Ethambutol Dispersible Tablets 100 mg

Indications

• Tuberculosis, in combination with other drugs (standard treatment)
• Multiple-drug resistant pulmonary tuberculosis, in combination with other drugs

Dosage

Children: Child: 20 mg/kg once daily for 2 months (initial phase) or 30 mg/kg 3 times a week for 2 months (initial phase).

Adults: Adult: 15 mg/kg once daily for 2 months (initial phase) or 100 mg twice daily for 24 weeks, continue appropriate combination therapy after delamanid.

Mechanism of action

Ethambutol inhibits the enzyme arabinosyl transferase, which is involved in the biosynthesis of the mycobacterial cell wall component, arabinogalactan. This inhibition disrupts the integrity of the bacterial cell wall, leading to bacterial cell death.

Pharmacodynamics

Ethambutol exhibits bacteriostatic activity against M. tuberculosis. Its action is concentration-dependent, and effectiveness can be enhanced when used in combination with other antitubercular agents. Resistance can develop through mutations in the gene encoding arabinosyl transferase, leading to decreased drug efficacy.

Pharmacokinetics

Ethambutol is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 4 hours post-administration. The drug has a half-life of approximately 3 to 5 hours and is primarily excreted unchanged in urine. Dose adjustments may be necessary in patients with renal impairment, as the drug's clearance is significantly affected by renal function.

Contra-indications

• Optic neuritis
• Poor vision

Adverse effects

• Anxiety
• Appetite decreased
• Asthenia
• Chest pain
• Cough
• Depression
• Dyslipidaemia
• Dyspnoea
• Ear pain
• Electrolyte imbalance
• Gastrointestinal discomfort
• Haemoptysis
• Headache
• Hyperhidrosis
• Hypertension
• Hypotension
• Malaise
• Muscle weakness
• Nausea
• Oropharyngeal pain

Interactions

• Cycloserine
• Deltyba (Delamanid)

Precautions

• Monitor serum albumin and electrolytes before and during treatment
• Monitor blood-cycloserine concentration if creatinine clearance is less than 50 mL/min
• Use with caution in elderly and young children
• Patients should be able to report symptomatic visual changes accurately

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk, as it crosses the placenta.

Breast-feeding

Present in milk, but amount is too small to be harmful.

Storage

Dispense in original container (contains desiccant).

Formulations

• Capsule
• Tablet

Indications

• Skin disinfection
• Preparation of skin before injections
• Cleansing minor wounds

Dosage

Children: Apply to the skin as required; consult product literature for specific guidance.

Adults: Apply to the skin as required for disinfection.

Mechanism of action

Alcohol exerts its antiseptic effect by denaturing proteins, disrupting cell membranes, and dehydrating microbial cells, leading to cell lysis and death.

Pharmacodynamics

Alcohol has broad-spectrum antimicrobial activity, effective against bacteria, fungi, and viruses. Its efficacy is influenced by concentration, with higher concentrations generally being more effective.

Pharmacokinetics

Alcohol is rapidly absorbed through the skin and mucous membranes. It is metabolized primarily in the liver, with a half-life that varies based on the individual's metabolic rate and the amount consumed.

Contra-indications

• Concomitant use with lithium
• Regular use in neonates
• Patients with severe burns when diathermy has been preceded by application of alcoholic skin disinfectants

Adverse effects

• Eye erythema
• Punctate keratitis
• Cytotoxicity
• Eye discolouration

Interactions

• Increases risk of visual disturbances with antiepileptics
• Increases concentration with methylphenidate
• Increases risk of facial flushing and skin irritation with topical pimecrolimus
• Increases concentration with retinoids
• Increases concentration with acitretin
• Increases risk of facial flushing and skin irritation with topical tacrolimus
• Decreases antidiuretic effect with vasopressin

Precautions

• Avoid regular application to inflamed or broken skin or mucosa
• Avoid broken skin
• Flammable

Pregnancy

Sufficient iodine may be absorbed to affect the fetal thyroid in the second and third trimester.

Breast-feeding

Avoid regular or excessive use.

