IC13 drugs for gout, OA, RA

Question 1

normal plasma urate concentration?

Answer 1

2-7mg/dL

Question 2

drug induced hyperuricaemia?

Answer 2

thiazide or loop diuretics
low dose aspirin
ciclosporin

Question 3

MOA of colchicine

Answer 3

use for acute attacks
reduces leukocyte migration into the joint

1) binds to tubulin (cytoskeleton)
2) prevents tubulin polymerisation into microtubules
3) inhibits leukocyte migration and phagocytosis
4) inhibits leukotriene B4 (LTB4) and prostaglandin (PG) production.

Question 4

what NSAIDs are contraindicated for gout?

Answer 4

aspirin and salicylates

induce kidney retention of uric acid [23-27]. However, low-dose aspirin used for cardiovascular prophylaxis should be continued during the treatment of a gout flare despite this effect

Question 5

which gc recommended for gout

Answer 5

prednisolone

Question 6

SE of colchicine

Answer 6

gi side effects (due to effects on proliferation of gi wall): n/v, diarrhoea, abdo pain
muscle weakness
pale lips
change in amount of urine.

risk of myopathy, neuropathy, pancytopenia (blood dyscrasia related to bleeding) esp in renal or hepatic impairment

Question 7

caution for colchicine

Answer 7

renal impairment
esp crcl<30 or for prolonged duration increases toxicity

drug drug interaction w pgp cyp3a4 inhibitors and inducers.
- macorlides, azoles, antiarrhythmic (verapamil, diltiazem…)§, rifampin, atorvastatin

Question 8

onset of colchicine

Answer 8

relief pain in 24 to 36 hours

Question 9

MOA of allopurinol and febuxostat and use

Answer 9

uric acid synthesis inhibitors

used to prevent recurrence
DO NOT USE during acute attacks

Question 10

allopurinol (and xanthine oxidase inhibitor) warning

Answer 10

allopurinol hypersensitivity syndrome (AHS)

severe cutaneous adverse reaction (SCAR) warning (allopurinol > febuxostat)

febuxostat = MACE warning

Question 11

risk factors for SCAR

Answer 11

renal impariment;: crcl <60, thiazide therapy, hlab5801 genotype (common in han Chinese)

reduce dose if renally impaired

Question 12

side effect of xanthine oxidase inhibitors

Answer 12

maculopapular rash (related to hypersensitivity),
n/v, diarrhoea, stomach pain
fever, sore throat
dark urine
jaundice

Question 13

probenecid use?

Answer 13

uricosuric agent
increases uric acid excretion

used to prevent recurrence
DO NOT USE during acute attacks, may increase risk of uric acid kidney stone formation

Question 14

moa of uricosuric agents

Answer 14

inhibit proximal tubule anion transport
inhibit uric acid re-absorption
increase uric acid excretion

Question 15

when to start probenecid

Answer 15

2-3 weeks after flare

Question 16

probenecid pracutions and C/I

Answer 16

1) take plenty of fluid (≥2L of water) to minimise renal stone formation (CONTRAINDICATED in PMH urolithiasis)

2) keep urine pH > 6 by administration of alkaline (eg potassium citrate)

risk of hemolytic anaemia in patients w g6pd deficiency

not recommended if crcl<50

Question 17

SE of probenecid

Answer 17

n/v
painful urination
lower back pain
allergic reaction
rash

proBACK(pain)neACID(urine = pain)

Question 18

another drug for oa other than nsaids

include MOA

Answer 18

intra articular hyaluronic acid (slow-acting)

moa: shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain and stiffness

induces biosynthesis of HA (in the synovial fluid) and extracellular matrix

Question 19

methotrexate mechanism of action

Answer 19

major: increase adenosine levels due to AICAR and/or ATIC inhibition

minor: inhibits (i) dihydrofolate reductase and (ii) thymidylate synthetase.

overall effects: increased extracellular adenosine level and activation of adenosine A2a receptor =
(i) antiproliferative effects on T cells
(ii) inhibition of macrophage functions,
(iii) decrease in pro-inflammatory cytokines, adhesion molecules, chemotaxis, phagocytosis.

