Fosfomax

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)

Indications

• Acute uncomplicated lower urinary tract infections

Mechanism of action

Fosfomycin exerts its bactericidal effects by covalently binding to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme. This inhibition prevents the enzyme from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), disrupting the production of the peptidoglycan precursor UDP-N-acetylmuramic acid (UDP-MurNAc) and ultimately interfering with bacterial cell wall synthesis. Fosfomycin enters bacterial cells via the L-alpha-glycerophosphate system and the hexose-6-phosphate transporter system. Additionally, it reduces bacterial adhesion to epithelial cells in the urinary and respiratory tracts.

Pharmacodynamics

Fosfomycin is primarily used for treating urinary tract infections but is also effective against various difficult-to-treat strains of bacteria. It has demonstrated the ability to act synergistically with other antibiotics, which enhances its efficacy against clinically relevant pathogens. The drug has low cross-resistance with other antibiotics due to its unique mechanism of action. Furthermore, fosfomycin possesses immunomodulating properties, influencing cytokine responses and enhancing neutrophil activity against pathogens. It effectively penetrates biofilms, reducing microbial load and altering biofilm structure.

Pharmacokinetics

Fosfomycin is administered intravenously and has a bioavailability that can vary depending on the formulation. It is primarily eliminated through renal excretion, with a clearance that may be affected by renal function. The drug's half-life and distribution in body tissues can vary, and monitoring of renal function is advised during treatment, especially in patients with compromised renal function.

Adverse effects

• Abdominal pain
• Diarrhoea
• Headache
• Nausea
• Vomiting
• Skin reactions
• Dizziness
• Vulvovaginal infection
• Antibiotic associated colitis

Precautions

• Monitor electrolytes and fluid balance with intravenous use
• Caution in patients with cardiac insufficiency, elderly patients, hyperaldosteronism, hypernatraemia, hypertension, and pulmonary oedema
• Severe hepatic impairment requires caution

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk-no information available.

Breast-feeding

Present in milk in small amounts, but absorption from gastrointestinal tract is negligible.

Storage

Store in a cool, dry place away from direct sunlight. Follow specific storage instructions on the label.

Formulations

• Fomicyt 2g powder for solution for infusion vials
• Fomicyt 4g powder for solution for infusion vials

Indications

• Thickening agent in topical formulations
• Anti-caking agent in powders
• Carrier for active pharmaceutical ingredients

Dosage

Children: Refer to specific formulation guidelines in the BNF for Children.

Adults: Refer to specific formulation guidelines in the BNF.

Mechanism of action

Aerosil exerts its effects primarily through its surface characteristics. The interaction of silica particles with biological systems can lead to cytotoxicity and cellular transformation, which are influenced by the distribution of silanol groups and the presence of trace metals such as iron. The cytotoxic effects are related to the ability of silica to generate reactive oxygen species, leading to oxidative stress in cells. The biological response to aerosil is sensitive to the composition and structural features of the silica surface, indicating that its activity is a surface-originated phenomenon.

Pharmacodynamics

The pharmacodynamic properties of aerosil are related to its ability to modify the rheological properties of formulations, improve flowability, and prevent clumping. Its cytotoxic effects at high concentrations can lead to cellular stress and transformation, although these effects are primarily of concern in occupational exposure rather than therapeutic use. The dose-response relationship can vary based on the specific type of silica and its surface modifications.

Pharmacokinetics

Aerosil is not absorbed systemically when used in pharmaceutical formulations due to its high molecular weight and physical properties. Inhalation of silica dust can lead to pulmonary exposure, where it may elicit inflammatory responses and potentially lead to silicosis over prolonged exposure. Its elimination from the body does not occur via typical metabolic pathways; instead, silica particles may be cleared from the lungs by macrophage action and mucociliary clearance mechanisms.

Indications

• Enhancement of taste in food and beverages
• Improvement of palatability in nutritional products
• Masking undesirable flavors in medications

Dosage

Children: There is no specific pediatric dosage for flavor agents as they are used as needed to improve the taste of food and beverages.

Adults: There is no specific dosage for flavor agents as they are used as needed to achieve the desired taste and aroma in food and beverages.

Mechanism of action

Flavor compounds interact with taste receptors on the tongue, stimulating the sensory neurons responsible for taste perception. This interaction influences the overall flavor profile of food and beverages, enhancing the eating experience. Some flavors may also have a psychological effect, stimulating appetite or evoking pleasant memories associated with certain tastes.

Pharmacodynamics

While flavor agents are primarily used for sensory enhancement in food, their pharmacodynamic effects are minimal as they are not designed to elicit a pharmacological response. However, certain flavors may influence digestion and metabolism indirectly by enhancing saliva production or affecting gut motility. The enjoyment of flavored products can also lead to increased food intake and satisfaction.