Storage

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

Formulations

• Betadine 2.5% dry powder spray
• Industrial methylated spirit
• Povidone-Iodine 25 mg per 1 gram

Indications

• Thickening agent in topical formulations
• Anti-caking agent in powders
• Carrier for active pharmaceutical ingredients

Dosage

Children: Refer to specific formulation guidelines in the BNF for Children.

Adults: Refer to specific formulation guidelines in the BNF.

Mechanism of action

Aerosil exerts its effects primarily through its surface characteristics. The interaction of silica particles with biological systems can lead to cytotoxicity and cellular transformation, which are influenced by the distribution of silanol groups and the presence of trace metals such as iron. The cytotoxic effects are related to the ability of silica to generate reactive oxygen species, leading to oxidative stress in cells. The biological response to aerosil is sensitive to the composition and structural features of the silica surface, indicating that its activity is a surface-originated phenomenon.

Pharmacodynamics

The pharmacodynamic properties of aerosil are related to its ability to modify the rheological properties of formulations, improve flowability, and prevent clumping. Its cytotoxic effects at high concentrations can lead to cellular stress and transformation, although these effects are primarily of concern in occupational exposure rather than therapeutic use. The dose-response relationship can vary based on the specific type of silica and its surface modifications.

Pharmacokinetics

Aerosil is not absorbed systemically when used in pharmaceutical formulations due to its high molecular weight and physical properties. Inhalation of silica dust can lead to pulmonary exposure, where it may elicit inflammatory responses and potentially lead to silicosis over prolonged exposure. Its elimination from the body does not occur via typical metabolic pathways; instead, silica particles may be cleared from the lungs by macrophage action and mucociliary clearance mechanisms.

Dosage

Children: Refer to the specific product guidelines for appropriate use, as dosages may vary depending on the product formulation.

Adults: Refer to the specific product guidelines for appropriate use, as dosages may vary depending on the product formulation.

Mechanism of action

Aspartame is metabolized into aspartic acid, phenylalanine, and methanol. These components are then absorbed into the bloodstream and utilized in normal physiological processes, similar to how these amino acids are used when derived from protein-rich foods.

Pharmacodynamics

Aspartame functions as a low-calorie sweetener, providing sweetness without significant caloric contribution. It is composed of naturally occurring amino acids, aspartic acid and phenylalanine, which are utilized by the body in the same way as those derived from dietary proteins. The sweetening effect of aspartame is primarily due to its high sweetness potency compared to sucrose.

Pharmacokinetics

Upon ingestion, aspartame is hydrolyzed in the gastrointestinal tract into its individual components: aspartic acid, phenylalanine, and methanol. These metabolites are then absorbed into the bloodstream. They do not accumulate in the body and are utilized in metabolic processes similar to those of their natural counterparts found in food.

Contra-indications

• Phenylketonuria (PKU)

Adverse effects

• Headaches
• Allergic reactions
• Gastrointestinal disturbances
• Mood changes

Precautions

• Use with caution in individuals with phenylketonuria due to phenylalanine content.

Pregnancy

Considered safe for use during pregnancy, but it is advisable to consult with a healthcare provider.

Breast-feeding

Considered safe for use during breastfeeding, but it is advisable to consult with a healthcare provider.

Storage

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

Formulations

• Tablets
• Powder
• Liquid sweeteners

Indications

• Tablet formulation
• Capsule formulation
• Bulking agent
• Binder in pharmaceutical formulations

Dosage

Children: Refer to specific formulation guidelines and manufacturer's instructions for dosage recommendations, as Avicel is used as an excipient.

Adults: Refer to specific formulation guidelines and manufacturer's instructions for dosage recommendations, as Avicel is used as an excipient.

Mechanism of action

Avicel acts as an inert filler and binder in pharmaceutical formulations. It does not have a direct pharmacological effect but provides structural integrity to tablets and capsules, aiding in the controlled release of active ingredients. Its properties allow it to form a gel when hydrated, which can influence the release profile of drugs in formulations.

Pharmacodynamics

As an excipient, Avicel does not exhibit pharmacodynamic effects characteristic of active pharmaceutical agents. However, it plays a crucial role in ensuring the stability and efficacy of drug formulations by enhancing their mechanical properties, such as hardness and disintegration time. Its ability to absorb moisture and form gels can also affect the bioavailability of drugs.

