Appetag Bolus

Uses

Cobalt is a metal element used in various nutritional products.

Copper is a transition metal found in a variety of supplements and vitamins, including intravenous solutions for total parenteral nutrition (TPN).

For use in the supplementation of total parenteral nutrition and in contraception with intrauterine devices .

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.

Appetag Bolus is also used to associated treatment for these conditions: Emergency Contraception, IUD, Trace Element Deficiency, Dietary supplementationCaloric Intake, Electrolyte and fluid balance conditions, Hydration, Hypokalemia, Potassium

How Appetag Bolus works

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2 . It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%).

Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor . It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor.

Copper appears to reduce the viabilty and motility of spermatozoa . This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect . The exact mechanism of copper's effect on sperm are unknown.

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

Copper toxicity is belevied to be due to fenton-type redox reactions occuring with high copper concentrations which produce damaging reactive oxygen species .

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

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

Copper absorption varies inversely with intake. Absorption range is 12-65%.

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

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

Copper appears to be eliminated primarily through bile .

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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