Pregasafe 150

Indications

• Epilepsy
• Neuropathic pain
• Generalized anxiety disorder

Dosage

Adults: The usual starting dose is 150 mg daily, divided into two or three doses. The dose may be increased to a maximum of 600 mg daily based on clinical response and tolerability. Refer to the BNF for specific dosing adjustments in

Mechanism of action

Pregabalin binds presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding modulates the release of several excitatory neurotransmitters, including glutamate, substance P, norepinephrine, and calcitonin gene-related peptide. By preventing the trafficking of the alpha2-delta subunit from the dorsal root ganglia to the spinal dorsal horn, pregabalin contributes to its anticonvulsant and analgesic effects.

Pharmacodynamics

Pregabalin increases the density of GABA transporters in cultured neurons but does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors. It does not affect dopamine, serotonin, or opiate receptors, nor does it modulate sodium channels or cyclooxygenase activity. Its primary action is through the inhibition of excitatory neurotransmitter release, which helps in controlling seizures and alleviating neuropathic pain.

Pharmacokinetics

Pregabalin is rapidly absorbed after oral administration, with peak plasma concentrations usually reached within 1 hour. It has a bioavailability of approximately 90%, and its plasma concentration does not significantly change with increasing doses. Pregabalin is not extensively metabolized; it is primarily excreted unchanged in the urine. The elimination half-life is about 6 hours, and dose adjustments may be necessary in patients with renal impairment.

Adverse effects

• Dizziness
• Somnolence
• Dry mouth
• Edema
• Weight gain
• Blurred vision
• Difficulty concentrating
• Euphoria
• Depression
• Angioedema

Interactions

• CNS depressants may enhance the sedative effects of pregabalin
• Concurrent use with opioids may increase the risk of respiratory depression
• Antiepileptic drugs may have additive effects

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor for signs of angioedema, especially in patients with a history of angioedema
• Caution in patients with renal impairment, as dosage adjustments may be necessary

Pregnancy

Pregabalin is classified as category C. Animal studies have shown adverse effects, and there are no well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Pregabalin is excreted in breast milk. The effects on a nursing infant are unknown, and caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg
• Oral solution: 20 mg/mL
• Chewable tablets: 50 mg

Indications

• Caffeine sensitivity
• Fatigue management
• Attention deficit hyperactivity disorder (ADHD)
• Weight loss adjunct
• Respiratory stimulant in apnea of prematurity

Dosage

Children: Refer to specific drug guidelines or product information for dosing as it varies by indication and formulation.

Adults: Refer to specific drug guidelines or product information for dosing as it varies by indication and formulation.

Mechanism of action

The mechanism of action for anhydrous substances varies depending on the specific drug in its anhydrous form. Generally, the absence of water can alter the solubility and absorption of the drug, enhancing its bioavailability. For example, in the case of anhydrous caffeine, it acts as a central nervous system stimulant by antagonizing adenosine receptors and increasing the release of neurotransmitters like dopamine and norepinephrine.

Pharmacodynamics

Pharmacodynamics of anhydrous formulations depends on the specific active ingredient. In the case of stimulants such as caffeine, the pharmacodynamic effects include increased alertness, reduced perception of fatigue, and improved cognitive performance. The anhydrous form may allow for faster onset of action and increased potency compared to its hydrated counterpart.

Pharmacokinetics

Pharmacokinetics will vary by compound, but generally, anhydrous forms may exhibit altered absorption rates due to their increased solubility. The distribution, metabolism, and excretion profiles can also be influenced by the absence of water, potentially leading to quicker therapeutic effects or side effects. For instance, anhydrous caffeine is rapidly absorbed in the gastrointestinal tract, with peak plasma concentrations occurring within 30 to 60 minutes.

Pregnancy

The safety of anhydrous substances during pregnancy has not been thoroughly established. It is advisable to consult healthcare professionals before use.

Breast-feeding

It is recommended to exercise caution and seek professional advice before using anhydrous substances while breastfeeding.

Storage

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

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Used as a binder in tablet formulations
• Serves as a disintegrant to enhance drug release
• Utilized in the formulation of granules and powders

Dosage

Children: Refer to specific formulation guidelines as doses vary based on the formulation and active ingredients.

Adults: Refer to specific formulation guidelines as doses vary based on the formulation and active ingredients.

Mechanism of action

Pregelatinized starch acts primarily as a binder and disintegrant in tablet formulations. When exposed to moisture, it swells and rapidly absorbs water, leading to the disintegration of the tablet and facilitating the release of the active pharmaceutical ingredients.