Pharmacokinetics

Avicel is not absorbed in the gastrointestinal tract, as it is a non-digestible polysaccharide. Instead, it passes through the digestive system intact. Its presence in formulations does not contribute to pharmacokinetic parameters, as it does not interact with drug metabolism or excretion processes.

Adverse effects

• Gastrointestinal discomfort
• Bloating
• Flatulence
• Abdominal cramps

Precautions

• Use with caution in individuals with gastrointestinal disorders
• Ensure adequate hydration when using as a bulk-forming agent

Pregnancy

Generally regarded as safe for use during pregnancy, but consult a healthcare provider for individual assessment.

Breast-feeding

Considered safe; however, it is advisable to consult with a healthcare provider.

Storage

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

Formulations

• Powder
• Tablet

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

• Constipation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to product-specific guidelines or literature for appropriate dosage.

Adults: Refer to product-specific guidelines or literature for appropriate dosage.

Mechanism of action

Cellulose functions primarily as a bulk-forming laxative. It absorbs water in the intestine, which increases stool bulk and promotes intestinal peristalsis. This action helps to alleviate constipation and regulate bowel movements. Cellulose also slows the absorption of sugars and fats, contributing to improved glycemic control and lipid metabolism.

Pharmacodynamics

As a non-digestible fiber, cellulose does not undergo significant metabolism or absorption in the gastrointestinal tract. Its primary pharmacodynamic effects include increasing stool bulk, enhancing bowel movement frequency, and improving overall digestive health. It also contributes to satiety, which can aid in weight management.

Pharmacokinetics

Due to its indigestible nature, cellulose is not absorbed into the bloodstream. It passes through the gastrointestinal tract largely unchanged. The effects are primarily local within the intestines, as it promotes mechanical action rather than systemic pharmacological effects. The time for cellulose to exert its effects can vary depending on individual gastrointestinal transit times.

Adverse effects

• Bloating
• Gas
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in individuals with gastrointestinal disorders
• Ensure adequate fluid intake to prevent gastrointestinal blockage

Pregnancy

Considered safe for use during pregnancy, but consult a healthcare professional.

Breast-feeding

Considered safe for use while breastfeeding, but consult a healthcare professional.

Storage

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

Formulations

• Powder
• Tablets
• Capsules

Indications

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

The safety of colloidal solutions during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

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

• Tablet formulation
• Capsule formulation
• Rapid release of active pharmaceutical ingredients

Dosage

Children: Refer to specific product guidelines for exact formulations. Typically used in concentrations of 1-5% in solid dosage forms.

Adults: Refer to specific product guidelines for exact formulations. Typically used in concentrations of 1-5% in solid dosage forms.

Mechanism of action

Crosscarmellose sodium works by swelling upon contact with water, leading to the rapid disintegration of the dosage form. This process increases the surface area of the active ingredient, promoting faster dissolution and absorption in the gastrointestinal tract. It does not possess any pharmacological activity of its own but acts as a functional excipient.

Pharmacodynamics

As a disintegrant, crosscarmellose sodium aids in the breakdown of solid dosage forms, allowing for quicker release and absorption of active ingredients. Its effectiveness is influenced by factors such as the formulation's composition, the presence of other excipients, and the conditions within the gastrointestinal environment.

Pharmacokinetics

Crosscarmellose sodium is not absorbed in the gastrointestinal tract and does not undergo metabolism. It functions primarily as a physical agent that enhances the disintegration of the dosage form. Its safety profile is well-established, and it is considered non-toxic and non-irritating.

Pregnancy

Crosscarmellose is considered safe for use during pregnancy as it is not systemically absorbed, but consult a healthcare provider for specific cases.

Breast-feeding

Crosscarmellose is not absorbed systemically and is generally considered safe during breastfeeding, but consult a healthcare provider for specific cases.

Storage

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

Formulations

• Tablets
• Capsules
• Powders

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Indications

• Pulmonary tuberculosis
• Tuberculosis in combination therapy

Dosage

Children: For children, refer to the BNF for Children for appropriate dosing guidance.

Adults: The usual adult dose is 15 mg/kg daily, up to a maximum of 1.6 g per day, in combination with other anti-tuberculosis agents.

