TIARE 60

Indications

• Cerebral edema
• Elevated intracranial pressure
• Acute kidney injury
• Oliguria
• Glaucoma
• Renal function diagnostic aid

Dosage

Adults: For cerebral edema, administer 0

Mechanism of action

Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. This action reduces cerebral edema and intracranial pressure. As a diuretic, it increases the osmolality of glomerular filtrate, leading to increased urinary excretion of water and preventing sodium and chloride reabsorption in the renal tubules. Mannitol also facilitates the urinary excretion of toxic substances and can help in assessing renal function by measuring glomerular filtration rate (GFR).

Pharmacodynamics

Mannitol is classified as an osmotic diuretic. It is chemically similar to other sugar alcohols but has a unique ability to promote diuresis by remaining unabsorbed in the renal tubules. Its use is indicated for conditions associated with increased body fluids, such as cerebral edema and glaucoma. Mannitol may be combined with other diuretics to enhance diuretic efficacy. Inhaled formulations are used in cystic fibrosis, though they may cause bronchospasm and hemoptysis.

Pharmacokinetics

Mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption, which allows for its urinary excretion rate to serve as a measurement of GFR. It does not undergo significant metabolism and is eliminated primarily through the kidneys. The onset of action occurs within 30 to 60 minutes after intravenous administration, with effects lasting for several hours. Administration may require monitoring of renal function and fluid balance.

Contra-indications

• Anuria
• Severe dehydration
• Severe renal impairment
• Intracranial bleeding

Adverse effects

• Asthenia
• Gastrointestinal disturbances
• Dry mouth
• Confusion
• Visual impairment
• Hypotension
• Electrolyte imbalances
• Pulmonary edema
• Hemoptysis (with inhalation use)
• Bronchospasm (with inhalation use)

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• Other diuretics may have additive effects
• Caution with nephrotoxic agents

Precautions

• Caution in patients with diabetes mellitus
• Caution in the elderly
• Caution in patients with gout
• Caution in patients with hepatic impairment
• Monitor renal function and electrolytes regularly
• May cause blue fluorescence of urine

Pregnancy

Manufacturer advises avoid due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises avoid due to lack of information available.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Solution for injection
• Inhalation powder
• Oral solution

Indications

• Prevention of atherothrombotic events in patients with acute coronary syndrome
• Management of patients undergoing percutaneous coronary intervention

Dosage

Adults: Initially, 180 mg orally, followed by 90 mg twice daily, in combination with aspirin.

Mechanism of action

Ticagrelor antagonizes the P2Y12 receptor, which is coupled with Gαi2 and other Gi proteins. This interaction inhibits adenylyl cyclase, reduces cyclic adenosine monophosphate (cAMP) levels, and subsequently decreases platelet activation and aggregation. The drug also inhibits the reuptake of adenosine into erythrocytes, which may contribute to its cardiovascular effects.

Pharmacodynamics

As a P2Y12 receptor antagonist, ticagrelor effectively reduces the formation of occlusive thromboses, thus lowering the incidence of myocardial infarction and ischemic stroke. It has a moderate duration of action and is usually administered twice daily. The drug's therapeutic index is wide, making it well tolerated even at higher doses. Common adverse effects include bleeding, dyspnea, and bradyarrhythmias, necessitating patient counseling.

Pharmacokinetics

Ticagrelor is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 3 hours. The drug undergoes significant hepatic metabolism, primarily by cytochrome P450 enzymes, and has an elimination half-life of approximately 7 hours. It is excreted mainly through feces and urine, with caution advised in patients with hepatic or renal impairment due to increased bleeding risk.

Contra-indications

• Severe hepatic impairment
• Active bleeding
• History of hypersensitivity to ticagrelor or any component of the formulation

Adverse effects

• Anaemia
• Haemorrhage
• Skin events
• Thrombocytopenia
• Dyspnea
• Bradyarrhythmias
• Angioedema

Interactions

• Cobicistat: Severe (increases exposure)
• Idelalisib: Severe (increases exposure)
• Mitotane: Severe (decreases exposure)
• Rifampicin: Severe (decreases exposure)
• Amiodarone: Moderate (increases exposure)
• Cenobamate: Moderate (decreases exposure)
• Ciclosporin: Moderate (increases exposure)
• Azithromycin: Moderate (increases exposure)
• Ranolazine: Moderate (increases exposure)
• Dabigatran: Moderate (increases exposure)

Precautions

• Use with caution in patients with renal impairment
• Use with caution in patients with moderate hepatic impairment
• Elderly patients at increased risk of bleeding
• Discontinue at least 7 days before elective surgery if antiplatelet effect not desirable

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises to avoid due to lack of information available.

