HEKOTOS (MINT)

Indications

• Fluid and electrolyte imbalances
• Hypoglycemia
• Nutritional supplementation
• Diabetic emergencies

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: The dosage varies based on the clinical condition and specific formulation used. For intravenous administration, consult product literature for precise dosing.

Mechanism of action

Glucose supplies energy to tissues by undergoing glycolysis, which begins with its phosphorylation by hexokinase to form glucose 6-phosphate. This activates glucose for breakdown, ultimately generating ATP and NADH. The aerobic metabolism of glucose can yield up to 36 ATP molecules. Glucose also serves as a precursor for other biomolecules and regulates various physiological processes including gene transcription and hormone secretion.

Pharmacodynamics

Glucose is an obligatory energy source for cellular activities and plays a significant role in metabolic signaling. It is oxidized to yield energy through glycolysis, the citric acid cycle, and oxidative phosphorylation. Glucose can be converted into fat for energy storage and is stored as glycogen in the liver and muscles. Its administration increases blood glucose levels and stimulates insulin secretion, particularly through oral routes that activate gut incretin hormones.

Pharmacokinetics

Glucose is rapidly absorbed from the gastrointestinal tract or directly into the bloodstream when administered intravenously. It is distributed widely throughout the body and metabolized primarily in tissues requiring energy. The body maintains glucose homeostasis through regulatory mechanisms involving insulin and glucagon. Excess glucose can be stored as glycogen or converted to triglycerides for long-term energy storage.

Adverse effects

• Hyperglycemia
• Increased osmolarity
• Fluid overload
• Electrolyte imbalances

Interactions

• Insulin - may require dose adjustments

Precautions

• Use with caution in patients with diabetes mellitus
• Monitor blood glucose levels in patients receiving parenteral glucose
• Adjust dosage in renal impairment

Pregnancy

Glucose is generally considered safe in pregnancy; however, monitoring is advised, especially in diabetic patients.

Breast-feeding

Glucose is considered safe during breastfeeding, as it is a natural sugar found in breast milk.

Storage

Store at room temperature, away from light. Avoid freezing.

Formulations

• Glucose 5% solution for infusion
• Glucose 10% solution for infusion
• Glucose 0.9% solution for injection
• Glucose sodium chloride combination solutions

Indications

• Advanced ovarian cancer
• Small cell lung cancer
• High-risk seminoma (stage I) testicular germ cell tumors (adjuvant treatment)
• Bladder cancer
• Cervical cancer
• Head and neck cancer

Dosage

Children: Paediatric dosing should be determined based on specific clinical guidelines and product literature, as this information is not directly provided in the BNF.

Adults: The dosage for adults varies based on the specific type of cancer being treated and should be determined by consulting product literature. Typically, it is administered by intravenous infusion.

Mechanism of action

Cisplatin exerts its anticancer effects primarily through the formation of DNA cross-links. The drug binds to DNA, forming interstrand and intrastrand cross-links that inhibit DNA replication and transcription, triggering cellular apoptosis. This mechanism is facilitated by the activation of cellular signaling pathways that respond to DNA damage, leading to cell cycle arrest and subsequent cell death.

Pharmacodynamics

Cisplatin is a cytotoxic agent that targets the DNA of cancer cells, causing significant damage that disrupts the normal processes of cell division and function. It is particularly effective against rapidly proliferating tumors. The drug's efficacy is influenced by factors such as the tumor type, stage, and cellular repair mechanisms.

Pharmacokinetics

Cisplatin has a variable pharmacokinetic profile, with a distribution half-life of approximately 30 minutes and a terminal half-life of about 48 to 100 hours. It is primarily eliminated through the kidneys, and renal function significantly affects its clearance. The drug is known to have dose-dependent nephrotoxicity, necessitating careful monitoring of renal function during treatment.

Contra-indications

• Hypersensitivity to cisplatin or any of its components
• Severe renal impairment
• Myelosuppression
• Pregnancy

Adverse effects

• Nausea
• Vomiting
• Alopecia
• Nephrotoxicity
• Ototoxicity
• Leukopenia
• Thrombocytopenia
• Anaphylactoid reactions
• Cardiac arrest (rare)
• Acute leukemia (rare)

Interactions

• Other nephrotoxic drugs (e.g., aminoglycosides, NSAIDs)
• Ototoxic agents (e.g., loop diuretics)
• Anticonvulsants (may require dosage adjustments)
• Radiation therapy (increased risk of toxicity)

Precautions

• Careful monitoring of renal function
• Hydration before and after administration to reduce nephrotoxicity
• Monitoring for signs of ototoxicity
• Caution in patients with pre-existing hearing impairment
• Use with caution in patients with cardiovascular disorders

Pregnancy

Cisplatin is classified as a Category D drug. It is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

Cisplatin is not recommended during breastfeeding due to potential excretion in breast milk and risk to the infant.