Pharmacokinetics

Flavour compounds are typically ingested and metabolized by the body. Their absorption rates can vary depending on their chemical structure and formulation. Once ingested, they may be rapidly metabolized in the liver and other tissues, with excretion primarily via urine. The specific pharmacokinetic profiles of flavor agents can vary significantly based on their source and chemical properties.

Pregnancy

Flavours are generally considered safe for use during pregnancy, but specific assessments should be made based on the type of flavouring agent.

Breast-feeding

Most flavouring agents are deemed safe during breastfeeding, although it's advisable to consult healthcare professionals regarding specific ingredients.

Storage

Store in a cool, dry place away from direct sunlight and heat sources. Ensure that the container is tightly sealed to prevent contamination.

Indications

• Antioxidant support
• Immune system enhancement
• Support for skin health
• Improvement of iron absorption
• General dietary supplementation

Dosage

Children: There are no specific dosing recommendations for mandarin; it is generally consumed as part of a balanced diet.

Adults: There are no specific dosing recommendations for mandarin; it is generally consumed as part of a balanced diet.

Mechanism of action

The health benefits of mandarins are primarily attributed to their high content of flavonoids, carotenoids, and ascorbic acid (vitamin C). These compounds exert their effects through various mechanisms, including the scavenging of free radicals, modulation of inflammatory pathways, and enhancement of immune function. Vitamin C plays a critical role in collagen synthesis and acts as a potent antioxidant.

Pharmacodynamics

The pharmacodynamic effects of mandarins are largely related to their bioactive compounds. The flavonoids found in mandarins, such as hesperidin and naringin, have been shown to exhibit anti-inflammatory and antioxidant effects. These compounds may help in reducing oxidative stress and inflammation in the body, which are linked to chronic diseases. The vitamin C content supports immune function and aids in the absorption of iron from plant-based foods.

Pharmacokinetics

The absorption of nutrients from mandarins occurs primarily in the gastrointestinal tract. Vitamin C is readily absorbed, with peak plasma levels reached within a few hours after consumption. The bioavailability of flavonoids can vary depending on the individual's gut microbiota and dietary habits. Metabolism of these compounds occurs mainly in the liver, and they are excreted through urine.

Pregnancy

Mandarins are generally considered safe to consume during pregnancy, providing essential nutrients and hydration.

Breast-feeding

Mandarins can be consumed during breastfeeding as they are nutritious and hydrating, but moderation is advisable to prevent potential digestive upset in infants.

Storage

Store mandarins in a cool, dry place or refrigerate them to extend freshness. Ensure they are kept in a well-ventilated area to prevent mold growth.

Dosage

Children: Refer to BNF for Children for specific recommendations regarding the consumption of orange juice in children.

Adults: There is no standard dosage for orange juice as it is typically consumed as a beverage. Moderation is advised, especially for individuals on certain medications.

Mechanism of action

The exact mechanism of action of orange juice is not fully understood, but it is known to contain compounds that can influence the metabolism of certain drugs. For instance, it may affect the activity of cytochrome P450 enzymes, particularly CYP3A4, which can alter the pharmacokinetics of medications.

Pharmacodynamics

Orange juice is known to enhance the bioavailability of certain nutrients and may influence the pharmacological effects of some drugs. Its high vitamin C content contributes to various physiological functions, including antioxidant activity, which may indirectly support overall health.

Pharmacokinetics

The pharmacokinetics of orange juice itself are not extensively studied, but it is generally absorbed well through the gastrointestinal tract. The compounds in orange juice can affect the absorption and metabolism of medications, leading to varied clinical effects depending on the drug in question.

Interactions

• orange juice + celiprolol: Unknown (decreases exposure)

Formulations

• juice
• whole fruit

Indications

• Management of diabetes
• Weight management
• Sugar substitutes in food and beverages

Dosage

Children: Refer to the BNF for Children for specific dosage information. Caution is advised when using artificial sweeteners in children.

Adults: Refer to the BNF for specific dosage information. Generally, saccharin is used in very small quantities due to its high sweetness intensity.

Mechanism of action

Saccharin activates specific T2R bitter taste receptors, contributing to the perception of sweetness and the bitter aftertaste associated with saccharin and acesulfame-K. Additionally, it has been shown to stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, which are present in taste receptor cells and nerve terminals throughout the oral cavity. The activation of TRPV1 may play a role in the aftertaste or metallic taste sensation often reported with saccharin consumption.

Pharmacodynamics

Due to its high sweetness intensity, saccharin can effectively mimic the taste of sugar without contributing to caloric intake. It alters taste perception by engaging receptors responsible for taste sensation, particularly affecting the sweet and bitter taste pathways. Its effect on TRPV1 receptors suggests a complex interaction that may enhance the sensory experience of sweetness while also causing potential off-tastes.

