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Clinical Pharmacology and Therapeutics > Pharmacology of Asthma > Flashcards

Pharmacology of Asthma Flashcards

1
Q

Describe the pathophysiology of asthma.

A

Th 2 - driven and eosinophilic inflammation causing mucosal oedema, bronchoconstriction, mucus plugging, and bronchial hyperresponsiveness.

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2
Q

What can we target in asthma therapy?

A

Smooth muscle function
Inflammation
Mast cell stablisation

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3
Q

What can make asthma worse, and how?

A

NSAIDs in some pts. NSAIDs prevent arachadonic acid from -> COX1 -> prostaglandins. More AAs are available to form cys LT1 which causes bronchospasm etc.

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4
Q

How do we manage asthma?

A

In a stepwise fashion

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5
Q

Who gives guidelines for asthma therapy?

A

NICE and the BTS

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6
Q

Which guidelines will I use here?

A

NICE

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7
Q

What is the first step on the NICE pathway?

A

Offer a SABA as reliever therapy to all adults with newly diagnosed asthma

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8
Q

Who can you consider SABA only in?

A

Adults with infrequent, short-lived wheee and normal lung function

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9
Q

Who is low dose ICS offered to first line?

A

Maintenance therapy if symptoms present 3 times a week or more, or causing waking at night, or if it is uncontrolled with only a SABA.

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10
Q

What is th enext step up from low dose ICS, and when do we escalate?

A

Escalate if asthma uncontrolled on low dose ICS.

Add on a LTRA to ICS and SABA

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11
Q

A pt is on SABA + ICS + LTRA, and their asthma is still uncontrolled. What is the next step?

A

SABA + Low dose ICS, and add on LABA.

Review LTRA according to how the pt feels and their response (or not) to LTRAs.

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12
Q

What is the step up from low dose ICS and LABA +- LTRA?

A

Change LABA to MART ( with low dose ICS +- LTRA)

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13
Q

If MART + low dose ICS +- LTRA doesnt work, what is the next step?

A

Increase ICS maintenance dose.

Also consider continuing MART or switching back to ICS with LABA.

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14
Q

After a moderate dose of ICS, what is the next step up?

A

Consider:

  • High maintenance dose (fixed dose regimen) with SABA
  • Trialling an additional drug such as LAMA or theophylline
  • Referal to asthma specialist.
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15
Q

What is considered controlled asthma?

A

Minimal symptoms during the day and night
Minimal need for reliever inhalers
No limitations or exacerbations on physical activity
Normal lung function

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16
Q

What is a key thing to check before initiating new treatment?

A

Compliance and technique with existing therapies

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17
Q

What lifestyle things can pts do the prevent asthma exacerbations?

A

Avoidance of triggers

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18
Q

What are SABAs?

A

Short acting Beta2 agonists

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19
Q

Name 2 SABAs.

A

Salbutamol

Terbutaline

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20
Q

What are the ADRs associated with B2 agonists?

A

Tachycardia
Palpitations
Tremor

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21
Q

How do SABAs work to relieve asthma?

A

Reverse bronchoconstriction and inhibiting mast cell degranulation in response to an allergen.

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22
Q

What is the issue with using SABAs too much?

A

Decreased asthma control as mast cell degranulation becomes more sensitive to allergen.

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23
Q

What are the other options for B2 agonists, other than SABAs?

A

LABAs!

Fast onset long duration, or slow onset long duration.

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24
Q

Which LABAs are fast onset with long duration?

A

Formoterol
Olodaterol
Indacaterol

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25
Q

Which LABAs are slow onset with long duration?

A

Salmeterol

Vilanterol

26
Q

How frequently do we review the response to treatment?

A

Every 4-8 weeks.

27
Q

How do ICS work (broadly speaking)?

A

Inhaled corticosteroids target inflammation, and reduce eosinophil count.

28
Q

What is the molecular action of steroids?

A

Bind to intracellular receptors (glucocorticoid receptor alpha) causing chaperone proteins to dissociate. The complex goes to the nucleus where it binds to DNA.

29
Q

What effect do steroids causes complexes on the DNA to have?

A
  • Transactivation of anti-inflammatory genes nd increase B2 receptors expression.
  • Transrepression by inhibiting proinflammatory gene transcription.
30
Q

What are pro-inflammatory genes normally triggered by for transcription?

