Tenectase

Indications

• Urea cycle disorders
• Hyperammonaemia types I and II
• Citrullinaemia
• Arginosuccinic aciduria
• Deficiency of N-acetyl glutamate synthetase
• Acute hyperammonaemia in carbamylphosphate synthetase deficiency
• Acute hyperammonaemia in ornithine transcarbamylase deficiency

Dosage

Children: Neonate: 100–300 mg/kg daily in 3–4 divided doses; Child (body-weight up to 40 kg): 6 mg/kg/hour; Child (body-weight 40 kg and above): 4 mg/kg/hour.

Adults: Refer to BNF for specific dosing based on condition; typically administered as 5–50 mg/kg twice daily, adjusted according to plasma ammonia concentration.

Mechanism of action

Arginine serves as a substrate for the synthesis of nitric oxide (NO), a crucial signaling molecule, and contributes to the urea cycle, facilitating the detoxification of ammonia in the liver.

Pharmacodynamics

As a precursor for nitric oxide, arginine plays a vital role in vasodilation and modulating blood flow. It also aids in protein synthesis and supports metabolic processes in the body.

Pharmacokinetics

Arginine is absorbed from the gastrointestinal tract and is distributed throughout the body. It undergoes hepatic metabolism, primarily via the urea cycle, and its half-life is influenced by renal function.

Pregnancy

Use only if clearly needed; consult specialist.

Breast-feeding

Use with caution; benefits should outweigh risks.

Storage

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

Formulations

• L-Arginine 500 mg tablets
• L-Arginine 1 gram tablets
• L-Arginine powder for solution
• L-Arginine 500 mg capsules
• L-Arginine 21% concentrate for solution for infusion

Indications

• Acute myocardial infarction
• Acute coronary syndromes

Dosage

Adults: 30–50 mg (maximum per dose 50 mg), administered intravenously over 10 seconds, initiated within 6 hours of symptom onset.

Mechanism of action

Tenecteplase is a genetically engineered variant of tissue plasminogen activator (tPA) that binds to fibrin in a thrombus (blood clot) and activates plasminogen, converting it to plasmin. This process leads to the degradation of fibrin, thus facilitating the dissolution of the clot and restoration of normal blood flow.

Pharmacodynamics

The pharmacodynamic effects of tenecteplase include rapid thrombolysis in patients with acute myocardial infarction. The drug's fibrin specificity and longer half-life compared to alteplase contribute to its efficiency in dissolving clots. It enhances the body's ability to recanalize occluded coronary arteries, resulting in improved myocardial perfusion.

Pharmacokinetics

Tenecteplase is administered intravenously, with a bioavailability approaching 100%. The drug has a half-life of approximately 20 to 25 minutes, allowing for rapid action. Its clearance is primarily through the liver, and plasma levels can be affected by factors such as age, weight, and renal function. Monitoring is essential to ensure effective dosing and minimize the risk of bleeding complications.

Contra-indications

• Aortic stenosis
• Cardiac tamponade
• Head trauma
• Toxic pulmonary oedema
• Recent history of myocardial infarction
• Susceptibility to angle-closure glaucoma
• Ventilation and perfusion abnormalities

Adverse effects

• Drowsiness
• Hemiparesis
• Venous thrombosis
• Arrhythmias
• Asthenia
• Cerebral ischaemia
• Dizziness
• Flushing
• Headache
• Hypotension
• Nausea
• Vomiting
• Circulatory collapse
• Diarrhoea
• Skin reactions

Interactions

• Nitrates may develop tolerance leading to reduced therapeutic effects
• Care should be taken when used with other anticoagulants or antiplatelet agents

Precautions

• Caution in elderly patients due to potential for postural hypotension and falls
• Patients on long-acting nitrates should have doses adjusted to avoid tolerance
• Monitor for signs of bleeding

Pregnancy

Manufacturer advises caution, as risk cannot be ruled out.

Breast-feeding

Manufacturer advises avoiding breastfeeding for 24 hours after dose; express and discard milk during this time.

