Enerzal

Uses

Calcium is a mineral found in over-the-counter supplements or prescription formulations used for the treatment of specific medical conditions related to calcium deficiency.

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. It is vital in cell signaling, muscular contractions, bone health, and signalling cascades.

Magnesium is a medication used for many purposes including constipation, indigestion, magnesium deficiency, and pre-eclampsia.

Healthy levels of magnesium can be achieved through a well balanced diet, but if food sources are insufficient, magnesium supplements can be used to prevent and treat magnesium deficiencies.

In medicine, various magnesium salts may be used in laxative and antacid products. For example, magnesium citrate is available over-the-counter and may be used to manage occasional constipation. Magnesium sulfate may be used on its own or with total parenteral nutrition to treat hypomagnesemia. Magnesium sulfate is also indicated to prevent seizures in pregnant women with pre-eclampsia, and to manage seizures associated with eclampsia.

Potassium is a medication used to treat hypokalemic conditions and to clear the colon prior to colonoscopy.

General uses of potassium

Potassium is indicated to treat a variety of conditions. Firstly, it used to replenish potassium that has been depleted by conditions including but not limited to malabsorption, decreased intake, or excess sodium intake. The causes of potassium deficiency are numerous. The following indications for potassium are not comprehensive, but include the main indications for which this nutrient is used. Various products and preparations contain potassium.

Potassium chloride

Potassium chloride is one of the main preparations of potassium used in a clinical setting. The oral solution is indicated for the prevention and treatment of hypokalemia presenting with or without metabolic alkalosis, in patients who have failed conservative management with potassium-rich foods or diuretic dose titrations. The injection form of potassium chloride is indicated to replenish potassium in patients who are not feasible candidates for oral potassium. Highly concentrated potassium is intended for the treatment of potassium deficiency in fluid restricted individuals who cannot tolerate fluid volumes normally associated with injected potassium solutions that contain lower concentrations. Finally, the extended-release tablet preparation of potassium chloride is used to treat hypokalemia with or without metabolic alkalosis, to treat digitalis intoxication, and to manage patients with hypokalemic familial periodic paralysis. It is also used in the prevention of hypokalemia in those who are at a high risk of negative clinical outcomes if hypokalemia occurs; patients on digitalis or those with cardiac arrhythmias would be at particular risk of negative outcomes.

Potassium chloride with dextrose and sodium chloride

This liquid preparation is is indicated in a clinical setting as a source of water, calories and electrolytes. Potassium acetate solution is meant as an alternative to potassium chloride, replenishing potassium and added to large volume infusion fluids for intravenous injection.

Potassium citrate

The potassium citrate preparation is used for the management of renal tubular acidosis (RTA) with calcium stones (nephrolithiasis); calcium oxalate stones by any cause, and uric acid nephrolithiasis (with or without calcium stones). This regimen also includes adequate water intake (leading to a urine out put of 2 L/day or more) and sodium restriction.

Enerzal is also used to associated treatment for these conditions: Calcium Deficiency, Deficiency, Vitamin D, Osteodystrophy, Osteomalacia, Osteoporosis, Chronic Hypocalcemia, Chronic Hypocalcemia caused by anticonvulsant medications, Care of the Joint, Mineral supplementation, Nutritional supplementationCalcium Deficiency, Magnesium Deficiency, Zinc DeficiencyCaloric Intake, Electrolyte and fluid balance conditions, Hydration, Hypokalemia, Potassium

How Enerzal works

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than 500 human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca2+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is 1,500 milligrams per day for women not taking estrogen and 800 milligrams per day for women on estrogen. There is close to 300 milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available.

Magnesium is a cofactor for at least 300 enzymes and is important for several functions in the body with some key processes identified below. Enzymes that rely on magnesium to operate help produce energy through oxidative phosphorylation, glycolysis and ATP metabolism. They are also involved in nerve function, muscle contraction, blood glucose control, hormone receptor binding, protein synthesis, cardiac excitability, blood pressure control, gating of calcium channels and transmembrane ion flux.

The mitochondrial intracellular space is rich in magnesium, since it is required to produce the active form of ATP (adenosine triphosphate) from ADP (adenosine diphosphate) and inorganic phosphate, and behaves as a counter ion for the energy rich molecule. Additionally, magnesium is essential for ATP metabolism.

Potassium ion is the primary intracellular cation found in virtually all body tissues. The total amount of body potassium in adults is estimated at 45 millimole (mmol)/kg body weight (about 140 g for an adult weighing 175 pounds; 1 mmol = 1 milliequivalent or 39.1 mg of potassium). Potassium mainly stays in cells, and a small amount can be found in the extracellular fluid. The amount of potassium that stays in the cell (intracellular) is 30 times that of extracellular concentration, creating a transmembrane gradient, regulated by the sodium-potassium (Na+/K+) ATPase transporter. This is an important gradient for nerve conduction, muscle contractions, and renal function. Vomiting, diarrhea, renal disease, medications, and other conditions that alter potassium excretion or shift it inside or outside of cells. In healthy patients individuals with normal renal function, markedly high or low potassium levels are rare.

Effect on blood pressure

Potassium decreases reduces intravascular volume, by reducing sodium reabsorption through an increase in urinary sodium excretion. This short-term effect, however, does not explain the long-term effects of potassium on blood pressure. Increased plasma potassium levels that occur through intake are associated with vasodilation occurring via stimulation of the sodium-potassium adenosine triphosphatase pump (Na+/-K+ATPase) and opening of potassium channels of the sodium-potassium adenosine triphosphatase pump. Other possible mechanisms of action for potassium may include alterations in barroreflex sensitivity and hormone sensitivity in vascular smooth muscle and cells of the sympathetic nervous system.

