Iohexol 350 mg I/mL Solution for Injection

Indications

• Metabolic acidosis
• Severe hyperkalaemia
• Renal artery stenosis
• Nephrotic syndrome
• Severe heart failure
• Potassium depletion due to diuretics

Dosage

Children: Dosing in children should be appropriate to the body weight and clinical

Adults: Dosage must be tailored to the individual patient's acid-base status and clinical condition. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Trometamol is a weak base that functions as a proton acceptor. Upon intravenous administration, it binds to hydrogen ions and associated acid anions, leading to their excretion in urine. It is capable of combining with lactic, pyruvic, and other metabolic acids, thereby reducing hydrogen ion concentration in the body. The drug's ionized form predominates at physiological pH, allowing it to penetrate cell membranes and interact with intracellular acids. This action increases bicarbonate concentration and decreases carbon dioxide tension, potentially leading to hypoventilation.

Pharmacodynamics

Trometamol reduces acidity in the body by acting on acid-base buffers, thus shifting the balance towards alkalinity. It increases the flow of alkaline urine, enhancing diuresis and electrolyte excretion. The correction of metabolic acidosis can improve various physiological functions, but caution is required due to the potential for respiratory depression caused by decreased carbon dioxide tension.

Pharmacokinetics

Trometamol is administered intravenously and rapidly distributes into extracellular fluids. It is metabolized primarily in the liver, with renal excretion of the resultant salts. The onset of action is typically quick, and the duration of effect depends on the severity of acidosis and the therapeutic context. Monitoring of plasma potassium levels is essential, particularly in patients with renal impairment.

Contra-indications

• Anuria
• Chronic respiratory acidosis

Adverse effects

• Hepatic necrosis in neonates
• Hypoglycaemia
• Respiratory depression

Interactions

• Potassium salts may cause nausea and vomiting
• Drugs exacerbating hyperkalaemia should be reviewed and stopped as appropriate

Precautions

• Extravasation can cause severe tissue damage
• Use with caution in renal impairment due to risk of hyperkalaemia

Pregnancy

Limited information available, management of hyperkalaemia may harm fetus.

Breast-feeding

No information available.

Storage

Store in a cool, dry place. Protect from light.

Formulations

• Solution for infusion (Trometamol 363.4 mg per 1 ml, Tris 36.34% solution for infusion)

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as this varies widely.

Adults: Refer to specific drug guidelines for adult dosing, as this varies widely.

Mechanism of action

The mechanism of action will vary depending on the specific drug referred to as 'adjust'. Generally, medications designed to 'adjust' physiological parameters may work by modulating neurotransmitter systems, altering hormonal levels, or affecting enzyme activity to achieve therapeutic effects.

Pharmacodynamics

Pharmacodynamics will depend on the specific drug, but typically involves the interaction of the drug with its receptor sites, leading to a biological response. The efficacy and potency of the drug are influenced by its affinity for the target receptors and the subsequent signaling pathways activated.

Pharmacokinetics

Pharmacokinetics, including absorption, distribution, metabolism, and excretion, will vary by drug. Common factors influencing pharmacokinetics include bioavailability, half-life, and the presence of food or other drugs that may affect the drug's metabolism and elimination from the body.

Dosage

Children: Refer to specific product guidelines as dosages may vary based on the active ingredient and clinical condition.

Adults: Refer to specific product guidelines as dosages may vary based on the active ingredient and clinical condition.

Mechanism of action

The specific mechanism of action for a concentrated drug depends on the active ingredients present in the formulation. Generally, concentrated drugs exert their effects by interacting with specific receptors or enzymes in the body, altering physiological processes. For example, concentrated analgesics may inhibit cyclooxygenase enzymes, leading to reduced production of prostaglandins, resulting in pain relief. Similarly, concentrated antibiotics may inhibit bacterial cell wall synthesis, leading to bacterial death.

