MELBEK 7.5 mg

Indications

• Pain and inflammation in musculoskeletal disorders
• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis

Dosage

Children: For children aged 16-17 years, the dose is 7.5 mg once daily, increased if necessary up to 15 mg once daily. For children aged 12-17

Adults: The typical adult dosage is 15 mg once daily, reduced to 7.5 mg once daily if necessary.

Mechanism of action

Meloxicam inhibits prostaglandin synthetase (cyclooxygenase 1 and 2) enzymes, resulting in decreased synthesis of prostaglandins that sensitize neuronal pain receptors. This inhibition leads to its analgesic and anti-inflammatory effects. It preferentially inhibits COX-2, which may reduce gastrointestinal irritation compared to non-selective NSAIDs.

Pharmacodynamics

Meloxicam exhibits anti-inflammatory, analgesic, and antipyretic effects. It has been shown to decrease markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), in patients with rheumatoid arthritis. While meloxicam is designed to cause less gastrointestinal irritation due to its COX-2 selectivity, it still carries risks associated with gastrointestinal symptoms, including inflammation, bleeding, and ulceration.

Pharmacokinetics

Meloxicam is well-absorbed following oral administration, with peak plasma concentrations typically reached within 4 to 5 hours. It has a half-life of approximately 15 to 20 hours, allowing for once-daily dosing. The drug is extensively metabolized in the liver, and its metabolites are primarily excreted in the urine. Patients with renal or hepatic impairment may require dose adjustments or careful monitoring due to altered pharmacokinetics.

Contra-indications

• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• History of gastrointestinal bleeding related to previous NSAID therapy
• History of significant renal impairment
• History of coronary artery bypass graft surgery
• History of hypersensitivity to aspirin or any other NSAID, including those who have experienced asthma, angioedema, urticaria, or rhinitis precipitated by these agents

Adverse effects

• Gastrointestinal discomfort
• Gastrointestinal bleeding
• Nausea
• Vomiting
• Headache
• Constipation
• Diarrhea
• Renal impairment
• Cardiovascular events
• Delayed onset of labor
• Potential exacerbation of asthma symptoms

Interactions

• Increased risk of gastrointestinal side effects when used with other NSAIDs
• May interfere with the effects of antihypertensive medications
• Caution advised with anticoagulants due to increased bleeding risk
• May reduce the effectiveness of diuretics

Precautions

• Use with caution in patients with a history of gastrointestinal disorders, such as ulcerative colitis or Crohn's disease
• Use with caution in elderly patients due to increased risk of serious side effects
• Monitor renal function in patients with renal impairment
• Long-term use may lead to decreased female fertility, which is reversible upon discontinuation

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to risk of fetal ductus arteriosus closure and potential persistent pulmonary hypertension in the newborn.

Breast-feeding

Use with caution; present in milk in animal studies, manufacturer advises avoiding use during breastfeeding.

Storage

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

Formulations

• Meloxicam 7.5 mg oral tablets
• Meloxicam 15 mg oral tablets
• Meloxicam 500 mg oral suspension

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

• Hypovolemia
• Shock
• Severe burns
• Trauma
• Surgery

Dosage

Children: Refer to specific product guidelines and clinical protocols for dosing.

Adults: Refer to specific product guidelines and clinical protocols for dosing.

Mechanism of action

Colloidal solutions work by increasing the oncotic pressure in the blood vessels, which draws fluid into the circulation from the interstitial spaces. This helps to restore blood volume and improve tissue perfusion. The particles in colloidal solutions, such as hydroxyethyl starch or dextran, do not easily cross capillary membranes, allowing them to exert sustained osmotic effects.

Pharmacodynamics

The pharmacodynamic effects of colloidal solutions include an increase in intravascular volume, which leads to improved circulation and oxygen delivery to tissues. The onset of action can be relatively quick, as the infusion of colloidal solutions can lead to immediate hemodynamic improvements. The duration of effect depends on the specific type of colloid used and the rate of distribution and elimination from the body.

Pharmacokinetics

Colloids display unique pharmacokinetic properties due to their large molecular size. They remain in the vascular compartment longer than crystalloids, which can rapidly diffuse out of the circulation. The distribution volume of colloids is generally limited to the intravascular space, and their elimination is mainly through the reticuloendothelial system. The half-life can vary based on the specific colloid and individual patient factors.

