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 30- 300

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. Glucosaminsulphate2. Chondroitinsulphate3. Hyaluronic acid