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)

Non-steroidal anti- inflammatory drugs (NSAIDs)

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.

1.Analgesic effect 2.Antipyretic effect 3.Antiflogistic effect (mainly higher doses) 4.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) 5.Other effects- for example reduced incidence of some tumors (for example colorectal carcinoma), uricosuric effekt...

 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...

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

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%

 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

Traditional drugs: methotrexate (antagonist of folic acid) hydroxychloroquine leflunomid sulfasalazine penicillamine azahtioprine ciclosporin gold salts

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

Rapid acting drugs 1. Analgetic drugs – paracetamol, metamizol Nonsteroidal antiinflammatory drugs 1. Weak opioids – tramadol 2. Topic transdermal treatment 1. NSAID (diclofenac, ketoprofen) 2. Iritanciá (capsaicin, menthol) 3. Steroid antiflogistic drugs (corticoids) intraarticular (triamcinolone, betametazone) Slowly acting drugs -chondroprotectives 1. Disease modifying drugs (DMOAD) 1. Glucosaminsulphate 2. Chondroitinsulphate 3. Hyaluronic acid