I did some reading about beta blockers again. It seems that everytime I do, I learn something new.
There are three generations of beta blockers. The drugs belonging to the 1st generation are used mostly for treating portal hypertension, arrhythmia and thyroid conditions.
The 2nd generation of beta blockers is used in people with CAD, arterial hypertension, arrhythmia and heart failure. The drugs in the 3rd generation of beta blockers have additional vasodilating effects and are used in treating arterial hypertension and heart failure. Nebivolol, the new drug we've been hearing about, is in this group of beta blockers. The third generation of beta blockers is said to have a reduced incidence of new onset of diabetes mellitus, and fewer or no metabolic side effects.
There are many differences between individual beta blockers and they should not be considered interchangable. Some of these differences include selectivity, lipid solubility, partial agonist activity, bioavailability, local anesthetic action, and the very important elimination half-life. The half-life ranges from 10 minutes (Esmolol) to 14-24 hours (Nadolol). My beta blocker, Bisoprolol, has a half life of 9-12 hours. Bioavailability, which is dose-dependent, ranges from 0 (Esmolol) to >90 with Penbutolol. Atenolols' bioavailability is 40, Propranolol 30, Bisoprolol 80, Labetalol 30 according to my drug book.
The low bioavailability of Propranolol and other drugs means that the oral administration leads to a much lower drug concentration than would be achieved with the same dose intravenously. Due to the differences between individual people, the plasma concentrations of the same dose of a drug vary. Some people are poor metabolizers and their plasma concentrations are very high after administration (up to ten times higher) than of those people who are good metabolizers. This is seen especially with metoprolol. I wonder what symptoms such person experiences with the plasma concentration ten times the normal. Severe side effects, maybe? I'll have to look into it further.(I am still looking for the reasons behind my severe breathing problems.) Most of the beta-receptor antagonists are absorbed well with peak concentration in 1-3 hours.
Lipid solulibility makes a difference also. The more lipid soluble beta blockers are taken up and metabolized rapidly by the liver (Metoprolol). The less lipid soluble ones (Nadolol) are not metabolized in the liver and are mostly excreted by the kidneys unchanged. The result is that plasma half-life and duration of action is much longer.
The reason beta blockers should not be used in people with asthma is that no agent is purely cardioselective, especially in large doses. The beta1 blockers antagonize mainly cardiac beta1 receptors in the heart BUT
the degree of beta2 blockade varies in other tissues. No tissue has just one group of receptors - all tissues have both
with one predominating - for instance beta1 in the heart, beta2 in bronchioles. Thus, during an asthma attack, even a minimal
degree of beta2 blockade from cardioselective beta1 Bisoprolol can cause big trouble. Pre-existing asthma and other forms of airway obstruction worsen with beta blocker use. Even a very mild asthma can become SEVERE after a beta receptor blockade. Beta blockers should not be used at all in people with reactive airways. If they are, it must be with great caution
. I am on a low dose of a beta blocker with 20% decrease in pulmonary function when tested last year. Probably should not be on it at all.
Good place to stop for now.