolites
SE: liver function abnormalities, increase in gout flares d/t mobilization. Increase of MI and stroke in pts on Febuxostat
Use: chronic hyperuricemia

Question 5

Pegloticase

Answer 5

Mechanism: PEGylated recombinant form of Urate oxidase enzyme (uricase) which converst uric acid to allantoin (inactive metabolite)
Kinetics: IV, half 6-13 days–> low urate levels for 21 days
SE: infusion reactions, gout flare, some pt show immune response
Use: chronic gout

Question 6

Probenecid

Answer 6

Mechanism: inhibition of organic acid transporter (URAT-1) –> increase uric acid excretion
Kinetics: highly bound to plasma proteins, majority of drug secreted by proximal tubule
Side effect: mild GI irritation, ineffective in pts with renal insufficiency, contraindicated in pts w/uric acid kidney stone
Use: hyperuricemia associated with gout or gouty arthritis
Blunted by co-admin w/ salicylates; enhance toxic effects of loop diuretics, decrease diuretic effect of diuretics, increase serum concentraiton of loop diuretics. Toxic when administered with PGP or CYP3A4 inhibitors and colchicine

Question 7

NSAID

Answer 7

provide symptomatic relief for gout
Indomethacin: often prescribed for gout

Question 8

Steroid

Answer 8

Glucocorticoids reduce access of cells to target tissues, prevent nuetrophil adherence to endothelium, inhibit action of chemotatic factors. In macrophage: inhibit antigen processing, inhibition of IL-1 release. In T cel: interfere with macrophage antigen processing, interfere with lympholines, reduce IL2 synthesis. suppression inflammation: inhibits AA release, inhibit inductin of COX by cytokines, decrease capillary permeability.

Question 9

Adalimumab

Answer 9

Mechanism: chimeric IgG monoclonal antibody that binds to both soluble and transmembrane TNFa. Inhibits TNFa from binding with its receptor
Kinetics: subQ
SE: infection site reactions. Infection URI
Use: moderate to severely active RA (w/MTX)

Question 10

Etanercept

Answer 10

Mechanism: recombinant, fully human TNF Receptor fusion protein
Kinetics: 1-2 weeks onset of action
Adverse effect: injection site reaction, fatal infections in pts taking immunosuppresive medication
Use: moderate to severely active RA

Question 11

Infliximab

Answer 11

Mechanism: chimeric (human and murine) IgG monoclonal antibody. Bothes to both soluble and transmembrane TNFa
kinetics: IV
SE: acute infusion reaction, infection- URI
Use: moderate to severe Active RA

Question 12

Abatacept

Answer 12

Mechanism: selective costimulation modulator (inhibits T cell activation by binding to CD80 and CD86) on APC
kinetics: IV
SE: headache, hypersensitivity, increased risk of infection ( do not use with anakinra or TNF blocker)
use: mild to severely active RA

Question 13

Rituximab

Answer 13

Mechanism: monoclonal antibody against CD20 on B cell. Activates ADCC
SE: IV infusion
SE: severe infusion reaction. Tumor lysis syndrome–> acute renal failure
Use: moderate to severe active RA in combo with MTX (inadequate response to TNF antagonists)

Question 14

Tocilizumab

Answer 14

Mechanism: binds to soluble and membrane bound IL6 receptor–> inhibit signaling
Kinetics: IV
SE: URI, headache, HTN, elevated liver enzymes. GI perfs reported, neutropenia and reduction in platelet counds occur occasionaly and lipids should be monitored
Use: moderate to severely active RA (inadequate response to TNF antagonists)

Question 15

Tofacitinib

Answer 15

Mechanism: JAK inhibitor ( inhibits signaling)
Kinetics: metabolism mediated by CYP 34A
SE: higher risl of opportunisitic infections. GI perfs reported. Increased blood cholesterol levels
Use: moderate to severely active RA (inadequte response to MTX)

Question 16

anakinra

Answer 16

Mechanism: IL-1 receptor antaognist
Kinetics: subQ
SE: injectin site reaction, infection (may lead to reactivation of latent TB)
Use: moderate to severely active RA ( who have failed one or more DMARDs)

Question 17

Azathioprine

Answer 17

Mechanism: purine antimetabolite that inhibits purine biosynthesis
Use: severe refractory RA
Toxicity: affects rapdily growing cells –> leukopenia, thrombocytopenia and GI toxicity

Question 18

Hydroxychloroquine

Answer 18

Mechanism: not understood.
Use: oral treatment for patients with early mild erosive disease
Toxicity: long term tx is irreversible retinal damage

Question 19

Leflunomide

Answer 19

Mechanism: acts as an immuno modeulatory agent by causing cell arrest of autoimmune lymphocytes by inhibiting Dihydoorotate dehydorgenase
Toxicity: diarrhea, rash, alopecia, elevated liver function

Question 20

Methotrexate

Answer 20

Mechanism: inhibits DHFR–> inhibts folate dependent steps in purine synthesis (inhibits DNA synthesis)
Toxicity: use associated with hepatic toxicity and bone marrow suppression