The P-I-E-N-O Parkinsn's List Drug Database
atenolol /TenorminTM
ANTIHYPERTENSIVE:,
Cardioselective beta blockers
Description: Atenolol is a competitive, œA-selective adrenergic antagonist, similar to metoprolol. Atenolol has a longer plasma half-life than does metoprolol, which may allow for less frequent dosing. As with all "selective" œ-blockers, high doses result in attenuated or lost selectivity for the œA-receptor. Unlike pindolol, atenolol does not have intrinsic sympathomimetic properties. Atenolol also does not possess membrane-stabilizing activity as pindolol and propranolol do. In addition, atenolol has the lowest lipid solubility within the class, which affects its route of elimination and, theoretically, its potential for causing CNS side effects. Atenolol was approved by the FDA in 1981.
Mechanism of Action: œ-adrenergic antagonists counter the effect of sympathomimetic neurotransmitters (i.e., catecholamines) by competing for receptor sites. Similar to metoprolol, atenolol, in low doses, selectively blocks sympathetic stimulation mediated by œA-adrenergic receptors in the heart and vascular smooth muscle. The pharmacodynamic consequences of this activity include: reduction of resting heart rate and, subsequently, cardiac output; reduction of both systolic and diastolic blood pressure at rest and with exercise; and possible reduction of reflex orthostatic hypotension. With higher doses (>100 mg/day), atenolol also competitively blocks œA-adrenergic responses in the bronchial and vascular smooth muscles. In addition, serum free fatty acid concentrations are decreased and triglyceride levels increased by atenolol.
A critical effect of œ blockade is to provide prophylaxis and reduction in myocardial ischemia and potentially prevent the severity of subsequent myocardial infarction. Part of this effect also may be attributed to the antiarrhythmic properties of œ blockade at the nodal level of pacemaker control.
Actions that make atenolol useful in treating hypertension include: a negative chronotropic effect that decreases heart rate at rest and after exercise; a negative inotropic effect that decreases cardiac output; reduction of sympathetic outflow from the CNS; and suppression of renin release from the kidneys. Thus, atenolol, like other œ-blockers, affects blood pressure via multiple mechanisms. Atenolol is used to treat angina because the drug decreases the oxygen demand of the heart, both by decreasing heart rate and contractility and by lowering blood pressure. However, in patients with cardiac failure, the opposite may be true (i.e., the drug can increase the oxygen demand of the heart.)
Atenolol possesses numerous mechanisms that may contribute to its efficacy in preventing migraine headaches. œ-blockade can prevent arterial dilation, inhibit renin secretion, and block catecholamine-induced lipolysis. Blocking lipolysis, decreases arachidonic acid synthesis and subsequent prostaglandin production. Inhibition of platelet aggregation is due to this decrease in prostaglandins and blockade of catecholamine-induced platelet adhesion. Other actions include increased oxygen delivery to tissues and prevention of coagulation during epinephrine release.
Pharmacokinetics: After oral administration of atenolol, about 50- 60% of the dose is rapidly absorbed. The onset of heart rate reduction occurs in about 1 hour, with the peak effect achieved within 2-4 hours. The duration of action is roughly 24 hours. After parenteral administration, the peak effect is seen in 5 minutes and lasts less than 12 hours. Effects on blood pressure do not coincide with effects on heart rate, nor does the antihypertensive effect exhibit a linear dose/pharmacodynamic response. Atenolol is distributed throughout the body and into breast milk. It also crosses the placenta, with fetal serum atenolol concentrations approaching those of the mother. Unlike propranolol, atenolol distribution into the CNS by crossing the blood-brain barrier is minimal. Atenolol is minimally bound to plasma proteins, averaging only 10%, which, along with it low lipophilicity, may explain some of its distribution characteristics.
The serum half-life of atenolol in patients with normal renal function is 6-7 hours in adults and about 4.6 hours in children. Half-life increases progressively as renal function worsens, and, although dosing should be conservative in patients with renal failure, atenolol has been given safely to these patients. Minimal, if any, metabolism occurs in the liver, and 40-50% of an oral dose is excreted renally as unchanged drug. The rest of the dose is excreted via the fecal route as unchanged drug. It is important to note that atenolol is removed by hemodialysis, so supplemental doses may be required following this procedure.
CONTRAINDICATIONS/PRECAUTIONS: Abrupt discontinuation of any œ-adrenergic blocking agent, including atenolol, particularly in patients with preexisting cardiac disease, can cause myocardial ischemia, infarction, ventricular arrhythmias, or severe hypertension.
