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Respiratory System > Airway Pharmacology > Flashcards

Airway Pharmacology Flashcards

1
Q

How do beta-2-adrenergic receptor agonists cause airway smooth muscle relaxation?

A

Salbutamol activates beta 2 receptors

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2
Q

How do Phosphodiesterase inhibitors cause ASMC to relax?

A

Theophyline reduces cAMP breakdown

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3
Q

How do long acting muscarinic receptor antagonists cause relaxation of airway smooth muscle cells?

A

Tiotropium blocks Ach induced contraction

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4
Q

What intracellular effects are associated with ASMC relaxation?

A
  • PKA activation
  • Increased Ca2+ mobilisation
  • Inhibition of cAMP breakdown
  • Increasing cAMP production
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5
Q

Outline how corticosteroids produce anti-inflammatory effects

A
  1. Diffuses through cell membrane
  2. Binds glucocorticoid receptor
  3. Translocates to nucleus
  4. Complex binds DNA and affects transcription
  5. Reduced pro-inflammatory protein expression
  6. Reduced proliferation, activation and trafficking of
    leukocytes
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6
Q

Which pro-inflammatory mediator is blocked by Montelukast and why?

A

Leukotrienes are blocked by Montelukast to reduce inflammation

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7
Q

How effective are anti histamine drugs in allergic asthma therapy?

A

Not at all - do not aid allergic asthma therapy

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8
Q

What adverse effects does Salbutamol cause?

A
  • tachycardia
  • tremor
  • palpitations
  • anxiety
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9
Q

What adverse effects are caused by the use of Corticosteroids?

A
  • Hypercortisolism
  • Osteoporosis
  • Depression
  • Candidiasis
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10
Q

How often should inhaled Corticosteroids (e.g. beclometasone) be administered?

A

Inhaled Corticosteroids must be administered on a continual (bi-daily) basis to achieve maximum efficacy

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11
Q

Why are Inhaled Corticosteroids administered twice a day?

A

They are preventer drugs which work on a gradual basis, by preventing symptoms, rather than reversing them once they’ve occurred

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12
Q

When is an inhaled Corticosteroid administered?

A

When asthma symptoms aren’t adequately controlled by single short-acting beta-2 agonist (Salbutamol) therapy, an inhaled Corticosteroid should be added

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13
Q

If a patient presents with:
Ongoing breathing difficulties and regular periods of wheezing, whilst taking Salbutamol and avoiding allergen exposure,
What medication should be administered?

A

Continue with Salbutamol alone

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14
Q

How effective are drugs at treating respiratory disease?

A

Drugs are effective at treating some aspects of respiratory disease but not all

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15
Q

What are the advantages of respiratory drugs usage?

A

Good at reducing / treating symptoms:

  • reverse airway smooth muscle contraction
  • reduce mucus secretion
  • reduce allergic inflammation of airways
  • reduce sensitivity to irritating stimuli
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16
Q

What areas are respiratory drugs not so good at??

A

Drugs aren’t good at healing the underlying cause of pathology e.g:

  • Resolving causes of inflammation
  • Reverse airway / lung remodelling
  • Repair damage to tissues
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17
Q

What pathological changes are induced by inflammatory mediators, during an asthma attack?

A

Airway smooth muscle contraction
Increased mucus secretion + microvascular leak
Airway oedema + swelling

18
Q

What is the effect of the pathological changes caused by inflammatory mediators?

A

The changes combine to substantially decrease airway lumen size, increase airway resistance, limiting airflow

19
Q

How is airway smooth muscle contraction prevented?

A

Bronchodilators e.g.

Beta-2 adrenergic receptor agonists

  • SABA e.g. Salbutamol
  • LABA e.g. salmeterol

Long acting muscarinic receptor antagonists
- triptropium

Phosphodiesterase inhibitors
- theophyline

20
Q

How do bronchodilators relieve asthmatic symptoms?

A

Work by relaxing airway smooth muscles

21
Q

What are the contractile mediators involved in Airway smooth muscle contraction?

A

Ach, Prostaglandins, CYsLTs bind to GPCRs (M3) activating Gq/11 pathway :

  • activates phospholipase C
  • Ca2+ stores in SR mobilised
  • Interacts with calmodulin => contraction
22
Q

What mechanism causes the relaxation of airway smooth muscle?

