EPSYLAM DT 50

Indications

• Monotherapy of focal seizures
• Monotherapy of primary generalized tonic-clonic seizures
• Monotherapy of secondary generalized tonic-clonic seizures
• Adjunctive therapy in partial-onset seizures
• Seizures associated with Lennox-Gastaut syndrome
• Bipolar disorder management

Dosage

Adults: Initially, 25 mg once daily for 14 days, then increased to 50 mg once daily for a further 14 days, with adjustments of up to 100 mg every 7–14 days; maintenance dose of 100–200 mg daily in 1–

Mechanism of action

Lamotrigine exerts its effects by inhibiting voltage-sensitive sodium channels, which stabilizes neuronal membranes and reduces the release of presynaptic excitatory neurotransmitters. It selectively binds to inactive sodium channels, which suppresses sodium currents and contributes to its anticonvulsant properties. Additionally, lamotrigine displays weak binding to various receptors, including serotonin and adenosine receptors, contributing to its diverse pharmacological effects.

Pharmacodynamics

Lamotrigine effectively prevents seizures and mood symptoms by stabilizing presynaptic neuronal membranes, thus preventing the release of excitatory neurotransmitters such as glutamate that are implicated in seizure activity. Its metabolite can cause dose-dependent cardiovascular effects, such as prolongation of the PR interval and widening of the QRS complex, although this metabolite is present in trace amounts in humans.

Pharmacokinetics

Lamotrigine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring about 1.5 to 3 hours after oral administration. It undergoes hepatic metabolism through glucuronidation, and its half-life can be affected by concurrent medications and hepatic function. The presence of enzyme inducers can significantly reduce its plasma concentration, while enzyme inhibitors can increase it, necessitating careful monitoring and dose adjustments.

Adverse effects

• Dizziness
• Headache
• Nausea
• Rash
• Insomnia
• Blurred vision
• Aseptic meningitis
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome

Interactions

• Cenobamate may decrease lamotrigine concentration
• Desmopressin may increase the risk of hyponatraemia when used with lamotrigine
• Hormonal contraceptives (desogestrel, etonogestrel, levonorgestrel, norethisterone) may have decreased effectiveness with lamotrigine
• Ritonavir may decrease lamotrigine exposure
• Nirmatrelvir boosted with ritonavir may decrease lamotrigine concentration

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of serious skin reactions
• Counsel patients regarding driving and skilled tasks due to potential dizziness
• Monitor neurodevelopment in infants if used during breastfeeding

Pregnancy

Specialist sources indicate caution in use, potential risks should be evaluated against benefits.

Breast-feeding

Use with caution only if no suitable alternative; present in milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Lamotrigine 2 mg tablets
• Lamotrigine 5 mg tablets
• Lamotrigine 25 mg tablets
• Lamotrigine 50 mg tablets
• Lamotrigine 100 mg tablets
• Lamotrigine 200 mg tablets
• Oral solution available

Dosage

Children: Refer to specific guidelines or literature for dosing information.

Adults: Refer to specific guidelines or literature for dosing information.

Pregnancy

Consult healthcare professionals before use. Safety during pregnancy is not well established.

Breast-feeding

Consult healthcare professionals before use. Safety during breastfeeding is not well established.

Storage

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

Mechanism of action

Carbonate ions participate in buffering reactions that help maintain pH homeostasis in biological systems. They can react with acids to form bicarbonate and carbon dioxide, thus neutralizing excess acidity in the body. This mechanism is crucial in processes such as respiration and metabolism.

Pharmacodynamics

As a buffer, carbonate helps to stabilize pH levels in different biological environments, preventing excessive acidity or alkalinity that could impair cellular functions. It is involved in the transport of carbon dioxide in the blood and plays a role in maintaining the acid-base equilibrium necessary for physiological processes.

Pharmacokinetics

Carbonate ions are readily absorbed in the gastrointestinal tract when ingested and can be found in various body fluids. They are involved in the bicarbonate buffering system, where they are converted to bicarbonate (HCO3-) and carbon dioxide (CO2) through reactions with acids. The kidneys regulate the levels of bicarbonate and carbonate in the body, excreting or reabsorbing them as needed to maintain homeostasis.

