Lecture 14 - Corticosteroids And NSAIDS

Question 1

Drugs used as antiinflammatory drugs

Answer 1

• simple analgesics
• NSAIDS
• antiinflammatory corticosteroids
• disease modifying anti-rheumatic drugs
• anti TNFalpha monoclonal antibodies
• other immunosuppressants

Question 2

Anti inflammatory corticosteroids clinical indications

Answer 2

• systemic immunological inflammatory disorders (RA, SLE, vasculitis)
• asthma
• skin and eye and nasal disease
• immunosuppression

Question 3

2 major groups of corticosteroids

Answer 3

• mineralocorticosteroids (Aldosterone)

- Glucocorticosteroids (Cortisol)

Question 4

Hydrocortisone

Answer 4

• G:M 1:1

- short acting

Question 5

Prednisolone

Answer 5

• G:M 4:0.8

- intermediate duration of action

Question 6

Dexamethasone

Answer 6

• only glucocorticosteroid

- long

Question 7

Mineralocaorticosteroids

Answer 7

• electrolyte (Na+ and K+) and water balance

Question 8

Glucocorticosteroids

Answer 8

• glucose, protein, fat metabolism

- anti-inflammatory activity parallels glucocorticoid

Question 9

Corticosteroid molecular mechanisms

Answer 9

• 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

Question 10

Lipoxygenase:

Answer 10

• convert arachidonic acid to leukotrienses

Question 11

Cyclooxygenase:

Answer 11

• convert arachidonic acid to PG

Question 12

Corticosteroid side effect mechanism

Answer 12

• 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

Question 13

Antiinflammatory effects of corticosteroids

Answer 13

• inhibit early inflammation: initial redness, heat, pain

- inhibit late manifestation of inflammation: late wound repair, proliferative reactions seen in chronic inflammation

Question 14

Dose- response

Answer 14

• low dose: physiological
• intermediate dose: anti-inflammatory
• high dose: immunosuppressant

Question 15

Prednisone

Answer 15

• a pro drog
• metabolised by the liver
• prednisolone most commonly rpescrived

Question 16

Corticosteroid short term side effects

Answer 16

• only at high doses
• weight gain
• mood change
• increased blood glucose
• hypokalaemia
• HPA axis suppressin

Question 17

Corticosteroids: long term side effects

Answer 17

• Mineralocorticoid: Na+/water, edema, weight gain
• glucocorticoid: osteoporosis, increased blood glucose, muscle wasting and thin skin
• viral or fungal infection
• TB
• CV risk

Question 18

Cushing’s syndrome

Answer 18

• thinning of skin
• musle wasting
• moon face
• increased fat
• easy bruising
• poor wound healing

Question 19

Precautions in prescribing corticosteroids

Answer 19

• immunosuppression risk

- mood disorders

Question 20

Monitoring

Answer 20

• clinical: body weight, height, BP

- Lab: blood sugar, lipids

Question 21

Long term oral corticosteroids

Answer 21

• prevalent in older adults
• patients vulnerable to side effects
• aim for lowest dose and shortest duration of therapy
• prevention

Question 22

Topical treatment of corticosteroid

Answer 22

• ears, eyes, nose, skin, rectal

- adverse effects: eye infection, cataracts, increased intra ocular pressure, corneal thinning

Question 23

COX 1

Answer 23

• constitutive expression
• important in GI mucosa, kidney, platelets, endothelium
• prostanoids mediate homeostatic function

Question 24

COX2:

Answer 24

• induced mainly at sites of inflammation by cytokines
• constitutive expression in brain, kidney
• prostanoids mediate pain, inflammation, fever