Management Asthma 1 + 2 (2/02) Flashcards
1
Q
LO’s
A
- Describe the mechanism of action and clinical use of bronchodilator, leukotriene receptor antagonist drugs
- Describe the major pharmacokinetic characteristics which affect the clinical use of bronchodilator, leukotriene receptor antagonist drugs
- Describe the major side effects of bronchodilator, leukotriene receptor antagonist drugs
- Describe the principles of management and the step wise approach in the treatment of asthma and COPD
- Describe the mechanism of action and clinical use of drugs that affect cholinergic neurotransmission
- Describe the mechanism of action and clinical use of corticosteroids.
- Describe the major pharmacokinetic characteristics which affect the clinical use of corticosteroids.
- Describe the major side effects of corticosteroids.
- Describe the side effects of antimuscarinic drugs.
2
Q
What is the resistance equation, and how does it link to the bronchi?
A
1/r4
This shows that a small change in the radius of the bronchi can cause a large increase in resistance in the airways. Thus, the bronchi are the main site of resistance. How open the airways are depend on the ANS of the PNS.
3
Q
Describe the parasypathetic innervation of the bronchial smooth muscle?
A
- Bronchial smooth muscle is innervated by the Vagus Nerve AKA the 10th Cranial Nerve.
- Acetylcholine is released from the Vagus Nerve.
- The smooth muscle has muscarinic receptors (M3) that the acetycholine acts on to cause bronchoconstriction.
- When rest and digest don’t need to ventilate as much as when in flight/fight response.
4
Q
Describe the sympathetic innervation of the bronchial smooth muscle?
A
- There is no actual sympathetic nerves on the smooth muscle.
- But, the sypathetic nerves do supply the blood vessels and glands on the bronchi.
- When adrenaline is released into the blood, it acts on B2 Adrenoreceptors to cause bronchodilation.
- Medication manipulates this, for example Salbutamol is a B2 agonist (activator) so causes bronchodilation in asthma. This is the blue ‘reliever’ inhaler.
5
Q
What is the difference between intrinsic and extrinsic asthma?
A
- Allergic asthma is extrinsic. This normally occurs in children, and may be due to an allergy to pollen, dust mites, animals, peanuts or eggs.
- Intrinsic asthma is non-allergic. We do not know the cause of this asthma, but we know that it is made worse by irritants. Most people have this type.
6
Q
Describe the signs (doctor) and symptoms (patient tells) of asthma?
A
- Intermittent attacks of:
- Wheezing
- Shortness of breath
- Cough
- There will often be a trigger (dust, cold air, exercise…)
- Characterised by:
- Inflammation of airways
- Bronchial hyper-reactivity
- Reversible airways obstruction (COPD is not reversible)
- Acute severe asthma may result in hypoxaemia (low O2 in blood) and may be fatal.
7
Q
What is hyper-responsiveness in asthma a combination of?
A
- Hyper-responsiveness is a combination of hyper-sensitivity and hyper-reactivity.
- Hyper-sensitivity means that an asthmatic’s response to an irritant happens earlier, but to the same level of response.
- Hyper-reactivity means the asthmatic’s response is way larger than the normal persons.
- Combined, this means the asthmatic has a earlier, larger response to an irritant.
8
Q
Describe the airway changes in chronic asthma?
A
- The blood vessels supplying the airways are dilated due to inflammation.
- There are inflammatory cells like eosinophils and mast cells.
- This causes oedema in the wall of the bronchi, thickening them.
- This reduces the diameter of the lumen.
- There is excess mucas.
- Hypertrophied smooth muscle.
9
Q
What is the immediate phase of asthma and how is it treated?
A
- Asthma triggered by allergen (extrinsic) or non- specific stimulus (intrinsic asthma).
- Mast cells release histamine, cysLTs and spasmogens which cause bronchocospasm.
- This can be reversed by B2- aderenoreceptor agonists (activators) like Salbutamol, or by cysLTs receptor antagonist (blockers). Theophylline can also be given,as it competitively inhibits phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells. In vascular smooth muscle this increase in cAMP leads to smooth muscle relaxation.
10
Q
What is the late phase of asthma and how is it treated?
A
- Mast cells also release chemotaxins (stimulates the movement of leukocytes) and chemokines (signalling cytokine).
