Antolol
Antolol Uses, Dosage, Side Effects, Food Interaction and all others data.
The synthesis of atenolol resulted from attempts to produce a β-adrenoceptor antagonist that would competitively block β1 (cardiac) receptors but have no effect on β2-receptors. It is classified as a β1 selective (cardioselective) β-adrenergic receptor antagonist with no membranestability activity and no partial agonist activity. It is markedly the most hydrophilic of the currently available β- blockers and thus penetrates the lipid of cell membranes poorly
Antolol is a cardio-selective beta-blocker and as such exerts most of its effects on the heart. It acts as an antagonist to sympathetic innervation and prevents increases in heart rate, electrical conductivity, and contractility in the heart due to increased release of norepinephrine from the peripheral nervous system. Together the decreases in contractility and rate produce a reduction in cardiac output resulting in a compensatory increase in peripheral vascular resistance in the short-term. This response later declines to baseline with long-term use of atenolol. More importantly, this reduction in the work demanded of the myocardium also reduces oxygen demand which provides therapeutic benefit by reducing the mismatch of oxygen supply and demand in settings where coronary blood flow is limited, such as in coronary atherosclerosis. Reducing oxygen demand, particularly due to exercise, can reduce the frequency of angina pectoris symptoms and potentially improve survival of the remaining myocardium after myocardial infarction. The decrease in rate of sinoatrial node potentials, electrical conduction, slowing of potentials traveling through the atrioventricular node, and reduced frequency of ectopic potentials due to blockade of adrenergic beta receptors has led to benefit in arrhythmic conditions such as atrial fibrillation by controlling the rate of action potential generation and allowing for more effective coordinated contractions. Since a degree of sympathetic activity is necessary to maintain cardiac function, the reduced contractility induced by atenolol may precipitate or worsen heart failure, especially during volume overload.
The effects of atenolol on blood pressure have been established, although it is less effective than alternative beta-blockers, but the mechanism has not yet been characterized. As a β1 selective drug, it does not act via the vasodilation produced by non-selective agents. Despite this there is a sustained reduction in peripheral vascular resistance, and consequently blood pressure, alongside a decrease in cardiac output. It is thought that atenolol's antihypertensive activity may be related to action on the central nervous system (CNS) or it's inhibition of the renin-aldosterone-angiotensin system rather than direct effects on the vasculature.
Antolol produces CNS effects similar to other beta-blockers, but does so to a lesser extent due to reduces ability to cross the blood-brain barrier. It has the potential to produce fatigue, depression, and sleep disturbances such as nightmares or insomnia. The exact mechanisms behind these have not been characterized but their occurrence must be considered as they represent clinically relevant adverse effects.
| Trade Name | Antolol |
| Availability | Prescription only |
| Generic | Atenolol |
| Atenolol Other Names | Atenolol, Atenololum |
| Related Drugs | amlodipine, aspirin, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, escitalopram, alprazolam |
| Weight | 50mg, 100mg |
| Type | Tablet |
| Formula | C14H22N2O3 |
| Weight | Average: 266.3361 Monoisotopic: 266.16304258 |
| Protein binding | 6-16% bound in plasma. Atenolol binds to two sites on human serum albumin. |
| Groups | Approved |
| Therapeutic Class | Beta-adrenoceptor blocking drugs, Beta-blockers |
| Manufacturer | Spencer Pharma |
| Available Country | Pakistan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Antolol is used for: Hypertension, Angina pectoris, Cardiac arrhythmia, Myocardial infarction
Antolol is also used to associated treatment for these conditions: Alcohol Withdrawal Syndrome, Angina Pectoris, Atrial Fibrillation, Heart Failure, High Blood Pressure (Hypertension), Migraine, Myocardial Infarction, Refractory Hypertension, Secondary prevention Myocardial infarction, Supra-ventricular Tachyarrhythmias, Thyrotoxicosis, Ventricular Tachyarrhythmias
How Antolol works
Antolol is a cardioselective beta-blocker, called such because it selectively binds to the β1-adrenergic receptor as an antagonist up to a reported 26 fold more than β2 receptors. Selective activity at the β1 receptor produces cardioselectivity due to the higher population of this receptor in cardiac tissue. Some binding to β2 and possibly β3 receptors can still occur at therapeutic dosages but the effects mediated by antagonizing these are significantly reduced from those of non-selective agents. β1 and β2 receptors are Gs coupled therefore antagonism of their activation reduces activity of adenylyl cyclase and its downstream signalling via cyclic adenosime monophosphate and protein kinase A (PKA).
In cardiomyocytes PKA is thought to mediate activation of L-type calcium channels and ryanodine receptors through their phosphorylation. L-type calcium channels can then provide an initial rise in intracellular calcium and trigger the ryanodine receptors to release calcium stored in the sarcoplasmic reticulum (SR) and increased contractility. PKA also plays a role in the cessation of contraction by phosphorylating phospholamban which in turn increases the affinity of SR Ca2+
Similar inihibitory events occur in the bronchial smooth muscle to mediate relaxation including phosphorylation of myosin light-chain kinase, reducing its affinity for calcium. PKA also inhibits the excitatory Gq coupled pathway by phosphorylating the inositol trisphosphate receptor and phospholipase C resulting in inhibition of intracellular calcium release. Antagonism of this activity by beta-blocker agents like atenolol can thus cause increased bronchoconstriction.