Adverse effects

• Allergic reactions
• Fever
• Nausea
• Vomiting
• Headache
• Hypotension

Precautions

• Use with caution in patients with known allergies to any components of the colloid solution.
• Monitor for signs of allergic reactions during administration.
• Use cautiously in patients with renal impairment, as fluid overload may occur.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Safety during breastfeeding has not been established. Exercise caution and consult a healthcare professional.

Storage

Store at room temperature, away from direct light. Do not freeze. Ensure the solution is clear and free from particulate matter before use.

Formulations

• Hydroxyethyl starch solutions
• Gelatin solutions
• Dextran solutions

Indications

• Used as an excipient in solid dosage forms
• Facilitates drug disintegration and dissolution

Dosage

Children: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Adults: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Mechanism of action

Crospovidone acts by rapidly absorbing water and swelling upon contact with moisture. This action leads to the disintegration of solid dosage forms, thus increasing the surface area of the active ingredients and promoting their dissolution and subsequent absorption in the gastrointestinal tract. It does not affect the pH of the formulation, ensuring that the active ingredients remain stable.

Pharmacodynamics

Crospovidone exhibits properties that enhance the bioavailability of active ingredients in pharmaceutical formulations. Its ability to rapidly disintegrate tablets and capsules leads to quicker release and absorption of the drug into systemic circulation. As a disintegrant, it aids in the effective delivery of drugs that may otherwise be poorly soluble.

Pharmacokinetics

Crospovidone itself is not absorbed systemically when administered orally. It remains in the gastrointestinal tract, where it performs its function as a disintegrant. The pharmacokinetic profile of drugs formulated with crospovidone may be influenced by the enhanced dissolution and absorption rates provided by this excipient.

Pregnancy

Crospovidone is considered to have low toxicity and is generally regarded as safe for use during pregnancy, but specific studies are limited.

Breast-feeding

There is insufficient data on the excretion of crospovidone in human milk, but it is deemed safe for use during breastfeeding.

Storage

Store in a cool, dry place away from light and moisture, in tightly closed containers.

Formulations

• Powder
• Tablets

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 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

• 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

Indications

• Silicosis
• Chronic obstructive pulmonary disease (COPD)
• Lung cancer associated with silica exposure

Dosage

Adults: Silica is not administered as a drug, but rather

Mechanism of action

Silica, particularly crystalline forms like quartz and cristobalite, can induce cytotoxicity and morphological transformation in cells. The cytotoxic effects are attributed to the presence of silanol groups and trace iron on the silica surface, which can generate reactive oxygen species. These interactions lead to cellular damage and transformation, suggesting multiple molecular mechanisms underlying silica's biological effects. The activity is sensitive to the silica's surface structure and composition, indicating that the biological response is a phenomenon originating from the silica's surface characteristics.

Pharmacodynamics

Silica's pharmacodynamic effects are largely related to its cytotoxic and transforming properties, particularly in lung tissue. The inhalation of crystalline silica can lead to the activation of inflammatory pathways, oxidative stress, and apoptosis in alveolar macrophages and epithelial cells. This can result in chronic inflammation, fibrosis, and ultimately, diseases such as silicosis and lung cancer. The degree of these effects varies based on the type of silica, its crystalline structure, and the presence of surface modifications.

Pharmacokinetics

The pharmacokinetics of silica is complex as it is not absorbed systemically when inhaled or ingested. Instead, inhaled silica particles can deposit in the alveolar region of the lungs, where they may persist for long periods. The body responds to silica exposure through inflammatory processes, and macrophages attempt to phagocytize silica particles. However, the persistence of these particles can lead to chronic lung conditions. Clearance mechanisms are inefficient, leading to prolonged retention in lung tissue.

Adverse effects

• Cytotoxicity
• Morphological transformation of cells
• Respiratory issues
• Silicosis
• Lung cancer

Precautions

• Use caution in occupational settings with silica dust exposure
• Regular monitoring of lung function in exposed individuals

Pregnancy

There is insufficient data on the effects of silica on pregnancy. It is advised to minimize exposure.

Breast-feeding

Limited data available; caution is advised due to potential respiratory effects.

Storage

Store in a cool, dry place, away from moisture and incompatible materials.

