Lecture 9- Paracetamol, Anti-inflammatory Steroids + Disease-modifying Anti-rheumatoid Drugs Flashcards
Pharmacological actions of paracetamol
-not an NSAID
-it is a non-narcotic analgesic-antipyretic drug
-analgesic + antipyretic activity= related to inhibition of CNS prostaglandin synthesis
-weak anti-inflammatory activity
-does not share the gastric/platelet side effects of the other NSAIDS
Therapeutic uses of paracetamol
-suitable substitute for the analgesic + antipyretic effects of NSAIDS for:
*patients with gastric complaints
*people with a disadvantage of prolong bleeding
*those who do not require the anti-inflammatory action of NSAIDS
-main analgesic choice for children with viral infections
Side effects of paracetamol
-skin rash + minor allergic reactions occur frequently
Large doses= cause liver necrosis; paracetamol should be avoided in patients with severe hepatic impairment
-liver enzyme tests = should be monitored in patients on high-dose paracetamol
Anti-inflammatory steroids
*hydrocortisone
*cortisone
*prednisolone
*prednisone
*dexamethasone
*betamethasone
Pharmacological actions of anti-inflammatory steroids
-general effects on inflammation + immunity
*acute inflammation= decreased influx + activity of leucocytes
*chronic inflammation= decreased activity of mononuclear cells
*lymphoid tissues= decreased clonal expansion of T + B cells + decreased action of cytokine-secreting T cells
Pharmacological actions of anti-inflammatory steroids
*effects on inflammatory mediators;
- decreased production + action of cytokines; interleukins, tumour necrosis factor-alpha + granulocyte macrophage colony-stimulating factor
-reduced generation of eicosanoids
-decreased generation of IgG
-decrease in complement components in the blood
-increased release of anti-inflammatory factors; interleukin-10 + annexin 1
Pharmacological actions of anti-inflammatory steroids
*overall effects;
-reduction in the activity of the innate + acquired immune systems
-decreased healing + reduction in the protective aspects of the inflammatory response
Unwanted effects of anti-inflammatory steroids
Hormonal actions -> lead to the clinical picture of drug-induced Cushing’s syndrome
-occur with large doses/prolonged administration rather than replacement therapy
-suppression of the response to infection/injury
Wound healing may be impaired = ulceration may occur
Drugs used in anti-inflammatory + immunosuppressive therapy= metabolic actions + effects o water, electrolyte balance + organ systems = unwanted side effects
-tendency to hyperglycaemia that occurs with exogenous glucocorticoids = develop in diabetes
-osteoporosis= hazard of fractures - main limitation to long-term glucocorticoid therapy
Therapeutic uses of corticosteroids
*replacement therapy for adrenocortical insufficiency (Addison’s disease)= caused by adrenal cortex dysfunction
*relief of inflammatory symptoms;
-in asthma
-topically in various inflammatory conditions; skin, eye, ear/nose (eczema, conjunctivitis etc)
-hypersensitivity states (severe allergic reactions)
-diseases with autoimmune + inflammatory components; rheumatoid arthritis, IBD, anaemia, idiopathic thrombocytopenia purpura etc
-prevent graft-versus-host disease following organ/bone marrow transplantation
Rheumatoid arthritis
-inflammatory disease of the joints
-autoimmune disease; immune system attacks joints for unknown reasons
^WBC travel to the synovium + cause inflammation (redness, warmth, swelling & pain)
-inflammation process= synovium becomes thick & makes the joint swollen and puffy to the touch
-joint changes= represent an autoimmune reaction + erosion of cartilage and bone
-inflammatory cytokines = major role in the pathogenesis of arthritis
Disease-modifying anti-rheumatic drugs
DMARDS= used in treatment of RA
^group of drugs= unrelated chemical structures + different mechanisms of action
-slow the course of the disease; induce remission + prevent further destruction of the joints + tissues
Activity of DMARDS measured by;
-reduction in number of swollen + tender joints
-pain score, disability score & articular index on radiology
-serum concentration of acute-phase proteins
DMARD’S
-methotrexate
-sulfasalazine
-gold compounds
-penicillamine
-chloroquine
-anti-cytokine drugs; Anti-TNFa antibodies; infliximab
Methotrexate
-first choice DMARD
-folic acid antagonist with cytotoxic + immunosuppressant activity
-treatment= closely monitored because of blood dycrasias + liver cirrhosis
Chloroquine
*4-aminoquinoline drug= used in the prevention + treatment of malaria
-reserved for cases where other drugs have failed
*suppresses T-lymphocytes
*inhibits TNFa
*decreases lymphocyte chemotaxis
*traps free radicals + prevents tissue damage
Sulfasalazine
-used for early, mild RA in combination with chloroquine + methotrexate
-may act by scavenging the toxic oxygen metabolites produced by neutrophils
