Antirheumatic drugs & anti gout drugs PHARMACOLOGY REVISION NOTES

ANTIRHEUMATIC DRUGS &
anti gout drugs
TONY SCARIA 2010 KMC

DISEASE MODIFYING
ANTIRHEUMATIC DRUGS
• IMMUNOSUPPRESSANTS
• Methotrexate,
• Azathioprine,
• Cyclophosphamide
• Cyclosporine
• Cycloserine
• Mycophenolate mofetil
• Sulfasalazine
• Chloroquine or
Hydroxychloroquine
• Leflunomide
• Gold sod.thiomalate, Auranofin
• d-Penicillamine
BIOLOGIC RESPONSE MODIFIER
• TNF-α ANATGONIST
• Etanercept, Infliximab,
Adalimumab, Certolizumab,
Golimumab
• IL-1 ANTAGONIST: Anakinra
• IL-6 ANTAGONIST: Tocilizumab
• cd20 Mab: Rituximab
• T Cell INHIBITOR: Abatacept
ADJUVANT DRUGS
• CORTICOSTEROIDS
• NSAIDS

• DMARD
• Slow progression of disease
• NSAIDS
• Symptomatic relief

METHOTREXATE
• Drug of first choice among DMARD

MTX inhibits DHFR

• 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

• Uses of Methotrexate
• DMARD that is used clinically for RA,
• Ankylosing spondylitis
• psoriatic arthropathy and
• pustular psoriasis.
• ectopic pregnancy.

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.

Leflunomide inhibits DHODH

Hydroxychloroquine
• Suppress T lymphocytes
• Decreased IL1 from
monocyte
• Anti-chemotactic
• Concentrates in eye
• Slowly acting
• Safest DMARD in
pregnancy

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

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

Biological response modifiers

TNFα inhibitors
• Adalimumab
• Infliximab
• Etanercept
• Golimumab
• Certolizumab

Etanercept
• Recombinant receptor of TNF α receptor (p75)+ Fc
portion of IgG

Infliximab
• Chimeric monoclonal antibody (IG1)
• TNF-alpha blocker
• Given IV infusion
• Long acting (half life=10 days)
Uses
• 1. Rheumatoid arthritis
• 2. Crohn’s disease
• 3. Psoriatic arthropathy
• 4. sarcoidosis
• 5. wegeners granulomatosis

Uses of TNFα
• 1. Rheumatoid arthritis
• 2. JRA
• 3. Psoriasis
• 4. Psoriatic arthropathy
• 5. Ankylosing spondylitis
• 1. No value in Crohn disease

S/E of TNF α inhibitors
• Activate latent TB & hepatitis B
• Infusion related side effects
• Anti-nuclear antibody (SLE can occur)
• Lymphomas

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.

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

Rituximab
• Anti CD20

Tofacitinib
• Janus kinase inhibitor

• Anakinra
• interleukin 1 antagonist.
• Tocilizumab
• It is a interleukin 6 antagonist

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

Drugs in gout
• Drugs Used in a/c gout
• Drugs used in c/c gout

Drugs used in a/c gout
• Colchicine
• NSAIDs
• Steroids

• NSAIDs are DOC for a/c gout

• Oxaprozin
• 1. NSAIDs with mild uricosuric acid
• 2. Given in acute gout
• 3. Not used in uric acid stones (because it is uricosuric)

Colchicine
• 1. Oldest anti-gout drug
• 2. Most effective
• 3. Most toxicused 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

• Side effects
• 1. Diarrhea  mc & dose limiting S/E of colchicine
• 2. Neuropathy
• 3. Myopathy
• 4. Alopecia
• 5. Bone marrow depression

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

Drugs inhibiting uric acid synthesis

Allopurinol
• Xanthine oxidase inhibitor
• Also decrease metabolism of 6 MP & azathioprine
• Eliminated by bile  used in renal failure

Uses
• Organ preservation
• Kala azar
• Chronic gout
• Leish-Nehan syndrome
• Gout with renal failure
• Gout with /tophi/
• Urate nephropathy
• Tumor induced hyperuricemia

• C/I of allopurinol
• Reduce dose of azathioprine
• Inhibits metabolism of:
• –Cyclophosphamide
• –Oral anticoagulants
• –Probenacid

• Febuxostat
• 1. Non-purine xanthine oxidase inhibitor
• 2. Well absorbed; high first pass
• 3. Safer than allopurinol

Uricosuric drugs

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

• Losartan, amlodipine and Fenofibrate have uricosuric action.

Increasing catabolism of uric acid

• Urate oxidase enzyme, absent in humans and some higher primates,
converts uric acid to allantoin which is exreted by kidney

• 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.

• Rapid lowering of urate level by any means precipitate acute attack of
gout
• Seen with
• ALLOPURINOL
• PRBENACID

Antirheumatic drugs & anti gout drugs PHARMACOLOGY REVISION NOTES

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