Storage

Store in a cool, dry place away from light. Store the solution in the refrigerator and protect from light.

Formulations

• Cisplatin 1 mg/ml solution for infusion
• Cisplatin 50 mg/50 ml solution for infusion

Indications

• Management of asthma in adults and adolescents not adequately controlled with inhaled corticosteroids and short-acting beta-2 agonists
• Allergic rhinitis
• Nasal polyps

Dosage

Children: For children aged 12-17 years, initially 400 micrograms daily in 1-2 divided doses, single dose to be inhaled in the evening, reduced to 200 micrograms once daily if control is maintained.

Adults: 1 inhalation once daily; dosage may be increased to 400 micrograms twice daily if necessary.

Mechanism of action

Mometasone furoate works by binding to glucocorticoid receptors, leading to the modulation of gene expression. This results in the inhibition of pro-inflammatory cytokines and chemokines, thereby reducing inflammation in the airways and nasal passages. It also inhibits the activation of inflammatory cells such as eosinophils and mast cells, contributing to its therapeutic effects.

Pharmacodynamics

As a corticosteroid, mometasone furoate exhibits significant anti-inflammatory effects, which are crucial in the management of asthma and allergic conditions. The drug reduces airway hyper-responsiveness and decreases mucus production, leading to improved airflow and decreased symptoms such as wheezing and shortness of breath. Its rapid onset of action is beneficial for acute symptom relief.

Pharmacokinetics

Mometasone furoate is well-absorbed when administered by inhalation or nasal spray. It undergoes extensive first-pass metabolism in the liver, resulting in low systemic bioavailability. The drug is primarily excreted via the feces, with a small percentage eliminated through the urine. The half-life of mometasone furoate is approximately 5.8 hours, allowing for once-daily dosing in many cases.

Adverse effects

• Candida infection
• Nasal ulceration
• Throat irritation
• Headache
• Cough

Interactions

• Corticosteroids
• Beta2 agonists

Precautions

• Use with caution in patients with active or quiescent tuberculosis infections
• Monitor for signs of infection
• Use in hepatic impairment requires caution

Pregnancy

Use only if potential benefit outweighs risk-limited information available.

Breast-feeding

Avoid-present in milk in animal studies.

Storage

Store below 30°C. Protect from light and moisture.

Formulations

• {'form': 'Inhalation powder', 'strength': '200 micrograms per dose', 'brand': 'Asmanex Twisthaler'}
• {'form': 'Aqueous nasal spray', 'strength': '50 micrograms per dose', 'brand': 'Flixonase'}

Indications

• Monitoring respiratory function
• Assessment of metabolic status
• Management of respiratory acidosis
• Management of respiratory alkalosis

Dosage

Children: Dosing for interventions related to carbon dioxide levels in pediatric patients should be guided by clinical protocols and the BNF for Children.

Adults: Dosing for interventions related to carbon dioxide levels is typically based on clinical assessment and individual patient needs. Refer to clinical guidelines for specific scenarios.

Mechanism of action

Carbon dioxide acts primarily as a signaling molecule in the body, influencing respiratory drive and blood pH. It is produced during cellular respiration and is a critical component of the bicarbonate buffering system, which helps maintain acid-base homeostasis. Elevated levels of CO2 in the blood stimulate ventilation in the lungs, increasing the rate of gas exchange and facilitating the removal of excess CO2.

Pharmacodynamics

The pharmacodynamic effects of dioxides, particularly carbon dioxide, are closely related to its concentration in the blood. As CO2 levels increase, it leads to respiratory acidosis, which can stimulate the respiratory centers in the brain to increase ventilation. Conversely, low levels of CO2 can cause respiratory alkalosis, potentially leading to decreased respiratory drive. CO2 also plays a role in vasodilation and can affect blood flow and pressure through its influence on smooth muscle tone.

Pharmacokinetics

Carbon dioxide is produced endogenously during metabolic processes and is transported in the bloodstream primarily in three forms: dissolved in plasma, as bicarbonate ions (HCO3-), and bound to hemoglobin. The half-life of CO2 in the bloodstream is very short due to its rapid exchange with alveolar gas in the lungs. The elimination of CO2 occurs through exhalation, making it a dynamic component of respiratory physiology.

Pregnancy

Data on the effects of dioxide during pregnancy are limited. Caution is advised due to potential risks associated with exposure.

