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Respiratory-Pharmacology > Pharmacology of asthma > Flashcards

Pharmacology of asthma Flashcards

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1
Q

What is the dominant neuronal control innervation of the airways?

A

Parasympathetic cholinergic innervation

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2
Q

Which main nerve carries preganglionic fibres to the airways?

A

Vagus nerve

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3
Q

What effect does stimulation of the parasympathetic division have on the airways? (3)

A
  • Bornchial smooth muscle contraction, by ACh acting on M3 muscarinic ACh receptors
  • Increased mucous secretion, by ACh acting on M3 muscarinic ACh receptors
  • Overall increase in airway resistance
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4
Q

What does stimulation of the sympathetic division have on the airways? (4)

A
  • Bronchial smooth muscle relaxation (via B2-adrenoceptors activated by adrenaline released from the adrenal gland)
  • Decreased mucous secretion by B2 receptors
  • Increased mucociliary clearance mediated by B2 receptors
  • Overall decreased airway resistance
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5
Q

What is asthma?

A

A recurrent and reversible obstruction to the airways in response to a substance or stimuli

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6
Q

Name causes of asthma attacks (8)

A
  • Allergens
  • Exercise
  • Cold air
  • Dry air
  • Respiratory infections (e.g. viral)
  • Smoke
  • Dust
  • Environmental pollutants
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7
Q

What are the symptoms of asthma?

A

Coughing

Wheezing

Difficulty breathing

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8
Q

What is the pathological cause of asthma? (5)

A
  • Increased mass of smooth muscle (Hypertrophy and hyperplasia)
  • Accumulation of interstitial fluid (Oedema)
  • Increased secretion of mucous
  • Epithelial damage (exposing sensory nerve endings)
  • Overall narrowing of airways
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9
Q

What effect does asthma have on the FEV1 and PEFR?

A

Decrease in both

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10
Q

What are the two components of bronchial hyper-responsiveness in asthma?

A
  • Hypersensitivity

- Hyperreactivity

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11
Q

What is the pathology behind bronchial hyper-responsiveness in asthma?

A

Epithelial damage–> Exposure of sensory nerve endings–> Increased sensitivity of the airways to bronchoconstrictor infulences

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12
Q

What test reveals hyper-responsiveness?

A

Provocation tests with inhaled bronchoconstrictors (e.g. histamine or methacholine)

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13
Q

What are the two classes of drugs that can be used in treatment of asthma?

A
  • Relievers

- Preventers

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14
Q

What action do relievers have on bronchial tissue?

A

-Bronchodilation

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15
Q

What two classes are B2 agonists used in asthma treatment separated into?

A
  • Short acting B2 agonists (SABA)

- Long acting B2 agonists (LABA)

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16
Q

What types of bronchodilators are available in asthma treatment?

A
  • B2 Agonists

- CysLT1 receptor antagonists

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17
Q

What are preventers and what action do they have on the airways?

A

Anti inflammatory agents that reduce airway inflammation

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18
Q

What types of preventers are available in asthma treatment?

A
  • Glucocorticoids
  • Chromoglicate
  • Humanised monoclonal IgE antibodies
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19
Q

What is the function of myosin light chain kinase?

A

Causes contraction of actin and myosin

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20
Q

What is the mechanism of action of B2 agonists? (6)

A
  • Activation of B2 receptors
  • Activation of enzyme adenylyl cyclase
  • Formation of Cyclic adenosine-mono-phosphate (cAMP) from ATP
  • Activation of enzyme protein kinase A (PKA)
  • Phosphorylation of Myosin light chain kinase (MLCK)
  • Airway smooth muscle relaxation
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21
Q

What causes receptor desensitisation and endocytosis resulting in loss of function of receptor?

A

Persistent activation of the receptor

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22
Q

How does PKA affect B2 Adrenoceptors?

A

Phosphorylates receptor, causing reduced G protein coupling, preventing relaxation pathway.

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23
Q

Give an example of a SABA.(1)

A

-Salbutamol (Albuterol)

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24
Q

What drug is the first line treatment for mild intermittent asthma?

