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Y4 Respiratory > Respiratory pharmacology > Flashcards

Respiratory pharmacology Flashcards

1
Q

What are the 2 main groups of Beta2 adrenoreceptor agnoists and what do they do ?

A

Short-acting (SABA) & long-acting (LABA) - both cause airway smooth muscle relaxation, increase mucus clearance and decrease mediator release from mast cells and monocytes

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2
Q

What are the 2 main SABA’s used ?

A

Salbutamol aka albuterol & terbutaline

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3
Q

What is the use of SABA’s ?

A

1st line treartment of asthma

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4
Q

What are the main side effects of SABA use?

A
  • Fine tremor the most common.
  • However, tachycardia, cardiac dysrhythmia and hypokalaemia can occur
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5
Q

What are the 2 main LABA’s ?

A

Salmeterol & formoterol

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6
Q

What must LABA’s always be co-administered with ?

A

A glucocorticoid [for this purpose combination inhalers such as Symbicort (budesonide and formoterol) and Seratide (fluticasone and salmeterol) are available, but costly

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7
Q

The use of non-selective b-adrenoceptor antagonists (e.g. propranolol) in asthmatic patients is contraindicated, why?

A

Due to risk of bronchospasm

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8
Q

What is the mechanism of action of LTRA’s?

A
  • Antagnoists of the CysLT1 receptor on mast cells and inflammatory cells
  • Resulting in relaxation of bronchial smooth muscle
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9
Q

What are the 2 main LTRA’s ?

A

Montelukast & zafirlukast - think ‘lukast’

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10
Q

When are LTRA’s used ?

A

As an add on therapy in the treatment of asthma

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11
Q

What are the main side effects of LTRA’s?

A

Headache and GI upset sometimes seen

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12
Q

What are the 2 main Methylxanthines?

A

Theophylline and aminophylline - think ‘phylline’

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13
Q

What is the mechanism of action of methylxanthines ?

A

Uncertain molecular mechanism of action - might involve inhibition of isoforms of phosphodiesterases that inactivate cAMP and cGMP

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14
Q

What is the effect of methylxanthines ?

A
  • Relax smooth muscle, anti-inflammatory and increase mucus clearance
  • Also increase diaphragmatic contractility and reduce fatigue
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15
Q

What is important to remember about methylxanthines and what would suggest going outwidth this ?

A

They have a very narrow theraputic window

If supratheraputic dose given then may develop:

  • Dysrhythmia
  • Seizures
  • Hypotension
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16
Q

What are the main side effects of methylxanthines seen at theraputic concentrations ?

A
  • Nausea & vomiting
  • Abdominal discomfort and headache
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17
Q

What are the 2 major classes of steroid hormones released into the body from the adrenal cortex ?

A

Glucocorticoids and Mineralocorticoids

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18
Q

What is the main glucocorticoid produced in the body and what are its effects on the body ?

A

The main hormone (in man) is cortisol (hydrocortisone) regulates numerous essential processes:

  • It decreases inflammatory & immunological responses
  • Increases liver glycogen deposition ­
  • Increases gluconeogenesis ­
  • Increases glucose output from liver ­
  • Decreases glucose utilization
  • Increases protein catabolism ­
  • Increases bone catabolism ­
  • Increases gastric acid and pepsin secretion ­
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19
Q

What is the main mineralocorticoid produced in the body and what is its main effects ?

A

Aldosterone - regulates the retention of salt (and water) by the kidney

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20
Q

In the treatment of inflammatory conditions what main group of steroids do exogenous steroids want to have a similar action to ?

A

Glucocorticoids (but they may also have unwanted mineralocorticoid actions)

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21
Q

Glucocorticoids have no direct bronchodilator action and are ineffective in relieving bronchospasm when given acutely - T or F?

A

True

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22
Q

What is the use of glucocorticoids in the treatment of asthma?

A

They are the mainstay for the prophylaxis of asthma

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23
Q

What is the mechanism of action of glucocorticoids relevant to asthma ?

A

They act via the glucocorticoid receptor in cells to increase transcription of genes encoding anti-inflammatory proteins and decrease transcription of genes encoding inflammatory proteins.

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24
Q

What are the effects of glucocorticoids relevant to asthma ?

A
  • They suppress the inflammatory component of asthma – (1) prevent inflammation and (2) resolve established inflammation
  • Short term, they do not alleviate early stage bronchospasm but long term treatment is effective in doing so (particularly in combo with a LABA)
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25
Q

List some of the main glucocorticoids used in the treatment of asthma ?

