CIPRIS

Indications

• Bacterial infections
• Urinary tract infections
• Respiratory tract infections
• Skin and soft tissue infections
• Acute pyelonephritis
• Severe diabetic foot infections
• Anthrax (treatment and post-exposure prophylaxis)
• Disseminated gonococcal infection (unlicensed)

Mechanism of action

Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. It binds to the alpha subunits of DNA gyrase, preventing the supercoiling of bacterial DNA, which is essential for DNA replication. This inhibition leads to bacterial cell death. Ciprofloxacin exhibits bactericidal activity during both logarithmic and stationary growth phases, particularly against organisms like Escherichia coli and Pseudomonas aeruginosa.

Pharmacodynamics

Ciprofloxacin is characterized by its potent activity against many Gram-negative and some Gram-positive bacteria, achieved through its mechanism of action on DNA gyrase and topoisomerase IV. It binds with significantly higher affinity to bacterial DNA gyrase compared to mammalian enzymes, thus minimizing potential side effects. There is no cross-resistance between ciprofloxacin and other antibiotic classes, which enhances its use in cases of antibiotic resistance. Additionally, ciprofloxacin is under investigation for potential effects against malaria, cancers, and AIDS.

Pharmacokinetics

Ciprofloxacin is rapidly absorbed after oral administration, with bioavailability around 70-80%. It is widely distributed in body tissues and fluids, including the lungs, liver, kidneys, and prostate. The drug undergoes hepatic metabolism and is primarily excreted via the kidneys, with a half-life of about 4 hours. Dosing adjustments may be necessary in renal impairment. Ciprofloxacin's pharmacokinetic profile supports its efficacy in treating systemic infections.

Contra-indications

• Hypersensitivity to ciprofloxacin or other quinolones
• Concurrent use with tizanidine

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Tendon rupture
• QT interval prolongation
• Photosensitivity
• Rash
• Superinfection

Interactions

• Severe: ciprofloxacin + tizanidine (increases exposure)
• Moderate: ciprofloxacin + aminophylline (increases exposure)
• Moderate: ciprofloxacin + antiepileptics (affects concentration)
• Moderate: ciprofloxacin + fosphenytoin (affects concentration)
• Moderate: ciprofloxacin + phenytoin (affects concentration)
• Moderate: ciprofloxacin + antipsychotics (increases concentration)
• Moderate: ciprofloxacin + clozapine (increases concentration)
• Moderate: ciprofloxacin + olanzapine (increases exposure)
• Moderate: ciprofloxacin + dopaminereceptor agonists (increases exposure)

Precautions

• Risk of arthropathy in children
• History of tendon disorders
• Concurrent use of drugs that prolong the QT interval
• Ensure adequate hydration to prevent crystalluria
• Monitor for signs of superinfection

Pregnancy

Avoid in pregnancy due to potential risk of arthropathy in animal studies; safer alternatives should be considered.

Breast-feeding

Ciprofloxacin is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Oral tablet: 250 mg, 500 mg, 750 mg
• Intravenous infusion: 400 mg/200 mL
• Eye drops: concentration may vary

Indications

• Acidulant in food and beverages
• Preservative in pharmaceutical formulations
• pH adjuster in various chemical preparations

Dosage

Children: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Adults: Refer to product-specific guidelines for appropriate dosing based on formulation and indication.

Mechanism of action

Citric acid acts by chelating metal ions, which can enhance the solubility of certain compounds and improve their bioavailability. It also contributes to the acidity of the environment, which can influence enzymatic activity and metabolic pathways, particularly in the degradation of citronellol.

Pharmacodynamics

Citric acid exhibits mild pharmacological effects primarily attributed to its role in metabolic processes. It aids in the regulation of pH levels, which can impact enzymatic reactions and biochemical pathways. The acid's chelating properties may help to reduce the toxicity of certain metal ions in biological systems.

Pharmacokinetics

Citric acid is rapidly absorbed after oral administration and is metabolized in the liver. It undergoes conversion to various metabolites in the citric acid cycle, contributing to energy production. The elimination primarily occurs through urine, with minimal accumulation in the body.

Pregnancy

Citric acid is generally regarded as safe during pregnancy when used in food amounts. However, consult a healthcare provider for advice on medicinal use.

Breast-feeding

Citric acid is considered safe during breastfeeding when consumed in food amounts. For medicinal use, consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

Indications

• Lead poisoning
• Zinc toxicity
• Cadmium poisoning
• Iron overload disorders

Dosage

Adults: Refer to the BNF for specific dosing recommendations for adults, as it may vary based on the condition being treated and the severity of metal poisoning.

Mechanism of action

The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate forms with any metal that can displace calcium from the molecule, which includes lead, zinc, cadmium, and iron. The excretion of zinc is significantly increased, while the effect on calcium excretion is minimal. The chelation process helps to reduce the toxicity of heavy metals in the body by promoting their urinary excretion.