Storage

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

Formulations

• Ticagrelor 90 mg tablets

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

Indications

• Used as a disintegrant in tablet formulations
• Improves dissolution of active pharmaceutical ingredients
• Facilitates the breakdown of solid dosage forms

Dosage

Children: Refer to specific product information for dosing guidelines, as croscarmelose is used as an excipient and not dosed independently.

Adults: Refer to specific product information for dosing guidelines, as croscarmelose is used as an excipient and not dosed independently.

Mechanism of action

Croscarmelose functions by rapidly absorbing water and swelling upon hydration. This swelling action creates pressure within the tablet, leading to disintegration into smaller particles. The increased surface area of the drug particles enhances dissolution and absorption in the gastrointestinal tract, ultimately improving the pharmacokinetic profile of the active ingredients.

Pharmacodynamics

As a disintegrant, croscarmelose does not exert a pharmacological effect on its own but plays a critical role in the formulation of oral solid dosage forms. Its pharmacodynamic properties are primarily related to its ability to facilitate the release of active ingredients from their dosage forms, thereby influencing the onset and duration of action of the administered medication.

Pharmacokinetics

Croscarmelose is not absorbed systemically when ingested, as it functions primarily within the gastrointestinal tract. It is excreted unchanged in the feces following its role in aiding the dissolution and disintegration of solid dosage forms. Its safety profile is well-established, and it is considered non-toxic, with minimal adverse effects when used in recommended amounts.

Pregnancy

Croscarmelose is generally considered safe for use during pregnancy as it is an inert substance and does not have systemic effects.

Breast-feeding

Croscarmelose is not absorbed systemically and is considered safe for use during breastfeeding.

Storage

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

Formulations

• Tablet
• Capsule
• Powder

Indications

• Calcium deficiency
• Osteoporosis prevention
• Osteomalacia
• Rickets
• Dietary supplementation in individuals with increased calcium and phosphorus requirements

Dosage

Children: Refer to established guidelines for specific dosing based on clinical indications and individual patient needs.

Adults: Refer to established guidelines for specific dosing based on clinical indications and individual patient needs.

Mechanism of action

Dicalcium phosphate dissociates in the gastrointestinal tract to release calcium and phosphate ions. Calcium plays a vital role in various physiological processes, including muscle contraction, neurotransmitter release, and blood coagulation. The phosphate ions are essential for energy metabolism and are integral to the formation of ATP (adenosine triphosphate), nucleic acids, and cellular membranes. The availability of these ions supports bone mineralization and overall skeletal integrity.

Pharmacodynamics

The pharmacodynamics of dicalcium phosphate involves its role in maintaining calcium and phosphate homeostasis in the body. Adequate levels of calcium are critical for normal bone metabolism, while phosphate is necessary for the formation of hydroxyapatite in bone tissue. The balance of these minerals is regulated by hormones such as parathyroid hormone and calcitriol, which modulate their absorption in the intestines and reabsorption in the kidneys. Supplementation with dicalcium phosphate can help alleviate deficiencies and support bone health.

Pharmacokinetics

Dicalcium phosphate is absorbed in the gastrointestinal tract, with varying absorption rates depending on the presence of other dietary components. Calcium absorption occurs primarily in the small intestine, while phosphate absorption can occur throughout the gastrointestinal tract. After absorption, calcium is distributed to bones, teeth, and soft tissues, while excess calcium is excreted through urine. The pharmacokinetics may be influenced by factors such as age, dietary habits, and the presence of gastrointestinal disorders.

Adverse effects

• Gastrointestinal disturbances (nausea, constipation)
• Hypercalcemia
• Kidney stones
• Fatigue
• Muscle weakness

Interactions

• May interact with calcium channel blockers
• Increased risk of hypercalcemia with thiazide diuretics
• May affect the absorption of certain antibiotics (e.g., tetracyclines)

Precautions

• Use with caution in patients with renal impairment
• Monitor calcium levels in patients receiving high doses
• Consider potential interactions with other medications

Pregnancy

Dicalcium is generally considered safe in pregnancy when used as directed, but high doses should be avoided.

Breast-feeding

Calcium is an essential nutrient during breastfeeding, but excessive supplementation should be approached with caution.

Storage

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

Formulations

• Tablets
• Powders
• Chewable tablets

Indications

• Used as an excipient in pharmaceutical formulations
• Improves solubility and stability of active ingredients
• Facilitates drug absorption

Dosage

Children: Refer to specific product guidelines as hydroxypropyl is typically used as an excipient and not dosed independently.

Adults: Refer to specific product guidelines as hydroxypropyl is typically used as an excipient and not dosed independently.

