Tissue Orchid Pulls
Tissue Orchid Pulls 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.
Indapamide is a diuretic antihypertensive. It appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. It has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.
Classified as a sulfonamide diuretic, indapamide is an effective antihypertensive agent and by extension, has shown efficacy in the prevention of target organ damage.Administration of indapamide produces water and electrolyte loss, with higher doses associated with increased diuresis. Severe and clinically significant electrolyte disturbances may occur with indapamide use - for example, hypokalemia resulting from renal potassium loss may lead to QTc prolongation. Further electrolyte imbalances may occur due to renal excretion of sodium, chloride, and magnesium.
Other indapamide induced changes include increases in plasma renin and aldosterone, and reduced calcium excretion in the urine. In many studies investigating the effects of indapamide in both non-diabetic and diabetic hypertensive patients, glucose tolerance was not significantly altered. However, additional studies are necessary to assess the long term metabolic impacts of indapamide, since thiazide related impaired glucose tolerance can take several years to develop in non-diabetic patients.
| Trade Name | Tissue Orchid Pulls |
| Generic | Atenolol + Indapamide |
| Type | |
| Therapeutic Class | |
| Manufacturer | Shogun Diapers Ltd |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Atenolol is used for: Hypertension, Angina pectoris, Cardiac arrhythmia, Myocardial infarction
Indapamide is used for the treatment of essential hypertension . It is effective in treating hypertension in patients with renal function impairment, although its diuretic effect is reduced. Indapamide is also used for the treatment of salt and fluid retention associated with congestive heart failure.
Tissue Orchid Pulls 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), Recurrent Nephrolithiasis, Sodium and fluid retention
How Tissue Orchid Pulls 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.
Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule where it inhibits the Na+/Cl- cotransporter, leading to reduced sodium reabsorption. As a result, sodium and water are retained in the lumen of the nephron for urinary excretion. The effects that follow include reduced plasma volume, reduced venous return, lower cardiac output, and ultimately decreased blood pressure.
Interestingly, it is likely that thiazide-like diuretics such as indapamide have additional blood pressure lowering mechanisms that are unrelated to diuresis. This is exemplified by the observation that the antihypertensive effects of thiazides are sustained 4-6 weeks after initiation of therapy, despite recovering plasma and extracellular fluid volumes.
Some studies have suggested that indapamide may decrease responsiveness to pressor agents while others have suggested it can decrease peripheral resistance. Although it is clear that diuresis contributes to the antihypertensive effects of indapamide, further studies are needed to investigate the medication’s ability to decrease peripheral vascular resistance and relax vascular smooth muscle.
Dosage
Tissue Orchid Pulls 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.
One tablet daily preferably in the morning. In more sever case Indapamide can be combine with other categories of anti-hypertensive agent. The safety and effectiveness in pediatric patients have not been established
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.
Side effects of Indapamide include headache, anorexia, gastric irritation,nausea, vomiting, constipation, diarrhoea etc.
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.
Indapamide overdose symptoms may include but are not limited to nausea, vomiting, gastrointestinal disorders, electrolyte disturbances and weakness. Other signs of overdose include respiratory depression and severe hypotension. In cases of overdose, supportive care interventions may be necessary to manage symptoms. Emesis and gastric lavage may be recommended to empty the stomach; however, patients should be monitored closely for any electrolyte or fluid imbalances.
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.
Monitoring of potassium and uric acid serum levels is recommended, especially in subjects with a predisposition or sensitivity to hypokalemia and in patients with gout. Although no allergic manifestations have been reported during clinical trials, patients with a history of allergy to sulfonamide derivatives should be closely monitored.
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.
Other antihypertensive: Indapamide may add to or potentiate the action of other antihypertensive drugs.
Norepinephrine: Indapamide like thiazides, may decrease arterial responsiveness to norepinephrine.
Lithium: In general, diuretics should not be given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity.
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.
Some sources report an apparent volume of distribution of 25 L for indapamide, while others report a value of approximately 60 L.
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.
The bioavailability of indapamide is virtually complete after an oral dose and is unaffected by food or antacids. Indapamide is highly lipid-soluble due to its indoline moiety - a characteristic that likely explains why indapamide’s renal clearance makes up less than 10% of its total systemic clearance. The Tmax occurs approximately 2.3 hours after oral administration. The Cmax and AUC0-24 values are 263 ng/mL and 2.95 ug/hr/mL, respectively.
Half Life
6-7 hrs.
Indapamide is characterized by biphasic elimination. In healthy subjects, indapamide's elimination half-life can range from 13.9 to 18 hours. The long half-life is conducive to once-daily dosing.
Clearance
Total clearance is estimated at 97.3-176.3 mL/min with a renal clearance of 95-168 mL/min.
Indapamide's renal and hepatic clearance values are reported to be 1.71 mL/min and 20-23.4 mL/min, respectively.
Elimination Route
85% is eliminated by the kidneys following IV administration with 10% appearing in the feces.
An estimated 60-70% of indapamide is eliminated in the urine, while 16-23% is eliminated in the feces.
Pregnancy & Breastfeeding use
Pregnancy Category D. Caution should be exercised when Atenolol is administered to a nursing woman.
There are no adequate and well-controlled studies in pregnant women and so Indapamide is not recommended. Mothers taking Indapamide should not breast feed.
Contraindication
Atenolol is contraindicated for: Second and third degree heart block, Untreated heart failure, Overt cardiac failure, Cardiogenic shock.
This drug must not be taken in the following conditions:
- Hypersensitivity to sulfonamides
- Severe renal failure
- Hepatic encephalopathy or severe hepatic failure
- Hypokalaemia
Special Warning
Safety and effectiveness in pediatric patients have not been established.
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.
Symptoms: These could include: allergies, skin rashes, epigastric pain, nausea, photosensitivity, dizziness, weakness and paraesthesia.Treatment: Treatment is supportive and symptomatic, directed at correcting the electrolyte abnormalities.
Storage Condition
Store in a cool and dry place. Protect from light and moisture.
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