Mechanism of action

Ethambutol diffuses into Mycobacterium cells and inhibits the arabinosyltransferases (embA, embB, and embC). This inhibition prevents the formation of arabinogalactan and lipoarabinomannan, which are essential for the integrity of the bacterial cell wall. The resultant decrease in arabinogalactan reduces binding sites for mycolic acid, leading to its accumulation and consequently impairing cell division. Additionally, reduced levels of lipoarabinomannan interfere with the interaction of mycobacteria with host cells. Ethambutol's bacteriostatic action is effective only when the bacteria are actively dividing.

Pharmacodynamics

Ethambutol is indicated for use in combination with other anti-tuberculosis drugs for the treatment of pulmonary tuberculosis. Its long duration of action allows for daily administration, which is beneficial for patient adherence. However, it is important for patients to be informed about potential side effects, including the risk of optic neuritis and hepatic toxicity, which are associated with its use.

Pharmacokinetics

Ethambutol is well absorbed from the gastrointestinal tract, with a peak plasma concentration occurring approximately 2 to 4 hours after administration. It has a volume of distribution that suggests good tissue penetration. The drug is primarily excreted unchanged in the urine, with a half-life of about 3 to 4 hours in individuals with normal renal function. Dosage adjustments may be necessary in patients with renal impairment.

Contra-indications

• Optic neuritis
• Severe renal impairment

Adverse effects

• Optic neuritis
• Visual disturbances
• Nausea
• Vomiting
• Loss of appetite
• Rash
• Hepatic toxicity

Interactions

• Antacids may reduce absorption
• Aluminium-containing antacids may decrease ethambutol serum concentration

Precautions

• Regular monitoring of visual acuity is recommended
• Use with caution in patients with renal impairment
• Periodic liver function tests may be necessary

Pregnancy

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

Breast-feeding

Ethambutol is excreted in breast milk; caution should be exercised when administered to a nursing mother.

Storage

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

Formulations

• Tablets
• Oral suspension

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

• Anxiety disorders
• Nausea and vomiting
• Allergic conditions
• Preoperative sedation
• Pruritus

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the indication and patient characteristics.

Mechanism of action

Hydroxyzine works by antagonizing the H1 histamine receptors, leading to a reduction in the effects of histamine in the body. This action helps alleviate symptoms of allergic reactions and promotes sedation. Additionally, it may exert effects on serotonin and adrenergic receptors, which could contribute to its anxiolytic properties. Hydroxyzine is also involved in various metabolic pathways, including selenium metabolism and the degradation of reactive oxygen species.

Pharmacodynamics

The pharmacodynamic effects of hydroxyzine include sedation, anxiolysis, and reduction of allergic symptoms. Its sedative effects can make it useful in managing anxiety and inducing sleep, while its antihistaminic properties help to relieve symptoms such as itching and rashes associated with allergic reactions. The onset of action is typically within 15 to 30 minutes when taken orally, with peak effects occurring within 1 to 2 hours.

Pharmacokinetics

Hydroxyzine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 hours after oral administration. It is extensively metabolized in the liver, with metabolites, including cetirizine, possessing their own therapeutic effects. Hydroxyzine has a half-life of approximately 20 hours, allowing for once or twice daily dosing. It is primarily excreted in the urine, with less than 1% of the unchanged drug found in urine.

Interactions

• hydroxyzine+antiepileptics: Severe (increases risk of overheating and dehydration)
• hydroxyzine+zonisamide: Severe (increases risk of overheating and dehydration)
• hydroxychloroquine+penicillamine: Severe (increases risk of haematological toxicity)
• hydroxychloroquine+agalsidase alfa: Unknown (decreases effects)
• hydroxychloroquine+agalsidase beta: Unknown (decreases exposure)
• hydroxychloroquine+oral cholera vaccine: Unknown (decreases efficacy)
• live vaccines+hydroxy carbamide: Unknown (increases risk of generalised infection (possibly life-threatening))
• lanthanum+hydroxychloroquine: Unknown (decreases absorption)
• macrolides+hydroxychloroquine: Unknown (increases risk of serious cardiovascular adverse effects)
• hydroxychloroquine+remdesivir: Unknown (decreases effects)

Pregnancy

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

Breast-feeding

Use with caution. Hydroxychloroquine is excreted in breast milk, and effects on the infant are unknown.

