Coeors Pro

Uses

Bacillus clausii is a probiotic used to restore normal gastrointestinal flora.

Dextrose is administered as a parenteral nutrition solution in the treatment of carbohydrate depletion and hypoglycaemic coma. Because of its high dextrose content it is used in the treatment of cerebral edema, shock, circulatory collapse, unconsciousness and to correct hyperkalaemia with or without insulin.

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.

Zinc is an essential element commonly used for the treatment of patients with documented zinc deficiency.

Zinc can be used for the treatment and prevention of zinc deficiency/its consequences, including stunted growth and acute diarrhea in children, and slowed wound healing. It is also utilized for boosting the immune system, treating the common cold and recurrent ear infections, as well as preventing lower respiratory tract infections .

Coeors Pro is also used to associated treatment for these conditions: Abdominal Pain, Abnormal Intestinal Absorption, Diarrhoea, Flatulence, Intestinal Bacteria Flora DisturbanceArrhythmia, Caloric Deficit, Edema of the cerebrum, Metabolic Alkalosis, Hypoglycemic reaction, Blood Specimen Collection, Electrolyte replacement, Nutritional supplementation, Parenteral Nutrition, Parenteral rehydration therapy, Plasmapheresis, Positive cardiac inotropic effect, Total parenteral nutrition therapy, Urine alkalinization therapy, Fluid and electrolyte maintenance therapyCaloric Intake, Electrolyte and fluid balance conditions, Hydration, Hypokalemia, PotassiumCandidiasis, Common Cold, Diaper Dermatitis, Diaper Rash, Eye redness, Iron Deficiency (ID), Ocular Irritation, Skin Irritation, Sunburn, Wilson's Disease, Zinc Deficiency, Dietary and Nutritional Therapies, Dietary supplementation

How Coeors Pro works

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into 2 main phases where the preparatory phase is initiated by the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. This energy-producing reactions of glucose is limited to D-glucose as L-glucose cannot be phosphorlyated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation in order to preserve cellular and whole body metabolic integrity .

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).

Zinc has three primary biological roles: catalytic, structural, and regulatory. The catalytic and structural role of zinc is well established, and there are various noteworthy reviews on these functions. For example, zinc is a structural constituent in numerous proteins, inclusive of growth factors, cytokines, receptors, enzymes, and transcription factors for different cellular signaling pathways. It is implicated in numerous cellular processes as a cofactor for approximately 3000 human proteins including enzymes, nuclear factors, and hormones .

Zinc promotes resistance to epithelial apoptosis through cell protection (cytoprotection) against reactive oxygen species and bacterial toxins, likely through the antioxidant activity of the cysteine-rich metallothioneins .

In HL-60 cells (promyelocytic leukemia cell line), zinc enhances the up-regulation of A20 mRNA, which, via TRAF pathway, decreases NF-kappaB activation, leading to decreased gene expression and generation of tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8 .

There are several mechanisms of action of zinc on acute diarrhea. Various mechanisms are specific to the gastrointestinal system: zinc restores mucosal barrier integrity and enterocyte brush-border enzyme activity, it promotes the production of antibodies and circulating lymphocytes against intestinal pathogens, and has a direct effect on ion channels, acting as a potassium channel blocker of adenosine 3-5-cyclic monophosphate-mediated chlorine secretion. Cochrane researchers examined the evidence available up to 30 September 2016 .

Zinc deficiency in humans decreases the activity of serum thymulin (a hormone of the thymus), which is necessary for the maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans [A342417].

The change of Th(1) to Th(2) function leads to cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this causes decreased activity of natural-killer-cell (NK cell) and T cytolytic cells, normally involved in killing viruses, bacteria, and malignant cells [A3424].

In humans, zinc deficiency may lead to the generation of new CD4+ T cells, produced in the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production .

In another study, zinc supplementation in human subjects suppressed the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers [A3424]. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In such cells, zinc was found to induce A20, a zinc finger protein that inhibited NF-kappaB activation by the tumor necrosis factor receptor-associated factor pathway. This process decreased gene expression of pro-inflammatory cytokines and oxidative stress markers .

The exact mechanism of zinc in acne treatment is poorly understood. However, zinc is considered to act directly on microbial inflammatory equilibrium and facilitate antibiotic absorption when used in combination with other agents. Topical zinc alone as well as in combination with other agents may be efficacious because of its anti-inflammatory activity and ability to reduce P. acnes bacteria by the inhibition of P. acnes lipases and free fatty acid levels .

Dosage

Coeors Pro dosage

The volume and rate of infusion of dextrose solution will depend upon the requirements of the individual patient and the judgement of the physician.

The maximum rate at which dextrose can be infused without producing glycosuria is 0.5 gm/kg/hr.

The usual recommended flow rate for adult is 10-35 drops per minute infused intravenously.

Intravenous-

Hyperkalaemia:

• Adult: 25-50 g combined with 10 units of regular insulin, administered over 30-60 minutes; may repeat if necessary. Alternatively, 25 g combined with 5-10 units of regular insulin infused over 5 minutes; may repeat if necessary.
• Child and infants: 0.5-1 g/kg (using 25% or 50% solution) combined with regular insulin (1 unit for every 4-5 g dextrose given); infuse over 2 hr, may repeat if necessary.

