Anti-inflammatory Drugs

Question 1

What can Anti-inflammatory agents do?

Answer 1

• Preventative; do not reverse an attack
• Target late phase of asthma response

Question 2

What are other names for corticosteroids?

Answer 2

• Glucocorticosteroids
• Glucocorticoids
• Steroids

Question 3

What are the types of steroid?

Answer 3

Steroids act at intracellular glucocorticoid receptor.

Inhaled:
* Beclometasone
* Budesonide
* Ciclesonide
* Fluticasone
* Mometasone

Oral:
* Prednisolone e.g. Acute asthma attack

IV:
* Hydrocortisone e.g. Life threatening acute asthma

Question 4

How do steroids work?

Answer 4

• Lead to an increase in Gene expression
• (see PP)

Question 5

What are Adrenal steroids?

Answer 5

Have both Mineralocorticoid and Glucocorticoid action.

Glucocorticoids:
* Cortisol & Corticosterone
1. Affect Carbs and protein metabolism
2. Anti-inf and immune suppressing effects
3. Mineralocorticoid effects as well e.g. water+electrolyte balance

Mineralocorticoid:
1. Aldosterone

Question 6

Compare the effects of Mineralocorticoid and Glucocorticoid action.

Answer 6

Question 7

What are the 2 effects of Gucocorticoid receptors?

Answer 7

1. Activation of Genes
2. Repression of genes

Question 8

What genes do Glucocorticoid receptors activate?

Answer 8

• Annexin A1
• B2-adrenoceptors
• IkB
• MKP1
• Anti-inf cytokines(IL-10 etc)

Question 9

What genes do Glucocorticoid receptors repress?

Answer 9

• Inflammatory cytokines (IL-2, IL-3, IL-6, TNF-a)
• Chemokines
• Inf enzymes (iNOS, COX-2)
• Inf peptides (Enothelin-1)

Question 10

What is Annexin A1?

Answer 10

• Upregulation of anti-inf genes e.g. annexin A1
• Annexin A1 appears to act theough formyl peptide receptors
  1. Inhibits release of histamine from mast cells
  2. Inhibits cPLA2-PGs

Question 11

How do steroids interact with B-adrenoceptor expression?

Answer 11

• Steroids inc transcription of B2-Ar
• Protect Against downregulation of B2-AR after long-term use
• Benefits of co-admin

Question 12

What are the side effects of corticosteroids?

Answer 12

• Throat infections with inhaled
• Osteoporosis Adrenal suppression in children
• 1. Monitor height
• Withdrawal effect (red oral steroids slowly)
• Also, inc hyoerglycaemia (effects on carb metabolism)
• Water retention-inc BP

Question 13

Why is steroid recistance problematic?

Answer 13

• Patients with severe asthma or COPD have poor response to steroids
• COPD is chronic inf
• Suggests steroid resistance
• Reasons for resistance are many:
  1. Genetic
  2. GR receptor modification
  3. Dec nuclear translocation of GR
  4. INc efflux of steroids

Question 14

What is the role of Leukotrines in Inflammation and asthma?

Answer 14

• Stimulate mucus secretion
• Casue bronchodialtion
• Role in airway remodelling
• Linked to hyperresponsiveness
• Link with excercise-induced asthma

Question 15

What are CysteinLeukotriene receptor antagonists?

Answer 15

• E.g. Montelukast
• Taken Orally
• Antagonise leukotrine receptors-block inf action of Cysteinylleukotrines
• Also blocks bronchoconstriction
• Lipoxygenase inhibitors–BLock synth of leukotrines

Question 16

What is Omalizumab?

Answer 16

• Used? in Severe, allergic asthma that cannot be controlled by steroids
• Monoclonal antibody against free IgE
• Prevents IgE from binding to immune cells, thus prev allergen-induced mediator release.
• S.c. Injection every 2-4 weeks

Question 17

Bronchoconstriction as an adverse drug reaction

Answer 17

• ~15% of asthmatics
• NSAIDs-inhibit cox (May provoke asthma in number of sensitive patients)
  –> More AA leukotrine prod
• B-adrenoceptor antagonists
  1. Especially non-selective e.g. propanolol
  2. ‘selective’ e.g. atenolol also contraindicated in asthma/COPD
• Drug allergy e.g. Penicillins etc

Question 18

What are cromones?

Answer 18

• Sodium cromoglicate
• Preventative (both early+late)
• May be of benefit in excercise-induced asthma
• Inhalation
• Uncertain action
• Though to prevent mast cell degranulation, possibly through enhanced action of annexin A1