Storage

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

Formulations

• Tablets
• Oral solution

Indications

• Antiseptic for skin disinfection
• Solvent in pharmaceutical formulations
• Cleaning agent in laboratories and healthcare settings

Dosage

Children: For pediatric use, consult specific guidelines in the BNF for Children, as dosing may vary based on age, weight, and clinical circumstances.

Adults: For skin antisepsis, apply isopropyl alcohol topically in a concentration of 70% to the affected area. Dosage may vary based on clinical indication and setting.

Mechanism of action

Isopropyl alcohol works primarily as an antiseptic by denaturing proteins and disrupting cell membranes of bacteria, viruses, and fungi, leading to cell lysis and death. Its efficacy is enhanced by the presence of water, which facilitates the penetration of the alcohol into microbial cells.

Pharmacodynamics

Isopropyl alcohol exhibits a rapid onset of action against a variety of pathogens, including gram-positive and gram-negative bacteria, fungi, and some viruses. Its antimicrobial activity is concentration-dependent, with higher concentrations generally providing a broader spectrum of activity. It is commonly used in concentrations ranging from 60% to 90%, with 70% being optimal for disinfection due to its ability to penetrate the cell wall effectively.

Pharmacokinetics

Isopropyl alcohol is readily absorbed through the skin and mucous membranes. After absorption, it is metabolized primarily in the liver to acetone, which is then further metabolized and excreted, mostly via urine. The elimination half-life of isopropyl alcohol varies but is typically around 2 to 3 hours. Its effects can be influenced by factors such as dosage, route of exposure, and individual metabolic differences.

Pregnancy

Isopropyl alcohol should be used with caution during pregnancy. It is a category C drug, indicating that risk cannot be ruled out.

Breast-feeding

Caution is advised when using isopropyl alcohol during breastfeeding, as it is not known if it is excreted in human milk.

Storage

Isopropyl alcohol should be stored at room temperature, away from heat and flame. Keep the container tightly closed and in a well-ventilated area.

Formulations

• Isopropyl alcohol 70% solution
• Isopropyl alcohol 99% solution

Indications

• Nutritional support
• Source of carbohydrates
• Dietary fiber source
• Animal feed

Dosage

Children: As with adults, there are no specific dosing recommendations for maize for children. It can be introduced into the diet in age-appropriate forms and quantities, keeping in mind the overall dietary balance.

Adults: There are no specific dosing recommendations for maize as it is typically consumed as part of a balanced diet. It can be included in daily meals in various forms such as whole kernels, flour, or as part of dishes.

Mechanism of action

Maize primarily acts as a source of energy due to its high carbohydrate content. The complex carbohydrates in maize are broken down into glucose, which is then utilized by the body for energy production. It also contributes to dietary fiber intake, which can aid in digestive health and regulation of blood sugar levels.

Pharmacodynamics

The consumption of maize influences blood glucose and insulin levels due to its carbohydrate content. It has a relatively low glycemic index when consumed in whole form, which can help in managing blood sugar levels. The dietary fiber present in maize can also promote satiety and aid in weight management.

Pharmacokinetics

The digestion of maize begins in the mouth with salivary amylase breaking down starches into simpler sugars. In the stomach and small intestine, enzymes further break down these carbohydrates. The resultant glucose is absorbed into the bloodstream, where it is transported to cells for energy production. The absorption rate can vary based on the form of maize consumed (e.g., whole kernels versus processed forms).

Pregnancy

Maize is generally considered safe for consumption during pregnancy as it is a staple food and provides essential nutrients.

Breast-feeding

Maize is safe to consume while breastfeeding and can provide important nutrients to both the mother and the infant.

Storage

Store in a cool, dry place, away from moisture and pests. Properly sealed containers can help prolong shelf life.

Formulations

• Whole maize grains
• Maize flour (cornmeal)
• Maize starch
• Maize oil

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.

Dosage

Children: Refer to BNF for Children for specific recommendations regarding the consumption of orange juice in children.

Adults: There is no standard dosage for orange juice as it is typically consumed as a beverage. Moderation is advised, especially for individuals on certain medications.