Pharmacodynamics

Edetate calcium acts as a heavy metal chelating agent, forming stable, water-soluble complexes with metal ions that can be excreted in urine. One gram of edetate calcium can theoretically bind up to 620 mg of lead, though actual urinary excretion rates are lower, with approximately 5 mg of lead excreted per gram of EDTA in lead-poisoned patients. It is relatively ineffective against mercury, gold, or arsenic poisoning but can mobilize and eliminate zinc, cadmium, copper, iron, and manganese.

Pharmacokinetics

After intravenous administration, edetate calcium disodium is rapidly distributed in the blood and has a half-life that can vary based on the patient's condition and the presence of heavy metals. The drug is primarily excreted unchanged in the urine. Calcium levels may be transiently lowered during infusion, but significant mobilization of body calcium stores is usually not observed unless very slow infusions are administered. The effects on metal ion excretion are dose-dependent and vary according to the specific metal involved.

Contra-indications

• Hypersensitivity to edetate calcium disodium or any component of the formulation
• Pre-existing renal impairment
• Calcium deficiency states

Adverse effects

• Hypocalcemia
• Renal impairment
• Gastrointestinal disturbances such as nausea and vomiting
• Headache
• Hypotension
• Electrolyte imbalances

Interactions

• Increased risk of toxicity when used with nephrotoxic agents
• May interfere with the absorption of certain minerals and vitamins
• Should not be mixed with other intravenous drugs due to potential chemical interactions

Precautions

• Monitor renal function during treatment
• Use caution in patients with cardiovascular disease due to potential hypotensive effects
• Evaluate calcium levels periodically in patients receiving prolonged therapy
• Use with caution in patients with a history of seizures

Pregnancy

Limited data available on the use of edetate calcium disodium in pregnant women. Use only if clearly needed.

Breast-feeding

It is not known whether edetate calcium disodium is excreted in human milk. Caution is advised.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Edetate calcium disodium injection

Indications

• Adjustment of pH in pharmaceutical formulations
• Facilitation of drug absorption
• Used in sterile preparations

Dosage

Children: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Adults: Refer to specific product guidelines for dosing information, as hydrochloric acid is typically used in a controlled setting based on formulation requirements.

Mechanism of action

Hydrochloric acid dissociates in aqueous solution to release hydrogen ions (H+), leading to a decrease in pH. This acidic environment promotes the activation of pepsinogen to pepsin, an enzyme essential for protein digestion. Additionally, the acidity aids in the absorption of certain minerals and drugs that require an acidic environment for optimal bioavailability.

Pharmacodynamics

The primary pharmacodynamic action of hydrochloric acid is the maintenance of gastric acidity, which is essential for normal digestive processes. The acidic environment helps in denaturing proteins, activating digestive enzymes, and providing a barrier against pathogenic microorganisms. Its effects can influence the absorption and efficacy of various medications, particularly those that are pH-dependent.

Pharmacokinetics

Hydrochloric acid does not undergo significant systemic absorption when used in its normal contexts, as it acts locally within the gastrointestinal tract. The amount of hydrochloric acid produced by the stomach varies with food intake and physiological needs. It is secreted by parietal cells in the gastric mucosa, and its secretion is regulated by neural, hormonal, and local factors. The half-life of hydrochloric acid is not applicable as it is continuously produced and neutralized within the gastrointestinal tract.

Contra-indications

• Hypersensitivity to hydrochloric acid or any of its components
• Severe renal impairment
• Active gastrointestinal bleeding

Adverse effects

• Abdominal pain
• Diarrhea
• Nausea
• Vomiting
• Esophageal irritation
• Gastric mucosal irritation
• Electrolyte imbalances

Interactions

• May interact with alkaline substances, potentially neutralizing hydrochloric acid
• Caution with antacids as they may affect the efficacy of hydrochloric acid

Precautions

• Use with caution in patients with a history of gastritis or gastric ulcers
• Monitor electrolytes in prolonged use
• Use cautiously in patients with respiratory conditions due to potential aspiration risks

Pregnancy

Hydrochloric acid is classified as a category C drug. Use during pregnancy only if clearly needed and the potential benefits justify the risks to the fetus.

Breast-feeding

There is limited data on the excretion of hydrochloric acid in human milk. Use with caution during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight and heat. Ensure the container is tightly closed.

Formulations

• Oral solutions
• Injectable forms
• Tablets

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Metabolic acidosis
• Lactic acidosis
• Support in shock or severe dehydration
• Exercise physiology research

Dosage

Children: Refer to clinical guidelines for specific dosing recommendations based on the clinical condition being treated.

Adults: Refer to clinical guidelines for specific dosing recommendations based on the clinical condition being treated.

Mechanism of action

Lactic acid primarily functions by contributing to the acid-base balance in the body. It can serve as a substrate for gluconeogenesis in the liver and is utilized in the Cori cycle, where it is converted back to glucose. Furthermore, lactic acid can act as a signaling molecule in various physiological processes, influencing metabolism and cellular responses during hypoxic conditions.

Pharmacodynamics

Lactic acid dissociates into lactate and hydrogen ions in solution, which can lead to a decrease in pH (acidosis) when produced in excess. Its accumulation in the body is indicative of anaerobic metabolism, often observed during intense exercise or in conditions of oxygen deprivation. The body can buffer the effects of lactic acid through bicarbonate and other mechanisms, maintaining homeostasis.