Pregnancy

There is no specific information available regarding the use of carbonate compounds during pregnancy. Consult a healthcare provider for advice.

Breast-feeding

There is no specific information available regarding the use of carbonate compounds while breastfeeding. Consult a healthcare provider for advice.

Storage

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

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Dosage

Children: Refer to the specific product monograph or guidelines for paediatric dosing, as this varies widely by drug.

Adults: Refer to the specific product monograph or guidelines for adult dosing, as this varies widely by drug.

Mechanism of action

The mechanism of action for drugs referred to as 'current' varies widely depending on the specific drug in question. Generally, drugs exert their effects through various pathways such as receptor binding, enzyme inhibition, or modulation of ion channels, leading to a physiological response that alleviates symptoms or treats disease.

Pharmacodynamics

Pharmacodynamics of 'current' drugs is dependent on their specific pharmacological class and intended use. Generally, this involves understanding how these drugs interact with biological systems at the cellular level, impacting processes such as neurotransmission, immune response, or metabolic pathways. The efficacy and safety of these drugs are also evaluated through their therapeutic indices, dose-response relationships, and potential for adverse effects.

Pharmacokinetics

Pharmacokinetics for drugs categorized as 'current' can vary significantly among different pharmaceuticals. Key factors include absorption rates, distribution volumes, metabolism primarily through hepatic pathways, and the excretion of active metabolites. Understanding the pharmacokinetic profile is essential for optimizing dosing regimens and ensuring therapeutic effectiveness while minimizing toxicity.

Pregnancy

Current data suggests that this drug may have potential risks during pregnancy, and its use should be carefully evaluated by a healthcare provider.

Breast-feeding

It is unclear whether this drug is excreted in human milk. Caution is advised when administering this drug to nursing mothers.

Storage

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

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

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

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

Indications

• Diarrhea
• Cholesterol management
• Hyperlipidemia

Dosage

Children: Refer to specific product guidelines or consult a pharmacist for dosing information.

Adults: Refer to specific product guidelines or consult a pharmacist for dosing information.

Mechanism of action

Polacrilin works by adsorbing bile acids and other substances in the gastrointestinal tract, thereby reducing their availability for absorption. This mechanism helps in reducing fat absorption and managing conditions such as diarrhea by decreasing the osmotic load. The polymer structure of polacrilin allows it to interact with various ions and molecules, facilitating its role as an ion-exchange resin.

Pharmacodynamics

Polacrilin exhibits a high capacity for binding bile acids, which contributes to its effectiveness in lowering cholesterol levels and managing diarrhea. The binding of bile acids leads to increased fecal excretion of bile salts, which can result in decreased cholesterol reabsorption and subsequently lower serum cholesterol levels. Additionally, the absorbent properties of polacrilin aid in the reduction of stool frequency and fluidity in cases of diarrhea.

Pharmacokinetics

Polacrilin is not significantly absorbed systemically due to its high molecular weight and polymeric nature. It acts locally within the gastrointestinal tract, where it exerts its effects. The elimination of polacrilin occurs through fecal excretion, as it is not metabolized by the body. Its effects are dose-dependent, with higher doses leading to greater binding capacity and an increased impact on gastrointestinal motility.

Adverse effects

• Constipation
• Diarrhea
• Abdominal discomfort
• Bloating

Precautions

• Use with caution in patients with gastrointestinal disorders
• Monitor for potential electrolyte imbalances

Pregnancy

Polacrilin is classified as a category C drug. Its safety during pregnancy has not been established, and it should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether polacrilin is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Oral suspension
• Tablet form

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Caloric reduction in food and beverages
• Management of diabetes
• Weight management

Dosage

Children: Refer to the BNF for Children for specific guidelines on the use of sucralose in pediatric populations.

Adults: Sucralose is typically used in food and beverage products as a sweetener. There are no specific dosage recommendations for adults, as it is used according to taste preference and product formulation.