Mechanism of action

The exact mechanism of action of orange juice is not fully understood, but it is known to contain compounds that can influence the metabolism of certain drugs. For instance, it may affect the activity of cytochrome P450 enzymes, particularly CYP3A4, which can alter the pharmacokinetics of medications.

Pharmacodynamics

Orange juice is known to enhance the bioavailability of certain nutrients and may influence the pharmacological effects of some drugs. Its high vitamin C content contributes to various physiological functions, including antioxidant activity, which may indirectly support overall health.

Pharmacokinetics

The pharmacokinetics of orange juice itself are not extensively studied, but it is generally absorbed well through the gastrointestinal tract. The compounds in orange juice can affect the absorption and metabolism of medications, leading to varied clinical effects depending on the drug in question.

Interactions

• orange juice + celiprolol: Unknown (decreases exposure)

Formulations

• juice
• whole fruit

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

• Hyperthyroidism
• Graves' disease
• Thyroid storm

Dosage

Children: Refer to the BNF

Adults: The usual initial dose of propylthiouracil in adults is 300 mg per day, divided into 3 doses. The maintenance dose is typically 100-150 mg per day, adjusted based on thyroid function tests.

Mechanism of action

Propylthiouracil acts by inhibiting the enzyme thyroid peroxidase, which is involved in the iodination of tyrosine residues in thyroglobulin, a precursor of thyroid hormones. By blocking this enzyme, PTU reduces the production of thyroxine (T4) and triiodothyronine (T3), leading to decreased thyroid hormone levels in circulation. Additionally, PTU inhibits the conversion of T4 to T3 in peripheral tissues, further contributing to its antithyroid effects.

Pharmacodynamics

The pharmacodynamic effects of propylthiouracil are primarily centered around its ability to lower thyroid hormone levels, which helps alleviate symptoms of hyperthyroidism such as increased heart rate, weight loss, and anxiety. The onset of action can vary, but therapeutic effects may be observed within several weeks of initiation. Monitoring thyroid function tests is essential to assess the efficacy and adjust dosing as needed.

Pharmacokinetics

Propylthiouracil is well absorbed from the gastrointestinal tract, though its bioavailability can be affected by factors such as food intake. The drug is extensively metabolized in the liver, and its elimination half-life averages around 1-2 hours. Most of the drug is excreted in urine as metabolites. It is important to note that due to its rapid metabolism, multiple daily doses may be required to maintain therapeutic levels.

Interactions

• propylthiouracil+metyrapone: Severe (decreases effects)

Indications

• Tinea pedis (athlete's foot)
• Tinea corporis (ringworm)
• Candidiasis (fungal infections caused by Candida species)
• Tinea cruris (jock itch)
• Onychomycosis (fungal nail infections)

Dosage

Children: Refer to pediatric dosing guidelines in the BNF for Children for age-specific information.

Adults: Refer to product-specific guidelines for dosing, as it varies based on the formulation and severity of the infection.

Mechanism of action

Silcified acts primarily by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes. By disrupting ergosterol production, it compromises the integrity of the fungal cell membrane, leading to cell lysis and death. This mechanism places it in the class of antifungals known as azoles.

Pharmacodynamics

Silcified demonstrates fungistatic activity against a variety of fungi, meaning it halts the growth and reproduction of the fungi without necessarily killing them outright at lower concentrations. The drug's efficacy is influenced by factors such as fungal species, concentration, and the duration of exposure. It is typically administered topically for localized infections, where it can achieve high tissue concentrations.

Pharmacokinetics

Silcified is well-absorbed when administered topically, with minimal systemic absorption which reduces the risk of systemic side effects. The drug is metabolized in the liver, and its metabolites are primarily excreted via the kidneys. The half-life varies depending on the dosage form and route of administration, with topical applications generally leading to localized effects and minimal systemic circulation.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and the potential benefits outweigh the risks.

Breast-feeding

It is not known whether silcified is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Indications

• Potential role in bone health
• Support for connective tissue formation
• May aid in mineral metabolism

Dosage

Children: There is no established clinical dosage for silicon in paediatric populations, as it is not classified as an essential nutrient.

Adults: There is no established clinical dosage for silicon in adults, as it is not classified as an essential nutrient.

