24. Pharmacology of the Airways Flashcards Preview

Year 1 - Term 2: Carriage of Oxygen > 24. Pharmacology of the Airways > Flashcards

Flashcards in 24. Pharmacology of the Airways Deck (17):

What is asthma?

List some signs and symptoms.

Long-term inflammatory disease of lungs, characterised by episodic acute limitation of air flow due to obstruction to expiratory airflow, reversing spontaneously on in response to treatment. 

Signs: wheezing on auscultation -> intercostal recession (chid) -> unable to speak (severe attack)

Symptoms: wheezing, cough, SoB


What are these two images showing?

Q image thumb

Intercostal recession

Tripod stance


= RESPIRATORY DISTRESS: intercostal recession, tripod stance and use of accessory muscles of respiration


List 3 reasons why airflow becomes limited in asthma.

List some things that excite or depress the respiratory centre.

What affect does the sympathetic and parasympathetic NS have on airways?


Bronchoconstriction/bronchospasm of SM, oedema, mucus. All 3 can occur, some individuals have more reactive airways/excessive responses

Excite: impulses from higher centres, peripheral chemoreceptors (CO2/H+)

Depress: Anaesthetics, analgesics, neuromuscular blocking drugs

Sympathetic: adrenergic tone -> bronchodilation

Parasympathetic: cholinergic tone -> bronchoconstriction


Why does constriction occur at bronchiole level?

What 4 things would you observe in an airway during asthma symptoms?

Name 2 analgesics that depress the respiratory centre.

Because they don't have hyalilne cartilage skeleton to keep airways open

Tightened muscles constrict airway, thickened/inflamed airway wall, narrowed lumen, mucus

Morphine, codeine 

A image thumb

List some triggers of asthma.

An asthmatic has hyper-responsive airways. What are the 2 components of hyperresponsiveness?

Cold, exercise, infection, dust (mites), fumes/chemicals, pollens, drugs

1. Hyper-sensitivity - normal response to very low levels of a stimulus

2. Hyper-reactivity - exaggerated response to stimulus


Describe the sequence of events culminating in the symptoms and signs of allergen-driven asthma.

Allergen or non-specific stimulus e.g. cold -> mast cell activation -> mediator release (e.g. chemokines - histamine, leukotrienes) -> bronchospasm.

The chemokines cause -> infiltration and activation of inflammatory cells -> mediator release e.g. leukotrienes, EMBP  (eosinophil major basic protein) -> airway inflammation and hyperreactivity, bronchospasm, wheezing, coughing, epithialial damage by EMBP

A image thumb

Compare normal immune response to asthmatic immune response.

 Normal: antigens produce low-level T-helper (Th)-2 lymphocyte response -> normal physiologic IgG response

Asthma: antigens cause immature CD4 (Th) cells to differentiate to activated Th-2 lymphocytes -> realease cytokines IL4 and IL5 that recruit multiple inflammatory eosinophils, mast cells, IgE-producing B cells -> inflamm. characterised by bronchoconstriction, oedema, and mucus production

T-cells also induce direct asthmatic response


Name 3 genes associated with immune responses and implicated in asthma.

1. HLA (human leucocyte antigens)

2. IL (interleukin)

3. PRG2 (proteoglycan 2)


Give 2 examples of drugs that may trigger asthma/bronchospasm, and describe why.

1. Beta blockers. Blocking beta-1 receptors affects heart rate, cardiac conduction and contractility. Bronchial SM beta-2 receptors mediate bronchodilataion. Blocking these causes bronchospasm; beta-blockers block beta-1 at low doses but may block beta-2 at higher doses

2. COX-blocking drugs. E.g. aspirin, NSAIDs (diclofenac, ibuprofen) cause relative increase in arachidonic acid shunted to lipoxygenase pathway leading to increased leucotrine production -> mediates inflammation -> bronchospasm in susceptible people


How is lung function in asthma measured and monitored? When is it considered life threatening?

