PATHOPHYSIOLOGY OF ASTHMA

characterized by fluctuating airways obstruction, with diurnal variation and nocturnal

exacerbations.
SS: the triad of wheeze, cough and breathlessness.
due to a combination of constriction of bronchial smooth muscle, edema of the mucosa lining
the small bronchi, and plugging of the bronchial lumen with viscous mucus and inflammatory
cells
categorized into non-allergic and allergic, but there is considerable overlap.
In allergic asthma, which is usually of early onset, extrinsic allergens produce a type I allergic
reaction in atopic subjects. Type I reactions are triggered via reaginic antibodies (IgE) ,
eosinophils.
Patients with non-allergic (late-onset) asthma do not appear to be sensitive to any single well-
defined antigen, although infection (usually viral) often precipitates an attack.
Inflammatory mediators implicated in asthma include histamine, several leukotrienes (LTC4/D4
and E4) 5-hydroxytrypta- mine (serotonin), prostaglandin D2, platelet-activating factor (PAF),
neuropeptides and tachykinins.
Adrenaline:anticholinergic:muscarinic: bronchoconstriction.
Ach:B receptors:bronchodilation

COPD
Acute exacerbation
Controlled oxygen therapy (e.g. FiO2 2428%);
Nebulized 2-agonists (salbutamol every 24 hours, if needed) or intravenously if refractory;
Nebulized anticholinergics, such as ipratropium bromide;
Antibiotics (e.g. clarithromycin, co-amoxiclav, levofloxacin).
Short-term oral prednisolone.

Chronic disease
Stop smoking cigarettes.
Optimize inhaled bronchodilators (salbutamol/ipratropium bromide) and their administration.
Consider oral theophylline and/or inhaled glucocorticosteroids.
Treat infection early and aggressively with antibiotics.
Offer long-term oxygen therapy (LTOT) for at least 15 hours per day for cor pulmonale.
Diuretics should be used for peripheral oedema.
Consider venesection for severe secondary polycythaemia.
Exercise, within limits of tolerance.

Terbutaline similar to salbutamol
Salmeterol: prophylaxis to exercised induced asthma

Bronchodilator agents
2-Agonists.
Bronchodilate by increasing intracellular cAMP.
Short-acting, rapid-onset agents (e.g. salbutamol) are used as needed to relieve bronchospasm in
asthma.
Long-acting, slower-onset agents (e.g. salmeterol) are used regularly twice daily.
Common side effects include tremor, tachycardias, vasodilatation, hypokalaemia and hyperglycaemia.

Anticholinergics
Antagonist at M2 and M3 muscarinic receptors in the bronchi, causing bronchodilatation.
Slow onset of long-lasting bronchodilatation (given six- to eight-hourly), especially in older patients.
Bitter taste.

Anti-inflammatory agents cromoglicate and glucocorticosteroids
Sodium cromoglicate
Its mechanism of action is unclear. It has an anti- inflammatory effect.
Largely superseded in chronic prophylactic therapy of allergic asthma by glucocorticosteroids.
Prevents exercise-induced asthma.
Inhaled therapy is administered via metered-dose inhaler or dry powder.
Side-effects are minimal (headache, cough).
Its use is very safe in children.

Glucocorticosteroids
Mechanism is anti-inflammatory.
They are administered systemically (i.v./p.o.) in severe acute and chronic asthma.
They are inhaled topically or nebulized in chronic asthma.
Glucocorticosteroids are well absorbed from the gastro- intestinal tracthepatic (CYP3A) metabolism.
Dosing is once daily for oral glucocorticosteroids and twice daily for inhaled agents.
Side effects are minimal with topical therapy (oral thrush, hoarse voice, HPA suppression only at high
dose).
Side effects with systemic therapy are the features of Cushings syndrome.

Leukotriene modulation in asthma
Leukotriene B4 is a powerful chemo-attractant (eosinophils and neutrophils) and increases vascular
permeability producing mucosal oedema.
Leukotrienes C4, D4 and E4 (cysteinyl leukotrienes) are potent spasmogens and pro-inflammatory
substances (SRS-A).
Clinically used agents that modulate leukotrienes are leukotriene antagonists (which antagonize
cysteinyl leukotrienes LTD4, LTC4 at the Cys-LT1 receptor)
Leukotriene antagonists (e.g. montelukast) are effective as oral maintenance therapy in chronic
persistent asthma. Montelukast has antiinflammatory properties and is a mild, slow-onset
bronchodilator.
Accolate (zafirlukast) is a leukotriene modifier and is used for the prophylaxis and chronic treatment
of asthma

Adverse Effects of Theophylline:
- Dose related acute toxicities include: tachycardia, nausea and vomiting, tachyarrhythmias
(SVT), central nervous system stimulation, headache, seizures, hematemesis, hyperglycemia, and
hypokalemia.
- Adverse effects at usual therapeutic doses: insomnia, gastric upset, aggravation of ulcer or
reflux, increase in hyperactivity in some children, and difficulty in urination in elderly males with
prostatism.

Respiratory failure
Type I (hypocapnic hypoxaemia) and type II (hypercapnic hypoxaemia).
Therapy for type I is supportive with high-percentage oxygen (FiO2 4060%).
Therapy for type II is low-percentage oxygen (FiO2 2428%) and treatment of reversible factors
infection and bronchospasm (with antibiotics, bronchodilators and glucocorticosteroids).
Type I or type II respiratory failure may necessitate mechanical ventilation.
Central nervous system (CNS)-depressant drugs (e.g. opiates, benzodiazepines) may exacerbate or
precipitate respiratory failure, usually type II.
Sedatives are absolutely contraindicated (unless the patient is already undergoing mechanical
ventilation).

FVC: Forced Vital Capacity - This is the total amount of air that you can forcibly blow out after full
inspiration, measured in liters.
FEV
1
: Forced Expiratory Volume in 1 Second - This is the amount of air that you can forcibly blow out in
one second, measured in liters. Along with FVC it is considered one of the primary indicators of lung
function.
FEV
1
/ FVC - This is the ratio of FEV 1 and FVC, which showing the amount of the FVC that can be
expelled in one second. In healthy adults this should be approximately 80%.
PEF: Peak Expiratory Flow - This is the speed of the air moving out of your lungs at the beginning of the
expiration, measured in liters per second.