A

Beta-2 adrenergic receptor activation of Gs pathway, induces ASMC relaxation via adenylate cyclase and PKA

23
Q

Outline how salbutamol (beta-2 adrenergic receptor agonist) causes ASMC relaxation

A

Salbutamol binds to beta-2 adrenergic receptor activating Gs pathway

  • increased AC -> cAMP
  • Activates PKA
  • Decreases Ca2+ mobilisation causing relaxation
24
Q

How do muscarinic receptor antagonists (e,g, tiotropium) cause ASMC relaxation?

A

Muscarinic receptor antagonists relax ASMC by inhibitng the contractile mechanism of Ach at the M3 receptor

25
Q

Which Leukotriene functions are targeted when treating airway inflammation ?

A
  • proliferation
  • Ab production; crosslinking + degranulation
  • Inflammatory mediator receptor binding
  • Tissue infiltration from blood stream (adhesion molecule
    expression)
  • Chemotaxis
  • Cytokine receptor binding
  • Cytokine production and release
  • Apoptosis
26
Q

What is the use of corticosteroids?

A

Used as preventor drug to reduce airway inflammation

27
Q

Give examples of inhaled corticosteroids

A

Fluticasone
Budesonide
Beclometasone

28
Q

Name oral systemic steroids used to reduce airway inflammation

A

predenisone

dexamethasone

29
Q

How do corticosteroids reduce inflammation?

A

affect function of various immune and structural cells
either increase:
- proinflammatory cytokines
- or inflammatory proteins

30
Q

Outline the mechanism of action of corticosteroids

A
  1. Corticosteroid (CS) administered
  2. CS diffuses through membrane + binds to intracellular
    glucocorticoid receptor
  3. Drug-Receptor complex translocates to nucleus
  4. Drug-receptor complex binds DNA
    • > altered gene transcription
  5. CS increase/decrease expression depending on gene/
    protein
  6. Gene translated to protein
31
Q

What are the advantages of drug treatments ?

A

drug efficacy

  • increased quality of life
  • less symptoms + disease severity - disease resolution
  • increased life expectancy
32
Q

What are the disadvantages of drug treatments?

A

Costs

  • decreased quality of life
  • increased risk of other disease developments
  • economic costs - not everyone can afford
33
Q

What are metered dose inhalers?

A

device delivering medication to the lungs, in the form of a short burst of aerosolized medicine; usually self-administered by patient via inhalation

34
Q

What is the benefit of using metered dose inhalers?

A

Maximises therapeutic : adverse effect ratio by administering drugs directly to desired tissue

Less drug reaches systemic circulation where it’s distributed to other tissues which cause side effects

Quicker rescue/reliever dose

35
Q

How do beta 2 agonists (salbutamol) cause side effects?

A

Beta-2 agonists (salbutamol) induce side effects by activating receptors in extra-respiratory tissues if long term / high doses administered

36
Q

Explain the effects of salbutamol on the heart?

A

Higher concentrations affect Beta-1 receptors on SAN/myocardium
cause tachycardia and palpitations

37
Q

What effects does salbutamol (beta-2 agonist) produce on airway smooth muscle?

A

cause bronchodilation via Beta-2 receptors

38
Q

What is the effect of salbutamol (beta 2 agonist) on skeletal muscle in other tissues?

A

Causes tremor and muscle growth

39
Q

What are the side effects caused by (salbutamol) beta 2 agonists when administered long term / in high doses?

A
  • growth retardation
  • osteoporosis
  • skin ulcerations
  • hypercortisolism
  • candidasis
  • depressions
40
Q

How is pharmacotherapy used to treat asthma?

A

Asthma Pharmacotherapy is administered in a step-wise manner:

  1. SABA as required
  2. add ICS
  3. Add LABA, ↑ ICS, add LTRA, PDEi
  4. max ICS dose and 4th drug
  5. Add oral CS refer to specialist care, anti-IgE
41
Q

How is COPD therapy carried out?

A

In a progressive one direction stepwise manner

Respiratory System (10 decks)

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