Question 20

side effects of methotrexate (related to mechanism)

Answer 20

inhibition of dihydrofolate reductase reduces the proliferation of other cell types (due to reduced purine and therefore DNA synthesis), more specifically those that are rapidly proliferating: skin and GI

• n/V
• mouth and GI ulcers
• hair thinning

Question 21

management of potential side effects of methotrexate

Answer 21

administration of folic or folinic acid or folate 12-24 hours after mtx to decrease toxicity.

Question 22

differences between management of mtx toxicity with folate vs folinic acid

Answer 22

folate = cheaper but require high doses due to depletion of n5, n10 methylene FH4

vs

folinic acid = rapidly converted to n5,n10 methylene FH4 = more efficient at rescuing toxicity s dihydrofolate reductase activity is bypassed

Question 23

sulfasalazine mechanism of action

Answer 23

metabolised by sulfapyridine and 5aminosalicylic acid
= effect on gut flora = decrease IgA, IgM rheumatoid factors, suppression of T and B cells, macrophages, decrease in inflammatory cytokines (eg IL1beta, TNF, IL6)

Question 24

side effects of sulfasalazine

Answer 24

GI: nausea, dyspepsia
CNS: headache, dizzy

Derm: rash

Haem: agranulocytosis, neutropenia, hemolytic anaemia

Genitourinary: oligospermia (reversible infertility in men),
urine discolouration

Infection

Question 25

MOA of leflunomide

Answer 25

converted to teriflunomide = inhibit dihydroorotate dehydrogenase = (i) decrease pyrimidine synthesis and arrest G1 phase (ii) (decrease t cell, b cell) inhibit T cell proliferation, B cell autoantibody production (iii) inhibit NF-KB activation of pro-inflammatory pathway

Question 26

caution and management for leflunomide

Answer 26

very long half life (years) can manage with colestyramine (bile salt binding resin) to wash out (eg before pregnancy) TERATOGENIC

Question 27

side effects of leflunomide

Answer 27

GI: diarrhoea, nausea CNS: headache, liver: increase transaminases derm: alopecia, rash heme: myelosuppression Infection

Question 28

moa of hydroxychloroquine

Answer 28

reduced MHC class II expression and antigen presentation reduced TNF, IL1 and cartilage resorption antioxidant activity

Question 29

SE of hydroxychloroquine

Answer 29

gi: n/v, stomach pain ophth: retinopathy derm: photosx, hyperpigmentation, hairloss cvs: qtc prolongation metabolic: hypoglycaemia cns: headache, dizziness, neuropsychiatric smx

Question 30

ADR of tofacitinib

Answer 30

cytopenia of neutrophils, lymphocytes, platelets, NK cells = immunosuppression = opportunistic infections (eg herpes zoster) anemia (affect jak2 activation by erythropoietin) hyperlipidemia | TO(lesterol)fA(nemia)ci(topenia)tinib

Question 31

MOA of tofacitinib

Answer 31

JAK janus kinase pathway inhibitor - blocks cytokine production by blocking JAK/STAT activation of gene transcription

Question 32

what are the bDMARDS

Answer 32

TNF: infliximab, adalimumab, etanercept, (GOLIMUMAB) IL1: anakinra IL6: tocilizumab CD20 rituximab CD28 abatacept

Question 33

side effects of TNF blockers

Answer 33

infection: resp and skin autoimmune: multiple sclerosis malignancy: increased risk of lymphoma ophth: optic neuritis heme: leukopenia, aplastic anemia

Question 34

C/I for TNF blockers

Answer 34

live vaccination hep B

Question 35

monitoring for TNF blockers

Answer 35

screen for latent or active TB

Question 36

side effect of anakinra

Answer 36

infections injection site reactions

Question 37

side effect of tocilizumab

Answer 37

stomatitis skin eruptions increase ALT/AST (transaminases) fever, infections,neutropenia | sTOmach ci(skin) li(ver) zu mab (neutropenia, fever, infection)

Question 38

tocilizumab interactions

Answer 38

cyp450: 1A2, 2C9, 3A4