Atenolol dosing

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. 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

After po doses, atenolol is rapidly but incompletely absorbed ( 50%) from the GI tract, and 50% is excreted unchanged in the feces. Six to 16% of the plasma concentration is bound to protein. Atenolol undergoes Httie first-pass metaboHsm. Peak plasma concentrations occur in 2—4 h after po doses. The elimination half-hfe of atenolol is 6—7 h. Excretion of absorbed dmg is mainly by the kidneys and elimination can be impaired in patients having renal failure. The adverse effects of atenolol are similar to those seen for propranolol therapy (98,99,108). 

Van Den Heuvel, C. J., Reid, K. J. Dawson, D. (1997). Effect of atenolol on nocturnal sleep and temperature in young men reversal by pharmacological doses of melatonin. Physiol. Behav. 61, 795-802. 

Atenolol 5 mg IV dose, followed 5 minutes later by a second 5-mg IV dose then 50 to 100 mg orally every day beginning 1 to 2 hours after the IV dose. The initial IV therapy may be omitted. 

Atenolol, betaxolol, bisoprolol, and metoprolol are cardioselective at low doses and bind more avidly to /Ij-receptors than to /J2-receptors. As a result, they are less likely to provoke bronchospasm and vasoconstriction and may be safer than nonselective /1-blockers in patients with asthma, chronic obstructive pulmonary disease, diabetes, and PAD. Cardioselectiv-ity is a dose-dependent phenomenon, and the effect is lost at higher doses. 

Blockers blunt the peripheral autonomic symptoms of arousal (e.g., rapid heart rate, sweating, blushing, and tremor) and are often used to decrease anxiety in performance-related situations. For specific SAD, 10 to 80 mg of propranolol or 25 to 100 mg of atenolol can be taken 1 hour before the performance. A test dose should be taken at home on a day before the performance to be sure adverse effects will not be problematic. 

If the patient has missed one or several doses there might be a need to overcompensate for the missing doses and to restore steady-state levels fast, but general rules are hard to give. Nowadays, this information is often available in the package leaflet for each medication. The information is also available on EMEA home page (EMEA 2008). Fore many medications there is no recommendation. For some medications like simvastatin, citalopram and atenolol the advice is not to compensate for missing doses. 

Q60 When a patient who is receiving atenolol is started on terazosin, there is an increased risk of first-dose hypotension. Terazosin is an alpha-adrenoceptor agonist which causes vasodilatation. 

Propranolol is considerably more potent (albeit less selective) than atenolol. Thus despite a much higher clearance than atenolol, both agents have a daily clinical dose size of around 25-100 mg. 

In turn, a- and )3-adrenoblockers are subdivided into selective and nonselective groups. Nonselective 8-adrenoblockers exhibit affinity for both and Sj-adrenoreceptors. Included in this category are propranolol, nadolol, timolol, and labetalol (a combined a- and )3-adrenoblocker). Selective jS -blockers are acebutol, atenolol, esmolol, and meto-prolol, which in therapeutic doses predominantly binds to jS -adrenoreceptor regions. 

Compounds that exhibit roughly the same affinity to and j32 rsceptors independent of dosage such as nadolol, propranolol, pindolol, timolol, and labetalol (combined a- and j3-adrenoblocker) are classified as nonselective blockers. Drugs which in therapeutic doses have higher affinity to -receptors than to j32-receptors such as acebutol, atenolol, metoprolol, and esmolol, are called selective or cardioselective j3-adrenoblockers. 

Because of their relative - selectivity, low doses of metoprolol, acebutolol, bisoprolol, and atenolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Bradycardia Metoprolol produces a decrease in sinus heart rate in most patients this decrease is greatest among patients with high initial heart rates and least among patients with low initial heart rates. 

Concomitant use of calcium channel blockers (atenolol) Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta-blockers are administered with verapamil or diltiazem. Patients with preexisting conduction abnormalities or left ventricular dysfunction are particularly susceptible. Recent acute Ml (sotalol) Sotalol can be used safely and effectively in the long-term treatment of life-threatening ventricular arrhythmias following an Ml. However, experience in the use of sotalol to treat cardiac arrhythmias in the early phase of recovery from acute Ml is limited and at least at high initial doses is not reassuring. 