Atenolol should be used with caution in patients with hyperthyroidism or thyrotoxicosis because the drug can mask the tachycardia that occurs in this condition. Abrupt withdrawal of atenolol in a patient with hyperthyroidism can precipitate a thyroid storm. Note that œ-blockers are, in general, useful in treating hyperthyroid-related states. Because these drugs depress conduction through the AV node, œ- blockers are contraindicated in patients with severe bradycardia or advanced AV block. In general, œ-blockers should not be used in patients with cardiogenic shock or systolic congestive heart failure, particularly in those with severely compromised left ventricular dysfunction, because the negative inotropic effect of these drugs can further depress cardiac output. In some patients with heart failure, however, œ-blockers given in low doses have been beneficial. Many œ-blockers are used in the treatment of hypertrophic cardiomyopathy. œ-blocker monotherapy should be used with caution in patients with a pheochromocytoma or vasospastic angina (Prinzmetal's angina) because of the risk of hypertension secondary to unopposed ›-receptor stimulation. In the treatment of myocardial infarction, œ-blockers are contraindicated in patients with hypotension (SBP < 100 mmHg).
Atenolol should be used with caution in patients with diabetes mellitus because the drug can mask symptoms of hypoglycemia such as tachycardia, palpitations, blood pressure changes, tremor, and anxiety. However, atenolol usually does not mask some other symptoms of hypoglycemia (sweating and dizziness), nor does it, in usual doses, cause insulin-induced hypoglycemia. In addition, œ-blockers can precipitate hyperglycemia via inhibition of glycogenolysis. While œ-blockers probably should not be used in patients with brittle diabetes, they may be used cautiously in more stable patients.
Although œA-adrenergic selective œ-blockers such as atenolol are preferred over nonselective agents for use in patients with asthma or pulmonary conditions in which bronchospasm would put them at risk (e.g., COPD, emphysema, bronchitis), all œ-blockers should nevertheless be used with caution in these patients, particularly with high-dose therapy.
Patients receiving atenolol before or during surgery involving the use of general anesthetics with negative inotropic effects (e.g., ether, cyclopropane, or trichlorethylene) should be monitored closely for signs of heart failure. Severe, protracted hypotension and difficulty in restarting the heart have been reported after surgery on patients receiving œ-blockers. If discontinuation of the drug is indicated, therapy should be stopped 2 days prior to surgery.
Reduced doses of atenolol should be used in patients with renal impairment because of reduced excretion of the drug.
Atenolol is classified as a pregnancy category D drug by the FDA, and appropriate consideration of risks/benefits of use during pregnancy is necessary. In addition, the manufacturers do not recommend the use of atenolol while breast-feeding because of the potential risk of hypotension and bradycardia in the nursing infant.
Atenolol is relatively contraindicated in patients with Raynaud's disease or peripheral vascular disease because reduced cardiac output and the relative increase in › stimulation can exacerbate symptoms.
The actual relationship between depression and œ-blockers has not been definitively established. œ-blockers should be used with caution in patients with major depression. Although much less common in hydrophillic drugs, CNS depression can occur, resulting in mental depression, fatigue, and, in some cases, vivid dreams.
œ-blockers may exacerbate conditions such as psoriasis.
œ-blockers may potentiate muscle weakness and double vision in patients with myasthenia gravis.
œ-blockers can be used safely in elderly patients, however these patients may have unpredictable responses to œ-blockers. They may be less sensitive to the antihypertensive effects of the drug, however, reduced excretion may increase the potency of œ- blockers in this population. The elderly have age-related peripheral vascular disease and the relative increase in › stimulation can exacerbate symptoms. Geriatric patients are at increased risk of œ-blocker-induced hypothermia.
DRUG INTERACTIONS:
The antihypertensive effects of atenolol are additive with other antihypertensive agents. This effect is often used advantageously in treating hypertension; however, lower doses of one or more agents may be necessary. In general, atenolol can be administered safely with most other antihypertensives.
While additive effects are possible with all other antiarrhythmics, particular attention should be given to using atenolol in combination with diltiazem, verapamil, or other antiarrhythmic agents (e.g., amiodarone) that possess significant effects on AV nodal conduction. When used with atenolol or other œ-blockers, these agents can cause complete AV block.
œ-blockers exert complex actions on the body's ability to regulate blood glucose. Because of this, œ-blockers may cause a pharmacodynamic interaction with antidiabetic agents. œ-blockers can prolong hypoglycemia by interfering with glycogenolysis (secondary to blocking the compensatory actions of epinephrine) or can promote hyperglycemia (by inhibiting insulin secretion and decreasing tissue sensitivity to insulin). Also, œ-blockers can blunt the tachycardic response to and exaggerate the hypertensive response to hypoglycemia. Although no pharmacokinetic interaction has been observed between œ-blockers and antidiabetic agents, patients receiving œ-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response. Selective œ-blockers, such as acebutolol, atenolol, or metoprolol, can cause fewer problems with blood glucose regulation, although these agents can still mask the symptoms of hypoglycemia.
