s2-L28-Anti-inflammatory drugs

Question 1

Name 2 types of anti-inflammatory drugs?

Answer 1

1. Non-steroidal anti-inflammatory drugs
   (NSAIDs)
2. Steroids

Question 2

Examples of NSAIDs

Answer 2

Aspirin
Ibuprofen
Paracetamol

Question 3

Name 3 effects of NSAIDs

Answer 3

1). Analgesia
Low to moderate intensity pain (throbbing)
(but also combo with opiates)
Prevent PG synthesis- sensitise nerve endings

2). Anti-inflammatory
Prevent PG synthesis

3). Anti-pyretic - reduce fever, reduce body temp.
Pyrogens (IL-1) released by macrophages
Cause PG release in hypothalamus

Question 4

Describe the mechanisms of action of NSAIDs

Answer 4

(1) Irreversible inhibition of cyclooxygenase (COX) - e.g. aspirin

(2) Reversible inhibition of COX - e.g. ibuprofen

(3) Reversible non-competitive inhibition of COX? - e.g. paracetamol

Question 5

Name 2 types of COX enzyme and their function

Answer 5

COX-1:
constitutive enzyme
ubiquitously expressed
responsible for gut effects

COX-2 :
induced expression
inflammatory cells
responsible for inflammation

Question 6

Examples of steroids and where are they secreted by ?

Answer 6

-Glucocorticoids, mineralocorticoids & androgens
-Secreted by adrenal cortex

Question 7

Effects of steroids

Answer 7

1. Metabolism - glucose, protein synthesis, lipid, minerals.
2. Negative feedback - diagram in the book
3. (i)anti-inflammatory &
   (ii) immunosuppressive
   👇
   (i) early - redness, pain, swelling
   late - wound healing, proliferation

(ii) suppress function of immune cells.- by lowering immune response, these treatments help control inflammation and prevent rejection of transplanted organs.

Question 8

Uses of steroids

Answer 8

1. replacement therapy
2. anti-inflammatory
   - severe asthma- Inhaler (beclomethasone)
   - severe arthritis
   - skin disorders(eczema)
3. immunosuppressive
   -organ transplant recipients
4. Emesis
   -synergey with 5-HT3 R antagonists

Question 9

Side effects of steroids

Answer 9

-Suppressed response to infection/injury

-Atrophy of adrenal cortex

-Disrupted metabolism- iatrogenic Cushing’s syndrome

Question 10

Describe the mechanism of actions of nuclear receptors - slide notes for how steroid works

Answer 10

-Lipophilc glucocorticoid x cell membrane
- Nuclear receptor in cytoplasm
- Glucocorticoid engagement causes homodimerisation
- Homodimeric receptor translocates to nucleus
-Bind to positive or negative GREs
👉 Transactivation (e.g. lipocortin)
👉 Transrepression- via disrupting NFkB-induced transactivation
(e.g. IL-1b, TNFa)

Question 11

Write the mechanism of action- nuclear receptors OR how steroids actually work? - understandable version

Answer 11

-Steroids can readily cross the cell membrane bc the nuclear receptors for steroids are in the cytoplasm - lipophilic glucocorticoid.
- Once the nuclear receptor is engaged by the steroid, there are multiple receptors (homodimerization).
-This is where 2 similar proteins comes together to dimerise. and this dimerised receptor steroid complex(DRSC) is translocated to the cell nucleus.
4. DRSC 😂 then binds to glucocorticoid response element(PROMOTER) on genes.
5. This causes either:
👇
(i) transactivation where genes are expressed. ie: lipocortin protein - TURN ON GENES
(ii) transrepression - activate inflammasome, if you suppress NFkappaB pathway then you suppress inflammation.