Acebutolol - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Acebutolol is a beta blocker that is cardioselective and mainly treats hypertension and arrhythmias. It is a beta-adrenergic antagonist that can affect the bronchial receptors. It shows the reverse effect of epinephrine. It blocks beta-1 receptor activity and lowers blood pressure and heart rate. It is available in capsule form and comes in 200 and 400 mg dosages. It is commonly used, although it has warnings and precautions. It was approved by the Food and Drug Administration in March 1984.

Indications of Acebutolol:

• Hypertension: Acebutolol is indicated in cases of hypertension in adults. It can be used along with other antihypertensive drugs. It is mainly used in thiazide-type diuretics.

• Ventricular Arrhythmias: Acebutolol is used to manage cases of ventricular arrhythmias. The use of Acebutolol can decrease the number of premature beats and ventricular ectopic beats along with R and T beats.

Contraindication of Acebutolol:

• It is contraindicated in cases of persistent bradycardia.

• It is contraindicated in cases of second-degree and third-degree heart blockage.

• It is contraindicated in cases of cardiac failure.

• It is contraindicated in cases of cardiogenic shock.

Dosage:

• Dose Form: Capsules.

• Dose Strength: 200 mg and 400 mg.

Acebutolol is available as opaque purple and orange color-coated capsules.

Warning:

• Cardiac Failures: The patient who has decreased myocardial contractility and beta-adrenergic receptor blockade may have more failures. As beta blockers are avoided in cardiac failures, the use of Acebutolol is done cautiously in patients with heart failures and in patients who were under digitalis and diuretics. If in these cases, cardiac failure occurs, then Acebutolol should be stopped.

• Cardiac Failure History Patients: Patients who have valvular diseases of the heart can suffer depression of the myocardium with beta-blocking agents. If the signs of failure occur, then diuretics are started and if the cardiac failure persists then withdrawal of the Acebutolol is done.

• Exacerbation of Ischemic Heart Diseases After Withdrawal of Acebutolol: When there is the cessation of therapy, the blocking agents present in the coronary artery disease or angina pectoris patient can exacerbate the cases and causes myocardial infarction and death in the patients. So, these patients should cautiously use Acebutolol and should not stop the therapy without a doctor's recommendation.

• Peripheral Vascular Diseases: The use of beta blockers decreases cardiac output and increases the symptoms of arterial insufficiency leading to peripheral vascular diseases. So, cautious use of Acebutolol is done.

• Bronchospastic Diseases: The patient who is suffering from the bronchospastic disease should not have a beta-blocker. If required, then low levels are recommended with cautious use of Acebutolol is done.

• Anesthesia and Major Surgery: If the beta blockers are withdrawn before the surgery, then there is a chance of altered heart response to beta-adrenergic mediated reflex stimuli. And the risk of myocardial depression can occur after giving general anesthesia. Heartbeat maintenance can also be a challenging problem while anesthesia delivery. So, a low adjustment dose of Acebutolol is given to the patient but cautiously.

• Diabetes and Hypoglycemia: There are chances that patients can develop insulin-induced hypoglycemia. The use of Acebutolol can mask hypoglycemia and its symptoms like tachycardia, dizziness, and sweating.

• Thyrotoxicosis: A sudden withdrawal of Acebutolol can lead to the development of thyrotoxicosis. So, close supervision of the patient is required during the withdrawal period. As the usage of Acebutolol can mask hyperthyroidism and its symptoms.

Precautions:

• Risk of Developing Anaphylactic Reactions: The patient who is suffering from a severe anaphylactic reaction from the allergens can have a reactive response. Such patients can have no response from the doses of Epinephrine that are used to treat allergic reactions.

• Renal or Hepatic Impairments: The dose of Acebutolol is taken orally, and is eliminated by the kidneys. So, in cases of renal impairment patients, if the creatinine clearance levels are less than 50 mL/min then the dose of Acebutolol is reduced to 50 %, and if the creatinine clearance levels are less than 25 mL/ min then the dose is reduced to 75 %.

Special Considerations:

• Pregnancy: Studies regarding Acebutolol have been performed on pregnant women. It has depicted that Acebutolol can cross the placental barrier. And the babies who have been subjected to Acebutolol in the womb have low birth weight and decreased heart rate and blood pressure. The newborns have Acebutolol half-life elimination to be 6 to 12 hours.

• Labor and Delivery: There are no studies performed regarding the effects of Acebutolol during the labor and delivery period in humans, however, in animals studies have been performed and results have shown no effects.

• Nursing Mothers: The presence of Acebutolol in breast milk has been seen, so it is recommended not to use Acebutolol while breastfeeding the child.

• Pediatric Use: The use of Acebutolol in pediatric patients has not been determined, hence its safety and effectiveness are not known.

• Geriatric Use: The studies performed regarding Acebutolol have not been adequate to determine the safety and effectiveness of the drug in old age patients. Since older patients can show more bioavailability, low doses of Acebutolol are used in these patients.