- This causes infiltration by Th2 and monocytes (which both release cytokines). It activates inflammatory cells like eosinophils:
- This causes eosinophil cationic protein (ECP) and eosinophil major basic protein (EMBP) are both toxic to the epithelium and damage it.
- This also causes cysLTs to be activated and cause airway inflammation and hyper-reactivity.
- Overall, this causes bronchospasm, wheezing and coughing, especially in the morning (process happens more than a few hours adter the asthma attack).
- It is treated by using glucocorticoids, which inhibit inflammation associated chemicals likes prostoglandin being formed.
- Also, 5-lipoxygenase inhibitor and leukotriene antagonists stop leukotrienes being made, so leukotrienes can’t cause bronchoconstrictors
or promote mucus secretion or recruit immune cells which enhance airway inflammation.
11
Q
What are the two groups of treatment for asthma?
A
-
Preventers/ Controllers:
- Anti-inflammatory agents
- Corticosteroids
- Leukotriene receptor antagonists
-
Relievers:
- B2 adrenoceptor agonists
- Methylxanthines
- Anticholinergics
12
Q
In what ways is asthma medication given directly to the airway and why?
A
- Given directly into the airway because this minismises side effects.
- Metered-Dose Inhaler: compressed gas propels fixed dose, but requires coordination between inhalation and activation of device. The normal brown and blue inhalers. For children can be used with a spacer.
- Dry Powder Inhaler: this is a circular, disk shaped inhaler that propels dry powder instead of gas into the lungs.
- Nebulizers: battery-powered machines that turn liquid asthma medicine into a fine mist. This mist comes through a tube that is attached to a mouthpiece or facemask.
13
Q
What are the steps in the treatment of asthma in adults?
A
- Inhaled short-acting B2 agonist/ activator. Stimulating B2 Adrenoreceptors causes bronchodilation in the sypathetic innervation of the airways. EG: Salbutamol- the blue ‘reliever’ inhaler.
- Add inhaled steroid 200-800 mcg/day.
-
Add inhaled long-acting B2 agonist (LABA). Then assess control of asthma:
- If good response to LABA, continue at that dose.
- If there is benefit from LABA but control still inadequate then continue LABA and increase inhaled steroid dose to 800 mcg.
- If no response to LABA – stop LABA and increase inhaled steroid to 800 mcg/day.
- Increasing steroid further, up to 2000 mcg/day. Addition of a fourth drug EG: leukotriene receptor antagonist, SR Theophylline, B2 agonist tablet.
- Use daily steroid tablet in lowest dose providing adequate control. Maintain high dose inhaled steroid at 2000 mcg/day. Consider other treatments to minimise use of steroid tablets. Refer patient for specialist care.
14
Q
What are the steps in the treatment of asthma in kids?
For children the doses are not as high:
- Inhaled steriod only up to 200-400mcg compared to 200-800mcg for adults.
- Steriod can be increased to 800mcg for children in step four if LABA doesnt work, but for adults it can be increased to 2000mcg.
A
- Inhaled short-acting B2 agonist/ activator. Stimulating B2 Adrenoreceptors causes bronchodilation in the sypathetic innervation of the airways. EG: Salbutamol- the blue ‘reliever’ inhaler.
- Add inhaled steroid 200-400 mcg/day.
- Add inhaled long-acting B2 agonist (LABA). Then assess control of asthma:
- If good response to LABA, continue at that dose.
- If there is benefit from LABA but control still inadequate then continue LABA and increase inhaled steroid dose to 400 mcg.
- If no response to LABA – stop LABA and increase inhaled steroid to 400 mcg/day.
- Increasing steroid further, up to 800 mcg/day. Addition of a fourth drug EG: leukotriene receptor antagonist, SR Theophylline, B2 agonist tablet.
- Use daily steroid tablet in lowest dose providing adequate control. Maintain high dose inhaled steroid at 800 mcg/day. Consider other treatments to minimise use of steroid tablets. Refer patient for specialist care.
15
Q
How do B2 Adrenoceptor Agonists work?
A
- B2 receptor agonists activate B2 adrenceptors, this stimulates the Gs protein to form cAMP which causes vasodilation in smooth muscle.
- Isoprenaline (isoproterenol) the blue inhaler is a selective B agonist. In smooth muscle it causes bronchodilation, but in cardiac muscle it causes contraction.
- Adrenaline/ Epinephrine is non-selective doe a, b1 and b2 receptors.
