Drug control in Asthma

Question 1

Asthma definition

Answer 1

recurrent reversible obstruction of airflow in airwaves in response to non-noxious stimuli

• genetic susceptibility
• Allergic in >30%

Question 2

Extrinsic

Answer 2

-atopic, allergic

Question 3

Intrinsic

Answer 3

non-atopic, non-allergic

Question 4

Antigen induces antibody synthesis:

Answer 4

-mast cells - IgE

Question 5

Cells release chemical mediators (cytokines):

Answer 5

• interleukins
• prostaglandins (PG)
• leukotrienes (LT)
• thromboxanes (Tx)
• histamine
• platelet activating factor (PAF)

Question 6

Effects of cytokine mediators:

Answer 6

• vasodilation
• pain/itch
• oedema
• smooth muscle contraction

Question 7

Immediate phase of Asthma:

Answer 7

bronchoconstriction +- vasodilation (anaphylaxis –> death)

Question 8

Late phase of Asthma:

Answer 8

• oedema –> congestion
• hypersecretion –> mucus
• inflammatory cells
• bronchoconstriction + hyperreactivity

Question 9

Innervation:

Answer 9

• parasympathetic
• sympathetic
• non-adrenergic non-cholinergic (NANC)
• sensory - irritation –> reflex constriction via parasympathetic

Question 10

affect on Upper airways:

Answer 10

-constricted by ACh via M3 receptors (parasympathetic nerves)

Question 11

affect on Lower airways:

Answer 11

-constricted by excitatory NANC transmitters; relaxed by inhibitory NANC transmitters (eg NO) and circulating adrenaline (beta2)

Question 12

Blood vessel smooth muscle:

Answer 12

-constricted by NA from sympathetic nerves (alpha1); relaxed by circulating adrenaline (beta2)

Question 13

Glands:

Answer 13

• mucus secretion decreased by sympathetic system and increased by parasympathetic system
• inflammatory mediators and chemical/physical stimuli

Question 14

Drug therapy:

Immediate phase

Answer 14

-smooth muscle relaxants (to treat bronchoplasm)

Question 15

Drug therapy:

Late phase

Answer 15

-steroids (treat inflammation)

Question 16

DRUGs USED:

Answer 16

1. Beta-adrenoceptor agonists
2. Muscarinic antagonists
3. Theophylline
4. Antihistamines
5. LT antagonists
6. Glucocorticoids

Question 17

1. B-adrenoceptor agonists:

Answer 17

adrenaline:
alpha + beta agonist
beta1 - heart
beta2- bronchi

Question 18

Beta-adrenoceptor agonists:

Salbutamol:

Answer 18

• beta2 only
• inhaled aerosol or powder

-Relaxed bronchioles:
  decreased secretion and increased FEV1
-Mechanism:
- increased adenylate cyclase
- increased cAMP 
-decreased Ca2+ entry

Question 19

2. Muscarinic antagonists:

Answer 19

Ipratropium: N+ (poor absorption)

• blocks bronchoconstriction due to parasympathetic reflex
• more useful in bronchitis

Tiotropium:

• prolonged (24hr) M3 selective muscarinic antagonist
• better than the older ipratropium

Question 20

3. Theophylline:

Answer 20

• bronchodilator; relaxes smooth muscle by inhibition of phosphodiesterase
• also increased release of NA and Adr (?)

Question 21

4. Antihistamines

Answer 21

-little benefit in asthma

Question 22

5. Antagonists of Leukotrienes (LTs)

Answer 22

-drugs to block either the LT receptor or the synthesis of LTs
(eg MONTELUKAST)

Question 23

6. Glucocorticoids (anti-inflammatory steroids)

Answer 23

Beclomethasone - very important as prophylactic 
-suppress immune system by:
decreased:
-lymphocyte &mast cell no. 
-mediator synthesis & release

Question 24

Mechanism of Glucocorticoid:

Answer 24

• cytoplasmic receptor; nuclear binding; RNA for lipocortin (Annexin-1), block PLA2
• Block COX-2

Question 25

Advantages of inhalation

Answer 25

• rapid response
• targetted at bronchi
• need less drug
• less side effects
• avoid liver metabolism