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Drugs: From molecules to man > Drugs for Asthma > Flashcards

Drugs for Asthma Flashcards

1
Q

describe the structure of the bronchial tract

A

the trachea is held open by lots of cartilage

moving down the airways, there’s less cartilage and more smooth muscle (constriction can occur)

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2
Q

where must air reach for gas exchange?

A

alveoli

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3
Q

what are the pathological changes in asthma? (7)

A
  • Narrowed peripheral pathways in the lung
  • inflammation
  • mucas- filled air passages
  • less cilia
  • hypertrophy (bigger muscle) and Hyperplasia (more muscle) in smooth muscle
  • more immune cells
  • oedema
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4
Q

Are asthma and COPD primarily imflammatory?

A

yes

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5
Q

describe the early phase of an asthma attack?

A
  • occurs quicky
  • bronchoconstriction
  • the first 30 minutes of attack
  • reduced FEV1
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6
Q

describe the late phase of an asthma attack

A
  • longer lasting
  • after early phase there’s a period of a few hours where lung function returns to normal.
  • Six hours after the start further inflammation occurs from the activation of the immune system
  • reduced FEV1
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7
Q

What do mast cells contain?

A

granules with pre-formed mediators e.g. histamine, proteases, proteoglycan and chemotactic factors
also later mediators are synthesised by the mast cell and are derived from membrane lipids e.g. leukotrienes, prostoglandins, thromboxones and postcyclin

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8
Q

What causes these mediators to be released from the mast cell?

A

when the allergen binds to receptors on the mast cell

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9
Q

what do histamines do in asthma?

A

cause constriction of airways (smooth muscle)
increase vascular permeability
increase bronchial secretions (mucus)

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10
Q

What do chemotactic factors do in asthma?

A

infiltrate tissue by neutrophils and eosinophils

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11
Q

what to leukotrienes and prostoglandin do in asthma?

A

constrict airways (smooth muscle)
increase vascular permeability
increase bronchial secretions

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12
Q

what do eosinophils do in asthma?

A

cause epithelial desquamation and cell death

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13
Q

what are the 2 types of anti-asthma drugs?

A
  • Relievers/ Bronchodilators

- Preventers/ Prophylactic agents

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14
Q

what types of drugs are included in relievers? (4)

A

B2 adrenoreceptor agonists
leucotriene antagonists
theophylline
mAChR agonists

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15
Q

give an important/ widely used example of a B2 adrenoreceptor agonist

A

salbutamol

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16
Q

what types of drugs are included in preventers? (4)

A
  • long acting B2 agonists
  • glucocorticosteroids
  • monodonal antibodies
  • Leukotriene antagonists
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17
Q

what type of treatment will you receive if you are having fewer than 2 asthma attacks a week?

A

only a reliever/ bronchodilator (blue inhaler)

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18
Q

what type of treatment will you receive if you are having over 2 asthma attacks a week?

A

a reliever as well as a preventer (brown inhaler)

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19
Q

name the 3 non-selective agonists of the beta-adrenoreceptor from most to least potent

A

Isoprenaline
Adrenaline
Noradrenaline

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20
Q

name the 2 selective agonists of the beta- adrenoreceptor

A

salbutamol and dobutamine

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21
Q

Name the 3 non-selective antagonists at the beta- adrenoreceptor

A

propranalol
phenoxybenzamine
Phentolamine

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22
Q

Which is the most potent non- selective antagonist at the beta-adrenoreceptor?

A

Propranalol

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23
Q

what are Theophylline, lukasts, anti-muscarinics and LABAs often used with? (2)

A

Beta-2 agonists or glucocorticoids if symptoms aren’t controlled

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24
Q

What do Lukasts offer an alternative to?

A

glucocoticoids (often used in children/ for exercise-induced asthma)

