Drugs for Systemic Autoimmune disease

Question 1

what’s the point of being COX-2 selective

Answer 1

there are two cyclooxyrgenase enzymes
COX-1: physiological function in the gut and kidney
COX-2: induced in inflammation and repair

by being selective for COX-2 you avoid GI side effects

Question 2

NSAIDs that are not COX-2 selective

Answer 2

ibuprofen, diclofenac, naproxen, ketoprofen

Question 3

NSAIDs that are COX-2 selective

Answer 3

meloxicam, celecoxib, etoricoxib

Question 4

cardiovascular toxicity of NSAIDs

Answer 4

increases rates of vascular events, hypertension and heart failure

Question 5

do non-selective or selective NSAIDs increase cardiovascular risk

Answer 5

both

Question 6

how corticosteroids are used

Answer 6

usually prednisolone or prednisone
used for things like RA, SLE, cranial arteritis, polymyalgia rheumatica etc.

Question 7

how corticosteroids are used

Answer 7

usually prednisolone or prednisone
used for things like RA, SLE, cranial arteritis, polymyalgia rheumatica etc.

Question 8

problems with corticosteroids

Answer 8

obesity, muscle wasting
osteoporosis, bone loss, minimal trauma fractures
increased risk fo sepsis (immunosuppressive)
raised BSL
hypertension
increased rate of vascular events - myocardial infarction and stroke

Question 9

mechanism of action of antimalarials

Answer 9

antilysosomal
interferes with antigen processing, decreased stimulation of T cells, decreased cytokine release

Question 10

what are antimalarials used for to treat systemic autoimmune disease

Answer 10

used as single agent in RA and Lupus

Question 11

mechanism of action of sulphasalazine

Answer 11

binding of sulphapyridine molecule with acetylsalicylic acid via an azo bond
inti inflammatory, action on folate metabolising enzymes, action on inhibiting neutrophils

Question 12

toxicity of sulphasalazine

Answer 12

GIT, rash (may be severe), headache, pancytopenia, hepatitis,

Question 13

pharmacology of methotrexate

Answer 13

forms monoglutamates and poly glutamates
higher blood levels in renal impairment
can be used in combination with NSAIDs, probenecid imparts its clearance
immunomodulatory effects in RA

Question 14

toxicity of methotrexate

Answer 14

nausea, vomiting, diarrhoea
general fatigue and higher function problems, concentration and memory
bone marrow suppression, hepatic toxicity (particularly with alcohol) and mouth ulceration, hair loss
pneumonitis
can reduce folic acid

Question 15

monitoring for sulphasalazine

Answer 15

FBC, LFTs

Question 16

monitoring for methotrexate

Answer 16

FBCs, LFTs, AST, U&Es monthly
reduce 2-3 monthly

Question 17

leflunomide is a

Answer 17

prodrug

Question 18

pharmacology of leflunamide

Answer 18

blocks pyrimidine synthesis and interferes with T cell function
blocks dihydroorotate dehydrogenase

Question 19

toxicity for leflunomide

Answer 19

GIT, hypertension, peripheral neuropathy, rash, hepatic, bone marrow, pneumonitis

Question 20

monitoring for leflunomide

Answer 20

FBS, LFTs

Question 21

pharmacology of azathioprine

Answer 21

purine analogue
blocks HGPRT synthase
reduces purine synthesis
lymphocytes can’t proliferate (B and T cells)

Question 22

problem with Azathioprine

Answer 22

some people have functional genetic polymorphisms affecting the TPMT enzymes responsible for metabolism.
low activity of the TPMT enzyme causes metabolites of 6-MP (6TGN) to accumulate.
this causes bone marrow toxicity

Question 23

azathioprine is metabolised into

Answer 23

6-MP

Question 24

low TPMT causes what to accumulate

Answer 24

6TGN

Question 25

6TGN causes

Answer 25

bone marrow toxicity

Question 26

toxicity of azathioprine

Answer 26

GIT increased rate of infection and malignancies bone marrow and hepatic toxicity

Question 27

cyclosporin A pharmacology

Answer 27

fungal metabolite lipophilic cyclic peptide inhibits T cell proliferation

Question 28

mycophenylate mofetil

Answer 28

calcineurin inhibitor used for lupus, polymyositis, vasculitis

Question 29

tacrolimus is used for

Answer 29

used in SLE

Question 30

cyclophosphamide

Answer 30

alkylating agent severe lupus, scleroderma lung

Question 31

list some Anti-TNF inhibitors

Answer 31

etanercept, alalimumab, infliximab, certolizumab, pegol, golimumab

Question 32

toxicity of anti-TNF inhibitors

Answer 32

usual and atypical infections (also very expensive)

Question 33

anti-TNF inhibitors are contraindicated in

Answer 33

TB, skin cancers, heart failure contraindicated and in demyelinating conditions can produce autoimmune conditions

Question 34

anti-T cell inhibitor - abatacept

Answer 34

blocks interaction with CD28 blocks T cell costimulation and activation combine with methotrexate

Question 35

anti L6 inhibitor: tocilizumab

Answer 35

use without methotrexate blocks IL-6, suppresses synovitis and joint damage and the acute phase response

Question 36

what to monitor for anti L6 inhibitor tocilizumab

Answer 36

monitor FBC, increased rate of common and atypical infections

Question 37

anti B cell inhibitor: rituximab

Answer 37

significantly reduces B cell numbers and immunoglobulin levels combine with methotrexate can be repeated every 6-12 months

Question 38

new biologics and small molecules

Answer 38

anti IL17 and anti IL22 molecules - can be combined JAK kinase inhibitor

Question 39

apremilast

Answer 39

phosphodiesterase inhibitor for psoriatic arthritis