Storage

Store in a cool, dry place. Protect from light. Store vials in the original package until use.

Formulations

• Powder for solution for infusion

Indications

• Hypophosphatemia
• Calcium phosphate deficiency
• Nutritional supplementation
• pH adjustment in pharmaceutical formulations

Dosage

Children: Refer to BNF for Children for specific dosing recommendations based on indication.

Adults: Refer to clinical guidelines or BNF for specific dosing recommendations based on indication.

Mechanism of action

Phosphoric acid provides phosphate ions that are critical for numerous biochemical reactions in the body. These phosphate ions are involved in the formation of ATP, which is essential for energy transfer within cells. The acid itself dissociates in aqueous solutions, releasing hydrogen ions and contributing to pH levels, which can affect enzymatic activities and cellular functions.

Pharmacodynamics

Phosphoric acid acts by replenishing phosphate levels in the body, which can be important in various physiological processes including energy metabolism, bone mineralization, and the synthesis of nucleic acids. Its effects on pH regulation can also influence metabolic pathways, particularly in managing acidosis or alkalosis.

Pharmacokinetics

Phosphoric acid is generally administered orally or intravenously, depending on the therapeutic application. Following administration, it is absorbed in the gastrointestinal tract, with phosphate ions distributed throughout the body. The kidneys play a significant role in regulating phosphate homeostasis, with excess phosphate being excreted in urine. The half-life of phosphoric acid is not well defined, as it is rapidly metabolized and utilized in various metabolic pathways.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hypophosphatemia

Precautions

• Use with caution in patients with renal impairment
• Monitor phosphate levels in patients receiving long-term therapy
• Consider potential for gastrointestinal irritation

Pregnancy

Phosphoric acid is generally considered safe in pregnancy when used in recommended doses, but caution is advised.

Breast-feeding

Phosphoric acid is excreted in breast milk, use with caution and under medical supervision.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral solutions
• Tablets
• Syrups

Indications

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

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

Formulations

• Polysorbate 20
• Polysorbate 80

Indications

• Surgical procedures
• Injection of medications
• Preparation of sterile pharmaceutical products
• Management of open wounds
• Use in controlled environments such as hospitals and laboratories

Dosage

Children: Refer to specific drug monographs for dosage information as sterile itself is not a pharmacological agent.

Adults: Refer to specific drug monographs for dosage information as sterile itself is not a pharmacological agent.

Mechanism of action

Sterility itself does not have a mechanism of action as it is a state of cleanliness and does not interact with biological systems. However, the methods used to achieve sterility, such as heat or chemical agents, act by denaturing proteins, disrupting cellular structures, or damaging nucleic acids in microorganisms, leading to their inactivation or destruction.

Pharmacodynamics

The pharmacodynamics of sterile techniques primarily involves the prevention of microbial infection and contamination when administering medications. By ensuring that products are sterile, the risk of adverse effects related to infections is minimized. The effectiveness of sterilization methods can be influenced by factors such as temperature, duration of exposure, and the type of microorganisms present.

Pharmacokinetics

As sterility does not pertain to a specific drug, pharmacokinetics is not applicable. However, the pharmacokinetics of a drug will depend on its formulation, route of administration, and the presence of preservatives or stabilizers that may be used alongside sterile preparations.

Pregnancy

Sterile preparations are generally considered safe during pregnancy as they are used to provide hydration, nutrition, or medications in a controlled manner, but specific formulations should be assessed individually.

Breast-feeding

Sterile solutions used for hydration or nutritional support are typically safe during breastfeeding, but any specific additives or medications within the solutions should be evaluated for safety.

Storage

Sterile solutions should be stored in a cool, dry place, protected from light, and should be used before the expiration date. Once opened, they may have specific storage requirements based on the formulation.

Formulations

• Sterile saline solution
• Sterile water for injection
• Sterile dextrose solution
• Sterile electrolyte solutions

Mechanism of action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacodynamics

Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.