Dosage
Antolol dosage
Hypertension: 50 mg once daily, the daily dose can be raised to 100 to 200 mg.
Angina pectoris: 50 to 100 mg daily.
Cardiac arrhythmia: Antolol in low dose, 25-50 mg once daily, can be used in combination with digoxin to control the ventricular rate in atrial fibration or atrial flutter which is refractory to digoxin alone.
Side Effects
In general, atenolol is well tolerated although in a small number of patients (approximately 2-3%) therapy must be withdrawn because of troublesome symptomatic adverse effects. The commonest of these are cold extrimities, fatigue, vivid dreams, insomnia, diarrhoea, constipation, impotence and paraesthesia. Bronchospasm has been occurred with atenolol although this is very much less common than with the non-selective β-blockers.
Toxicity
LD50 Values
Mouse: 2 g/kg (Oral), 57 mg/kg (IV), 134 mg/kg (IP), 400 mg/kg (SC)
Rat: 2 g/kg (Oral), 77 mg/kg (IV), 600 mg/kg (SC)
Rabbit: 50 mg/kg (IV)
Carcinogenicity & Mutagenicity
Studies in rats and mice at doses of 300 mg/kg/day, equivalent to 150 times maximum recommended human dose, for durations of 18 and 24 months showed no carcinogenicity. One study in rats at doses of 500-1500 mg/kg/day, 250-750 times maximum human dose, resulted in increases benign adrenal medullary tumors in both sexes and increase mammary fibroadenomas in females.
Antolol showed no mutagenicity in the Ames test using S. typhinarium, dominant lethal test in mice, or in vivo cytogenetics test in chinese hamster ovary cells.
Reproductive Toxicity
No adverse effects on fertility were observed in either male or female mice after receiving doses of 200 mg/kg/day, equivalent to 200 times the maximum human dose. In humans, atenolol is known to cross the placenta and fetuses exposed to the drug have been reported to be smaller than expected considering gestational age. Embryo-fetal resorption has been observed in rats at doses of 50mg/kg/day, 50 times the max human dose, but not in rabbits at doses of 25mg/kg/day.
Lactation
Antolol appears in breast milk at a ratio of 1.5-6.8 to plasma concentrations. It has been estimated that infant exposure occurs at 5.7-19.2% maternal weight-adjusted dosage. Effects in infants include bradycardia, hypothermia, and lethargy.
Precaution
Patients already on a β-blocker must be evaluated carefully before Antolol is administered. Antolol may aggravate peripheral arterial circulatory disorders. Impaired Renal Function: Caution should be excised.
Interaction
Catecholamine-depleting drugs (e.g., Reserpine) and Calcium channel blockers may have an additive effect when given with Antolol. Clonidine and aspirin may have some drug reactions.
Food Interaction
No interactions found.[Moderate] GENERALLY AVOID: Orange juice may moderately reduce the bioavailability of atenolol by interfering with its absorption from the gastrointestinal tract.
In a pharmacokinetic study, subjects ingested 200 mL orange juice 3 times daily for 3 days and twice daily on the fourth day, and took 50 mg atenolol with 200 mL orange juice on day 3.
The average peak plasma concentration (Cmax) of atenolol fell by 49% and the area under the concentration-time curve (AUC) fell by 40% in comparison to subjects who drank only water.
In addition, the presence of food may reduce the bioavailability of atenolol by 20%.
The clinical significance is unknown.
MANAGEMENT: Patients treated orally with atenolol should be advised to take atenolol at the same time each day and to avoid consumption of large amounts of orange juice to prevent any undue fluctuations in serum drug levels.
Monitoring for altered efficacy of atenolol may be advisable.
Antolol Alcohol interaction
[Moderate]
Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.
Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
Caution and close monitoring for development of hypotension is advised during coadministration of these agents.
Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.
Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.
Antolol Cholesterol interaction
[Moderate] Beta-adrenergic receptor blocking agents (aka beta-blockers) may alter serum lipid profiles.
Increases in serum VLDL and LDL cholesterol and triglycerides, as well as decreases in HDL cholesterol, have been reported with some beta-blockers.
Patients with preexisting hyperlipidemia may require closer monitoring during beta-blocker therapy, and adjustments made accordingly in their lipid-lowering regimen.
Antolol multivitamins interaction
[Moderate] ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers.
The exact mechanism of interaction is unknown.
In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively.
The elimination half-life increased by 44%.
Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone.
However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments.
The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.
It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours.
Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.