For Patients:

Why Is Acebutolol Prescribed?

Acebutolol is a beta blocker medicine that is mainly used to treat high blood pressure and irregular heartbeats. It acts on the blood vessels and relaxes them while slowing the heart rate to enhance the blood flow and decrease the blood pressure.

What Is the Need to Treat High Blood Pressure?

Although high blood pressure is a commonly found condition. But if it is not treated, it can damage other organs of the body like the brain, blood vessels, and kidneys. And damage to these organs can further cause heart disease, making the patient more prone to heart attacks, heart failure, strokes, kidney failure, and other problems. So, it is important to control and treat high blood pressure levels. High blood pressure is also controlled by having a controlled diet with low fat and salt and maintaining an ideal body weight by exercising for 30 minutes a day, and avoiding smoking and alcohol.

How Is Acebutolol Used?

Acebutolol is available as a capsule that is taken by mouth. It is taken once or twice a day as prescribed by the doctor. The dose is taken every day around the same time. And it should be taken as much as prescribed by the doctor and not taken less or more. Although Acebutolol controls high blood pressure, it cannot cure the condition. So, the patient should not stop taking it while realizing that it has overcome the high blood pressure levels. If the patient abruptly stops the dose, the chances of developing more severe heart problems like angina can occur.

What Are the Precautions While Having Acebutolol?

Precautions include:

• If the patient is allergic to Acebutolol or its ingredients then inform the doctor about it.

• If the patient is having any other prescribed medications then also, the patient needs to inform about those medications.

• The patient should inform the doctor if the patient had any heart, kidney, or liver diseases so that the doctor could adjust the dose as such. Even conditions like asthma, diabetes, or hyperthyroidism need to be informed.

• The patient should inform the doctor about the pregnancy or if they are planning to be pregnant. Informing the doctor about breastfeeding is also important.

• As Acebutolol can cause drowsiness, the patient should avoid driving or any other works that require attention and concentration.

• Avoid the use of alcohol with Acebutolol as it can lead to a more drowsy effect.

What Are the Special Dietary Instructions That Are Required to Follow With Acebutolol?

The patient should continue taking the regular diet until the doctor recommends any supplementary diet.

What to Do if the Patient Forgets to Have a Regularly Scheduled Dose?

If the patient forgets the regularly scheduled dose, then take the dose soon after remembering it. If the time for the next dose is near then skip the missed dose and take the next scheduled dose, without doubling the dose at the same time.

What Are the Side Effects of Acebutolol?

Side effects are:

• Dizziness.

• Light headaches.

• Tiredness.

• Headache.

• Constipation.

• Diarrhea.

• Upset stomach.

• Muscle aches.

Few side effects need immediate medical attention. Some of these side effects are:

• Shortness of breath.

• Wheezing.

• Chest pain.

• Swelling of legs and feet.

How to Store and Dispose of Acebutolol?

The medicine is stored in tightly closed containers and kept away from the reach of children. These medicines are kept at room temperature and away from heat and moisture. The unused medicines are disposed of especially, instead of flushing them in the toilet or throwing them out anywhere. The medicine is disposed of through special take-back programs provided or can see the FDA (Food and Drug Administration) site to safely dispose of the medicine.

What If Overdose Occurs?

If the patient develops symptoms like troublesome breathing, seizures, or collapse, they require medical attention. In these conditions, the patient should visit the doctor immediately.

For Doctors:

Acebutolol is a hydrophilic beta-adrenergic receptor-blocking agent with an intrinsic sympathomimetic effect that is used to treat hypertensive patients and ventricular arrhythmic patients. It is available in capsule forms and taken orally. This capsule contains the main ingredient as hydrochloride salt and other inactive ingredients as gelatin, povidone, starch, stearic acid, and titanium dioxide. Acebutolol is a white to off-white powder form which is easily soluble in water but less soluble in alcohol. It has a chemical formula (±)N-[3-Acetyl-4-[2- hydroxy-3- [(1-methylethyl)amino] propoxy]phenyl] butanamide.

What Is the Dosage of Acebutolol?

• Hypertension: The starting dose of Acebutolol should be 400 mg for mild to moderate cases of hypertension. It is given as a single dose but if required the dose can be twice a day also to control 24 hours of blood pressure while having a dosage of 400 to 800 mg per day. Some patients with more severe hypertension levels can have a 1200 mg dosage.

• Ventricular Arrhythmias: When the patient suffers from ventricular arrhythmias he/she can have 400 mg initially twice daily given as 200 mg. But can gradually increase the dose up to 600 to 1200 mg per day. And if the treatment is not continued further then gradually decrease the dose in two weeks instead of abruptly withdrawing it.

• Older Patients: The older population has a two-fold increase in bioavailability with low maintenance doses. So, 800 mg dosage or above 800 mg is avoided in these patients.