Pharmacokinetics

Saccharin is not metabolized by the body and is excreted unchanged in the urine. Its absorption occurs in the gastrointestinal tract, but due to its non-nutritive nature, it does not undergo significant metabolic processes. The pharmacokinetic profile indicates that saccharin has a rapid onset of action with a prolonged sweet taste effect, although individual responses may vary.

Adverse effects

• Allergic reactions
• Headaches
• Nausea
• Gastrointestinal disturbances

Precautions

• Use with caution in individuals with a history of hypersensitivity to saccharin or its derivatives
• Avoid excessive consumption to prevent possible adverse effects

Pregnancy

Saccharin is generally not recommended during pregnancy due to potential risks, although human studies have shown no clear evidence of harm.

Breast-feeding

Saccharin is excreted in breast milk; caution is advised when used by nursing mothers.

Storage

Store in a cool, dry place away from light.

Formulations

• Tablets
• Powder

Indications

• Providing energy in dietary supplementation
• Enhancing flavor in food products
• Replacement of carbohydrates in certain medical nutrition therapies

Dosage

Children: Refer to general dietary guidelines for carbohydrate intake in children. No specific dosing guidelines provided.

Adults: Refer to general dietary guidelines for carbohydrate intake. No specific dosing guidelines provided.

Mechanism of action

Sugar is metabolized in the body to provide energy. Upon ingestion, sucrose is broken down by the enzyme sucrase into its constituent monosaccharides, glucose and fructose, which are then absorbed into the bloodstream. These monosaccharides can be utilized by cells for energy or stored as glycogen in the liver and muscles.

Pharmacodynamics

As a simple carbohydrate, sugar elevates blood glucose levels rapidly after consumption, leading to increased insulin secretion from the pancreas. This insulin facilitates the uptake of glucose by tissues, promoting energy production. The rapid increase in blood sugar can provide quick energy but may also lead to potential negative effects on metabolism and weight if consumed in excess.

Pharmacokinetics

After oral administration, sugar is quickly hydrolyzed in the gastrointestinal tract. Peak plasma glucose concentrations typically occur within 30 minutes to 2 hours post-ingestion, depending on the amount consumed and individual metabolism. The half-life of glucose in the bloodstream is relatively short, as it is rapidly taken up by tissues or converted into glycogen.

Pregnancy

Sugar is generally considered safe for use during pregnancy, but excessive intake should be avoided to prevent gestational diabetes and excessive weight gain.

Breast-feeding

Sugar is safe during breastfeeding; however, excessive consumption should be avoided.

Storage

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

Formulations

• Granulated sugar
• Brown sugar
• Powdered sugar
• Liquid sugar

Mechanism of action

Fosfomycin exerts its bactericidal effects by binding covalently to a cysteine in the active site of the UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) enzyme, rendering it inactive. By preventing MurA from catalyzing the condensation of phosphoenolpyruvate (PEP) with UDP-N-acetylglucosamine (UNAG), fosfomycin inhibits the production of the peptidoglycan precursor UDP N-acetylmuramic acid (UDP-MurNAc). Ultimately, the first step of bacterial cell wall synthesis is disrupted. In _Escherichia coli_, fosfomycin gains entry into bacterial cells via two mechanisms: the L-alpha-glycerophosphate system and the hexose-6-phosphate transporter system. Fosfomycin also has important effects on cell adhesion. For example, the adhesion of bacterial cells to urinary epithelial cells is reduced in the presence of fosfomycin. The adhesion of _Streptococcus pneumoniae_ and _Haemophilus influenzae_ to respiratory epithelial cells is also reduced

Pharmacodynamics

Although used primarily to treat urinary tract infections, fosfomycin has been shown to act synergistically with other antibiotics against clinically relevant bacteria. There is also growing interest in the potential of fosfomycin to treat more complex infections since it has retained activity against many difficult-to-treat strains of bacteria including methicillin-resistant _Staphylococcus aureus_ (MRSA) and multidrug-resistant enterobacteria. Further, since fosfomycin has a unique and singular mechanism of action, the risk of cross-resistance with other antibiotics is low. Fosfomycin also demonstrates immunomodulating properties. For example, the antibiotic may influence components of the acute inflammatory cytokine response and enhances neutrophil phagocytic destruction of pathogens. Fosfomycin penetrates biofilms effectively and is capable of not only reducing or eliminating microorganisms in biofilms but can also alter the biofilm structure.

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

...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and

Mechanism of action

...it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. ... /This study/ addressed the question of whether /they/ could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the ... aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca(2+) imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons,... /it was found/ that in both systems, .../sweeteners/ activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. ... /it was/also found that TRPV1 receptors were activated by CuSO(4), ZnSO(4), and FeSO(4), three salts known to produce a metallic taste sensation. In summary, .../the/ results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.