Antolol Drug Interaction
Moderate: alprazolam, alprazolamMinor: aspirin, aspirin, levothyroxine, levothyroxineUnknown: duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, atorvastatin, atorvastatin, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Antolol Disease Interaction
Major: hemodialysis, renal dysfunction, bradyarrhythmia/AV block, cardiogenic shock/hypotension, CHF, diabetes, hypersensitivity, ischemic heart disease, PVDModerate: cerebrovascular insufficiency, glaucoma, hyperlipidemia, hyperthyroidism, myasthenia gravis, pheochromocytoma, psoriasis, tachycardia, asthma/COPD
Volume of Distribution
Total Vd of 63.8-112.5 L. Antolol distributes into a central volume of 12.8-17.5 L along with two peripheral compartments with a combined volume of 51-95 L. Distribution takes about 3 hrs for the central compartment, 4 hrs for the shallower peripheral compartment, and 5-6 hrs for the deeper peripheral compartment.
Elimination Route
Approximately 50% of an oral dose is absorbed from the gastrointestinal tract, with the remainder being excreted unchanged in the feces. Administering atenolol with food can decrease the AUC by about 20%. While atenolol can cross the blood-brain barrier, it does so slowly and to a small extent.
Half Life
6-7 hrs.
Clearance
Total clearance is estimated at 97.3-176.3 mL/min with a renal clearance of 95-168 mL/min.
Elimination Route
85% is eliminated by the kidneys following IV administration with 10% appearing in the feces.
Pregnancy & Breastfeeding use
Pregnancy Category D. Caution should be exercised when Antolol is administered to a nursing woman.
Contraindication
Antolol is contraindicated for: Second and third degree heart block, Untreated heart failure, Overt cardiac failure, Cardiogenic shock.
Special Warning
Safety and effectiveness in pediatric patients have not been established.
Acute Overdose
Overdosage with Antolol has been reported with patients surviving acute doses as high as 5 gm. One death was reported in a man who may have taken as much as 10 gm acutely.
Innovators Monograph
You find simplified version here Antolol
Antolol contains Atenolol see full prescribing information from innovator Antolol Monograph, Antolol MSDS, Antolol FDA label
FAQ
What is Antolol used for?
Antolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of migraines and treatment of certain irregular heart beats. If you have high blood pressure, taking atenolol helps prevent future heart disease, heart attacks and strokes.
How safe is Antolol?
Antolol is generally safe to take for a long time. If you're taking it for a heart condition or to prevent migraines, it works best when you take it long term. You'll need to have your blood pressure checked regularly if you're taking Antolol for a long time for migraines.
How does Antolol work?
Antolol works by changing the way your body responds to some nerve impulses, including in the heart.
What are the common side effects of Antolol?
Common side effects of Antolol are include:
- Blurred vision.
- cold hands or feet.
- difficult or labored breathing.
- dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly.
- shortness of breath.
- tightness in chest.
- wheezing.
Is Antolol safe during pregnancy?
It is concluded that Antolol is safe and it usually effective in the control of the hypertension complicating pregnancy.
Is Antolol safe during breastfeeding?
Antolol is also considered to pose a low risk. Antolol are favoured least because of relatively high milk levels and possible side effects in breastfed infants.
Can I drink alcohol with Antolol?
During the first few days of taking Antolol or after an increase in your dose, it's best to stop drinking alcohol until you see how the medicine affects you.
Can I drive after taking Antolol?
Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking Antolol.
When should be taken of Antolol ?
You'll usually take Antolol once or twice a day. When you start taking Antolol, your doctor may advise you to take your first dose before bedtime because it can make you feel dizzy. After the first dose, if you do not feel dizzy.
Can I take Antolol on an empty stomach?
Antolol does not usually upset your tummy, so you can take it with or without food. It's best to do the same each day.
How long does Antolol take to work?
Antolol starts to work after about 3 hours to reduce high blood pressure, but it can take up to 2 weeks to reach its full effect.
How long does Antolol stay in my system?
If you stop taking Antolol, it'll take about 1 to 2 days for it to be completely out of your body.
Can I take Antolol for a long time?
Antolol is generally safe to take for a long time. If you're taking it for a heart condition or to prevent migraines, it works best when you take it long term. You'll need to have your blood pressure checked regularly if you're taking Antolol for a long time for migraines.
Who should not take Antolol?
You should not use this Antolol if you have a serious heart condition such as "AV block," very slow heartbeats, or heart failure.
What happen If I suddenly stop taking Antolol?
Suddenly stopping Antolol may cause chest pain, heart attack, or irregular heartbeat. Your doctor will probably decrease your dose gradually.
What happens if I miss a dose?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
What happens if I overdose?
Seek emergency medical attention.Overdose symptoms may include extreme weakness or lack of energy, very slow heart rate, shortness of breath, or fainting.
Can Antolol affect my heart?
Antolol may cause heart failure in some patients.
Is Antolol safe for my kidneys?
The traditional teaching is that Antolol, a water-soluble β-blocker, is highly dependent on renal elimination, and prescribing guidelines recommend lower doses and careful monitoring in CKD patients to avoid side effects related to drug accumulation.
Can Antolol affect fertility?
Antolol are generally considered safe for use during pregnancy in helping to reduce high blood pressure and aren't thought to affect your ability to get pregnant.
