Beta blockers about

This is not the end of the story about beta blockers. Subsequent research demonstrated that there are two subclasses of beta receptors, termed beta-1 and beta-2. Both are activated by adrenaline. Both are blocked by propranolol. Beta-1 receptors are found mostly in heart muscle but not much in the lungs, whereas beta-2 receptors are found mostly in the lungs but not much in the heart. These facts provided the opportunity for better drugs. Here is the argument. 

Coadministration of beta-blockers can potentiate rebound hypertension upon discontinuation of medications, and it is therefore recommended that the beta-blocker be withdrawn before the tt2 agonist (Physicians Desk Reference, 2001). Tricyclic antidepressants may also produce changes in sinus node and AV conduction, and it is recommended that they be used cautiously in combination with tt2 agonists (Physicians Desk Reference, 2001). However, in child psychiatric practice, there has been debate about whether there are adverse interactions related to concomitant use of tricyclics and tt2 agonists. Finally, the tt2 agonists may potentiate the effects of CNS depressants (e.g., barbiturates) or other medications that produce sedation, so lower doses of each may be warranted. 

Although iodide is effective in treating hyperthyroidism for short periods, the effects of this drug begin to diminish after about 2 weeks of administration.35 Consequently, iodide is used in limited situations, such as temporary control of hyperthyroidism prior to thyroidectomy. In addition, iodide may cause a severe hypersensitive reaction in susceptible individuals. Therefore, the use of iodide has been replaced somewhat by other agents such as antithyroid drugs and beta blockers. 

In terms of ADMET, following oral administration about half of the atenolol dose is absorbed. Plasma-protein binding is minimal (3-5%). Peak plasma concentrations, as well as peak action, are reached in 2-4 h. Atenolol has low lipid solubility, and only small amounts cross the blood-brain barrier. Thus, atenolol s CNS side effects are less than with other beta-blockers [75]. Atenolol is excreted mainly by the kidneys, with little or no hepatic metabolism. It crosses the placenta, and concentrations in breast milk can be similar or even higher than those in maternal blood [76]. Atenolol is not recommended in asthma, even though its high beta-1 selectivity makes it safer in obstructive pulmonary disease than nonselective beta-blocking agents. Atenolol s important ADMET characteristics are listed in Tab. 8.2. 

BETA-BLOCKERS DIAZEPAM May occasionally cause t sedation during metoprolol and propranolol therapy Propranolol and metoprolol inhibit the metabolism of diazepam Warn patients about t sedation... 

A beta-blocker may be used in the treatment of primary open-angle glaucoma, but these drugs are contraindicated for use in persons with chronic obstructive pulmonary disease and heart block (see Chapter 10). A careful history should be taken before initiating therapy to avoid potentially fatal ramifications. It is advisable to monitor patients who are taking beta-blockers (e.g., pulse, blood pressure) and to inquire about side effects at periodic follow-up examinations. 

Conversely, the much-touted ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) study found that treating with beta blockers, diuretics, or both increased the risk of developing diabetes by about 40 percent and had some other side effects as well. 

Drugs that are metabolized by the cytochrome P-450 (CYP) isoenzymes CYP2D6, CYP2C9, and CYP2C19 also exhibit genetic polymorphisms. An example of CYP2D6 metabolism is debrisoquine. In about 5-10 /o of Caucasians in North America and Europe and about 1% of Asians, 4-hydroxylation of debrisoquine is reduced, and such individuals are at increased risk for toxicity (orthostatic hypotension). Beta blockers (metoprolol and timolol), antiarrhythmic drugs (encainide and flecainide), tricyclic antidepressants... 

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