Mechanism of action

Hydroxypropyl functions primarily as a solubilizing agent, which aids in the dissolution of poorly soluble drugs. It interacts with water and other solvents to improve the dispersion of pharmaceutical compounds, thereby enhancing their bioavailability. Hydroxypropyl may also facilitate the permeability of drug molecules through biological membranes, contributing to their overall efficacy.

Pharmacodynamics

The pharmacodynamics of hydroxypropyl relate to its role in improving the physicochemical properties of drug formulations. By increasing solubility and stability, hydroxypropyl can enhance the absorption of drugs administered via various routes, including oral and topical. Its non-toxic nature allows for safe incorporation into formulations, making it suitable for a wide range of applications.

Pharmacokinetics

The pharmacokinetics of hydroxypropyl have not been extensively studied as it primarily acts as an excipient rather than an active pharmaceutical ingredient. When used in formulations, it is typically not absorbed into systemic circulation in significant amounts, thereby minimizing potential systemic effects. Hydroxypropyl is generally regarded as safe when used in appropriate amounts in drug formulations.

Pregnancy

Hydroxypropyl is not classified for use during pregnancy, and its safety has not been established. Caution is advised.

Breast-feeding

There is limited information on the excretion of hydroxypropyl in human milk. Caution is advised when administering to breastfeeding women.

Storage

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

Indications

• Tablet coating
• Granule coating
• Improvement of drug stability
• Taste masking
• Aesthetic enhancement of pharmaceuticals

Dosage

Children: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Adults: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Mechanism of action

Opadry functions primarily as a coating polymer that adheres to the surface of tablets or granules, creating a protective layer. This layer can control the release of the active ingredient and protect it from environmental factors such as moisture and light. The specific composition of Opadry can vary, but it typically includes film-forming agents, plasticizers, and colorants that work together to achieve the desired coating characteristics.

Pharmacodynamics

The pharmacodynamics of Opadry is largely focused on its physical and chemical properties rather than specific biological interactions. The coating alters the dissolution characteristics of the drug, potentially leading to modified release profiles. This can enhance drug bioavailability or control the release rate of the active ingredient, thereby impacting the therapeutic effect.

Pharmacokinetics

As a coating agent, Opadry itself is not absorbed into the systemic circulation and does not have pharmacokinetic properties related to absorption, distribution, metabolism, or excretion of an active pharmaceutical ingredient. Its impact on pharmacokinetics is indirect, as it affects how the active drug is released and absorbed in the gastrointestinal tract.

Pregnancy

Opadry is a film-coating agent, and specific studies on its effects during pregnancy are not well-documented. Generally, it is advisable to use medications cautiously during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited data are available regarding the safety of Opadry during breastfeeding. It is recommended to consult a healthcare provider before use.

Storage

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

Formulations

• Opadry OY - a coating system for oral solid dosage forms
• Opadry II - a polymer-based coating system for tablet and capsule applications

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.

Pregnancy

No specific data available, consult a healthcare professional.

Breast-feeding

No specific data available, consult a healthcare professional.

Storage

Store in a cool, dry place away from light.

Mechanism of action

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance. MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER. ...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Pharmacodynamics

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

Mechanism of action

Ticagrelor is a P2Y₁₂ receptor antagonist. The P2Y₁₂ receptor couples with Gα_i2 and other G_i proteins which inhibit adenylyl cyclase. G_i mediated signalling also activates PI3K, Akt, Rap1b, and potassium channels. The downstream effects of these activities mediate hemostasis and lead to platelet aggregation. Antagonism of the P2Y₁₂ receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke. Ticagrelor, a cyclopentyltriazolopyrimidine derivative, is a nonthienopyridine, P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist. In contrast to the thienopyridines (e.g., clopidogrel, prasugrel), ticagrelor binds reversibly to the P2Y12 ADP receptor and does not require hepatic transformation to exert its pharmacologic effect. Ticagrelor exhibits noncompetitive and reversible binding to the P2Y12 platelet ADP receptor, preventing signal transduction of the cyclic adenosine monophosphate (cAMP) pathway. This results in reduced exposure of fibrinogen binding sites to the platelet glycoprotein (GP) IIb/IIIa complex and subsequent inhibition of platelet activation and aggregation. In addition to platelet ADP-receptor blockade, ticagrelor inhibits reuptake of adenosine into erythrocytes, a mechanism that may account for some of the beneficial cardiovascular effects of the drug, while potentially contributing to some of its adverse effects (e.g., dyspnea, ventricular pauses).

Pharmacodynamics

Ticagrelor is a P2Y₁₂ receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke. It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated. Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.