Albuterol versus Levalbuterol: What have we concluded?

Editors Tip:  If a doctor prescribes levalbuterol for a patient Q4,
it's highly recommended he not prescribe albuterol Q2prn
The is because albuterol has the S-Isomer, which would offset
any advantages of using levalbuterol (the R-Isomer).  

Albuterol (Ventolin,Proventil) is the best selling asthma drug of all time, and there isn't even a close second.  It was approved by the FDA in 1981, and it was quickly proven to be safe and effective in relieving bronchospasm.  Then levalbuterl was introduced to the market and it was initially proven to be safer and stronger than albuterol. After several years of using these two drugs side by side, is there any evidence that any one is better than the other?  Let us examine the evidence.

Albuterol is a beta adrenergic medicine, which means it was made to mimic the bronchodilating effect of adrenaline.  As of 1999, all beta adrenergic drugs were considered racemic drugs, containing a mixture of 50% R-Isomer and 50% S-Isomer.  Levalbuterol is 100% R-Isomer.  So, what are these Isomers?

1. R-Isomer:  This is the good isomer that causes bronchodilation.  I remember it because I think of r is for relief.  I call it the relief isomer.  They cause bronchodilation and clinical benefit.  They make people breathe better. Another name for the R-Isomer once it was isolated was levalbuterol. 
2. S-Isomer:  It is the bad isomer.  I remember it's bad because s is for shit.  I call it the shit isomer.  It has no clinical benefit. It may oppose the bronchodilation effect over time, and may also be pro inflammatory, thus exacerbating airway reactivity.  It is slowly metabolized by the body, and therefore it sticks around for a while, perhaps causing paradoxical bronchospasm long term, thus requiring the need for even more albuterol, and this becomes a vicious lifelong cycle.  

So a theory developed that the S-Isomer may lead to inert bronchospasm and worse asthma in those who use albuterol every day.

Another theory developed that occupational exposure to albuterol may cause asthma, as what occurs in the profession of respiratory therapy.  Of 2,086 Rhode Island respiratory therapists and 2,030 physical therapists, physicians diagnosed 16% of the respiratory therapists with asthma, and only 8% of the physical therapists with asthma.  Even when asthma is not diagnosed until after entry into the profession, 7.4% of RTs were diagnosed with asthma compared with 2.8 of PTs being diagnosed with asthma.

Of course their are other reasons an RT might be more likely to develop asthma other than occupational exposure (such as increase awareness of the disease among the RT community), so the study does not prove albuterol causes asthma, only that it could cause asthma. Yet other studies came up with similar findings. 

When the S-Isomer is taken out of albuterol you have levalbuterol (Xopenex).  I will delve into studies comparing albuterol and levalbuterol in a later post.  All of the problems of the S-Isomer are completely avoided with levalbuterol.  In other words, levalbuterol is a much stronger medicine than albuterol due to the absence of the S-Isomer.  

Studies have confirmed, however, that there is no clinical benefit to using levalbuterol over albuterol in the clinical setting.  While levalbuterol is considered stronger than albuterol, it is also more expensive.  Studies have shown that simply by giving greater amounts of albuterol generates the same effect as when lower doses of levalbuterol are given.  

Also, studies have confirmed that patients entering the emergency room with exacerbations of asthma or COPD are equally likely to be discharged or admitted regardless of whether albuterol or levalbuterol is used.

Likewise, since both albuterol and levalbuterol are beta adrenergic medicine, and both attracted to B2 agonists throughout the body, side effects (such as tachycardia, and tremors) are the same (albeit negligible) regardless of which of these two medicines is used.  This conclusion is contrary to earlier studies.

So, based on the evidence, the less expensive albuterol should be used on most patients admitted to the hospital.  Only when there is no perceived benefit from albuterol should levalbuterol be trialed.  

References:

1. Handley, D., "The asthma-like pharmacology and toxicology of (S)-isomers of beta agonists," Journal of Allergy and Clinical Immunology, August, 1999, 104(2) pages 69-76.
2. Borkowski Jaime, Marsha Crader, "Nebulized albuterol versus levalbuterol in pediatric and adult patients: A review," Formulary Journal of Modern Medicine, April 1, 2009, http://formularyjournal.modernmedicine.com/formulary-journal/news/clinical/clinical-pharmacology/nebulized-albuterol-versus-levalbuterol-pediat, accessed 1/28/2014
3. Christiani, David C., David G. Kern, "Asthma risk and occupation as a respiratory therapist," September, 1993, 148 (3), pages 671-674

How long does a medicine stay in your system?

Your question:   How long does a medicine last?  How long does it stay in the patient's system?

My humble answer:  I don't want to pretend to be a pharmacologist, yet there is some basic pharmacology that can be understood by your basic layman.

Enzymes in the liver or other organs break down the medicine, and it is excreted by the kidneys by urine.

When referring to how long a medicine stays in the system is usually referred to as half life, or how long it takes for the human body to break a medicine into half it's original strength or level.  How long this takes depends on three things:

1. Chemical composition of the medicine
2. The physical condition of the patient (the chemical composition the medicine is put into)
3. The patient's condition (age, kidney function).

For instance, Albuterol is chemically composed in such a way that the medicine will stay in a person's system for up to 4-6 hours.  Advair is chemically composed in such a way the medicine stays in the system for up to 12 hours.

Some medicines may stay in a person's system longer if that person has decreased kidney function due to disease or aging.  If a patient has diseased kidney's a doctor might consider a smaller dose because the kidney's won't be able to break up the medicine as rapidly as most patients.

This also explains drug potency and efficacy.  The potency  and efficacy of a medicine is also determined by the above factors. Ideally you will want to use the least dose of a medicine to achieve the desired effect with the least side effects.

Reference:  Egan:  Fundamentals of Respiratory Care

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