FARMAKOTERAPI ASMA

SITI RAHMATUL AINI, S.F., APT., M.SCFAKULTAS KEDOKTERANUNIVERSITAS MATARAM

2012

Selective for b2-receptor subtype. Mekanisme :direct relaxation of airway smooth

muscle and consequent bronchodilation Directly to airways via inhalation. Classified as short- or long-acting.

◦ Short-acting : symptomatic relief of asthma, ◦ long-acting : prophylactically in treatment of asthma

b2 Adrenergic Receptor Agonists

Short-Acting b2 Adrenergic Receptor Agonists

Example : albuterol (PROVENTIL, VENTOLIN), levalbuterol (XOPENEX), metaproterenol (ALUPENT), terbutaline (BRETHAIRE), and pirbuterol (MAXAIR)

Terbutaline (BRETHINE, BRICANYL), albuterol, and metaproterenol also available in oral dosage form

Secara inhalasi :onset of action within 1 to 5 minutes and produces bronchodilation that lasts for about 2 to 6 hours.

Secara oral : oral terbutaline duration of action of 4 to 8 hours

Long-Acting b Adrenergic Receptor Agonists

Salmeterol xinafoate (SEREVENT) and formoterol (FORADIL)

Inhalation of salmeterol provides persistent bronchodilation lasting over 12 hours

Toxicity◦ increased heart rate◦ cardiac arrhythmias

Oral Therapy with b Adrenergic Receptor Agonists

Two primary situation- in young children (<5 years old) who cannot manipulate metered-dose inhalers. -patients with severe asthma exacerbations, any aerosol, whether delivered via a metered-dose inhaler or a nebulizer, can worsen cough owing to local irritation

Mechanism :◦ not directly relax airway smooth muscle and thus

have little effect on acute bronchoconstriction◦ effective in inhibiting airway inflammation by

-modulation of cytokine and chemokine production;- inhibition of eicosanoid synthesis; - marked inhibition of accumulation of basophils, eosinophils, and other leukocytes in lung tissue;-decreased vascular permeability

Glucocorticoid

Inhaled Glucocorticoids beclomethasone dipropionate (BECLOVENT,

VANCERIL), triamcinolone acetonide (AZMACORT), flunisolide (AEROBID), budesonide (PULMICORT), and fluticasone propionate (FLOVENT).

used prophylactically to control asthma

Toxicity◦ decreases in bone mineral density◦ Oropharyngeal candidiasis

Systemic Glucocorticoids- used for acute asthma exacerbations and chronic severe asthma.

Toxicity-mood disturbances, increased appetite, impaired glucose control in diabetics, and candidiasis

Leukotriene-Receptor Antagonists : Zafirlukast (ACCOLATE) and montelukast (SINGULAIR)◦ Zafirlukast and montelukast : selective high-

affinity competitive antagonists for cys-LT1 receptor

Leukotriene-Synthesis Inhibitors : Zileuton (ZYFLO) ◦ Zileuton :inhibitor of 5-lipoxygenase activity

inhibits formation of all 5-lipoxygenase products

Leukotriene-Receptor Antagonists and Leukotriene-Synthesis Inhibitors

prophylactic treatment for mild asthma as alternatives to low-dose inhaled steroids

for control of mild chronic asthma. Interaction with warfarin and

theophylline ???

Omalizumab (XOLAIR) first "biological drug" approved for asthma Omalizumab is recombinant humanized

monoclonal antibody targeted against IgE. IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophilspreventing allergic reaction at a very early step .

Anti-Ige Therapy

indicated for adults and adolescents older than 12 years of age with allergies and moderate-to-severe persistent asthma.

should not be used as a rescue medication

Mechanism of Action◦ inhibiting mediator release from bronchial mast

cells◦ reversing increased functional activation in

leukocytes obtained from the blood of asthmatic patients

◦ suppressing the activating effects of chemotactic peptides on human neutrophils, eosinophils, and monocytes

◦ inhibiting parasympathetic and cough

Cromolyn Sodium and Nedocromil Sodium

to prevent asthmatic attacks in individuals with mild to moderate bronchial asthma

Nedocromil : approved for asthmatic patients 12 years of age and older

Cromolyn : approved for all ages.

Toxicity- cough, joint swelling and pain, headache, rash, and nausea. -Nedocromil and cromolyn can cause a bad taste.

Theophylline ◦ competitive antagonist at adenosine receptors◦ inhibits synthesis and secretion of inflammatory

mediators from numerous cell types, including mast cells and basophils

◦ Indeks terapi sempit

Methylxanthine

Ipratropium bromide (ATROVENT) Menghambat kontraksi otot polos saluran

nafas yg diatur oleh vagus dan sekresi mukus

Combination of selective b2 adrenergic agonist and ipratropium should be considered in acute treatment of severe asthma exacerbations

Anticholinergic Agents

TERIMAKASIH