Calcium Acetate (PhosLo) [Calcium Supplement/ Anti arrhythmic/Mmeral/ Electrolyte] Uses ESRD-associated hyper-phos-phatemia Action Ca " supl w/o aluminum to X P04 absorption Dose 2-4 tabs PO w/ meals Caution [C, ] Contra t Ca Disp Gelcap SE Can t Ca, hypophosphatemia, constipation Interactions t Effects OF quinidine X effects W/ large intake of dietary fiber, spinach, rhubarb X effects OF atenolol, CCB, etidronate, tetracyclines, fluoroquinolones, phenytoin, Fe salts, thyroid hormones EMS Pts have reduced renal Fxn, monitor ECG for signs of electrolyte disturbances OD S/Sxs of hypercalcemia (confusion, weakness, GI upset, constipation, N, V, and cardiac arrhythmias) give IV fluid for diuresis symptomatic and supportive Calcium Carbonate (TumS/ Alka Mints) [Antacid/ Calcium Supplement/Mineral/ Electrolyte] [OTC] Uses Hyperacidity associated w/ peptic ulcer Dz, hiatal hernia, etc Action Neutralizes gastric acid Dose 500 mg—2 g PO PRN -1- in renal impair Caution [C, ] Disp Chew tabs, susp SE t -1- PO constipation Interactions X Effect OF tetracyclines, fluo-... 

Roughly half of an orally administered dose of atenolol (Tenormin) is absorbed. The drug is eliminated primarily by the kidney and unlike propranolol, undergoes little hepatic metabolism. Its plasma half-life is approximately 6 hours, although if it is administered to a patient with impaired renal function, its half-life can be considerably prolonged. 

Gorman et al. [1985] first reported the use of atenolol in an open trial of 10 patients with social phobia. Using doses ranging from 50 to 100 mg/day, the drug demonstrated good efficacy. Using patient rated questionnaires, 50% reported a marked reduction in symptoms, 40% endorsed a moderate... 

S. M. Turner et al. (1994) compared the uses of atenolol, flooding, and placebo in social phobia. Atenolol was used with a dose range of 25-100 mg/day. In this study, atenolol was shown to be the least effective treatment in terms of symptomatic improvement. Only 27% of atenolol-treated subjects displayed improvement, but the flooding and placebo groups, respectively, demonstrated 89% and 44% response rates. Weaknesses of this study included a high rate of comorbid disorders and dramatic placebo response rates. Additionally, the difference between response rates of the subtypes of social phobia was not addressed. 

Liebowitz et al. [1992] conducted a double-blind, placebo-controlled study of 74 subjects meeting DSM-lll-R (American Psychiatric Association 1987] criteria for social phobia with phenelzine, atenolol, or placebo for 8 weeks. Phenelzine daily doses were 60-100 mg. Phenelzine was found to be superior to both atenolol and placebo, and atenolol was not significantly different from placebo in measures of responsiveness of social phobia symptoms. 

Propranolol reduces the frequency and intensity of migraine headache. Other 13-receptor antagonists with preventive efficacy include metoprolol and probably also atenolol, timolol, and nadolol. The mechanism is not known. Since sympathetic activity may enhance skeletal muscle tremor, it is not surprising that 13 antagonists have been found to reduce certain tremors (see Chapter 28). The somatic manifestations of anxiety may respond dramatically to low doses of propranolol, particularly when taken prophylactically. For example, benefit has been found in musicians with performance anxiety ("stage fright"). Propranolol may contribute to the symptomatic treatment of alcohol withdrawal in some patients. 

Atenolol is not extensively metabolized and is excreted primarily in the urine with a half-life of 6 hours it is usually dosed once daily. Recent studies have found atenolol less effective than metoprolol in preventing the complications of hypertension. A possible reason for this difference is that once-daily dosing does not maintain adequate blood levels of atenolol. The usual dosage is 50-100 mg/d. Patients with reduced renal function should receive lower doses. 

Tremor is one of the most common adverse effects of lithium treatment, and it occurs with therapeutic doses. Propranolol and atenolol, which have been reported to be effective in essential tremor, also alleviate lithium-induced tremor. Other reported neurologic abnormalities include choreoathetosis, motor hyperactivity, ataxia, dysarthria, and aphasia. Psychiatric disturbances at toxic concentrations are generally marked by mental confusion and... 

Beta blockers without intrinsic sympathomimetic activity (eg, metoprolol, propranolol, atenolol) are effective therapeutic adjuncts in the management of thyrotoxicosis since many of these symptoms mimic those associated with sympathetic stimulation. Propranolol has been the 3 blocker most widely studied and used in the therapy of thyrotoxicosis. Beta blockers cause clinical improvement of hyperthyroid symptoms but do not typically alter thyroid hormone levels. Propranolol at doses greater than 160 mg/d may also reduce T3 levels approximately 20% by inhibiting the peripheral conversion of T4 to T3. 

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