Pharmacodynamics

Pharmacodynamics of concentrated drugs involves understanding the relationship between drug concentration at the site of action and the resulting therapeutic effect. Concentration-dependent effects may be observed, where higher concentrations lead to increased efficacy but also a risk of toxicity. The therapeutic window, which is the range between effective and toxic concentrations, is critical in guiding the safe use of concentrated formulations.

Pharmacokinetics

Pharmacokinetics of concentrated drugs encompasses absorption, distribution, metabolism, and excretion (ADME). Concentrated formulations may have altered pharmacokinetic profiles compared to standard formulations due to their higher potency. Absorption may be faster or more extensive, depending on the formulation. Distribution may be influenced by factors such as lipophilicity and plasma protein binding. Metabolism may occur in the liver, primarily through enzymatic pathways, while excretion typically occurs via renal or biliary routes.

Pregnancy

Consult a healthcare professional before use. Safety in pregnancy has not been established.

Breast-feeding

Consult a healthcare professional before use. Safety during breastfeeding has not been established.

Storage

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

Indications

• Lead poisoning
• Mercury poisoning
• Calcium overload
• Certain diagnostic procedures involving heavy metals

Dosage

Children: Refer to the BNF for Children for appropriate dosing information tailored for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, considering factors such as the severity of metal poisoning and renal function.

Mechanism of action

Edetate functions by forming stable complexes with divalent and trivalent metal ions, including lead and calcium, through its multiple carboxylate and amine groups. This chelation renders the metals more soluble and promotes their renal excretion, thereby reducing their toxic effects in the body.

Pharmacodynamics

The chelation of metals by edetate decreases the free metal concentration in the bloodstream, which mitigates the toxic effects associated with heavy metal accumulation. The efficacy of edetate in removing metals such as lead has been well documented, and its ability to bind calcium can influence calcium homeostasis in certain clinical scenarios.

Pharmacokinetics

Edetate is administered intravenously, with rapid distribution throughout the extracellular fluid. It is primarily excreted unchanged by the kidneys. The onset of action occurs quickly after administration, and the duration depends on the dose and the patient's renal function. The elimination half-life is approximately 1 hour but may vary based on renal clearance.

Contra-indications

• Hypersensitivity to edetate or any component of the formulation
• Severe renal impairment
• Active bleeding disorders

Adverse effects

• Hypocalcemia
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Rash
• Fever

Interactions

• May enhance the effects of anticoagulants
• Concurrent use with calcium supplements may reduce effectiveness
• May interfere with the absorption of certain medications due to changes in gastrointestinal motility

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels, particularly calcium, during treatment
• Assess the patient's hydration status before administration

Pregnancy

Limited data on the use of edetate in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known whether edetate is excreted in human milk. Weigh the risks and benefits before use.

Storage

Store in a cool, dry place, protected from light. Do not freeze.

Formulations

• Edetate disodium injection
• 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

• Myelography
• Arthrography
• Nephroangiography
• Arteriography
• Computed tomography (CT) scans with contrast

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on age, weight, and the type of procedure.

Adults: Refer to BNF for specific dosing guidelines based on the type of procedure and patient condition.

Mechanism of action

Organic iodine compounds block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. The degree of opacity produced by these compounds is directly proportional to the total amount of the iodinated contrast agent in the path of the x-rays. After intrathecal administration, diffusion of iohexol in the CSF allows visualization of the subarachnoid spaces of the head and spinal canal. After intravascular administration, iohexol makes opaque those vessels in its path of flow, allowing visualization of the internal structures until significant hemodilution occurs.

Pharmacodynamics

Iohexol is an effective non-ionic, water-soluble contrast agent used in various radiographic procedures such as myelography, arthrography, nephroangiography, and arteriography. Its low systemic toxicity is due to both low chemotoxicity and low osmolality, making it safer for patients compared to older contrast agents.

Pharmacokinetics

Iohexol is administered intravascularly or intrathecally, where it diffuses into the bloodstream or cerebrospinal fluid, respectively. It is excreted primarily through the kidneys; thus, renal function can affect its clearance. The half-life and distribution can vary based on the route of administration and the individual's physiological characteristics.