A
  • Beclometasone, Budesonide, Fluticasone - used for prophylaxis/maintanence treatment of asthma
  • Prednisolone or hydrocortisone - used for acute severe asthma/exacerbations
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26
Q

What are the 2 most common adverse effects (due to deposition of steroid in the oropharynx) of glucocorticoid use in the treatment of asthma ?

A
  1. Dysphonia (hoarse and weak voice)
  2. Oropharyngeal candidiasis (thrush)
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27
Q

List the common side effects seen from glucocorticoid use in general

A
  • Endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia
  • Cushing’s syndrome
  • Musculoskeletal: osteoporosis, proximal myopathy, AVN of the femoral head
  • Immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis
  • Psychiatric: insomnia, mania, depression, psychosis
  • Gastrointestinal: peptic ulceration, acute pancreatitis
  • Ophthalmic: glaucoma, cataracts
  • Suppression of growth in children
  • Intracranial hypertension
  • Neutrophilia
28
Q

Patients on long-term steroid use should have what done during intercurrent illness?

A

Their doses doubled during this period

29
Q

What is the main cromone drug ?

A

Sodium cromoglicate

30
Q

What is the mechanism of action of cromones ?

A

Mast cell stabiliser - with weak anti-inflammatory effects

31
Q

What is the use of sodium chromoglicate ?

A

Now infrequently used prophylactically in the treatment of allergic asthma (particularly children)

32
Q

What are the 2 new drug classes used in the treatment of asthma which are very expensive ?

A
  • Monoclonal antibodies directed against IgE (e.g. omalizumab)
  • Monoclonal antibodies directed against IL-5 (e.g. mepolizumab)
33
Q

When are Monoclonal antibodies directed against IgE (e.g. omalizumab) used in the treatment of asthma ?

A

For patients with severe persistent allergic asthma (raised IgE)–ie despite max therapy (step 5).

34
Q

How are the 2 different types of monoclonal antibodies used in the treatment of asthma given?

A

Via injection

35
Q

When are Monoclonal antibodies directed against IL-5 (e.g. mepolizumab) used in the treatment of asthma ?

A

For patients with severe refractory eosinophilic asthma (raised blood eosinophils >300 cell/ul) – despite max therapy (step 5)

36
Q

Give a very general overview of the effect of the parasympathetic and sympathetic divisions of the ANS in the regulation of airway function:

A

Stimulation of parasympathetics (cholinergic fibres) which act via M3 muscarinic ACh receptors, causes:

  1. Bronchial smooth muscle contraction
  2. Increased mucus secretion

Sympathetic stimulation which acts via via b2-adrenoceptors, causes:

  1. Bronchial smooth muscle relaxation
  2. Decreased mucus secretion
  3. Increased mucociliary clearance
37
Q

In relation to parasympathetic innervation of the airways what is an important treatment of COPD ?

A
  • Reducing parasympathetic neuroeffector transmission with muscarinic receptor antagonists (act as pharmacological antagonists of bronchoconstriction caused by smooth muscle M3 receptor activation)
38
Q

What are the 2 types of Muscarinic Receptor Antagonists used in the treatment of COPD ?

A
  1. Short acting muscarinic antagonist (SAMA)
  2. Long acting muscarinic antagonists (LAMAs)
39
Q

What is the name of the main SAMA ?

A

Ipratropium

40
Q

List the names of the different LAMAs

A
  • Tiotropium
  • Glycopyrronium
  • Aclidinium
  • Umeclidinium
41
Q

What part of the name suggests the drug is a muscarinic anatagonist ?

A

‘ium’ at the end

42
Q

What are the effects of Muscarinic Receptor Antagonists?

A
  • Delayed onset of bronchodilator action
  • Reduce bronchospasm caused by irritant stimuli and also block ACh-mediated basal tone
  • Decrease mucus secretion
43
Q

Do muscarnic receptor antagnoists have any effect on disease progression of COPD ?

A

No - they have little effect on the progression of COPD, their effect is mainly palliative

44
Q

Muscarinic Receptor Antagonists have few adverse effects - T or F?

A

True

45
Q

What is the benefit of LAMAs over Ipratropium (SAMA)?

A
  • LAMAs (tiotropium, glycopyrronium, aclidinium, umeclidinium) selectivley block M3 receptors
  • Whereas Ipratropium is a non-selective blocker of M1, M2 and M3 receptors
  • And Block of M3 (and M1) is desirable, but block of M2 is not because release of ACh from parasympathetic post-ganglionic neurones is increased by autoreceptor antagonism
46
Q

What is the effect of b-adrenoceptor agonists in the treatment of COPD ?