Formulations

• Crystalline silica
• Amorphous silica (diatomaceous earth)
• Silica gel

Mechanism of action

Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms. As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-2, but also exerts some activity against COX-1, causing gastrointestinal irritation. Meloxicam, an oxicam derivative that is structurally related to piroxicam, is a nonsteroidal anti-inflammatory agent (NSAIA) exhibiting analgesic, antipyretic, and anti-inflammatory actions. In vitro and in vivo studies indicate that meloxicam inhibits the cyclooxygenase-2 (COX-2) isoform of prostaglandin endoperoxide synthase (prostaglandin G/H synthase [PGHS]) to a greater extent than the COX-1 isoform. However, meloxicam's COX-2 selectivity is dose dependent and is diminished at higher dosages. Therefore meloxicam sometimes has been referred to as a "preferential" rather than "selective" COX-2 inhibitor. To investigate the effect of meloxicam on human polymorphonuclear leukocyte (PMN) adhesion to human synovial cell (HSC), and to explore its mechanism. MTT colorimetry was used to determine the adhesion effect of PMN to HSC. Cell-ELISA and RT-PCR methods were used to determine the expression of ICAM-1 and VCAM-1. Nuclear transcription factor-kappa B (NF-kappa B) was measured by electrophoretic mobility shift assay (EMSA) method. Meloxicam was found to effectively inhibit TNF-alpha (50 u.mL-1 for 12 hr) and IL-1 beta (50 u.mL-1 for 12 hr)-induced adhesion of PMN to HSC (IC50 3.38 X 10(-7) mol.L-1 and 3.56 X 10(-6) mol.L-1, respectively) in a concentration-dependent manner. ICAM-1 protein and mRNA expression induced by TNF-alpha (50 u.mL-1) were inhibited by meloxicam at 1 X 10(-6)-1 X 10(-5) mol.L-1. The activation of NF-kappa B was also inhibited by meloxicam at 1 X 10(-6)-1 X 10(-5) mol.L-1. These results suggest that meloxicam inhibit TNF-alpha stimulated PMN-HSC adhesion and expression of ICAM-1 by suppressing the activity of NF-kappa B. /Investigators/ compared the effects of therapeutically equivalent doses of meloxicam and indomethacin, a preferential inhibitor of the constitutive cyclooxygenase (COX-1), on platelet aggregation and platelet thromboxane formation, which are exclusively COX-1 dependent, physiological renal, and total body prostaglandin E2 (PGE2) production. In a randomized cross-over design, 14 healthy female volunteers received meloxicam 7.5 mg per day for 6 days or indomethacin 25 mg three times per day for 3 days; the wash-out period was 5 days, and drug intake was adapted to the menstrual cycle. On the day before treatment and on the last day of each treatment period the following parameters were evaluated: maximum platelet aggregation and thromboxane B2 (TXB2) formation in response to 1.0 mmol/L arachidonic acid; 24-hour urinary excretion of PGE2 and 7 alpha-hydroxy-5, 11-diketo-tetranor-prosta-1, 16-dionic acid (PGE-M), the index metabolites of renal and total body PGE2 synthesis, respectively, were assessed by gas chromatography/tandem mass spectrometry. Maximum platelet aggregation and TXB2 formation were almost completely inhibited by indomethacin (-87% and -99%, respectively; p < 0.001, each) as compared to control (100%), but remained unaffected by meloxicam (-1% and +4%, respectively). Meloxicam showed no significant effects on urinary PGE2 excretion (-13%) and only slight effects on PGE-M excretion (-22%; p < 0.05), whereas indomethacin reduced urinary PGE2 excretion (-43%; p < 0.05) as well as PGE-M excretion (-36%; p < 0.001). /This/ data shows, that meloxicam 7.5 mg per day is COX-1 sparing in humans in vivo.

Pharmacodynamics

Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever. Prostaglandins are substances that contribute to inflammation. This drug also exerts preferential actions against COX-2, which may reduce the possible gastrointestinal effects of this drug. In humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate(ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as aquaporin-1 expression. As with other NSAIDS, prolonged use of meloxicum can result in renal or cardiovascular impairment or thrombotic cardiovascular events. A note on gastrointestinal effects As meloxicam preferentially inhibits COX-2, it is thought to cause less gastrointestinal irritation compared to other NSAIDS. Despite this, it still carries a risk of gastric inflammation, bleeding and ulceration. In one study, patients on meloxicam suffered from gastrointestinal symptoms at a rate of 13% compared to 19% of those on [diclofenac]. GI events were found to be less severe in the meloxicam-treated patients.

Mechanism of action

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