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25
what does MART stand for?
Maintenance and reliever therapy
26
what group of chemicals does theophylline belong to?
Alkylxanthines
27
what is another important Alkylxanthine?
caffeine
28
what has more caffeine- tea or coffee?
coffee
29
what has more alkylxanthine- tea or coffee?
neither- they contain the same
30
what are the 2 main pharmacological effects of alkylxanthines?
- they inhibit the enzymes responsible for the breakdown of cAMP (the phosphdiesterases) (might impact of inflammatory processes and the bronchoconstriction seen in asthma - Antagonist of adenosine receptors- prevents bronchodilation
31
what is Aminophylline?
a water soluble complex of theophylline and ethylenediamine
32
how is aminophylline given?
controlled i.v. infusion pump
33
How is Theophylline given? (2)
- orally | - i.v.
34
does theophylline have a wide or narrow therapeutic window?
narrow (toxic dose is only around 2x therapeutic dose)
35
what affects the half-life of theophylline? (4)
- cardiac disease - liver disease] - smoking - other drugs
36
How can dosage regimen of theophylline be determined?
plasma or saliva assay
37
what enzyme metabolises Theophylline?
CYP1A2
38
give 3 other drugs metabolised by CYP1A2
- antidepressants - antipsychotic drugs - paracetamol - verapamil - propranolol
39
give 3 things that inhibit CYP1A2?
- verapamil - caffeine - amiodarone - grapefruit juice - many herbal teas
40
what 4 things induce CYP1A2?
- tobacco - broccoli - cauliflower - grilled meat
41
give 3 side effects of theophylline
- nausea/ vomiting - headache - fainting - tachycardia - cardiac dysrhythmias - convulsions
42
What's theobromine?
- the 'chocolate equivalent' of caffeine and theophylline - doesn't contain bromine - has bronchial dilating effects
43
which is the least potent agonist at the muscarinic ACh receptor: - acetylcholine - methacholine - muscarine - nicotine
nicotine
44
what is the most potent antagonist at the muscarinic ACh receptor: - atropine - tubocurarine
atropine
45
what sites in the bronchial tract (relevant to asthma) does acetylcholine work?
- Muscarinic receptors on goblet cells to increase the secretion of mucus - muscarinic receptors on smooth muscle to cause bronchocontriction
46
which subtypes of mAChR do the acetylcholine effects on the bronchial tract occur on?
M1 and M3
47
what are M1 and M3 receptors coupled to?
the phospholipase C signaling system via Gq
48
How could we reduce the effects of acetylcholine on the bronchial tract?
an antagonist at the mAChR
49
is atropine suitable for use in asthma?
no
50
why isn't atropine a suitable drug for asthma?
it's a tertiary amine and thus can esist in an uncharged form. This form is very lipid soluble so can cross through various membranes and barriers. Even if it was inhaled it would enter the systemic circulation and cause unpleasant side effects via its parasympathetic action
51
In what state must atropine be in to mimic acetylcholine and bind to mAChR agonist binding site?
positive (protonated)
52
what drug is used instead of atropine?
ipratropium
53
what is Ipratropium?
a relatively non-selective mAChR antagonist (beneficial in asthma)
54
does Ipratropium tend to be given alone or in combination?
in combination
55
What's tiotropium?
a drug similar to ipratropium but with a longer duration of action
56
How is Ipratropium given?
by inhalation
57
what does ipratropium do for asthma?
reduces irritant pathways | reduces bronchocontriction, mucus secretion and cough
58
why is it important that Ipratropium is taken by inhalation?
it's a quarternary amine, meaning it has a permanent positive charge and thus cannot cross membranes- so has to be delivered straight to the lungs (but cannot easily enter the system circulation)
59
Give 4 side effects of ipratropium
- dry mouth (most common) - urinary retention - blurring of vision - constipation
60
what's an important key player in inflammatory signaling?
an enzyme called phospholipase A2
61
what does phospholipase A2 do?
releases arachidonic acid from membrane phospholipids
62
what happens to arachidonic acid after release?
is further metabolized to a group of 20 carbon signaling moelcules called the eicoanoids
63
what are the 2 most important classes of eicoanoids?
leukotrienes and Prostanoids
64
What are Leukotrienes produced by? (4)
- mast cells - eosinophils - basophils - macrophages
65
what do Leukotrienes do molecularly in asthma?
Agonist at Cysteinyl-leukotriene (CysLT) receptor
66
what do Leukotrienes do physiologically? (3)
- contracts bronchial smooth muscle - stimulates mucus secretion - increases microvascular permeability
67
what do some of the most recent anti-asthma drugs target?
the receptors for the leukotrienes (CysLT receptors)
68
what's the main example of a competitive antagonist at CysLT receptor?
Montelukast
69
what do all competitive antagonsits at CysLT receptors names end in?
-lukast
70
How are competitive antagonists at CysLT receptors given?
orally
71
in what types of asthma are competitive antagonists at CysLT receptors given?
- add-on preventative therapy in mild to moderate asthma - reduces exercise-induced asthma - reduces aspirin- induced asthma
72
Give 3 side effects of competitive antagonists at CysLT receptors
- abdominal pain/ nausea - headache - psychiatric side effects

Drugs: From molecules to man (10 decks)

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