Therapeutic Management of Asthma

BRONCHODILATORS DRUGS:-

a) B2-adrenergic:

Examples:-
Salbutamol,Terbutaline,Ephedrine, Salmeterol,Formoterol,Bambuterol.

Mecanism of action:-
Dilate the bronchi by direct action on B2 adreno-receptors on smooth muscles. They relaxes bronchial muscles whatever spasmogen are involved. They also inhibit release of TNF-  release from monocytes, and increase mucus clearance by an action on cilia.

Unwanted effects:-
The commonest adverse effect of these drugs include: tremors; other side effects are tachycardia, cardiac dysrhythmia.

b) Methylxanthines:

Examples:-
Theophylline, Aminophyline,Choline theophyllinate.

Mecanism of action:-
1>Release of Ca+2 from sarcoplasmic reticulum, especially in skeletal and cardiac muscles.
2>Inhibition of phosphodiesterase enz.which degrades cyclic neucleotide intracellulary, so dilation occur.

Unwanted effects:-
The serious CVS effect is dysrhythmia; other effects are CNS & GIT disturbances.

c)Anticholinergics:

Examples:-
Atropine, Ipratropium bromide[Atrovent]

Mecanism of action:-
It causes bronchodilation by blocking cholinergic tone through blockadge of cholinergic receptor; act primarly in larger airways.

Unwanted effects:-
Dry mouth ,urinary retention ,hyperthermia  etc.

ANTI LEUKOTRIENE DRUGS:-

Examples:-
Montelukast, Zarfirlukast, Zileuton.(also inhibit LTB4 synthesis)

Mecanism of action:-
LT-C4 & LT-D4 are important mediators for bronchial asthma, these drugs competitively antagonize cys LT1 receptor mediated bronchoconstriction, increased vascular permeability  & recruitment of eosinophils.

Unwanted effects:-
Headache, skin rashes. Sometimes few cases of Churg-Strauss syndrome(vasculitis with eosinophilia)

ANTI INFLAMMATORY DRUGS

Corticosteroids:

Examples:-
Beclomethasone[Vanceril,Beclovent],Triamcinolone[Azmacort],Flunisolide[Aerobid],Fluticasone [Flovent] Dexamethasone

Mecanism of action:-
Corticosteroids penetrates into cells, bind to high affinity Cytoplasmic Receptor Protein (CRP) a structural change occur in steroid receptor complex that allow migration into nucleus & binding to Glucocorticoid Response Elements(GRE)-thereby inhibit transcription of  specific m-RNA, they are not bronchodilators.

Unwanted effects:-
Regular high dose can produces adrenal suppression in children .Other side effects are osteoporosis, susceptible to infection , palpitation of heart.

ANTI IgE DRUGS:-

Examples:-
Omalizumab.

Mecanism of action:-
Omalizumab is a recombinant humanized monoclonal antibody directed against IgE to inhibit the immune response to allergen exposure. This anti-IgE is directed against the binding site of IgE (Cepsilon3 domain) for the high-affinity receptor, and, as a result, prevents free-serum IgE from attaching to mast cells and other IgE receptor-expressing cells, preventing IgE-mediated responses.

Following allergen cross-linking of mast cell-bound IgE, these cells are activated and virtually immediately release a granule-associated substance, such as histamine. Within minutes, de novo synthesis of important lipid mediators (cysteinyl leukotrienes) is initiated from membrane phospholipids. Following a few hours, the activated mast cells are also capable of the transcription, translation, synthesis, and release of a large number of cytokines, including interleukin (IL)-4, IL-6, IL-9, IL-13, and tumor necrosis factor (TNF)-alpha.

Unwanted effects:-
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, tongue or throat); anxiety; cough; dizziness; fainting; fast or weak heartbeat; feeling unusually warm; flushing; hoarseness; new or worsening breathing problems, shortness of breath; numbness or tingling; symptoms of sinus or lung infection(congestion, cough, or fever); trouble swallowing; unusual lumps, growths, or moles; unusual swelling of the hands or feet; wheezing.