Contra-indications

• Known hypersensitivity to iohexol or any of its components
• Severe dehydration
• Severe renal impairment (eGFR <30 mL/min)

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Urticaria
• Anaphylactic reactions
• Renal impairment
• Extravasation

Interactions

• Other nephrotoxic agents may increase the risk of renal impairment when used with iohexol
• Metformin: there is a risk of lactic acidosis in patients with renal impairment after administration of iodinated contrast agents

Precautions

• Assess renal function prior to administration, especially in patients with pre-existing renal impairment
• Use caution in patients with a history of asthma or allergic reactions
• Ensure adequate hydration before and after the procedure to minimize the risk of nephrotoxicity
• Monitor for signs of anaphylaxis during and after administration

Pregnancy

Iohexol should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. It is classified as a Category B drug.

Breast-feeding

It is generally considered safe to use iohexol during breastfeeding, but it is advised to monitor the infant for any potential adverse effects.

Storage

Store at room temperature, between 15°C and 30°C. Protect from light. Do not freeze.

Formulations

• Iohexol injection (various concentrations available)

Indications

• Cryotherapy for the destruction of abnormal tissue
• Treatment of warts, moles, and other skin lesions
• Nitrogen narcosis in diving

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations in paediatric patients.

Adults: For cryotherapy, the dosage and duration depend on the specific condition being treated and should be determined by the healthcare provider. Refer to specific guidelines for each condition.

Mechanism of action

In cryotherapy, the mechanism of action involves three stages: heat transfer, cell injury, and inflammation. The boiling point of liquid nitrogen is -196°C, which initiates heat transfer, leading to cell injury during the thawing process. The inflammation stage follows, characterized by edema and erythema, resulting from cellular death and contributing to local cell destruction. Additionally, nitrogen can cause direct toxic effects on brain functions, leading to nitrogen narcosis, which impairs cognitive abilities and motor functions due to its impact on nerve conduction.

Pharmacodynamics

Nitrogen's pharmacodynamics relate to its behavior in cryotherapy and asphyxiation. In cryotherapy, it induces tissue destruction through rapid cooling, leading to apoptosis of abnormal cells. In high-pressure environments, nitrogen narcosis affects the central nervous system, producing symptoms similar to alcohol intoxication, ultimately decreasing reasoning, decision-making abilities, and manual dexterity.

Pharmacokinetics

Nitrogen does not undergo metabolism in the traditional sense, as it is an inert gas at physiological conditions. Its pharmacokinetics involve physical principles of gas exchange and partial pressures. In the case of nitrogen narcosis, the effects are influenced by the partial pressure of nitrogen in the bloodstream, which increases with depth during diving. Nitrogen is primarily eliminated from the body through respiration.

Adverse effects

• Narcotic effect at high pressures
• Stupor or euphoria
• Decreased motor function and manual dexterity
• Asphyxiation due to oxygen displacement

Precautions

• Careful monitoring in environments with high nitrogen pressures
• Avoidance of rapid ascents in diving to prevent nitrogen narcosis
• Use in controlled settings to prevent asphyxiation risks

Pregnancy

Nitrogen is generally considered safe in terms of direct effects during pregnancy; however, the safety of exposure in high-pressure environments should be assessed.

Breast-feeding

Nitrogen is not known to affect breastfeeding; however, caution is recommended in environments where nitrogen levels may displace oxygen.

Storage

Store in a cool, dry place away from heat sources; liquid nitrogen should be handled with care due to extreme cold.

