Lerez At
Lerez At 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
Atenolol 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.
Atenolol 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.
Lercanidipine is a dihydropyridine calcium-channel blocker which acts by inhibiting the influx of calcium ions through the slow channels of the vascular smooth muscle and myocardium during depolarization. Its main effect is vasodilatation because it has greater selectivity for vascular smooth muscle than cardiac smooth muscle.
Lercanidipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Lercanidipine is similar to other peripheral vasodilators. Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
| Trade Name | Lerez At |
| Generic | Atenolol + Lercanidipine |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Glenmark Pharmaceuticals |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Atenolol is used for: Hypertension, Angina pectoris, Cardiac arrhythmia, Myocardial infarction
Lercanidipine is used for the treatment of mild to moderate essential hypertension.
Lerez At 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 TachyarrhythmiasHigh Blood Pressure (Hypertension), Mild Hypertension, Moderate Essential Hypertension
How Lerez At works
Atenolol 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.
By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Lercanidipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Dosage
Lerez At 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: Atenolol 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.
Use in elderly: The recommended dosage is 10 mg orally once a day at least 15 minutes before meals; the dose may be increased to 20 mg depending on the individual patient's response. It may take about 2 weeks before the maximal anti-hypertensive effect is apparent. Some individuals, not adequately controlled on a single antihypertensive agent, may benefit from the addition of Lercanidipine to therapy with a beta-adrenoceptor blocking drug (atenolol), a diuretic (hydrochlorothiazide) or an ACE inhibitor (ramipril).
Use in children: Since there is no clinical data in patients under the age of 18 years, use in children is not currently recommended.
Use in renal or hepatic dysfunction: Special care should be exercised in patients with mild to moderate renal or hepatic dysfunction. Dosage above 20 mg daily must be approached with caution. Lercanidipine is not recommended for use in patients with severe hepatic or renal dysfunction.
Should be taken on an empty stomach. Take at least 15 min before meals.
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.
Treatment with Lercanidipine is generally well tolerated. The most common side effects are related to the vasodilatory properties of Lercanidipine such as flushing, peripheral edema, headache, dizziness and asthenia. Other side effects, which occurred in less than 1% of patients include fatigue; GI disturbances such as dyspepsia, nausea, vomiting, epigastric pain and diarrhea, polyurea, rash, somnolence and myalgia.
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.
Atenolol 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
Atenolol 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 Atenolol is administered. Atenolol may aggravate peripheral arterial circulatory disorders. Impaired Renal Function: Caution should be excised.
Special care should be exercised when Lercanidipine is used in patients with sick sinus syndrome, left ventricular dysfunction and ischaemic heart disease.
Interaction
Catecholamine-depleting drugs (e.g., Reserpine) and Calcium channel blockers may have an additive effect when given with Atenolol. Clonidine and aspirin may have some drug reactions.
Plasma concentration reduced by inducers of CYP3A4 eg rifampicin, phenytoin, carbamazepine. Bioavailability also reduced by metoprolol and possibly propranolol. Plasma concentrations increased by inhibitors of CYP3A4 eg imidazole antifungals, erythromycin, ritonavir, fluoxetine. Alcohol may potentiate vasodilating effect.
Volume of Distribution
Total Vd of 63.8-112.5 L. Atenolol 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 Atenolol is administered to a nursing woman.
Pregnancy Category C. There is no clinical experience with lercanidipine in pregnancy, but other dihydropyridine compounds have been found to cause irreversible malformations in animals. Therefore, lercanidipine should not be administered during pregnancy or to women with child-bearing potential unless effective contraception is used.
Use in lactation: There is no clinical experience with lercanidipine in lactation. Distribution into milk may be expected, due to the high lipophilicity of lercanidipine. Therefore, lercanidipine should not be administered to lactating women.
Contraindication
Atenolol is contraindicated for: Second and third degree heart block, Untreated heart failure, Overt cardiac failure, Cardiogenic shock.
Lercanidipine is contraindicated in patients with left ventricular outflow tract obstruction, untreated congestive cardiac failure, unstable angina pectoris, within 1 month of a myocardial infarction and known hypersensitivity to any dihydropyridine. Lercanidipine should not be taken with grapefruit juice.
Special Warning
Safety and effectiveness in pediatric patients have not been established.
Use in children: Since there is no clinical data in patients under the age of 18 years, use in children is not currently recommended.
Use in renal or hepatic dysfunction: Special care should be exercised in patients with mild to moderate renal or hepatic dysfunction. Dosage above 20 mg daily must be approached with caution. Lercanidipine is not recommended for use in patients with severe hepatic or renal dysfunction.
Acute Overdose
Overdosage with Atenolol 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.
There have been no recorded cases of Lercanidipine overdosage. As with other dihydropyridines, overdosage might be expected to cause excessive peripheral vasodilatation with marked hypotension and reflex tachycardia.
Storage Condition
Should be stored in cool and dry place
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