Clinical Pharmacology:

Pharmacodynamics:

Acebutolol is a cardioselective, beta-androgenic blocking agent with mild intrinsic sympathomimetic activity. As beta blockers are used to reduce the work of the heart and allow it to beat in a regular form. So, here Acebutolol works as a less antagonistic effect on the peripheral system after epinephrine stimulation. Also, the low levels of Acebutolol had fewer effects of bronchoconstriction than Propranolol.

Mechanism of Action:

Acebutolol is a selective beta-1 receptor antagonist. When these activate the beta-1 receptors through epinephrine increase the heart rate and blood pressure and also consume more oxygen. When Acebutolol is used then it blocks the receptors, lowers the blood pressure and heart rate, and reverses the epinephrine effect. As beta blockers inhibit the release of renin hormone which usually constrict the blood vessels. Acebutolol is metabolized to diacetolol, which is its metabolite.

Pharmacokinetics:

• Absorption: It is easily absorbed by the gastrointestinal tract, and has an absolute bioavailability of nearly 40 percent of the original formulated drug. It has also been seen that it has a protein binding of 26 percent.

• Metabolism: It has been seen that it goes through the first pass of metabolism to get metabolized by the liver.

• Elimination: 30 to 40 percent of the Acebutolol is eliminated by the kidneys and 60 to 70 percent is excreted by the intestinal pathways. The half-life of Acebutolol is 3 to 4 hours and diacetolol is 8 to 12 hours.

What Are the Drug Interactions of Acebutolol?

• Drugs like Reserpine (catecholamine-depleting) were shown to have additive effects with beta-blockers. So, if the patient is given Acebutolol along with catecholamine-depleting drugs, then the patient can have symptoms like bradycardia or hypotension and even changes in blood pressure.

• If beta-adrenergic agents are given along with alpha-adrenergic stimulants then hypertensive responses are exaggerated.

• The use of Digitalis glycosides with beta blockers slows the atrioventricular conduction and decreases the heart rate as concomitant use of these can lead to bradycardia.

• There have been no significant changes noticed while interacting with the Digoxin, Hydrochlorothiazide, Hydralazine, Sulfinpyrazone, oral contraceptives, Tolbutamide, and Warfarin.

Nonclinical Toxicology:

• Carcinogenesis: The studies performed have presented no carcinogenic effects of Acebutolol when studies on animals and humans were done.

• Mutagenesis: The studies performed on the animals have shown no mutagenic potentials of Acebutolol.

• Impairment of Fertility: The studies on animals have been performed on two generations, which has depicted no impacts on the reproductivity or fertility of the animals.

Adverse Effects:

• Cardiovascular Effects: Hypotension, bradycardia, and heart failure.

• Central Nervous System: Anxiety and hypoesthesia.

• Dermatological Variation: Pruritis.

• Gastrointestinal Effect: Vomiting and abdominal pain.

• Genitourinary Effect: Dysuria and nocturia.

• Liver and Biliary System: Increase levels of SGOT (serum glutamic oxaloacetic transaminase), SGPT (serum glutamic pyruvate transaminase), and LDH (lactate dehydrogenase). increase in bilirubin and alkaline phosphatase, along with fever, malaise, dark urine, anorexia, nausea, and headache.

• Musculoskeletal Effect: Back pain and joint pain.

• Respiratory System: Pharyngitis and wheezing.

• Eyes: Conjunctivitis, the dry eye with eye pain.

• Autoimmune Effects: Systemic lupus erythematosus.

Potential Adverse Effects:

• Central Nervous System: Mental depression leading to catatonia (acute syndrome with disorientation for time and place), clouded sensorium, short-term memory loss, and emotional lability.

• Cardiovascular System: AV (atrioventricular) block gets intensified.

• Allergic Reactions: Rashes, fever accompanied by sore throat, laryngospasm, and respiratory distress.

• Hematologic Effects: Thrombocytopenic purpura and nonthrombocytopenic effects.

• Gastrointestinal Effects: Mesenteric arterial thrombosis and ischemic colitis.

• Miscellaneous Effects: Alopecia (reversible) and Peyronie’s disease.

Overdose:

Although there is no specific treatment for overdose, when symptoms like bradycardia, atrioventricular block, ventricular conduction defects, hypotension, severe congestive heart failure, seizures with bronchospasm, and hypoglycemia occur, emergency treatment is required. The following steps to overcome the overdose are:

• Empty the stomach of the patient by using emesis.

• Bradycardia is to be controlled by Atropine given intravenously.

• Vasopressors are administered like epinephrine or dopamine while monitoring the blood pressure and pulse rate.

• Bronchospasms are controlled by using Aminophylline and Terbutaline.

• Administer the patient with a diuretic to overcome the cardiac failures.

• In a few cases, glucagon is used, and if required dialysis should be done.