A

Cytokines
LPs
Viruses

31
Q

Who responds best to ICS?

A

Pts with eosinophilic asthma

32
Q

What can happen with ICS?

A

ICS can be absorbed and join systemic circulation via the lungs causing the potential for systemic side effects A small fraction is also likely to be swallowed.

33
Q

What local side effect can ICS have, and how do we avoid it?

A

Candida infection in the throat. Avoid this by rinsing throat after using ICS inhaler, and having good inhaler technique.

34
Q

What ICSs are used in asthma?

A

Beclomethasone
Budesonide
Fluticasone

35
Q

Which 2 LABAs are the most commonly used?

A

Formoterol and salmeterol

36
Q

How frequently do pts take formoterol?

A

BD

37
Q

How frequently do pts take salmeterol?

A

BD

38
Q

Why must LABAs be prescribed alongside an ICS?

A

They have no anti-inflammatory effect, unlike ICSs.

39
Q

How can we make it easier for a pt on LABAs and ICSs?

A

Give a combination therapy, so ony have to use one inhaler for 2 drugs.

40
Q

What is an LTRA?

A

Leukotriene receptor antagonist

41
Q

What are the LTRAs?

A

Montelukast

Zafirlukast

42
Q

How do LTRAs work?

A

Block LTC4 released by mast cells and eosinophils, preventing broncoconstriction, mucus secretion, and mucosal oedema.

43
Q

What % of pts are LTRAs effective in?

A

15%

44
Q

What are the ADRs of LTRAs?

A 
Angioedema
Dry mouth
Anaphylaxis
Arthralgia
Fever
Gastric disturbance
Nightmares
45
Q

What kind of drug are theophylline and aminophylline?

A

Methylxanthines

46
Q

How do theophylline and aminophylline work?

A

Antagonise adenosine receptors, inhibit phosphodiesterase, and increase cAMP.

47
Q

What are the downsides to theophylline and aminophylline?

A

Poorly efficacious
Narrow therapeutic window
Bad ADRs

48
Q

What are the ADRs associated with theophylline and aminophylline?

A 
Nausea
Headache
Reflux
Arrhythmias
Seizures
49
Q

What are theophylline and aminophylline metabolised by?

A

CYP450, so increase in bioavailability when taken alongside cyp450 inhibitors such as erythromcin and ciprofloxacin.

50
Q

When are LAMAs indicated?

A

COPD and severe asthma (after a moderate ICS dose has been trialed) and asthma excerbations

51
Q

What is the main LAMA liscenced for asthma?

A

Tiotropium bromide

52
Q

What are the LAMAs liscenced for COPD, as well as tiotropium bromide?

A

glycopyrronium

usually used as part of a triple therapy inhaler

53
Q

When giving an oral corticosteroid, what dose is usually used?

A

10mg OD or more

54
Q

What is a MART?

A

Maintenace and Reliever therapy

55
Q

What biological therapies are there available for asthma?

A

Anti-IgE such as Omalizumab

Anti-IL-5 such as Mepolizumab/Reslizumab

56
Q

What can cause exaccerbations of asthma?

A

Allergens
Viral infection
Cold weather
Exercise

57
Q

What is there good evidence for, in terms of achieving the best outcomes in asthma?

A

Pts having a personal self-management plan with written instructions on when to step up or down.

58
Q

How do we identify acute severe asthma?

A

1 of:

  • Unable to complete sentances
  • Pulse over 110 bpm
  • RR over 25/min
  • Peak flow 33-50% of best/predicted.
59
Q

What is life threatening asthma classified by?

A

Any of the criteria for severe, plus any of:

  • PEF less than 33%
  • spO2 less than 92%
  • Silent chest
  • Cyanosis
  • Feeble resp effort
  • Hypotension
  • Bradycardic
  • Arrhythmia
  • Exhaustion
  • Confusion
  • Coma
60
Q

How do we treat a severe/life threatening acute asthma attack?

A

High flow O2
Nebulised salbutamol/ipratorpium bromide
Oral prednisolone
IV aminophlline if no response

61
Q

What is the difference between tiotropium and ipratropium bromide?

A

Ipratropium has a shorter duration of action.

Clinical Pharmacology and Therapeutics (26 decks)

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