1. Antirheumatics

4. Treatment of RA 1. Non-steroidal anti-inflammatory drugs (NSAIDs)
2. Glucocorticoids
3. Disease modifying
anti-rheumatic drugs - DMARDs
- imunosupressive effect
- slowly onset of the therapeutic
effect
- newest - biologic treatment
(monoclonal antibodies and
solubile receptors ) for example
inhibitors of TNF
(infliximab, adalimumab; etanercept)

5. Non-steroidal anti-inflammatory drugs (NSAIDs)

7. Non-steroidal anti-inflammatory drugs
Division according to COX selectivity:
Selective inhibitors of COX-1:
Acetylsalicylic acid (ASA)- in a dose of mg/day
Non-selective inhibitors of COX:
Acetylsalicylic acid- in a dose of 500 mg/day or more, ibuprofen, diclofenac, ketoprofen, tiaprofen, indomethacin and many more
Preferential inhibitors of COX-2:
nimesulide, meloxicam etc.
Selective inhibitors of COX-2:
celecoxib, rofecoxib, etoricoxib, valdecoxib etc.

8. Effects of NSAIDs Analgesic effect Antipyretic effect
Antiflogistic effect (mainly higher doses)
Antiaggregatory effect (not every NSAID, most important is ASA because of irreversible blocade of COX-1- be careful with combination of ASA for anti-aggregation and other NSAIDs- mostly ibuprofen)
Other effects- for example reduced incidence of some tumors (for example colorectal carcinoma), uricosuric effekt ...

9. NSAIDs – one of the most widely used drug groups → their ADRs represent a serious medical / public health / economical problem there are big differences between various NSAIDs in the level risk of particular possible ADRs

10. Adverse effects of NSAIDs
GIT- erosions and ulcers of the gastric mucosa (also in other localisations in the GIT), nausea, vomitus, meteorism, diarrhoea, constipation... (mainly inhibition of COX-1)
kidney- reduction of glomerular filtration, retention of Na and fluids, edema, hyperkaliemia, kidney failure, interstitial nephrits... (inhibition of COX-1 and 2)
CVS- thrombotic events, increase of blood pressure, heart failure... (mainly COX-2 (mostly in thrombotic events))
CNS- cephalea, weakness, sleap disorders, dizziness, epileptic seizures...
other- hepatotoxicity, bleeding, provocation of asthmatic attack, Ray´s syndrom, prolonged childbirth, urticaria, decreased number of white blood cells...

11. Gastrointestinal ADRs
most serious – ↓ production of prostaglandins in the gastric mucosa → peptic ulcer (most often in the stomach and duodenum; the mucosa can get damaged by NSAIDs also in other places in the GIT)
roughly 25 % of chronic NSAID users might develop erosions and ulcers, in 2-4 % perforation or bleeding can occure

12. Kidney ADRs
Decreased production of prostanoids → negative effect on the perfusion of the kidneys, glomerular filtration, excretion of sodium and water and on production of renin → circulation overload, oedemas, hypertension ; hyperkalemia ; in severe cases symptoms of acute kidney failure
serious complication– interstitial nephritis (immunological reasons)
Incidence of kidney ADRs is poughly 18%, severe cases- roughly 1%

13. Cardiovascular ADRs
Increased blood pressure- mostly in hypertensive patients treated with antihypertensives (mainly ACEIs, ARBs, beta blockers), there are big differences between various NSAIDs
Development/worsening of heart failure- the risk is highest during the first weeks of treatment, mainly in patients with preexisting congestive heart failure; possibly 19% of all cases of congestive heart failure could be caused (at least partially) by NSAID therapy
Thrombotic events- acute myocardial infarction, stroke, thromboembolic disease

14. NSAIDs Symptomatic treatment Analgetic effect: in several minutes
Antiinflammatory effect: in 7-14 days
Interindividual variability in response to different drugs
Different types of NSAIDs are not combined together

15. GLUCOCORTICOIDS The most effective symptomatic treatment
Their are applied only till DMARDs start to be effective
Given is the lowest effective dose and for the shortest time needed
Rebound effect!!! (prolonged administration cannot be stopped abruptly

16. DMARDs = disease-modifying antirheumatic drugs
Used nowadays are especially:
methotrexate (antagonist of folic acid) – drug of choice
sulfasalazine
hydroxychloroquine
leflunomid
If methotrexate not effective, use another DMARDs or combination therapy

17. DMARDs Biologic treatment Anti TNF:
infliximab, adalimumab, certolizumab, golimumab (monoclonal antibodies)
etanercept (solubile receptor)
Against IL-6 receptor:
tocilizumab
Against protein CD20 (on B lymphocytes):
rituximab
Against protein B7 (decrease the activity of T lymphocytes through inhibition of their interaction with antigen presenting cells):
abatacept

19. Treatment of OA Rapid acting drugs Slowly acting drugs
1. Analgetic drugs
Paracetamol, metamizol
Nonsteroidal antiinflammatory drugs
Weak opioids – tramadol
2. Topical transdermal treatment
NSAID (diclofenac, ketoprofen)
Irritants (capsaicin, menthol)
3. Steroid antiflogistic drugs (corticoids) intra-articular administration
triamcinolone, betametazone
avoid frequent administration
Slowly acting drugs
chondroprotectives
1. Disease modifying drugs (DMOAD)?
Glucosaminsulphate
Chondroitinsulphate
Hyaluronic acid
No proven agents that reverse osteoarthritis (alternative
to pharmacotherapy in advanced stages of the disease is surgery).