Mechanism of action

Sucralose acts as a positive allosteric modulator of the human sweet taste receptor. It interacts with the T1R taste receptor family, particularly enhancing the sweetness perception by binding to the hinge region of the receptor. This interaction induces a conformational change that stabilizes the active state of the receptor, increasing its responsiveness to sweet stimuli. This mechanism allows sucralose to mimic the taste of sugar without the associated caloric intake.

Pharmacodynamics

As a non-nutritive sweetener, sucralose does not undergo metabolic processing in the body, which means it does not contribute to energy intake. It provides intense sweetness at low concentrations, stimulating the sweetness receptors in the taste buds. The pharmacodynamic profile indicates minimal physiological effects beyond taste perception, making it suitable for dietary use without impacting blood glucose levels.

Pharmacokinetics

Sucralose is poorly absorbed in the gastrointestinal tract, with an estimated absorption rate of less than 15%. The majority of ingested sucralose is excreted unchanged in the urine. The elimination half-life is not well defined due to its minimal absorption, but it is generally considered to have a rapid clearance from the body. The pharmacokinetic properties support its use as a safe alternative to sugar for those managing caloric intake.

Pregnancy

Sucralose is generally considered safe during pregnancy, but it is recommended to consult a healthcare provider.

Breast-feeding

Sucralose is also considered safe during breastfeeding, although it is advisable to seek medical advice.

Storage

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

Formulations

• Granulated sucralose
• Liquid sucralose
• Tablets

Mechanism of action

The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM. Weak inhibitory effects were observed at sigma opioid receptors. An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects. Spectrophotometry with the Ca(++)-sensitive dye fura-2 was used to study the effect of lamotrigine (LAG) on the depolarization-evoked Ca++ influx in the acutely isolated basolateral amygdala neurons. Depolarization of the neurons with high K+ resulted in the elevation of intracellular Ca++ concentration [Ca++]i in a concentration-dependent manner. The K(+)-induced Ca++ influx was completely blocked in the Ca(++)-free solution or by Cd++, indicating that depolarization-induced increases in [Ca++]i were triggered largely, if not completely, by Ca++ entry from extracellular space and Ca++ entry occurred through voltage-dependent Ca++ channels. Application of LAG reduced the depolarization-evoked Ca++ influx in a concentration-dependent manner. The effect of LAG was markedly reduced in the presence of N-type Ca++ channel blocker omega-conotoxin-GVIA (omega-CgTX). These results suggest that the action of LAG is mediated, at least in part, by the modulation of N-type Ca++ channels. Lamotrigine (LAG) is an antiepileptic drug which is believed to suppress seizures by inhibiting the release of excitatory neurotransmitters. The present study was aimed at investigating the effect of LAG on the 4-aminopyridine (4AP)-evoked glutamate release in cerebrocortical nerve terminals (synaptosomes). LAG inhibited the release of glutamate evoked by 4AP in a concentration-dependent manner. This inhibitory effect was associated with a reduction in the depolarization-evoked increase in the cytoplasmic free Ca2+ concentration ([Ca2+]C). In addition, LAG did not alter the resting synaptosomal membrane potential or 4AP-evoked depolarization. Furthermore, ionomycin-evoked glutamate release was not affected by LAG. Based on these results, we suggest that presynaptic calcium influx blockade and inhibition of glutamate release may underlie the mechanism of action of LAG. These action may also contribute to their neuroprotective properties in excitotoxic injury.

Pharmacodynamics

Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity. A note on cardiovascular effects The metabolite of lamotrigine, 2-N-methyl metabolite (formed by glucuronidation), is reported to cause dose-dependent prolongations of the PR interval, widening of the QRS complex, and at higher doses, complete AV block. Although this harmful metabolite is only found in trace amounts in humans, plasma concentrations may increase in conditions that cause decreased drug glucuronidation, such as liver disease.

Mechanism of action

Positive allosteric modulators of the human sweet taste receptor ...developed as a new way of reducing dietary sugar intake .../can be used as/ ...valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, .../the study/ reveal how ...sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.