Erisol

Uses

Higher concentrations of Benzalkonium chloride is used as an antiseptic and disinfectant. This is also widely used as a preservative in eye-drops.

No FDA- or EMA-approved therapeutic indications on its own.

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.

Erisol is also used to associated treatment for these conditions: Diaper Dermatitis, Dry Eye Syndrome (DES), Eye and eyelid infections, Gingivitis, Hemorrhoids, Infantile Eczema, Mouth irritation, Pruritus Ani, Tonsillitis, Throat inflammation, Antisepsis, Disinfection therapy, Eye disinfection, Eye lubrication, Hand Hygiene, Skin disinfection, Wound treatmentAcne, Asthenopia, Ocular Irritation, Skin Mycoses, Eye discomfort, Skin disinfection, Irrigation of the ocular surface therapyCaloric Intake, Electrolyte and fluid balance conditions, Hydration, Hypokalemia, Potassium

How Erisol works

Although not entirely elucidated, the bactericidal action of benzalkonium chloride is believed to be due to the disruption of intermolecular interactions. Such disruption can cause the dissociation of cellular membrane lipid bilayers of bacteria, resulting in compromised cellular permeability control and the leakage of important cellular contents. Additionally, other important molecular complexes like enzymes which control the maintenance of a great range of respiratory and metabolic cellular activities, are also susceptible to such deactivation. Consequently, a variety of critical intermolecular interactions and tertiary structures in very highly specific biochemical systems that allow bacterial agents to function normally can be readily disrupted or deactivated by cationic surfactants like benzalkonium chloride. .

Information regarding the mechanism of action of boric acid in mediating its antibacterial or antifungal actions is limited. Boric acid inhibits biofilm formation and hyphal transformation of Candida albicans, which are critical virulence factors . In addition, arrest of fungal growth was observed with the treatment of boric acid .

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).

Dosage

Erisol dosage

• Tincture of benzalkonium chloride 1:750 is used for the preoperative disinfection of unbroken skin or treatment of superficial injuries.
• For preoperative disinfection of mucous membranes and denuded skin, benzalkonium chloride solution in concentrations of 1:10000 to 1:2000 is used.
• For irrigation of the eye, a solution of 1:10000 to 1:5000 is used.
• For urinary bladder and urethral irrigation, a solution 1:5000 to 1:20000 is used.
• For vaginal douche and irrigation, benzalkonium chloride solution 1:5000 to 1:20000.

Side Effects

Repeated application may cause hypersensitivity reactions. May cause nausea and vomiting if ingested.

Toxicity

An oral dose of 100-400 mg/kg or a parenteral dose of 5-15 mg/kg is believed to be fatal in humans .

A potential concern for larger concentrations of benzalkonium chloride to possibly cause corneal damage when implemented as an excipient ingredient in aqueous eye products is an issue that should be discussed between potential patents and their health care providers . Since decreased regular blinking and tear generation in patients experiencing dry eyes due to any number of eye conditions can result in reduced dilution of applied eye drops containing the benzalkonium chloride preservative , alternative options including benzalkonium chloride-free products should be considered.

Additionally, benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. In addition, benzalkonium chloride may cause eye irritation and is known to discolour soft contact lenses . There may also be the possibility of benzalkonium chloride containing eye drops to cause some stinging and pain .

There is the possibility of ototoxicity occurring when benzalkonium chloride containing ear drops are applied to the ear .

Benzalkonium chloride used as a preservative in nebulised solutions of anti-asthma drugs has been reported to cause dose-related bronchoconstriction especially in asthmatic patients and has been associated with the precipitation of respiratory arrest .

Despite the fairly widespread cutaneous use of benzalkonium chloride, only limited human evidence of sensitization in relatively small populations of individuals have been reported . Nevertheless, the main adverse effect for topical formulations of benzalkonium chloride is usually the warning 'may cause local irritation' .