Pharmacodynamics

The pharmacodynamic properties of pregelatinized starch are closely related to its physicochemical characteristics. It enhances the dissolution rate of poorly soluble drugs and helps in achieving a uniform distribution of the active ingredients within a formulation. Its ability to form a gel-like consistency in the presence of water aids in the controlled release of the drug.

Pharmacokinetics

As an excipient, pregelatinized starch is not intended to exert pharmacological effects on its own. It is generally regarded as safe and is not absorbed systemically. Its role is primarily mechanical, aiding in the formulation process of pharmaceutical products. The pharmacokinetics of any drug formulated with pregelatinized starch will depend on the active ingredients present in the formulation.

Pregnancy

Pregelatinized starch is generally considered safe for use during pregnancy as it is a food grade ingredient, but it is advisable to consult with a healthcare professional.

Breast-feeding

Pregelatinized starch is also considered safe during breastfeeding as it is unlikely to affect milk production or quality.

Storage

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

Formulations

• Powder
• Granules

Indications

• Nutritional supplementation
• Energy source in enteral nutrition
• Excipient in pharmaceutical formulations

Dosage

Children: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Adults: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Mechanism of action

Starch is broken down into glucose units by enzymes such as amylase during digestion. The glucose is then absorbed in the intestines and utilized for energy production in the body's cells. This pathway involves hydrolysis of the glycosidic bonds, converting starch into simpler sugars.

Pharmacodynamics

Starch primarily serves as an energy source. Its digestion and absorption lead to an increase in blood glucose levels, which provides energy for metabolic processes. In this context, it plays a crucial role in maintaining energy homeostasis in the body.

Pharmacokinetics

Starch is not absorbed in its polymeric form; it must first be enzymatically hydrolyzed into simpler sugars such as maltose and glucose. The digestion and absorption of starch occur predominantly in the small intestine, with glucose being readily absorbed into the bloodstream. The rate of absorption can vary depending on the type of starch and its physical form.

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

• Use with caution in individuals with known allergies to starch or starch derivatives
• Monitor for gastrointestinal symptoms in patients with a history of digestive disorders

Pregnancy

Starch is generally considered safe for use during pregnancy. However, it should be consumed in moderation as part of a balanced diet.

Breast-feeding

Starch is deemed safe for nursing mothers when used in moderation as part of a balanced diet.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Suspensions

Indications

• Used as an excipient in drug formulations
• Pleurodesis for the management of recurrent pleural effusions

Dosage

Children: Refer to specific guidelines for paediatric use, as dosing may differ based on age and clinical condition.

Adults: Refer to specific guidelines for the appropriate dosage in pleurodesis and other applications, as it may vary based on clinical context.

Mechanism of action

Talc exhibits very good absorptive properties, allowing it to absorb moisture and other substances effectively. This characteristic is particularly useful in pharmaceutical formulations, where it may enhance the stability and texture of the drug product.

Pharmacodynamics

Talc's primary pharmacodynamic effect is its ability to act as an inert filler and bulking agent in pharmaceutical preparations. It does not have any intrinsic pharmacological activity but serves to improve the physical properties of formulations, such as flowability and compressibility.

Pharmacokinetics

Talc is not absorbed systemically when used as an excipient or in medical procedures. Its effects are local, and it remains in the site of application, where it functions primarily as a mechanical agent. The pharmacokinetics of talc in the context of its use in pleurodesis involves its ability to promote adhesion of the pleural surfaces, thereby preventing fluid accumulation.

Pregnancy

Talc is classified as a substance with minimal systemic absorption, but safety during pregnancy has not been well established. Consult relevant guidelines.

Breast-feeding

Talc is not expected to be absorbed in significant amounts; however, caution is advised and consult guidelines.

Storage

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

Mechanism of action

Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models. By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. Pregabalin is an anticonvulsant that is structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA). Pregabalin also has demonstrated analgesic activity. Although pregabalin was developed as a structural analog of GABA, the drug does not bind directly to GABA-A, GABA-B, or benzodiazepine receptors; does not augment GABA-A responses in cultured neurons; and does not alter brain concentrations of GABA in rats or affect GABA uptake or degradation. However, in cultured neurons, prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in CNS tissues. ... In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, including glutamate, norepinephrine, and substance P, possibly by modulation of calcium channel function. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake. Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. ... Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. ... For more Mechanism of Action (Complete) data for PREGABALIN (6 total), please visit the HSDB record page.

Pharmacodynamics

Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors. Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system. Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.

Mechanism of action

It has very good absorptive properties.