Lecture 14 - Corticosteroids And NSAIDS Flashcards Preview

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Flashcards in Lecture 14 - Corticosteroids And NSAIDS Deck (24):
1

Drugs used as antiinflammatory drugs

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

2

Anti inflammatory corticosteroids clinical indications

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

3

2 major groups of corticosteroids

- mineralocorticosteroids (Aldosterone)
- Glucocorticosteroids (Cortisol)

4

Hydrocortisone

- G:M 1:1
- short acting

5

Prednisolone

- G:M 4:0.8
- intermediate duration of action

6

Dexamethasone

- only glucocorticosteroid
- long

7

Mineralocaorticosteroids

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

8

Glucocorticosteroids

- glucose, protein, fat metabolism
- anti-inflammatory activity parallels glucocorticoid

9

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

10

Lipoxygenase:

- convert arachidonic acid to leukotrienses

11

Cyclooxygenase:

- convert arachidonic acid to PG

12

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

13

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

14

Dose- response

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

15

Prednisone

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

16

Corticosteroid short term side effects

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

17

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

18

Cushing's syndrome

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

19

Precautions in prescribing corticosteroids

- immunosuppression risk
- mood disorders

20

Monitoring

- clinical: body weight, height, BP
- Lab: blood sugar, lipids

21

Long term oral corticosteroids

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

22

Topical treatment of corticosteroid

- ears, eyes, nose, skin, rectal

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

23

COX 1

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

24

COX2:

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