A

SABAs

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25
Are SABAs relievers or preventers?
Relievers
26
How are SABAs usually administered? Why this route?
Metered dose or dry powder devices in order to lessen systemic effetcs.
27
How long do SABAs take to act?
Often within 5 minutes
28
How long to SABAs effects persist?
4-6 hours
29
How long do SABAs take to reach maximal effect?
Around 30 minutes
30
What effect do SABAs have on mucous clearance and release of mediators from mast cells and neutrophils?
Increased mucous clearance and decreased mediator release.
31
What are some adverse effects of SABAs (2)
- Fine tremor | - Occasional tachycardia (Due to stimulation of B1 receptors in heart)
32
Name an example of a LABA
Salmeterol
33
What kind of asthma are LABAs effective in treating and why?
Nocturnal asthma due to their long half life
34
Should LABAs be used as a monotherapy?
No- should be used as add-on.
35
What adverse effect does Isoprenaline (Non specific B agonist) have?
Harmful stimulation of cardiac B1 adrenoceptors
36
Why are non selective B antagonists such as Propranolol contraindicated in asthmatic patients?
Due to their cause of bronchospasm
37
What part do CysLTs play in asthma? (4)
Derived from mast cells Cause smooth muscle contraction Cause Mucous secretion Cause oedema
38
Give an example of CysLT1 receptor antagonists. (2)
Montelukast Zafirlukast
39
What type of asthma are CysLT1 antagonists effective in?
-Add on therapy in mild persistent asthma and in combination with other treatments in more severe conditions
40
How are CysLT1 antagonists administered?
Orally
41
Give an example of a xanthine. (2)
Theophylline Aminophylline
42
How are xanhine drugs administered?
Orally
43
What adverse effects do xanthines cause? (4)
Nausea Vomiting Abdominal discomfort Headache
44
What is the suspected mechanism of action of xanthines?
Inhibition of isoforms of Phosphodiesterase-->inactivate cAMP and cGMP
45
Which drugs should xanthines be combined (added on) to?
B2 agonists and glucocorticoids
46
Do xanthines possess bronchodilator or anti inflammatory actions?
Some of both
47
Where are the two main classes of steroid hormone (Glucocorticoids and mineralocorticoids) synthesised in the body?
The adrenal cortex
48
Where are glucocorticoids synthesised in the adrenal cortex?
Zona fasiciculata
49
Where are mineralocorticoids synthesised in the adrenal cortex?
Zona glomerulosa
50
What is the main hormone in humans?
Cortisol (Hydrocortisone)
51
What are the two most important functions regulated by Cortisol (Hydrocortisone)?
- Inflammatory responses decrease | - Immunological response decrease
52
What are glucocorticoids primary function in asthma treatment?
Prophylactic treatment
53
Why are glucocorticoids preferably delivered by the inhalational route?
To prevent adverse systemic effects
54
How do glucocorticoids affect transcription of anti-inflammatory and inflammatory?
- Decrease transcription of genes encoding inflammatory proteins - Increase in transcription of genes encoding inflammatory proteins
55
What are the function of histone acetyltransferases?
Acetylation of histones (Causes DNA to unwind from histone allowing transcription).
56
How do glucocorticoids benefit asthma sufferers?
- Prevent inflammation | - Resolve established inflammation
57
Which inhaled glucocorticoid is often used in mild to moderate asthma/
- Beclometasone
58
What side effects does deposition of glucocorticoids in the oropharynx cause? (2)
- Dysphonia (Hoarse and weak voice) | - Oropharyngeal candidiasis (Thrush)
59
Which oral glucocorticoid is often used in severe or rapidly deteriorating asthma?
Prednisolone
60
What are cromolins?
Drug infrequently used as prophylactic therapy in allergic asthma (Particularly children)
61
What is Omalizumab?
Monoclonal antibody treatment directed against IgE
62
How is omalizumab administered?
IV

Respiratory-Pharmacology (1 decks)

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