Breast-feeding

Limited data are available regarding the excretion of dioxide in human milk. Caution is recommended.

Storage

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

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

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

Indications

• Topical analgesic for muscle and joint pain
• Cough suppressant in cough drops and lozenges
• Relief of minor throat irritation
• Cooling agent in various cosmetic and personal care products

Dosage

Children: Refer to BNF for Children for specific dosing guidelines, as doses may vary based on age and formulation.

Adults: For topical use, apply a thin layer to the affected area not more than 3 to 4 times daily. For cough drops, follow the product-specific instructions as per the formulation.

Mechanism of action

Menthol acts as an agonist for the transient receptor potential subtype M8 (TRPM8), a non-selective cation channel that is activated by cold temperatures. This activation leads to calcium influx in mast cells, inducing the release of histamine, which can trigger allergic responses such as urticaria, asthma, and rhinitis. Menthol's ability to induce histamine release via TRPM8 suggests potential therapeutic applications for TRPM8 antagonists in managing cold- and menthol-induced allergies.

Pharmacodynamics

Menthol produces a cooling effect by stimulating sensory neurons that convey cold sensations. It interacts with TRPM8 channels, leading to the activation of intracellular signaling pathways that can result in vasodilation and increased blood flow to the area of application. This cooling sensation can provide symptomatic relief in conditions characterized by pain or irritation.

Pharmacokinetics

Menthol is absorbed through the skin and mucous membranes, with systemic effects depending on the route of administration. Its bioavailability can vary, and it is metabolized primarily in the liver. The elimination half-life and excretion pathways have not been extensively characterized, but menthol is generally considered to have a rapid onset of action with effects lasting for a few hours.

Adverse effects

• Allergic reactions
• Urticaria
• Asthma
• Rhinitis
• Skin irritation

Precautions

• Use with caution in patients with known allergies to menthol or related compounds
• May exacerbate asthma in sensitive individuals

Pregnancy

There are no well-controlled studies of menthol in pregnant women. Menthol should be used during pregnancy only if clearly needed.

Breast-feeding

Menthol is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical ointment
• Cream
• Liquid

Indications

• Digestive issues
• Nausea
• Headaches
• Respiratory conditions
• Oral hygiene
• Muscle pain relief

Dosage

Children: Dosage should be determined based on age and formulation. Consult specific product instructions and healthcare providers.

Adults: Dosage varies based on preparation and indication. For herbal formulations, refer to specific product guidelines.

Mechanism of action

The active compounds in mint, particularly menthol and menthone, exert their effects primarily through activation of the TRPM8 receptor, which is a cold and menthol receptor. This activation induces a cooling sensation and may provide analgesic effects. Menthol also acts as a smooth muscle relaxant, which can help alleviate gastrointestinal discomfort.

Pharmacodynamics

Mint exhibits various pharmacological effects, including carminative, antispasmodic, and mild analgesic properties. It is known to enhance gastric motility and reduce symptoms of irritable bowel syndrome (IBS). The menthol component may also exhibit mild anti-inflammatory properties and has been used in topical formulations for its cooling and soothing effects.

Pharmacokinetics

After ingestion, mint compounds are rapidly absorbed in the gastrointestinal tract. Menthol is metabolized primarily in the liver, undergoing conjugation. The elimination half-life of menthol is roughly 1-3 hours. The compounds are excreted mainly through urine, with a small percentage being exhaled as volatile constituents.

Adverse effects

• Allergic reactions
• Gastrointestinal disturbances
• Heartburn
• Headaches

Interactions

• May interact with medications that affect the liver enzymes responsible for its metabolism
• Potential interaction with antacids

Precautions

• Use with caution in individuals with gastroesophageal reflux disease (GERD)
• May cause allergic reactions in sensitive individuals

Pregnancy

Generally considered safe when used in food amounts. High doses should be avoided due to potential effects on uterine tone.

Breast-feeding

Generally safe in usual dietary amounts. Consult healthcare provider for concentrated supplements.

Storage

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

Formulations

• Fresh leaves
• Dried leaves
• Essential oil
• Teas

Indications

• Asthma
• Allergic rhinitis
• Skin conditions (e.g., eczema, dermatitis)

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines.

Adults: Refer to the specific BNF guidelines for adult dosing, which may vary based on the condition being treated.