A

They provide bronchodilatation, but have no effect on underlying inflammation

47
Q

A combination of what? is superior to either drug alone in increasing FEV1 in the treatment of COPD?

A

A combination of a β2 agonist and a muscarinic antagonist

48
Q

What are Indacaterol and olodaterol?

A

Ultra-LABAs

49
Q

Go over this list of example combinations of muscarinic receptor antagnoists and beta-adrenoreceptor agnoists in the treatment of COPD

A
50
Q

What type of drug is Rofumilast and when may it be used in the treatment of COPD ?

A

A selective PDE4 inhibitor, suppresses inflammation and emphysema in animal models of COPD. Approved as oral treatment for severe COPD accompanied by chronic bronchitis, but has limiting adverse gastrointestinal effects

51
Q

What 3rd drug may be used in the treatment of COPD alongside b-adrenoceptor agonists and/or muscarinic receptor antagonists?

A

Glucocorticoids

52
Q

Triple inhalers (e.g. fluticasone/umeclidinium/vilanterol) have very recently been approved as once daily treatment for what?

A

Moderate/severe COPD

53
Q

What is the mechanism of action of glucocorticoids in the treatment of rhinitis ?

A

They reduce vascular permeability, recruitment and activity of inflammatory cells and the release of cytokines and mediators

54
Q

Give examples of the glucocorticoids used in the treatment of rhinitis

A
  • Beclometasone
  • Fluticasone
  • Prednisolone (oral)
55
Q

What types of rhinitis are glucocorticoids used in?

A

Mainstay of therapy for SAR and PAR and are of value in NARES and vasomotor rhinitis

56
Q

What is the mechanism of action of anti-histamines ?

A

H1 Receptor Antagonists which reduce the effects of mast cell derived histamine including:

  • Vasodilatation and increased capillary permeability
  • Activation of sensory nerves
  • Mucus secretion from submucosal glands
57
Q

What are the uses of anti-histamines in the treatment of rhinitis ?

A

Effective in SAR, PAR and EAR, less so in non-allergic rhinitis

58
Q

What is the name of the intranasal antihistamine spray?

A

Azelastine

59
Q

Give examples of the 1st and 2nd gen anti-histamines and state why second gen are preferred ?

A

Examples of 1st gen antihistamines:

  • chlorpheniramine

Examples of 2nd gen antihistamines:

  • loratidine
  • cetirizine
  • fexofenadine

1st generation antihistamines are sedating and have some antimuscarinic side-effects e.g. urinary retention, dry mouth

60
Q

What Anti-Cholinergic Drug (Muscarinic Receptor Antagonists) may be used in the treatment of rhinitis ?

A

Ipratropium

61
Q

What symptom is Ipratropium mainly useful for in the treatment of rhinitis ?

A

Rhinorrhoea

62
Q

What side-effects may be seen from the use of Ipratropium in the treatment of rhinitis ?

A

May cause dryness of nasal membranes, but no other adverse effects

63
Q

What is the mechanism of action of sodium chromoglycate ?

A

Allegedly mast cell stabilization, but this is uncertain

64
Q

If the person has ongoing symptoms and a history of asthma whilst using a regular intranasal corticosteroid preparation, what should be done ?

A

Consider adding in a leukotriene receptor antagonist such as montelukast to an oral or intranasal antihistamine.

65
Q

What is the mechanism of action of vasoconstrictors and what is the main one which may be used in the treatment of rhinitis ?

A
  • They act as directly, or indirectly, to mimic the effect of noradrenaline. Produce vasoconstriction via activation of a1-adrenoceptors to decrease swelling in vascular mucosa
  • Oxymetazoline, a selective a1-adrenoceptor agonist is the main one
66
Q

Nasal administration of oxymetazoline for more than a few days is not recommended, why?

A

Due to the development of a rebound increase in nasal congestion upon discontinuation (rhinitis medicamentosa).

67
Q

What are the benefits of using a spacer ?

A
  • Avoids coordination problems with pMDI
  • Reduces oropharyngeal and laryngeal side effects
  • Reduces systemic absorption from swallowed fraction
  • Acts a holding chamber for aerosol
  • Reduces particle size and velocity
  • Improves lung deposition

Y4 Respiratory (27 decks)

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