Transcript 1- Rheumatoid arthritis

Cause of disability.
Changes in the joint
inflammation,
proliferation of the
synovium,
errosion of cartilage &
bones.
1 in every 100 people suffer from
rheumatoid arthritis .
3:1 female preponderance.
Drugs with different chemical structure &
mechanism of action.
DMARDs improve symptoms &↓ disease
reactivity .
Measurment of improvement
A folic acid antagonist with cytotoxic &
immunosuppressive activity.
It is a first choice DMARD .
It is active in this condition at much
lower doses than those needed in
cancer chemotherapy.
Mechanism of action.
70% absorbed after oral
administration.
t½= 6–9 hours.
Methotrexate's concentration is
increased in the presence of
hydroxychloroquine.
A potent anti rheumatoid
drug, with a more rapid
onset of action than other
DMARD & less adverse
effects.
ADR:- pulmonary
fibrosis, progressive
dose-related
hepatotoxicity.
It is contraindicated in
pregnancy.
Rheumatoid arthritis,
chronic inflammatory
bowel disease.
It is split into its
components
[sulphapyridine & 5aminosalicylic acid ] by
bacteria in the colon.
↓ IgA and IgM rheumatoid factor
production are decreased.
½ T cell responses to concanavalin
↓ B cell proliferation.
Only 10–20% of orally administered
sulfasalazine is absorbed.
Sulfapyridine is excreted after hepatic
acetylation and hydroxylation.
t½= 6–17 hours.
ADR:- GIT disturbances, malaise,
headache, skin rash, leukopenia,
impairment of folic acid absorption.
Reversible infertility in men.
It causes
remission of
rheumatoid
arthritis but it does
not retard the
progression of
bone damage.
Mechanism of action:-suppression of
T lymphocyte responses to mitogens,
Decreased leukocyte chemotaxis,
Stabilization of lysosomal enzymes,
Inhibition of DNA and RNA synthesis,
Trapping of free radicals.
Pharmacokinetics:-rapidly absorbed
but only 50% protein-bound in the
plasma.
Extensively tissue-bound.
Deaminated in the liver , t½ =45 days.
Used in systemic & discoid lupus
ereythematosus.
Half the patients treated respond, effects
appear after a month.
ADR:-ocular toxicity may occur at high
dosages.
Dyspepsia, nausea, vomiting, abdominal
pain, rashes, and nightmares.
Wide range of cytokines are expressed in
the joints of rheumatoid arthritis patients, the
most important isTNFα.
TNF α effects cellular function via activation
of specific membrane-bound TNF receptors
(TNFR1, TNFR2).
Administered soluble TNF receptors, by
combining with soluble TNF α, can inhibit the
effects of the endogenous cytokine.
Infliximab is a chimeric (25% mouse, 75%
human) monoclonal antibody that binds
with high affinity to soluble and possibly
membrane-bound TNF-α.
Is given as an intravenous infusion every
8 weeks.
The terminal half-life is 9–12 days.
Infliximab elicits up to a 62% incidence of
human antichimeric antibodies.
methotrexate ↓ human antichimeric
antibodies.
Infliximab is effective:in rheumatoid arthritis
ulcerative colitis
psoriasis,
psoriatic arthritis,
juvenile chronic arthritis.
Infliximab plus methotrexate.
ADR:-Upper respiratory tract infections,
nausea, headache, sinusitis, rash, and
cough, activation of latent tuberculosis,
infusion site reactions
Quiz?
• Infliximab produces its antirheumatic
effects by direct
• (A) Inhibition of cAMP
phosphodiesterase in monocytic
leukocytes
• (B) Selective inhibition of COX-2
• (C) Enhancement of leukotriene
synthesis at the expense of
prostaglandin synthesis
• (D) Reduction of circulating active
TNF-α levels
• (E) Inhibition of the production of
autoantibodies
A 54-year-old woman
presented with signs and
symptoms consistent with an
early stage of rheumatoid
arthritis. The decision was
made to initiate NSAID
therapy.
Q1
• Which of the following patient
characteristics is a possible reason for
the use of celecoxib in the treatment of
her arthritis?
(A) A history of a severe rash after
treatment with a sulfonamide antibiotic
(B) A history of gout
(C) A history of peptic ulcer disease
• (D) A history of sudden onset of
bronchospasm after treatment with
aspirin
• (E) A history of type 2 diabetes
Q2
• Although the patient's disease was adequately
controlled with an NSAID and methotrexate for some
time, her symptoms began to worsen and radiologic
studies of her hands indicated progressive
destruction in the joints of several fingers. Treatment
with a new second-line agent for rheumatoid arthritis
was considered. This drug is available only in a
parenteral formulation; its mechanism of antiinflammatory action is antagonism of tumor necrosis
factor. The drug being considered is:• (A) hydroxychloroquine
• (B) infliximab
• (C) methotrexate
• (D) chloroquine
• (E) Sulfasalazine