Mechanism of action

Mometasone exerts its anti-inflammatory effects by crossing cell membranes and binding with high affinity to specific cytoplasmic glucocorticoid receptors. This interaction diminishes the release of leukocytic acid hydrolases, prevents macrophage accumulation at inflamed sites, interferes with leukocyte adhesion to capillary walls, reduces capillary membrane permeability, and inhibits the release of histamine and kinin. Additionally, mometasone inhibits the formation of scar tissue and acts through phospholipase A2 inhibitory proteins, known as lipocortins, which control the synthesis of potent inflammatory mediators like prostaglandins and leukotrienes.

Pharmacodynamics

Mometasone demonstrates medium potency as a corticosteroid, effectively reducing inflammation without significant systemic absorption due to extensive hepatic metabolism. Its local effects are favored over systemic effects, making it suitable for chronic conditions like asthma, where immediate symptom relief is not expected. The onset of action may take 1 to 2 weeks for maximum improvement in asthma symptoms following inhalation. Discontinuation of mometasone may allow for sustained asthma stability for several days.

Pharmacokinetics

Mometasone is extensively metabolized in the liver, resulting in a low systemic bioavailability. Its pharmacokinetic profile includes rapid absorption and distribution, with a half-life that supports once-daily dosing in many cases. The lack of active metabolites contributes to its safety profile, minimizing systemic effects while providing effective local action.

Interactions

• cobicistat+mometasone: Unknown (increases exposure)
• idelalisib+mometasone: Unknown (increases exposure)
• clarithromycin+mometasone: Unknown (increases exposure)

Pregnancy

Mometasone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution should be exercised when administering mometasone to nursing mothers, as it is not known whether it is excreted in human milk.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Mometasone furoate nasal spray
• Mometasone furoate inhalation aerosol
• Mometasone furoate cream
• Mometasone furoate ointment
• Mometasone furoate lotion

Indications

• Preservation of food products
• Preservation of pharmaceutical formulations
• Antimicrobial agent in cosmetic products

Dosage

Children: Refer to specific product guidelines for dosage as it varies by formulation and intended use.

Adults: Refer to specific product guidelines for dosage as it varies by formulation and intended use.

Mechanism of action

Sorbate acts primarily by inhibiting the growth of fungi and some bacteria. It interferes with the microbial cell membrane, disrupting its integrity and function, which leads to cell death. The presence of sorbate alters the pH and osmotic balance within the microbial cell, inhibiting key metabolic processes necessary for reproduction and survival.

Pharmacodynamics

Sorbate exhibits its antimicrobial effects at relatively low concentrations. It is most effective in acidic environments, typically at a pH of 4.5 or lower. The compound is more effective against yeasts and molds compared to bacteria. Its mode of action is primarily through the inhibition of fatty acid synthesis and alteration of membrane permeability in target microorganisms.

Pharmacokinetics

Sorbate is generally regarded as having low toxicity and is rapidly metabolized in the human body. It is absorbed in the gastrointestinal tract when ingested and is then distributed throughout the body. The compound undergoes conversion to various metabolites and is primarily excreted via the urine. Its half-life and specific metabolic pathways can vary depending on the form of administration and individual patient factors.

Pregnancy

There is limited data on the safety of sorbate in pregnancy. Use only if clearly needed and potential benefits justify the risks.

Breast-feeding

There is insufficient information regarding the excretion of sorbate in human milk. Caution is advised when administering to nursing mothers.

Storage

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

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

Indications

• Orthopedic implants
• Dental implants
• Prosthetic devices
• Surgical instruments

Mechanism of action

Titanium does not have a specific mechanism of action as it is not a drug in the traditional sense. Instead, its biocompatibility allows it to integrate with biological tissues without eliciting significant immune responses, making it suitable for use in implants and prosthetic devices. The presence of titanium ions can influence biological processes, including cell proliferation and differentiation.

Pharmacodynamics

Titanium itself does not exhibit pharmacodynamics as it is not administered as a drug. Its interactions within biological systems are primarily mechanical and structural, providing support and stability in orthopedic and dental applications. The biocompatibility of titanium allows for favorable tissue integration and reduced rejection rates compared to other materials.

Pharmacokinetics

As titanium is not a pharmacological agent, traditional pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion do not apply. Titanium is typically utilized in solid forms, such as implants, where it remains localized and does not undergo metabolism or systemic circulation.

Pregnancy

There is limited data on the use of titanium during pregnancy. Consult a healthcare professional before use.

Breast-feeding

There is limited data on the excretion of titanium in breast milk. Consult a healthcare professional before use.