Pharmacokinetics

Lactic acid is rapidly absorbed and distributed throughout the body. It is metabolized primarily in the liver, where it can be converted to glucose or further metabolized to carbon dioxide and water. The elimination half-life of lactate varies depending on the metabolic state of the individual and the presence of underlying conditions. Renal function also plays a role in the clearance of lactate from the body.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Hypersensitivity reactions

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Caution in patients with liver disease

Pregnancy

Lactic acid is generally regarded as safe, but clinical use should be evaluated on a case-by-case basis during pregnancy.

Breast-feeding

Considered safe for use during breastfeeding, but consult healthcare provider for individual cases.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Lactic acid injection
• Lactic acid oral solution

Mechanism of action

Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Ciprofloxacin's targeting of the alpha subunits of DNA gyrase prevents it from supercoiling the bacterial DNA which prevents DNA replication. The mechanism by which ciprofloxacin's inhibition of DNA gyrase or topoisomerase IV results in death in susceptible organisms has not been fully determined. Unlike beta-lactam anti-infectives, which are most active against susceptible bacteria when they are in the logarithmic phase of growth, studies using Escherichia coli and Pseudomonas aeruginosa indicate that ciprofloxacin can be bactericidal during both logarithmic and stationary phases of growth; this effect does not appear to occur with gram-positive bacteria (e.g., Staphylococcus aureus). In vitro studies indicate that ciprofloxacin concentrations that approximate the minimum inhibitory concentration (MIC) of the drug induce filamentation in susceptible organisms; high concentrations of the drug result in enlarged or elongated cells that may not be extensively filamented. Although the bactericidal effect of some fluoroquinolones (e.g., norfloxacin) evidently requires competent RNA and protein synthesis in the bacterial cell, and concurrent use of anti-infectives that affect protein synthesis (e.g., chloramphenicol, tetracyclines) or RNA synthesis (e.g., rifampin) inhibit the in vitro bactericidal activity of these drugs, the bactericidal effect of ciprofloxacin is only partially reduced in the presence of these anti-infectives. This suggests that ciprofloxacin has an additional mechanism of action that is independent of RNA and protein synthesis. Ciprofloxacin usually is bactericidal in action. Like other fluoroquinolone anti-infectives, ciprofloxacin inhibits DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 members of the DNA topoisomerase class of enzymes, DNA gyrase and topoisomerase IV. DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication. DNA gyrase, a type II DNA topoisomerase, was the first identified quinolone target; DNA gyrase is a tetramer composed of 2 GyrA and 2 GyrB subunits. DNA gyrase introduces negative superhelical twists in DNA, an activity important for initiation of DNA replication. DNA gyrase also facilitates DNA replication by removing positive super helical twists. Topoisomerase IV, another type II DNA topoisomerase, is composed of 2 ParC and 2 ParE subunits. DNA gyrase and topoisomerase IV are structurally related; ParC is homologous to GyrA and ParE is homologous to GyrB. Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur. Fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA-DNA gyrase complex or the DNA-topoismerase IV complex; these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death. ... Ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concn that deplete cells of mtDNA. The IC50 values for ciprofloxacin varied from 40-80 ug/ml depending on the cell line tested. Cytotoxicity required continuous exposure of cells to drug for 2-4 days, which corresponded to approx three or four cell doublings. Shorter times of drug exposure did not cause significant cytotoxicity. In addition, cells became drug resistant when they were grown under conditions that bypassed the need for mitochondrial respiration. Resistance was not due to a decr in cellular drug accumulation, ... /indicating/ that ciprofloxacin cytotoxicity is caused by the loss of mtDNA encoded functions. Analysis of mtDNA from ciprofloxacin treated cells revealed the presence of site specific, double stranded DNA breaks. ... Exonuclease protection studies indicated that the 5'-, but not the 3', ends of the drug induced DNA breaks were tightly assoc

Pharmacodynamics

Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase. There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective. Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.

Mechanism of action

The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron metabolized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased. Effects on rat liver glucocorticoid receptor in vitro was studied. At 4 °C, 10 mmole EDTA had a stablizing effect on unbound hepatic glucocorticoid receptors. Apparently, endogenous metal ions are involved in the processes of glucocorticoid-receptor complex stabilization and transformation. Edetate disodium injection forms chelates with the cations of calcium and many divalent and trivalent metals. Because of its affinity for calcium, edetate disodium will produce a lowering of the serum calcium level during intravenous infusion. Slow infusion over a protracted period may cause mobilization of extracirculatory calcium stores. Edetate disodium exerts a negative inotropic effect upon the heart. Edetate disodium likewise forms chelates with other polyvalent metals and produces increases in urinary excretion of magnesium, zinc and other trace elements. It does not form a chelate with potassium but may reduce the serum level and increase urinary loss of potassium.

Pharmacodynamics

Edetate calcium is a heavy metal chelating agent. The calcium in edetate calcium can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. In theory, 1 g of edetate calcium can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, edetate calcium also chelates and eliminates zinc from the body. Edetate calcium also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. Edetate calcium is relatively ineffective for use in treating mercury, gold or arsenic poisoning.