Pharmacology

Question 1

Transmission occurs between which fibres?

Answer 1

pre-ganglionic and post-ganglionic fibres

Question 2

True/False:

Bronchial smooth muscle is innervated

Answer 2

False:

It isn’t

Question 3

What 2 types of post-ganglionic fibres are there

Answer 3

cholinergic and non-cholinergic

Question 4

what do cholinergic fibres do…

Answer 4

Mediated by Muscarinic Receptors

• Bronchial SM contraction (M3 receptors on ASM)
• Inc mucus secretion (M3 on gland cells)

Question 5

What do non-cholinergic fibres do…

Answer 5

Mediated by B2 ADRs

• Bronchial SM relaxation
• Dec mucus secretion
• Inc mucociliary escalator
• Vascular SM contraction (A1 ADR)

Question 6

How is SM contraction controlled?

Answer 6

1. G protein converts Gg/11 to PLC
2. PLC converts PIP2 to IP3
3. IP3 binding to receptor triggers Ca2+ release

Question 7

How does SM contract?

Answer 7

1. Ca2+ > calmodulin Ca2+
2. Calmodulin Ca2+ activated MLC Kinase
3. MLC Kinase modulates binding of ATP to activate
4. Myosin cross bridge
   - MLCK regulated by adrenaline

Question 8

How does SM relax?

Answer 8

De-phosphorylation of MLCK by myosin phosphatase achieved by Ca2+ returning to basal levels.

Question 9

What is Asthma?

Answer 9

Reversible obstruction of airways due to antigen (bronchoconstriction)

Question 10

2 types of asthma are…

Answer 10

Intermittent: tight chest, wheeze, cough (can come on when cold or exercise)
Chronic: changes to bronchioles

Question 11

What are some changes that can come about to bronchioles in chronic asthma?

Answer 11

1. Inc in SM
2. Inc in mucus secretion
3. Epithelial damage

Question 12

What’re the 2 phases of an asthma attack and what do they consist of?

Answer 12

Immediate Phase: bronchospasm

Delayed Phase: inflammatory reaction

Question 13

What is allergic asthma?

Answer 13

Asthma caused by an antigen and immune response kicks in

Question 14

True/False:

TH2 response occurs in severe asthma and forms IgG antibodies

Answer 14

False:
TH2= mild asthma, IgE
TH1= severe, IgG

Question 15

Explain the pathogenesis of allergic asthma in terms of

• Induction
• Clonal Expansion & Maturation
• Effector Phase

Answer 15

1. Antigen binds to CD4+ T-Cells which cause the T cells to divide into TH0 helper T cells
   TH0 then mature into TH2 cells
2. Some TH0 become TH1 cells, while most become TH2 which activate B-Cells which themselves become plasma cells
3. Eosinophils activate (due to TH2 & IL-5)
   Mast cells degranulate (due to IgE binding to receptor)

Question 16

How are IgE receptors expressed?

Answer 16

In response to IL-4 and IL-13 being released by TH2

Question 17

*How is a memory reaction instigated?

Answer 17

• Cross-linking of IgE receptors cause Ca2+ influx
• This causes degranulation of pre-formed histamine and other inflammatory agents
• These cause SM contraction
• & Platelets and prostaglandins are released which attract inflammatory cells

Question 18

True/False:

Agonist mimics normal action

Answer 18

True

Antagonist blocks normal action

Question 19

What is the treatment for asthma

Answer 19

Bronchodilators: B2 ADR Agonists, CystLT1 Antagonist, xanthines
Anti-inflammatories: Glucocorticoids, Mineralocorticoids
Cromoglycate & Omalizumab

Question 20

Give a run down of SABA?

Answer 20

SABA
e.g: Salbutamol 
Used for: mild asthma 
Admin: Inhaled
Why g: Rapid 
Adverse Effects: Tremors, Tachycardia

Question 21

Give a run down of LABA?

Answer 21

e.g: Salmeterol 
Used for: chronic asthma 
Admin: Inhaled 
Why g: Nocturnal asthma 
Note: taken as dual therapy with glucocorticoids

Question 22

Give a run down of CysLT1 Antagonists

Answer 22

Eg: Montelukast 
Used for: mild asthma, exercise induced bronchoconstriction 
Admin: Oral
Why g: infiltrates inflammatory cells 
SE: may cause oedema

Question 23

How does the mixed asthma treatment Xanthines work?

Answer 23

Inactivates cAMP and cGMP

Question 24

Give a run down on Glucocorticoids

Answer 24

Examples: Prednisolone
Used for: mild asthma
Admin: Inhaled
Why g: inflammatory and immunological responses decrease

Question 25

Why are mineralocorticoids contraindicated?

Answer 25

Have many side effects so usually Cortisol used as mixed treatment

Question 26

What are cromoglycate and omalizumab used for?

Answer 26

Allergic asthma- reduce immune response.

Question 27

How do glucocorticoids work cellularly?

Answer 27

- inc transcription of anti-inflammatory proteins, dec transcription of inflammatory proteins - induce inflammatory cells to undergo apoptosis

Question 28

What is COPD?

Answer 28

chronic bronchitis and emphysema | inc resistance to airflow during expiration

Question 29

True/False: | COPD neurotransmission involves Ach binding to M3 muscarinic receptors causing bronchoconstriction

Answer 29

True

Question 30

Where are M1 receptors located and what do they do?

Answer 30

Ganglia; act on nicotine receptors

Question 31

Where are M2 receptors located and what do they do?

Answer 31

Post-ganglionic terminals; inhabit further release of Ach

Question 32

Where are M3 receptors located and what do they do?

Answer 32

ASM; airway SM contraction & inc in mucus secretion

Question 33

What is the overview for COPD treatment...

Answer 33

Muscarinic Receptor Antagonists, Glucocorticoids and phosphodiesterase inhibitors

Question 34

Give a run down of SAMA drugs...

Answer 34

``` e.g: Ipratropium Used for: Bronchodilation Admin: Inhaled Why g: Reduces mucus secretion - Palliative ```

Question 35

Give a run down of LAMA drugs...

Answer 35

``` e.g: Tiotropium Used for: Bronchodilation Admin: Inhaled Why g: Reduces mucus secretion - Palliative ```

Question 36

Why is it good to have a selective muscarinic receptor antagonist?

Answer 36

Because ideally M3 receptor should be blocked but not M2 as if M2 is also blocked then more Ach is released (causing more constriction) contradicting the antagonists effect

Question 37

How is muscarinic antagonist selectivity achieved?

Answer 37

Through rate of association and dissociation of antagonist to receptor

Question 38

Why are combination drugs more desirable?

Answer 38

B2 ADR agonists cause more bronchodilation and M3 Muscarinic antagonists cause less bronchoconstriction. Best at inc FEV1 by promoting ASM relaxation

Question 39

How do glucocorticoids and phosphodiesterase inhibitors work as treatment for COPD?

Answer 39

inflammatory suppressors. Usually added onto SAMA/LAMA.

Question 40

Give 4 similarities between rhinitis and asthma...

Answer 40

1. Allergen inc IgE levels 2. IgE binds to basophils and mast cells 3. Re-exposure causes rapid degranulation of inflammatory mediators by immune cells- sneezing etc 4. Delayed recruitment of lymphocytes and eosinophils causes congestion