Peak flow meter - PEFR (peak expiratory flow rate) - blow as hard and fast as you can. Useful reflection of response to treatment - should increase if improving. Compare to predicted PEFR values - if 30% less than predicted = life threatening!

NB: can be measured via FEV1/FVC and compared to predicted


Describe the treatment ladder of asthma.

a. Avoid triggers

b. Don't smoke


1. inhaled short acting beta-2 agonist (for acute asthma)

2. plus inhaled steroid 

3. plus inhaled long-acting beta-2 agonist (LABA) (for moderate-severe asthma)

4. increase inhaled steroid and poss. add 4th drug e.g. leukotriene receptor antagonist

5. daily steroid tablet


Describe the 5 bronchodilator drug treatments for asthma. Give examples.


1. beta-2 agonists (mimic sympathetic NS. Short-acting e.g. salbutamol, terbutaline. Long acting (LABAs e.g. salmeterol, formoterol) must be used with steroid preventers otherwise mortality increased. Not entirely selective- main side effect = TACHYCARDIA)

2. anti-muscarinics (block parasympathetic NS)

3. phosphodiesterase inhibitors (prolong cAMP impact -> phosphorylation of certain intracellular proteins -> bronchodilation)

4. anticholinergics (short-acting e.g. ipratroprium, triotropium, competitive antagonists for airway ACh receptors (M1-M4), anticholinergic SEs, not v. effective)

5. methylxanthines e.g theophylline, aminophylline (IV), PDE inhibitor, not v. effective, narrow theraputic window, cardio-toxic, more common used for COPD



Why are most commonly-used treatements for asthma inhaled?

To minimise/avoid extensive SEs that occur when doesed systematically e.g. anti-cholinergics may work on muscarinic receptors elsewhere causing constipation, urine retention, tacchycardia


Describe the 4 anti inflammatory drug treatments for asthma. Give examples.

Anti-inflammatory/mast cell stabilisers/monocolonal antibodies

1. corticosteroids: suppress multiple inflammatory genes that are activated in asthmatic airways by altering transcription of pro-inflammatory processes e.g. interleukins (that cause increased prod of inflam mediators e.g. cytokines). Inhaled to reduce SEs, oral if severe attack. Thus reduces bronchoconstriction, odema, mucus.

NB. treatment path: blue pump -> preventor  = low dose steroid inhaler -> tablet

2. leukotrine antagonists: FLAP inhibitors e.g. monteleukast, oral, only effective in some

3. Cromolyns: e.g. sodium cromoglycate, decreases activity of masy cells but limited

4. monocolonal anti-IgE antibodies


What are the most commonly used devices for delivering inhaled drugs?

Inhalers (metered dose inhaler, dry powder inhaler) +/- spacer

Nebulisers (air or oxygen-driven)


How does a metered dose inhaler (MDI) work? What are the 2 disadvantages? What can be used to improve it?

How does a dry powder inhaler (DPI) work? What is the disadvantage?

Propellant propels drug particles at high velocity into airway, flashes off, drug particles inhaled. Disad: requires hand-lung coordination to effectively deliver particles to site of action - diffucult for kids and old. HFAs (propellant) also environmental pollutants. Spacer improves by permitting drug to stay longer in aerosol form for inhalation.

Uses inspiration forces of breathing to deliver drug, no propellant. Disadv: requires high respiratory flow rate - hard in asthma attack.


NB: >90% pts can't use MDI properly - technique education important!


List 2 other treatments in asthma (aside from the 5 bronchodilator and 4 anti inflammatory ones).

Antibody therapy directed at IgE

1. omalizumab - humanised (mouse) recombinant monoclonal antibody, destroys IgE (imp. trigger for mast cell activation), option in moderate-severe astham poorly controlled with conventional, SE: anaphylaxis

2. Magnesium - potent SM relaxer, for severe asthma, affects Na/K ATPase, low toxicity

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