Lecture 14 - Corticosteroids And NSAIDS Flashcards
Drugs used as antiinflammatory drugs
- simple analgesics
- NSAIDS
- antiinflammatory corticosteroids
- disease modifying anti-rheumatic drugs
- anti TNFalpha monoclonal antibodies
- other immunosuppressants
Anti inflammatory corticosteroids clinical indications
- systemic immunological inflammatory disorders (RA, SLE, vasculitis)
- asthma
- skin and eye and nasal disease
- immunosuppression
2 major groups of corticosteroids
- mineralocorticosteroids (Aldosterone)
- Glucocorticosteroids (Cortisol)
Hydrocortisone
- G:M 1:1
- short acting
Prednisolone
- G:M 4:0.8
- intermediate duration of action
Dexamethasone
- only glucocorticosteroid
- long
Mineralocaorticosteroids
- electrolyte (Na+ and K+) and water balance
Glucocorticosteroids
- glucose, protein, fat metabolism
- anti-inflammatory activity parallels glucocorticoid
Corticosteroid molecular mechanisms
- transactivation (classical concept): synthesis of effector proteins
- transrepression: switch off many inflammatory genes
- post genomic effect: destabilises pro-inflammatory mRNA
- activation of HDAC: winding of DNA
Lipoxygenase:
- convert arachidonic acid to leukotrienses
Cyclooxygenase:
- convert arachidonic acid to PG
Corticosteroid side effect mechanism
- GCR bind to negative GRE in osteoblasts
- reduces osteocalcin synthesis
- osteocalcin required for bone bulding
- low osteocalcin -> osteoporosis
- also reduce calcium absorption and increase excretion
Antiinflammatory effects of corticosteroids
- inhibit early inflammation: initial redness, heat, pain
- inhibit late manifestation of inflammation: late wound repair, proliferative reactions seen in chronic inflammation
Dose- response
- low dose: physiological
- intermediate dose: anti-inflammatory
- high dose: immunosuppressant
Prednisone
- a pro drog
- metabolised by the liver
- prednisolone most commonly rpescrived
Corticosteroid short term side effects
- only at high doses
- weight gain
- mood change
- increased blood glucose
- hypokalaemia
- HPA axis suppressin
Corticosteroids: long term side effects
- Mineralocorticoid: Na+/water, edema, weight gain
- glucocorticoid: osteoporosis, increased blood glucose, muscle wasting and thin skin
- viral or fungal infection
- TB
- CV risk
Cushing’s syndrome
- thinning of skin
- musle wasting
- moon face
- increased fat
- easy bruising
- poor wound healing
Precautions in prescribing corticosteroids
- immunosuppression risk
- mood disorders
Monitoring
- clinical: body weight, height, BP
- Lab: blood sugar, lipids
Long term oral corticosteroids
- prevalent in older adults
- patients vulnerable to side effects
- aim for lowest dose and shortest duration of therapy
- prevention
Topical treatment of corticosteroid
- ears, eyes, nose, skin, rectal
- adverse effects: eye infection, cataracts, increased intra ocular pressure, corneal thinning
COX 1
- constitutive expression
- important in GI mucosa, kidney, platelets, endothelium
- prostanoids mediate homeostatic function
COX2:
- induced mainly at sites of inflammation by cytokines
- constitutive expression in brain, kidney
- prostanoids mediate pain, inflammation, fever
