92 Section 2/ Drugs Acting on CNSAfter oral administration it is rapidly
absorbed from the GI tract and undergoes
predominantly hepatic metabolism with
little unchanged drug recovered in the urine
and faeces. It is widely distributed into tis-
sues. All metabolites are inactive.
Adverse effects include headache, diar-
rhoea, rhinitis, nausea, sinusitis, dyspepsia,
abdominal pain etc.
It is used in rheumatoid arthritis, osteo-
arthritis and other conditions including
rheumatic pain, neuralgia, gout and
ankylosing spondylitis etc.
NABUMETONE
Nabumetone selectively inhibits COX-- It is metabolised into 6-methoxy-2-
naphthylacetic acid (MNA), that is a potent
inhibitor of COX-2. It has no inhibitory ef-
fect on COX-1 which is responsible for pros-
taglandin synthesis in gastric mucosa,
thereby minimising the risk of problems like
ulcers and hypertension. After oral admin-
istration 80% of dose is excreted in the urine.
Peak plasma concentration is reached after
2.5 to 4 hours.
Adverse effects include nausea, vomit-
ing, heartburn, diarrhoea, constipation,
headache and dizziness.
It is indicated in osteoarthritis, rheuma-
toid arthritis, inflammatory conditions and
soft tissue injuries.
DRUGS USED IN RHEUMATOID ARTHRITISRheumatoid arthritis (RA) is an autoim-
mune chronic inflammatory joint disease. It
is a progressive symmetrical, destructive
and deforming polyarthritis affecting proxi-
mal small joints of hand (usually) and large
joints as well. It is also associated with a
number of extra-articular and systemic fea-
tures. There is joint inflammation, synovial
proliferation and destruction of articular
cartilage by inflammatory cells. There is no
single treatment for RA and the principles
of treatment are directed towards relief of
symptoms and suppression of active and
progressive disease with conservation and
maintenance of joint function.
Initial treatment consists of NSAIDs, low
dose corticosteroids. If the symptoms are not
controlled then second line/disease modi-
fying drugs (DMDs) are added. Since it is a
progressive disease, spontaneous remis-
sions are rare and joint damage occurs early,
DMDs are started early and continued in-
definitely with regular monitoring.
The disease modifying drugs (DMDs/
DMARDs) used are gold, d-penicillamine,
hydroxychloroquine, sulfasalazine and
immuno-suppressants like methotrexate,
azathioprine, cyclosporin etc.GOLD COMPOUNDS
It appears to reduce immune respon-
siveness. It inhibits the migration of mono-
nuclear cells in area of inflammation. It may
also stabilise lysosomal membrane, hence
damage to cartilage is prevented.
It can be used orally and bioavailability
is 25%. After administration it binds exten-
sively to plasma albumin and is distributed
to inflamed synovium, liver and kidney.
Adverse effects include diarrhoea, der-
matitis, stomatitis, glossitis, pharyngitis,
pruritus, exfoliative dermatitis, alopecia,
blood dyscrasias including thrombocytope-