7. • The drug is well absorbed but does not enter blood brain barrier.
• Hence it is given intrathecally.
• It is 50% protein bound and is eliminated unchanged
• The dose of drug, therefore, in renal failure is reduced
• S/E
• Most common side hepatic fibrosis.
• pulmonary fibrosis and
• leukoencephalopathy when it is given intra-thecally.
• It should not be given with potassium sparing diuretics as they
interfere with renal elimination
TONY SCARIA 2010 KMC
8. • Uses of Methotrexate
• DMARD that is used clinically for RA,
• Ankylosing spondylitis
• psoriatic arthropathy and
• pustular psoriasis.
• ectopic pregnancy.
TONY SCARIA 2010 KMC
9. Leflunomide
• orotate dihydrogenase inhibitor (antipyrimidine)
• Rheumatoid arthritis.
• The drug is a DMARD and is used in late phase.
• It forms an active metabolite and has a good oral
absorption. Peak levels are reached in 6-12 hours.
• The drug has been shown to reduce radiological
progression of RA and produce symptomatic
improvement.
• S/E
• hepatotoxicity
• bone marrow depression leading to leucopenia or
thrombocytopeniA.
• Steven Johanson syndrome
• Interstitial lung disease.
TONY SCARIA 2010 KMC
12. Hydroxychloroquine
• Suppress T lymphocytes
• Decreased IL1 from
monocyte
• Anti-chemotactic
• Concentrates in eye
• Slowly acting
• Safest DMARD in
pregnancy
TONY SCARIA 2010 KMC
13. d-penicillamine
• It is a copper chelator and is used for Wilson’s disease and is also a
DMARD.
• It is a metabolite of penicillin but does not have antibiotic like activity.
The drug reduces activity of T lymphocytes, macrophages and IL-1.
• It also reduces the activity of RA factor as well.
• Side effects
• pemphigus like eruption and proteinuria.
• Myopathy can occur and can persist even after the withdrawal of the drug
TONY SCARIA 2010 KMC
14. Gold salts
• 1. Aurothiomalate
• 2. Aurothioglucose
• 3. Auranofin
• 1. Anti-macrophages
• 2. Well absorbed after IM injection
• 3. Long acting
• 4. High efficacy
• 5. High toxicity
• S/E
• 1. Rashes-MC
• 2. Nitritoid reactions (sweating, headache etc)
• 3. Neuropathy
• 4. Nephrotic syndrome
TONY SCARIA 2010 KMC
21. Uses of TNFα
• 1. Rheumatoid arthritis
• 2. JRA
• 3. Psoriasis
• 4. Psoriatic arthropathy
• 5. Ankylosing spondylitis
• 1. No value in Crohn disease
TONY SCARIA 2010 KMC
22. S/E of TNF α inhibitors
• Activate latent TB & hepatitis B
• Infusion related side effects
• Anti-nuclear antibody (SLE can occur)
• Lymphomas
TONY SCARIA 2010 KMC
23. Abatacept
• Abatacept (which contains the
endogenous ligand CTLA-4)
binds to CD80 and 86, thereby
inhibiting the binding to CD28
and preventing the activation
of T cells.
TONY SCARIA 2010 KMC
24. Abatacept
• 1. Given as IV infusion
• 2. Long acting (half life=10 days)
• 3. Use – Refractory rheumatoid arthritis
• Side effects
• 1. Infections
• 2. Lymphomas
• 3. Not combined with other TNF alpha blockers
TONY SCARIA 2010 KMC
27. • Anakinra
• interleukin 1 antagonist.
• Tocilizumab
• It is a interleukin 6 antagonist
TONY SCARIA 2010 KMC
28. Corticosteroids
• It down regulate T cells and are potent anti-inflammatory drugs.
• Corticosteroids can inhibit hypothalamic pituitary adrenal axis and
thus can reduce release of GnRH leading to azoospermiA
TONY SCARIA 2010 KMC
30. Drugs in gout
• Drugs Used in a/c gout
• Drugs used in c/c gout
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31. Drugs used in a/c gout
• Colchicine
• NSAIDs
• Steroids
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32. • NSAIDs are DOC for a/c gout
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33. • Oxaprozin
• 1. NSAIDs with mild uricosuric acid
• 2. Given in acute gout
• 3. Not used in uric acid stones (because it is uricosuric)
TONY SCARIA 2010 KMC
34. Colchicine
• 1. Oldest anti-gout drug
• 2. Most effective
• 3. Most toxicused only in Recurrent/refractory gout
• 4. Plant derived alkaloid (cochicine)
• 5. Anti-chemotactic
• inhibit release of chemokines
• Inhibit Granulocyte migration
• 6. Prevent microtubule polymerization
• 7. Causes metaphase arrest antimitotic
Suppresses gouty inflammation
TONY SCARIA 2010 KMC
35. • Side effects
• 1. Diarrhea mc & dose limiting S/E of colchicine
• 2. Neuropathy
• 3. Myopathy
• 4. Alopecia
• 5. Bone marrow depression
TONY SCARIA 2010 KMC
36. Drugs used in c/c gout
Drugs decreasing uric
acid synthesis
• Allopurinol
• Febuxostat
Uricosuric drugs
• Probenecid
• Sulfinpyrazone
• Benzbromarone
Increasing
metabolism of uric
acid
• Rasburicase
• Pegloticase
TONY SCARIA 2010 KMC
38. Allopurinol
• Xanthine oxidase inhibitor
• Also decrease metabolism of 6 MP & azathioprine
• Eliminated by bile used in renal failure
TONY SCARIA 2010 KMC
39. Uses
• Organ preservation
• Kala azar
• Chronic gout
• Leish-Nehan syndrome
• Gout with renal failure
• Gout with /tophi/
• Urate nephropathy
• Tumor induced hyperuricemia
TONY SCARIA 2010 KMC
40. • C/I of allopurinol
• Reduce dose of azathioprine
• Inhibits metabolism of:
• –Cyclophosphamide
• –Oral anticoagulants
• –Probenacid
TONY SCARIA 2010 KMC
41. • Febuxostat
• 1. Non-purine xanthine oxidase inhibitor
• 2. Well absorbed; high first pass
• 3. Safer than allopurinol
TONY SCARIA 2010 KMC
43. Probencid/sulfinpyrazone
• Uricosuric
• also used along with penicillin to decrease reanl excretion of
probenecid
• Use
• 1. Tophi
• 2. Frequent gout attacks
• 3. Gout refractory to allopurinol/febuxostat
TONY SCARIA 2010 KMC
47. • Urate oxidase enzyme, absent in humans and some higher primates,
converts uric acid to allantoin which is exreted by kidney
TONY SCARIA 2010 KMC
48. • Pegloticase
• recombinant mammalian uricase that is covalently attached to methoxy
polyethylene glycol (mPEG)
• Rasburicase
• converts purine into allantois which is a water soluble compound and goes
out of the body by urine.
TONY SCARIA 2010 KMC
49. • Rapid lowering of urate level by any means precipitate acute attack of
gout
• Seen with
• ALLOPURINOL
• PRBENACID
TONY SCARIA 2010 KMC