Intravenous-

Hypoglycaemia:

• Adult: 10-25 g (40-100 ml of 25% solution or 20-50 ml of 50% solution). Doses may be repeated in severe cases.
• Child: ≤6 mth: 0.25-0.5 g/kg/dose; >6 mth: 0.5-1 g/kg/dose. Doses may be repeated in severe cases. Max: 25 g/dose.

Oral-

Hypoglycaemia:

• Adult: 10-20 g as single dose; may repeat in 10 min if needed.
• Child: >2 yr: 10-20 g as single dose; may repeat in 10 min if needed.

It should not be administered by SC or IM route. Dextrose should be infused through the largest available peripheral vein.

Side Effects

Venous thrombosis, phlebitis, hypovolemia, hypervolemia, dehydration, oedema, fever, mental confusion, unconsciousness, hyperosmolar syndrome, hyperglycaemia, hypokalaemia, acidosis, hypophosphataemia, hypomagnesemia, polyuria, glycosuria, ketonuria, nausea, diarrhoea, polydipsia, vein irritation, tissue necrosis, pulmonary oedema, tachypnoea.

Toxicity

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and/or solute overloading resulting in dilution of the serum electrolyte concentrations, over-hydration, congested states, or pulmonary oedema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.

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.

According to the Toxnet database of the U.S. National Library of Medicine, the oral LD50 for zinc is close to 3 g/kg body weight, more than 10-fold higher than cadmium and 50-fold higher than mercury .

The LD50 values of several zinc compounds (ranging from 186 to 623 mg zinc/kg/day) have been measured in rats and mice .

Precaution

Concentrated dextrose solution should not be infused rapidly or for a long period. It may be hazardous in patients with impaired hepatic or renal function and severe sepsis.

Care should be taken to avoid circulatory overload, particularly in patients with cardiac insufficiency. Caution must be exercised in the administration of these injections to patients receiving corticosteroids or corticotropin. These injections should be used with caution in patients with overt or subclinical diabetes mellitus.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear and seal is intact.

Interaction

There is no drug drug interaction and none well documented.

Volume of Distribution

The mean volume of distribution after intravenous infusion is 10.6L.

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.

A pharmacokinetic study was done in rats to determine the distribution and other metabolic indexes of zinc in two particle sizes. It was found that zinc particles were mainly distributed to organs including the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender .

Elimination Route

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation. SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion . Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.

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.

Zinc is absorbed in the small intestine by a carrier-mediated mechanism . Under regular physiologic conditions, transport processes of uptake do not saturate. The exact amount of zinc absorbed is difficult to determine because zinc is secreted into the gut. Zinc administered in aqueous solutions to fasting subjects is absorbed quite efficiently (at a rate of 60-70%), however, absorption from solid diets is less efficient and varies greatly, dependent on zinc content and diet composition .

Generally, 33% is considered to be the average zinc absorption in humans . More recent studies have determined different absorption rates for various populations based on their type of diet and phytate to zinc molar ratio. Zinc absorption is concentration dependent and increases linearly with dietary zinc up to a maximum rate [L20902].

Additionally zinc status may influence zinc absorption. Zinc-deprived humans absorb this element with increased efficiency, whereas humans on a high-zinc diet show a reduced efficiency of absorption .

Half Life

The approximate half-life is 14.3 minutes following intravenous infusion. Gut glucose half-life was markedly higher in females (79 ± 2 min) than in males (65 ± 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001).

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.

The half-life of zinc in humans is approximately 280 days .

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglyglycemia.

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.

In one study of healthy patients, the clearance of zinc was found to be 0.63 ± 0.39 μg/min .

Elimination Route

Glucose can be renally excreted.

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.

The excretion of zinc through gastrointestinal tract accounts for approximately one-half of all zinc eliminated from the body .

Considerable amounts of zinc are secreted through both biliary and intestinal secretions, however most is reabsorbed. This is an important process in the regulation of zinc balance. Other routes of zinc excretion include both urine and surface losses (sloughed skin, hair, sweat) .

Zinc has been shown to induce intestinal metallothionein, which combines zinc and copper in the intestine and prevents their serosal surface transfer. Intestinal cells are sloughed with approximately a 6-day turnover, and the metallothionein-bound copper and zinc are lost in the stool and are thus not absorbed .

Measurements in humans of endogenous intestinal zinc have primarily been made as fecal excretion; this suggests that the amounts excreted are responsive to zinc intake, absorbed zinc and physiologic need .

In one study, elimination kinetics in rats showed that a small amount of ZnO nanoparticles was excreted via the urine, however, most of the nanoparticles were excreted via the feces .

Pregnancy & Breastfeeding use

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Contraindication

Concentrated dextrose solution is contraindicated in patients with Glucose-Galactose Malabsorption Syndrome and severe hydration. The infusion of hypertonic dextrose injections is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Acute Overdose

Reevaluate patient's condition and institute appropriate symptomatic treatment.

Storage Condition

Store at 25°C.

Innovators Monograph

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