Mechanism of action

Silicon is believed to enhance the synthesis of glycosaminoglycans and collagen, which are important for the structural integrity of connective tissues. It may also influence the activity of certain enzymes involved in bone mineralization, thus playing a role in maintaining bone density and health.

Pharmacodynamics

The pharmacodynamics of silicon is not fully elucidated; however, it is thought to involve the modulation of bone metabolism and the promotion of connective tissue health. Silicon may have a synergistic effect with other minerals, such as calcium and magnesium, aiding in their utilization and metabolism in the body.

Pharmacokinetics

The pharmacokinetics of silicon is complex, as it is not absorbed through typical gastrointestinal pathways. Instead, silicon is thought to be taken up in the form of silicates and then distributed throughout the body, particularly in connective tissues. The elimination of silicon occurs primarily through renal excretion, with some variations depending on dietary intake and individual metabolism.

Pregnancy

Silicon is generally considered safe during pregnancy, as it is a naturally occurring element in the human body. However, specific recommendations regarding supplementation should be followed based on the advice of a healthcare provider.

Breast-feeding

Silicon is present in breast milk in small amounts. Its safety during breastfeeding is generally regarded as acceptable, although supplementation should be approached with caution and under medical advice.

Storage

Silicon should be stored in a cool, dry place, protected from light and moisture. Follow specific storage recommendations provided by the manufacturer if available.

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

Dosage

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

Adults: Refer to specific guidelines or BNF for the appropriate dosing of substituted drugs as they vary widely based on the specific compound and its clinical use.

Mechanism of action

The mechanism of action for substituted drugs typically involves interaction with specific biological targets such as receptors, enzymes, or ion channels. By binding to these targets, substituted drugs can modulate various physiological processes, leading to desired therapeutic effects, such as analgesia, anti-inflammatory action, or modulation of neurotransmitter activity.

Pharmacodynamics

Pharmacodynamics of substituted drugs depends on their specific structure and target interactions. Generally, they exert effects through receptor activation or inhibition, leading to alterations in signaling pathways. This can result in enhanced or diminished cellular responses, contributing to the overall therapeutic outcome. The potency and efficacy of these drugs can vary widely based on their chemical modifications.

Pharmacokinetics

The pharmacokinetics of substituted drugs involves absorption, distribution, metabolism, and excretion (ADME). Factors such as the lipophilicity, molecular weight, and chemical stability of the substituents can affect how the drug is absorbed in the gastrointestinal tract, distributed throughout the body, metabolized by the liver, and ultimately excreted through the kidneys. Variations in these parameters will influence the drug's bioavailability, half-life, and duration of action.

Pregnancy

Consult healthcare provider before use. Safety during pregnancy has not been established.

Breast-feeding

Consult healthcare provider before use. Limited data available on safety during breastfeeding.

Storage

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

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

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

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

Mechanism of action

180 to 200 times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.

Pharmacodynamics

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a low-calorie sweetener used to sweeten a wide variety of low- and reduced-calorie foods and beverages, including low-calorie tabletop sweeteners. Aspartame is composed of two amino acids, aspartic acid and phenylalanine, as the methyl ester. Aspartic acid and phenylalanine are also found naturally in protein containing foods, including meats, grains and dairy products. Methyl esters are also found naturally in many foods such as fruits and vegetable and their juices. Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood and used in normal body processes. Neither aspartame nor its components accumulates in the body. These components are used in the body in the same ways as when they are derived from common foods.

Mechanism of action

Ethambutol diffuses into _Mycobacterium_ cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduces the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate. Lipoarabinomannan is a component of a cell surface molecule involved in the interaction with host cells. Reduced levels of lipoarabinomannan may interfere with mycobacterial interaction with host cells. Ethambutol is bacteriostatic in action. Although the exact mechanism of action has not been fully elucidated, the drug appears to inhibit the synthesis of one or more metabolites in susceptible bacteria resulting in impairment of cellular metabolism, arrest of multiplication, and cell death. Ethambutol is active against susceptible bacteria only when they are undergoing cell division.

Pharmacodynamics

Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis. It has a long duration of action as it is administered daily, and a moderate therapeutic window. Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.

Mechanism of action

It has very good absorptive properties.