Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
MANAGEMENT
Macrophage/
dendritic cell Mast cell
Eosinophil
Mucus plug
Epithelial shedding
Nerve activation
Subepithelial
fibrosis
Plasma leak
Sensory nerve
Oedema activation
Vasodilatation Cholinergic
Mucus reflex
New vessels
hypersecretion
Hyperplasia Bronchoconstriction
Hypertrophy / hyperplasia
Barnes PJ
Inflammatory processes
soldering flux
wood dust
Asthma diagnosis
Others
Allergens
exercise
animal dander
viral infection
dust mites smoke
Asthma severity is graded, in the GINA guidelines, according to the frequency of symptoms,
occurrence of symptoms at night, and PEF measurement before treatment.
Treatment goal: take control of
asthma
no chronic symptoms
no asthma attacks
no emergency visits
no need for quick relief (as needed) ß2-agonist
normal physical activity including exercise
lung function as close to normal as possible
no adverse effects from medicine
Relievers Controllers
inhaled fast-acting inhaled corticosteroids
ß2-agonists inhaled long-acting ß2-
inhaled anticholinergics agonists
inhaled cromones
oral anti-leukotrienes
oral theophyllines
oral corticosteroids
RELIEVERS MEDICATION
ORAL
PARENTERAL
Classes of ß2-agonists
Speed of
onset RESCUE MEDICATION
Mechanism of action:
Bronchodilator (They stimulate intracellular adenyl
cyclase, the enzyme that catalyzes the conversion of
adenosine triphosphate to cyclic-3',5'-adenosine
monophosphate (cAMP). Increased cAMP levels cause
relaxation of bronchial smooth muscle and inhibition of
release of mediators of immediate hypersensitivity from
cells, especially from mast cells)
Enhance mucociliary clearance
Modulate mediators release from mast cells and basophils
chemical structure
pharmacological properties:
mode of action in the ß2-receptor region
potency
efficacy (ie full / partial agonism)
selectivity
CONTROLLER MEDICATIONS
Oral : Prednisolone
Dexamethasone
Parenteral : Hydrocortisone
Methylprednisolone
Side effects
Local effects –
irritation
How to prevent ? – Mouth washing after inhalation &
use of spacer
Systemic adverse
effects depends on the dose and potency of
MECHANISM OF ACTION :
Block the synthesis of all leukotrienes (The
leukotriene receptor antagonists are selective and
competitive antagonists of the cysteinyl leukotriene
(Cys LT1) receptor. Cysteinyl leukotriene (LTC4,
LTD4 and LTE4) production and receptor occupation
have been correlated with the pathophysiology of
asthma, including airway edema, smooth muscle
constriction, and altered cellular activity associated
with the inflammatory process. Zafirlukast is the
first Cys LT1 receptor antagonist to be released)
Considerations:
*Zafirlukast should be taken one hour before meals or two hours after meals
because food can decrease the bioavail-ability.
*Montelukast should be taken in the evening
and may be taken without regard to food.
Cromolyn Sodium And Nedocromil
Mechanism of Action: Cromolyn and
nedocromil are mast-cell stabilizers. They
prevent the release of the mediators of
type I allergic reactions, including
histamine and slow-reacting substance of
anaphylaxis, from sensitized mast cells.
They also inhibit type III reactions to a
lesser extent. It has been suggested that
the drugs may block calcium channels in
mast cell membranes. The specific
mechanism(s) of action of the drug on
mast cells remains to be established
Cromolyn Sodium And Nedocromil
Use:
Adverse
Cromolyn
Effects:
or nedocromil is recommended for
1. prophylaxis of exercise induced bronchospasm or
Dryness of throat
2.
exposure
Bad Tasteto a known allergen. They are also
recommended as anti-inflammatory long-term
3. wheezing
control medications in patients with mild
4. nausea asthma.
persistent
*The therapeutic response may occur within the first two weeks of therapy,
but may take up to six weeks to determine the maximum benefit.
The primary advantage of these agents is safety.
R-DNA derived Monoclonal Antibodies
Mechanism: These bind to human IgE selectively,
this leads to decrease binding of IgE to the high
affinity IgE receptor on the surface of mast cells and
basophiles
Reduction in surface binding of IgE limits the degree of
release of mediators of the allergic response
Omalizumab useful for treatment of
moderate to severe allergic asthma
STEP 4: SEVERE PERSISTENT Step
CONTROLLER: daily multiple down
medications RELIEVER
• Inhaled steroid when
• Long-acting bronchodilator • Inhaled ß2- controlle
• Oral steroid agonist p.r.n. d
Avoid or control triggers
STEP 3: MODERATE PERSISTENT • Patient
CONTROLLER: daily education
medications RELIEVER
• Inhaled steroid and long-acting essential at
bronchodilator • Inhaled ß2- every step
• Consider anti-leukotriene agonist p.r.n. • Reduce
Avoid or control triggers therapy if
controlled for
STEP 2: MILD PERSISTENT at least
CONTROLLER: daily 3 months
medications RELIEVER • Continue
• Inhaled steroid • Inhaled ß2-
• Or possibly cromone, oral monitoring
theophylline or anti-leukotriene agonist p.r.n.
Avoid or control triggers
STEP 1: INTERMITTENT
RELIEVER Step up
CONTROLLER: none
• Inhaled ß2- if not controlled
agonist p.r.n. (after check on
inhaler technique
Avoid or control triggers and compliance)
TREATMENT
GINA Guidelines 1998
Step 1
Future?
stepping up and down should involve both LAßA and
Conclusion
Salmeterol/formoterol.
Have not been tested extensively in
pregnant women.
Theophyllines.
May aggravate the nausea and gastroesophageal
reflux.
May cause transient neonatal tachycardia and
irritability.
Inhaled corticosteroids.
Has good safety profile in pregnancy.
Anti-leukotrienes.
No data is available on the use of this agent in
pregnant women.
Oral corticosteroids.
Sometimes necessary for severe asthma but usually
only for short periods.
An increased risk of cleft palate has been reported in
animals given huge doses.
Breastfeeding.
Should be continued in women with asthma.