Acute oral LD50 is 2660 mg/kg in rat . Individuals are likely to be exposed to boric acid from industrial manufacturing or processing. Local tissue injury from boric acid exposure is likely due to caustic effects. Systemic effects from boric acid poisoning usually occur from multiple exposures over a period of days and involve gastrointestinal, dermal, CNS, and renal manifestations. Gastrointestinal toxicity include persistent nausea, vomiting, diarrhea, epigastric pain, hematemesis, and blue-green discoloration of the feces and vomit . Following the onset of GI symptoms, a characteristic intense generalized erythroderma follows . Management of mild to moderate toxicity should be supportive. In case of severe toxicity, dialysis may be required in addition to supportive treatment.

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.

Interaction

Disinfectants containing quaternary ammonium salts should not be used for skin preparation before injections of viscoelastic solutions. Hyaluronic acid will precipitate in the presence of these salts.

Volume of Distribution

When applied as a topical antibacterial, antiseptic, disinfectant, or sanitizer it is believed that molecules of benzalkonium chloride are poorly absorbed (perhaps due to their large, positively charged nature ), especially considering expectations for such topical applications to keep their biocidal agents available for action at the topical level and to not be absorbed significantly beyond it.

When benzalkonium chloride is implemented as an excipient preservative ingredient in various eye, nose, and ear aqueous products, such products will always have other active pharmacological agents whose volume of distribution will be of greater importance. In these cases the excipients will only ever be present at the minimal levels necessary to maintain the integrity of the product substance.

Moreover, Benzalkonium chloride is currently listed as a Category III ingredient by the United States Food and Drug Administration . Ingredients are listed in the FDA Category III when the data available about them are insufficient to classify as safe and effective, requiring further testing to determine more formal details about elements like human pharmacokinetic studies, and studies on the ingredients' absorption, distribution, metabolism, and excretion.

Volume of distribution ranges from 0.17 to 0.5 L/kg in humans, where large amounts of boric acid are localized in brain, liver, and kidney .

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

Percutaneous absorption is considered to be insignificant .

In one study, benzalkonium chloride absorption was evaluated in women using tampons containing the agent. Venous blood samples were drawn 15 minutes before the tampon application and then again at 15 min, 1 h, 3 h, and 24 h after application. Benzalkonium chloride was not detected in any of the blood samples at any time tested.

Similarly, in another study, benzalkonium chloride absorption was tested in women using tampons containing the agent. Venous blood and breast milk samples were taken 15 minutes before application and 3 h and 24 h after tampon administration. Benzalkonium chloride was not found in any of the subjects' samples. .

Moreover, in a study where benzalkonium chloride solution was placed on the corneal surface of rabbit subjects, at various intervals after administration, the rabbits' eyes would be washed with 1 mL saline and the following tissues and fluids were removed: bulbar and palpebral conjunctiva, aqueous humour, corneal epithelium, endothelium and stroma, iris-ciliary body, lens, vitreous, retina, and choroid. Plasma samples were obtained with direct cardiac punctures. After administration of one drop, benzalkonium chloride was found in the corneal epithelium, endothelium, and stroma, and in the bulbar and palpebral conjunctivae. Benzalkonium chloride loss from ocular tissues was such that about one-third to two thirds of its concentration (depending on the tissue) at 30 min remained after 24 hr; measurable values existed for as long as 120 hr. The administration of multiple drops led to continued accumulation of benzalkonium chloride. .

Boric acid is well absorbed from the gastrointestinal tract, open wounds, and serous cavities but displays limited absorption in intact skin . Following intraperitoneal injection in mice, the peak concentration was reached in about 1.0-1.5 hr in the brain whereas the value was 0.5 hr in other tissues .

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

According to human cases of poisoning, the elimination half-life of boric acid ranges from 13 to 24 hours .

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

A case report of acute boric acid poisoning following oral ingestion of 21 g of boric acid presents the total body clearance of 0.99 L/h before hemodialysis .

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

Administered benzalkonium chloride is likely eliminated largely in faeces, similar to other quaternary ammonium compounds .

Regardless the route of administration, boric acid predominantly undergoes rapid renal excretion of >90% of total administered dose as unchanged form. Small amounts are also excreted into sweat, saliva, and feces. Following administration as ointment, urinary excretion of boric acid accounted for only 1% of the administered dose .

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.

Contraindication

Incompatible with soaps and other anionic surfactants, citrates, iodides, nitrates, permanganates, salicylates, silver salts, tartrates, and zinc oxide and sulfate.

Storage Condition

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

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