5: Pharmacology of Asthma I

Question 1

Where are preganglionic nerve fibres found?

Answer 1

In the brainstem

Question 2

Where are respiratory postganglionic nerve fibres found?

Answer 2

Embedded in the walls of the respiratory tree

Question 3

Stimulation of parasympathetic CHOLINERGIC fibres causes…

Answer 3

bronchoconstriction

Question 4

Stimulation of parasympathetic NONCHOLINERGIC fibres causes…

Answer 4

bronchodilation.

Question 5

Bronchial smooth muscle has very little sympathetic innervation. So how can sympathetic stimulation cause bronchodilation?

Which receptor is involved?

Answer 5

ß₂ adrenoceptors are activated by adrenaline which is released by sympathetic stimulation - causes bronchodilation.

Question 6

What ion causes smooth muscle contraction?

Answer 6

Ca²⁺

Question 7

Which molecule is activated by Ca²⁺ during smooth muscle contraction?

Answer 7

Calmodulin

Question 8

During smooth muscle contraction, Ca²⁺ activates calmodulin which activates an enzyme - what is the enzyme called?

Answer 8

Myosin light chain kinase (MLCK)

Question 9

What is the function of Myosin light chain kinase?

Answer 9

Phosphorylates myosin so it binds to actin

i.e cross bridge formation

Question 10

What is the enzyme, opposite in function to MLCK, which causes smooth muscle relaxation?

Answer 10

Myosin phosphatase

Question 11

MLCK , Myosin phosphatase

Phosphorylation , Dephosphorylation

Smooth muscle contraction , Smooth muscle relaxation

Arrange in two tables.

Answer 11

MLCK , Phosphorylation , Smooth muscle contraction

Myosin phosphatase , Dephosphorylation , Smooth muscle relaxation

Question 12

Why must [Ca²⁺] be carefully controlled in smooth muscle cells?

Answer 12

Increasing [Ca²⁺] increases the rate of phosphorylation and therefore smooth muscle contraction

so [Ca²⁺] must be controlled to ensure appropriate smooth muscle behaviour.

Question 13

Extracellular signals regulate the enzymes controlling smooth muscle activity. Name two.

Answer 13

PDE (phosphodiesterase) - prevents action of PKA, causing smooth muscle CONTRACTION

PKA (protein kinase A) - inhibits MLCK and stimulates myosin phosphatase, causing smooth muscle RELAXATION

Question 14

What is asthma?

Answer 14

Recurrent, reversible airway obstruction in response to specific stimuli

Question 15

What are some common asthma triggers?

Answer 15

Allergens

Exercise (cold, dry air)

Respiratory infections (viral)

Dust, smoke, pollutants

Question 16

What are the characteristic symptoms of asthma?

Answer 16

Chest tightness

Wheeze

Breathlessness

Cough

Question 17

Chronic asthma involves pathological changes to the bronchioles with result from long-standing ___.

Answer 17

inflammation

Question 18

What two processes occur in smooth muscle of chronic asthma sufferers?

Answer 18

Hypertrophy AND hyperplasia

Question 19

Accumulation of interstitial fluid due to airway inflammation results in ___.

Answer 19

oedema

Question 20

Chronic asthma results in ___ mucus secretion.

Answer 20

increased

Question 21

What end stage process can occur in chronic asthma?

Answer 21

Fibrosis

Question 22

What the important cellular changes occuring in chronic asthma?

Answer 22

As a result of chronic inflammation:

1. Smooth muscle hypertrophy and hyperplasia
2. Oedema
3. Increased mucus secretion

eventually leading to epithelial damage and fibrosis.

Question 23

In chronic asthma, FEV₁ (increases / decreases) and PEFR (increases / decreases).

Answer 23

FEV₁ decreases

PEFR decreases

Question 24

Epithelial damage exposes ___ fibres in the airways.

Answer 24

nerve

Question 25

Exposed nerve fibres in the airways, caused by epithelial damage, cause the airways to become ___-___.

Answer 25

hyper-responsive

Question 26

Give an example of a spasmogen (inhaled bronchoconstrictor).

Answer 26

Histamine

Question 27

An asthma attack comprises of an ___ and ___ phase.

Answer 27

immediate , delayed

Question 28

For many individuals, the delayed phase of an asthma attack is (better / worse) than the immediate phase.

Answer 28

worse

Question 29

What type of hypersensitivity reaction makes up the immediate phase of an asthma attack?

Answer 29

Type I hypersensitivity reaction

Question 30

What type of hypersensitivity reaction makes up the delayed phase of an asthma attack?

Answer 30

Type IV hypersensitivity reaction

Question 31

Which type of T helper cell response is seen in nonatopic asthmatics?

Answer 31

T_H1 response (low-level)

Question 32

What kind of T helper cell response is seen in atopic asthmatics?

Answer 32

T_H2 response (strong, maybe a response to a Western hygenic lifestyle)

Question 33

Which kind of T lymphocyte produces T helper cells?

Answer 33

CD4⁺ T cells

Question 34

In allergic asthma, what cells are activated by presented allergens?

Answer 34

CD4⁺ T cells

Question 35

What do activated CD4⁺ T cells produce?

Answer 35

T helper cells (T_H1 and T_H2)

Question 36

What do T_H2 cells activate during the development of allergic asthma?

Answer 36

B cells (which produce antibodies)

Question 37

Which immune cells, apart from B and T cells, are involved in the development of allergic asthma?

Answer 37

Eosinophils

Mast cells

Question 38

What type of antibodies are produced in response to an allergen in allergic asthma?

Answer 38

IgE antibodies

Question 39

Which type of cytokine is heavily involved in the development of allergic asthma?

Answer 39

Interleukins

Question 40

Activated ___ cells degranulated and release ___ which stimulate smooth muscle contraction.

Answer 40

mast , leukotrienes

Question 41

What do activated mast cells do?

Which cytokine is released by this process?

What does this cytokine cause?

Answer 41

Degranulate

Leukotriene

Smooth muscle contraction

Question 42

Which cytokine, released by degranulating mast cells, triggers smooth muscle contraction?

Answer 42

Leukotrienes

Question 43

What do leukotrienes trigger in asthmatics?

Answer 43

Smooth muscle contraction