Effect on electrolyte balance and body systems

The potassium gradient across the membrane of a cell regulates cell membrane potential, maintained predominantly by the sodium-potassium (Na+/-K+ ATPase pump). Transmembrane electro-chemical gradients encourage diffusion of Na+ extracellularly and K+ intracellularly. Potassium supplementation prevents hypokalemia to maintain this balance and is often used in an oral solution or injection form in the clinical setting, preventing harmful effects such as arrhythmias, abnormal muscle function, and neurological disturbances. When activated, the Na+/-K+ ATPase pump exchanges two extracellular K+ ions for three intracellular sodium (Na+) ions, impacting membrane potential via either excitation or inhibition. This is especially important in the homeostasis of the nervous system, kidney, and cardiac muscle tissue. The body and cell distributions of potassium in normal conditions are known as internal and external balance, respectively. Reduced serum potassium (or imbalance) increases the risk of ventricular arrhythmia, heart failure and left ventricular hypertrophy (LVH).

Toxicity

The recommended dietary allowance of magnesium ranges from 30 mg for infants to 420 mg for males between the age of 31 and 50. According to the institute of Medicine (IOM), the majority of adults can tolerate 350 mg of magnesium per day without experiencing adverse effects. Symptoms of magnesium toxicity include diarrhea and other gastrointestinal effects, thirst, muscle weakness, drowsiness, severe back and pelvic pain, hypotension, dizziness, confusion, difficulty breathing, lethargy, and deterioration of kidney function. Other more severe symptoms associated with magnesium overdose include loss of consciousness, respiratory arrest, cardiac arrhythmias and cardiac arrest.

Regular use of laxatives containing magnesium may lead to severe and even fatal hypermagnesemia.

Discontinuation of magnesium products including supplements, laxatives, and antacids is usually sufficient to manage mild cases of magnesium overdose; however, patients should also be screened for renal impairment.

In severe cases of magnesium overdose, patients may require supportive care and interventions including intravenous fluids and furosemide, IV calcium chloride or calcium gluconate, renal dialysis and artificial respiratory support.

The oral LD50 of potassium chloride in rats is 2600 mg/kg.

Overdose information

An overdose of potassium may result in hyperkalemia, and in some cases, death due to various causes. Signs and symptoms of an overdose of potassium are mainly cardiovascular, neurological and musculoskeletal in nature. Arrhythmia, changes in cardiac conduction, including astystole, bradycardia, heart block, ventral fibrillation, and ventricular tachycardia may occur. In addition, hypotension may also occur along with cardiac ECG changes. Muscular weakness and respiratory muscle paralysis may occur, in addition to paresthesia. In case of an overdose, discontinue potassium administration, reduce the dose, and monitor fluid levels and electrolyte concentrations in addition to acid-base balance. Corrective therapy, such as insulin administration or potassium binding drugs, may be required. Offer supportive care and resuscitation as deemed necessary.

Important note regarding hyperkalemia

Normally, hyperkalemia is asymptomatic and only detected by laboratory testing (at values of 6.5-8.0 mEq/L) and ECG changes (peaked T- waves, lost P-waves, ST depression, and a prolonged QT interval). Muscle paralysis and cardiac arrest may occur in the advanced stages of hyperkalemia, at potassium concentrations of 9-12 mEq/L.

Volume of Distribution

According to a pharmacokinetic review, the volume of distribution of magnesium sulphate when used to manage patients with pre-eclampsia and eclampsia ranged from 13.65 to 49.00 L.

Potassium is present in almost all body tissues. Approximately 98% of potassium is maintained intracellularly in muscular tissue, the liver, and red blood cells. The remainder is distributed extracellularly.

Elimination Route

Approximately 24-76% of ingested magnesium is absorbed in the gastrointestinal tract, primarily via passive paracellular absorption in the small intestine.

When taken orally from a dietary source, potassium is mainly absorbed via passive diffusion in the small intestine. Approximately 90% of potassium is absorbed, and maintains concentrations both inside and outside cells. The kidneys can adapt to variable potassium intake in healthy individuals, but a minimum of 5 mmol (about 195 mg) dietary potassium is measured to be excreted in the urine.

Some studies have measured the absorption various forms of potassium from dietary supplements. Results from a clinical trial in 2016 showed that potassium gluconate supplements are 94% absorbed, which is similar to the absorption rate from potatoes. An older study advised that liquid forms of potassium are absorbed a few hours post-administration. Enteric coated tablets of potassium chloride are not absorbed as rapidly as liquid forms, due to their delayed release design.

Half Life

Magnesiums biologic half-life is reported to be approximately 1000 hours or 42 days.

In one clinical study, the apparent half-life of oral potassium was between 1.6 and 14 hours. A radio tracer study determined that the biological half-life of radiolabeled potassium ranges from 10 to 28 days.

Clearance

Potassium is freely filtered in the kidney with most of an ingested amount being reabsorbed into the circulation (70%–80%) by the proximal tubule and loop of Henle. Secretion of potassium by the distal nephron in the kidney varies and dependent on the intracellular potassium concentration, luminal potassium concentration concentration, in addition to cellular permeability.

Elimination Route

The kidney excretes 250 mmol a day in urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d.

The majority of magnesium is excreted renally.

Potassium is excreted primarily in the urine, excreted in small amounts in the stool, and negligibly in perspiration (sweat). The renal system regulates potassium excretion according to dietary intake. Potassium excretion rises quickly in healthy patients after ingestion unless body stores have been depleted. Potassium undergoes glomerular filtration, tubular reabsorption, and distal tubular secretion. Renal clearance of potassium shifts between net tubular secretion and reabsorption, depending on the clinical circumstances.

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