Care must be taken when abruptly stopping clonidine in favor of using atenolol or another œ-blocker because administration of œ- blockers during withdrawal of clonidine can precipitate severe rises in blood pressure as a result of unopposed › effects. It is possible, however, to gradually discontinue clonidine and add atenolol without sequelae.
Concurrent use of œ-blocking agents with sympathomimetics can result in mutual antagonism of either agent's desired therapeutic effects (œA- and/or œA- agonism or antagonism) and/or may result in unopposed › pharmacodynamic effects.
It may be wise to avoid using atenolol with reserpine or other rauwolfia alkaloids that have a high incidence of orthostatic hypotension, since œ-blockers will interfere with reflex tachycardia, thus worsening the orthostasis.
Although œ-blocking agents are used to treat or reduce the signs and symptoms of cocaine intoxication, and the subsequent cardiovascular manifestations of abuse of the drug, care must be exercised that unopposed › activity does not result, which can cause profound hypertension, bradycardia, or heart block.
Despite its selectivity for œA-receptors, atenolol should be expected to counteract the adrenergic agonists-even the ›- and œA-agonists-to some degree.
Note that atenolol can be used safely with aspirin, heparin, warfarin, and thrombolytic agents.
ADVERSE REACTIONS: Most adverse reactions to atenolol are manifestations of its therapeutic effect. Sinus bradycardia (3%) and hypotension are rarely serious and can be reversed with IV atropine, if necessary. AV block, secondary to depressed conduction at the AV node, may necessitate sympathomimetic and/or pressor therapy or use of a temporary pacemaker.
Congestive heart failure is more likely to occur in patients with preexisting left ventricular dysfunction and usually will respond to discontinuation of atenolol therapy.
Adverse CNS effects include dizziness (4-13%), fatigue (3-6%), and depression (0.6-12%).
Diarrhea and nausea/vomiting are the most common GI adverse effects (2-4%).
Wheezing and dyspnea are more likely to occur if the dose of atenolol is >100 mg/day, since the beta selectivity of the drug is lost. Patients with preexisting bronchospastic disease are at greater risk.
Both hypoglycemia and hyperglycemia can occur during atenolol therapy. Atenolol can interfere with glycogenolysis to cause hyperglycemia and also can mask signs of hypoglycemia. Atenolol should be used cautiously in brittle diabetics.
Rare but severe hematologic side effects, such as agranulocytosis, have been reported with atenolol therapy.
œ-blockers have been shown to cause hypertriglyceridemia and decrease plasma HDLs during therapy. A recent meta-analysis suggested that these effects are less pronounced with cardioselective agents, such as atenolol, particularly in diabetics. The clinical implications of these effects, in light of other cardiovascular advantages of œ-blocker therapy is not known.D Sexual dysfunction, specifically impotence, is less frequent adverse effects of beta-blocker therapy (<2%) than is generally perceived.
Dermatologic reactions with œ-blockers are usually mild and transient. Some of these reactions include pruritus, skin hyperpigmentation, reversible alopecia, xerosis, and exfoliative dermatitis.
PATIENT INFORMATION:
What do atenolol tablets do?
Atenolol (TenorminTM ) belongs to a group of medicines called beta- blockers. Beta-blockers reduce the workload on the heart and help it to beat more regularly. Atenolol controls, but does not cure, high blood pressure (hypertension). Atenolol also relieves chest pain (angina), and can be helpful after a heart attack. Generic atenolol tablets are available.
What should my doctor, dentist, or pharmacist know before I take atenolol?
They need to know if you have any of these conditions:
How should I take this medicine?
Take atenolol tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children.
Elderly patients may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses. There should be at least 8 hours between doses.
What other medicines can interact with atenolol?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking atenolol?
Serious side effects with atenolol include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with atenolol include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take atenolol?
Check your heart rate and blood pressure regularly while you are taking atenolol. Ask your doctor what your heart rate and blood pressure should be, and when you should contact him or her.
Do not stop taking this medicine suddenly. This could lead to serious heart-related side effects.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how atenolol affects you. To reduce the risk of dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can make you more drowsy, and increase flushing and rapid heartbeats. Avoid alcoholic drinks.
Atenolol can affect blood sugar levels. If you are diabetic check with your doctor before you change your diet or the dose of your diabetic medicine.
If you are going to have surgery, tell your doctor or dentist that you are taking atenolol.
Where can I keep my medicine? Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Protect from light. Throw away any unused medicine after the expiration date.
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