Because the early phase of asthma essentially involves mast cell degranulation and the immediate, direct effects of their released contents... anything that can inhibit these will be beneficial.

Sympathomimmetics will inhibit mast cell degranulation by binding B2 receptors.  They will also promote bronchodilation! (double whammy)

Antimuscarinics will reduce the parasympathetic bronchoconstrictive effect.

Chromones (chromolyn sodium) inhibit mast cell degranulation, and also inhibit axon reflexes in airway nerves.

Glucocorticoids are anti-inflammatory

The late phase involves the infiltration of the airway by inflammatory cells (largely eosinophils!)

Remember, you can inhibit leukocyte migration with glucocorticoids.  These also inhibit IgE induced mast cell degranulation. 
Chromolyn sodium can again be used

Anything that inhibits leukotrienes (zileuton)

Anything that inhibits IgE binding to mast cells (Omalizumab... but recall: glucocorticoids too)

Theophylline and Aminophylline are members of the methylxanthine class of drugs.  These drugs act by inhibiting phosphodiesterases (III and IV), thereby prolonging the life of cAMP and cGMP.  Remember that cAMP is increased by beta-agonists, so the downstream effects of these drugs is similar...

Another important property of methylxanthines is their ability to block the adenosine receptors! (aka: purinergic receptor)

Methylxanthines promote bronchodilation by increaseing cAMP levels.  (they are phosphodiesterase inhibitors)

Therefore, as with sympathomimmetics, methylxanthines are effective in the early phase of an asthmatic attack.

Adenosine can bind to A1 or A2 receptors.  A1 receptors inhibit adenylyl cyclase.  (the 1 in A1 looks like I in Inhibit) A2 receptors are mainly found in the blood vessels and result in the stimulation of adenylyl cyclase, causing vasodilation.

In the heart, adenosine binds A1 receptors.  (so in our one heart there are mainly A1 and B1 receptors).  This decreases cAMP, causing a decrease in HR and contractility

In the bronchioles, we have A1 receptors, so adenosine causes bronchoconstriction.

In the stomach, we have A1 receptors, which inhibit histamine-induced gastric acid secretion.

In the kidneys, A1 receptors decrease GFR by causing constriction of the afferent arteriole.  They also enhance Na+ reabsorption in the proximal tubule.

This explains why theophylline/aminophylline, which inhibit adenosine receptors, cause increased HR, bronchodilation, increases gastric acid, and increased GFR.

Children are strangely able to metabolize methylxanthines much faster than adults.

In fact, the half life of methylxanthine in adults is twice that found in children.

Methylxanthine toxicity stimulates the Na+/K+ ATPase and increases catecholamine release.  Both of these actions promote the uptake of K+ into cells, resulting in HYPOkalemia.

severe rhabdomyolysis can occur if K+ levels fall below 2mEq/L

Methylxanthines increase the responsiveness of the respiratory center to CO2 levels. 

They also improve skeletal muscle contractility, cortical arousal, and learning capacity.

Relaxation of the bronchial smooth muscle by beta-2 agonists is as follows:

Beta-2 activation stimulates Gs protein.  This activates adenylyl cyclase, which produces more cAMP.  cAMP activates protein kinase A (PKA), which then phosphorylates MLCK, inactivating it.  Inactivated myosin light chain kinase can no longer phosphorylate the myosin light chain, which therefore decreases contraction.  Additionally, PKA promotes the calcium efflux channels in the smooth muscle cells.

Short acting = Albuterol

Long acting = Salmeterol

(salmon migrate a long way?)

Albuterol is used acutely, whereas salmeterol is used chronically.

Tremors

Palpitations (from B2 receptors in heart AND reflex effects from B2 mediated vasodilation in skeletal muscle beds)

Hypoxemia! because it can throw the V/Q ration out of whack.

Hyperglycemia and Hypokalemia. 
B2 receptors increase K+ uptake into skeletal muscle.  Reason why you give B2 agonist and insulin in cases of hyperkalemia... both increase K+ uptake into cells.

Ach activates M3 receptors in the lungs.  These receptors stimulate Gq protein, which activates phospholipase C (PLC).  PLC increases the synthesis of IP3/DAG.  IP3 diffuses into the cytosol and increases cytosolic calcium.  This increases the Ca++/calmodulin complex and leads to MLC phosphorylation and smooth muscle contraction.  DAG remains on the plasma membrane and activates PKC, which also promotes MLCK function and smooth muscle contraction.

(draw it out)

In asthmatics, the bronchodilation produced by B2 agonists is greater.  In COPD patients, antimuscarinics often produce a more intense bronchodilation than the B2 agonists!

anitmuscarinics would be ipratropium(M1, M2, M3)

and tiotropium (M3 only)

Chromones block mast cell degranulation and axon reflexes in the airways.    This prevents bronchospasm, cough, and bronchial hyperreactivity. 

The main use of chromolyn sodium is in prophylaxis... aka prevention of an asthmatic attack.  It should be given shortly before exercise or before an unavoidable exposure to an allergen.

Chromolyn sodium is useful in the prevention of asthmatic attacks.  Use it before exercise or exposure to a known allergen. 

Because the chromones are not bronchodilators, they cannot be used in the treatment of an acute asthmatic episode.

Chromones can also be given in patients with allergic rhinitis and conjunctivitis.

*glucocorticoids by inhalatory route are superior to the chromone derivatives...

Glucocorticoids inhibit the motility of leukocytes to the peripheral tissues by inhibiting interleukins, collegenase, and elastase production.

They also block prostaglandin and leukotriene synthesis by inhibiting phospholipase A2.

Zafirlukast and montelukast block LTD4 and LTE4 receptors.  They prevent the inflammatory promotion of leukotrienes, but their onset of action is slow... (so not used in acute asthma)

Zafirlukast inhibits CYP450

(montelukast does not)

The mab ending tells you this drug is a monoclonal antibody.  It is injected parenterally and binds to IgE receptors, preventing the degranulation process of mast cells and basophils.

It is used in the prophylactic treatment of asthma

Zileuton inhibits 5-lipoxygenase, thereby blocking leukotriene synthesis

The end effect is anti-inflammatory and inhibitory to leukotriene-induced bronchoconstriction.

Some leukotrienes (LTB4) are chemotactic for inflammatory cells, some directly stimulate bronchoconstriction

I am Zileuton, the inhibitor of 5-lipoxygenase.

give me for chronic asthma control and to block bronchoconstriction in cases of aspirin hypersensitivity!

First try beta-2 agonists (albuterol)

If this should not give desired results, admit to the hostpital, administer O2 and glucocorticoids.  If this still does not help, try the methylxanthines and antimuscarinics.

Finally, when all else fails, you must intubate the patient

The antitussives are codeine and dextromethorphan.  They are both opioids and decrease the sensitivity of the cough center to incoming stimuli. 

Codeine has all of the adverse effects of opioids, while dextromethorphan is special in that it is highly selective and, at therapeutic doses, only affects the cough center!

Acetylcysteine is a mucolytic that helps clear the secretions of the lungs in bronchitis, COPD, Cystic Fibrosis. 

Recall: acetylcysteine is also the antidote used in acetaminophen poisoning!

Acetylcysteine and dornase alpha.

Dornase alpha is a deoxyribonuclease that hydrolyzes extracellular DNA in the airway secretions, reducing the viscosity of the secretions.