Formulations

• Liquid nitrogen
• Nitrogen gas (compressed)

Mechanism of action

Tromethamine is an alkalinizing agent which acts as a proton (hydrogen ion) acceptor. Tromethamine is a weak base; following IV injection, it attracts and combines with hydrogen ions and their associated acid anions and the resulting salts are excreted in urine. Tromethamine can combine with lactic, pyruvic, and other metabolic acids and with carbonic acid. ... At pH 7.4, approximately 70% of the tromethamine present in plasma is in the ionized (protonated) form; if pH is decreased from pH 7.4, the ionized fraction of the drug is increased. In contrast to the ionized fraction of tromethamine, which upon administration reacts only with acid in the extracellular fluids, the fraction of the dose which remains un-ionized at physiologic pH is thought to be capable of penetrating the cell membrane to combine with intracellular acid. Since administration of tromethamine reduces hydrogen ion concentration, there is a decrease in proton donor and an increase in proton acceptor concentrations in body buffers. In the bicarbonate:carbonic acid buffer, the concentration of dissolved carbon dioxide is decreased (at least until regulatory mechanisms compensate) and the concentration of bicarbonate is increased. The reduction of carbon dioxide tension removes a potent stimulus to breathing and may result in hypoventilation and hypoxia. Tromethamine ... acts as a weak, osmotic diuretic, increasing the flow of alkaline urine containing increased amounts of electrolytes. By removing protons from hydronium ions, ionization of carbonic acid is shifted so as to decrease pCO2 and to increase bicarbonate. Excess bicarbonate is then gradually excreted in kidney. /Tromethamine is an/ especially useful way to manage excessively high pCO2 in respiratory acidosis...

Mechanism of action

Organic iodine compounds block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. The degree of opacity produced by these compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. After intrathecal administration into the subarachnoid space, diffusion of iohexol in the CSF allows the visualization of the subarachnoid spaces of the head and spinal canal. After intravascular administration, iohexol makes opaque those vessels in its path of flow, allowing visualization of the internal structures until significant hemodilution occurs.

Pharmacodynamics

Iohexol is an effective non-ionic, water-soluble contrast agent which is used in myelography, arthrography, nephroangiography, arteriography, and other radiographic procedures. Its low systemic toxicity is the combined result of low chemotoxicity and low osmolality.

Mechanism of action

In cryotherapy, mechanism of action could be classified into three stages: 1. heat transfer, 2. cell injury and 3. inflammation. Boiling point of liquid nitrogen is -196°C, which is the responsible for creating the initial stage which is heat transfer. The second stage is cell injury which is induced during thawing conditions of the cells. The last step in the cryotherapy is the inflammation stage which is characterized by edema and erythema. Inflammation occurs as a result of cellular death and it helps in local cell destruction. ... Nitrogen also has a direct toxic action of its own, affecting brain functions and inducing a stupor or euphoria. Nitrogen narcosis ("rapture of the deep" or "the martini effect") results from a direct toxic effect of high nitrogen pressure on nerve conduction and produces effects similar to alcohol intoxication. Complex reasoning, decision-making ability, motor function, and manual dexerity decrease. Individuals vary in this response widely, but it typically can be noticed among divers at depths exceeding 100 ft (30 m). For example, certain individuals experience no effect at depths of < or = 130 ft, whereas others feel some effect at around 80 ft. Nonetheless, the narcotic effect increases with increasing depth so that each additional 50 ft incrementally produces the effect of "another martini". A simple asphyxiant, nitrogen's main toxicty arises from its ability to displace O2 and generate an atmosphere that does not support the chemical reactions needed for maintenance of life. The displacement of O2 can be complete or incomplete, leading to varying degrees of hypoxia. Nitrogen is an inert substance and does not exert a direct toxicological effect. Nitrogen acts by the physiological effect of simple asphyxia on the target species within a Controlled Atmosphere Treatment (CAT) bubble. The biocide action of nitrogen is due to its displacement of oxygen from an atmospheric oxygen level of 20.8% to levels < 0.2% v/v in the CAT bubble. The level of oxygen is the critical factor. Victims exposed to atmospheres deficient in oxygen, i.e. < 19%, will begin to display signs and symptoms of oxygen-deficient exposure of air due to an increase in nitrogen.