Storage

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

Mechanism of action

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into two main phases where the preparatory phase is initiated by the phosphorylation of glucose by hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for the subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where the total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. These energy-producing reactions of glucose are limited to D-glucose as L-glucose cannot be phosphorylated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number, and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation to preserve cellular and whole body metabolic integrity. Vascular calcification is a hallmark of type 2 diabetes. Glucose stimulates calcification in culture of vascular smooth muscle cells (VSMCs) but the underlying mechanisms remain obscure. We observed that high glucose levels stimulated mouse and human VSMC trans-differentiation into chondrocytes, with increased levels of Sox9, type II collagen, glycosaminoglycan and Runx2 expression, and increased alkaline phosphatase activity and mineralization. These effects were associated with increased expression of IL-1beta, which stimulated alkaline phosphatase and calcification, suggesting that glucose induces chondrocyte differentiation of VSMCs, possibly through IL-1beta activation.

Pharmacodynamics

Blood glucose is an obligatory energy source for humans involved in various cellular activities, and it also acts as a signaling molecule for diverse glucose-sensing molecules and proteins. Glucose undergoes oxidation into carbon dioxide, water, and yields energy molecules in the process of glycolysis and subsequent citric cycle and oxidative phosphorylation. Glucose is readily converted into fat in the body which can be used as a source of energy as required. Under a similar conversion into storage of energy, glucose is stored in the liver and muscles as glycogen. Glucose stores are mobilized in a regulated manner, depending on the tissues' metabolic demands. Oral glucose tablets or injections serve to increase the supply of glucose and oral glucose administration is more effective in stimulating insulin secretion because it stimulates the incretin hormones from the gut, which promotes insulin secretion.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.

Mechanism of action

Exposure to low temperatures often causes allergic responses or urticaria. Similarly, menthol, a common food additive is also known to cause urticaria, asthma, and rhinitis. However, despite the obvious clinical implications, the molecular mechanisms responsible for inducing allergic responses to low temperatures and menthol have not been determined. Because a non-selective cation channel, transient receptor potential subtype M8 (TRPM8) is activated by cold and menthol, we hypothesized that this channel mediates cold- and menthol-induced histamine release in mast cells. Here, we report that TRPM8 is expressed in the basophilic leukemia mast cell line, RBL-2H3, and that exposure to menthol or low temperatures induced Ca(2+) influx in RBL-2H3 cells, which was reversed by a TRPM8 blocker. Furthermore, menthol, a TRPM8 agonist, induced the dose-dependent release of histamine from RBL-2H3 cells. When TRPM8 transcripts were reduced by siRNA (small interfering RNA), menthol- and cold-induced Ca(2+) influx and histamine release were significantly reduced. In addition, subcutaneous injection of menthol evoked scratching, a typical histamine-induced response which was reversed by a TRPM8 blocker. Thus, our findings indicate that TRPM8 mediates the menthol- and cold-induced allergic responses of mast cells, and suggest that TRPM8 antagonists be viewed as potential treatments for cold- and menthol-induced allergies. /DL-Menthol/ Menthol's characteristic cooling sensation is due, in part, to the activation of sensory neurons generally termed transient receptor potential (TRP) channels, in particular transient receptor potential melastatin family member 8 (TRPM8) and transient receptor potential subfamily A, member 1 (TRPA1). Menthol acts upon TRPM8 receptors by rapidly increasing intracellular calcium and mobilizing calcium flux through the channels to induce cold response signals at the application site. Aside from its cold-inducing sensation capabilities, menthol exhibits cytotoxic effects in cancer cells, induces reduction in malignant cell growth, and engages in synergistic excitation of GABA receptors and sodium ion channels resulting in analgesia. /DL-Menthol/ In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgen-independent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p < 0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G(0)/G(1) phase (p < 0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent. /DL-Menthol/

Mechanism of action

Unbound corticosteroids cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Inflammation is decreased by diminishing the release of leukocytic acid hydrolases, prevention of macrophage accumulation at inflamed sites, interference with leukocyte adhesion to the capillary wall, reduction of capillary membrane permeability, reduction of complement components, inhibition of histamine and kinin release, and interference with the formation of scar tissue. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A₂ inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone.

Pharmacodynamics

Mometasone is a medium-potency synthetic corticosteroid with antiinflammatory, antipruritic, and vasoconstrictive properties. Studies in asthmatic patients have demonstrated that mometasone provides a favorable ratio of topical to systemic activity due to its primary local effect along with the extensive hepatic metabolism and the lack of active metabolites. Though effective for the treatment of asthma, glucocorticoids do not affect asthma symptoms immediately. Maximum improvement in symptoms following inhaled administration of mometasone furoate may not be achieved for 1 to 2 weeks or longer after starting treatment. When glucocorticoids are discontinued, asthma stability may persist for several days or longer. Mometasone has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone. The clinical significance of these findings is unknown.