Pharmacology of asthmatic drugs

Lecture slide, educational purpose only

1. Diponegoro University
School of Medicine
Asthmatics
Drugs
Pharmacology and Therapy I
Fadel Muhammad Garishah
Diponegoro University
School of Medicine

2. Diponegoro University, School of Medicine
Case I
A 56-year-old man presents to ED with the history of
shortness of breath for 45 minutes. He reports that he was feeling
well and in his usual state of health until about an hour ago, when
he smelled something burning. Twenty minutes later, he began to
fell short of breath and was wheezing. He tried using his albuterol
inhaler without success, so he proceeded to the ED. At the ED, he
was tachycardia, tachypnea, wheezing and hypertensive. His O2 sats
on RA were 87% to 88%. His last admission for an asthma attack
was 2 months ago.
•What is his acute asthma management?
•Long term managements?

3. Diponegoro University, School of Medicine
Bronchial Asthma
Asthma
–Asthma is defined as recurrent reversible airway obstruction, with
attacks of wheeze, shortness of breath and often nocturnal cough.
Severe attacks cause hypoxaemia and are life-threatening.
Asthmatic patients experience intermittent attacks of
wheezing, shortness of breath-with difficulty especially in
breathing out-and sometimes cough.
Essential features include:
–airways inflammation, which causes
–bronchial hyper-responsiveness, which in turn results in
–recurrent reversible airway obstruction.

4. Diponegoro University, School of Medicine
Pathogenesis involves exposure of genetically disposed
individuals to allergens; activation of Th2 lymphocytes and
cytokine generation promote:
–differentiation and activation of eosinophils
–IgE production and release
–expression of IgE receptors on mast cells and eosinophils.
Important mediators include leukotriene B4 and cysteinyl
leukotrienes (C4 and D4); interleukins IL-4, IL-5, IL-13;
and tissue-damaging eosinophil proteins.

5. Diponegoro University, School of Medicine
Inflammatory cells releasing Growth factors act on smooth
muscle cells
–causing hypertrophy and hyperplasia, and the smooth muscle
can itself release proinflammatory mediators and autocrine
growth factors schematically the changes that take place in the
bronchioles.
–Epithelial cell loss means that irritant receptors and C fibres are
more accessible to irritant stimuli-an important mechanism of
bronchial hyper-reactivity.

6. Diponegoro University, School of Medicine
Asthma Pathogenesis
cysteinyl leukotrienes
IgE

7. Diponegoro University, School of Medicine
Airway Narrowing: Acute Asthmatic Attacks
1.Contraction of airway smooth muscle
2.Inspissation of viscid mucus plugs in the airway lumen
3.Thickening of bronchial mucosa from edema, cellular
infiltration, and hyperplasia of secretory, vascular, and
smooth muscle cells.
Which is easily reversed? Requires sustained treatment?
Easily reversed : Contraction of Airway Smooth Muscle by
giving Bronchodilator drugs
Sustained treatment? Mucus Hypersecretion and
Thickening mucosa due to immune cells infiltration
maintained with antiinflammatory drugs

8. Diponegoro University, School of Medicine

9. Diponegoro University, School of Medicine
Antiasthmatic drugs include:
–bronchodilators
–anti-inflammatory agents.
Treatment is monitored by measuring forced expiratory
volume in 1 second (FEV1) or peak expiratory flow rate
and, in acute severe disease, oxygen saturation and arterial
blood gases.

10. Antiinflammatory drugs
Bronchodilators
Antiinflammatory drugs

11. Diponegoro University, School of Medicine
Severe acute asthma is a medical emergency requiring
hospitalisation.
Treatment includes (Bronchodilators reverse the
bronchospasm of the immediate phase; anti-inflammatory
agents inhibit or prevent the inflammatory components of
both phases )
–oxygen (in high concentration, usually ≥ 60%),
–inhalation of nebulised salbutamol, and
–intravenous hydrocortisone followed by a course of oral
prednisolone.
–Additional measures occasionally used include nebulised
ipratropium,
–intravenous salbutamol or aminophylline,
–and antibiotics (if bacterial infection is present).
–Monitoring is by PEFR or FEV
1
, and by measurement of arterial
blood gases and oxygen saturation.

12. Diponegoro University, School of Medicine
•Oxygen
•Salbutamol: β
2
-Adrenoceptor agonists act as physiological
antagonists of the spasmogenic mediators but have little or
no effect on the bronchial hyper-reactivity
•Glucocorticoids: These reduce the inflammatory
component in chronic asthma and are life-saving in status
asthmaticus (acute severe asthma).
•Theophylline (often formulated as aminophyllin)
relaxant effect on smooth muscle has been attributed to
inhibition of phosphodiesterase (PDE) isoenzymes, with
resultant increase in cAMP and/or cGMP
•ipratropium: Muscarinic receptor antagonists
•Cysteinyl leukotriene receptor antagonists
•Histamine H1-receptor antagonists

13. Diponegoro University, School of Medicine
•Cromoglicate and nedocromil: Given prophylactically, they
reduce both the immediate- and late-phase asthmatic
responses and reduce bronchial hyper-reactivity.
•Omalizumab is a humanised monoclonal anti-IgE
antibody. It is effective in patients with allergic asthma as
well as in allergic rhinitis. It is of considerable theoretical
interest (see review by Holgate et al., 2005), but it is
expensive and its place in therapeutics is unclear