Distem

Indications

• Mild to moderate pain
• Fever
• Headaches
• Muscle aches
• Arthritis
• Backaches
• Toothaches
• Colds

Dosage

Adults: For adults, the typical dosage is 500 mg to 1 g every 4 to 6 hours, with a maximum daily limit of 4 g. In cases of intravenous administration, the dosage is 15 mg/kg every

Mechanism of action

Paracetamol is thought to exert its analgesic effects by inhibiting cyclo-oxygenase (COX) enzymes, specifically COX-1 and COX-2, which are involved in the synthesis of prostaglandins responsible for pain sensation. Unlike most NSAIDs, paracetamol does not exhibit peripheral anti-inflammatory effects. Its antipyretic action is believed to result from direct action on heat-regulating centers in the brain, leading to peripheral vasodilation and sweating.

Pharmacodynamics

Paracetamol has been shown to have both antipyretic and analgesic effects, lacking any significant anti-inflammatory activity. It does not interfere with platelet aggregation or disrupt hemostasis, making it a safer option for individuals at risk of bleeding. Allergic reactions to paracetamol are rare. The drug does not affect uric acid secretion or acid-base balance when used at recommended doses.

Pharmacokinetics

Paracetamol is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 30 to 60 minutes after oral administration. It is primarily metabolized in the liver via conjugation with glucuronide and sulfate, with a minor pathway involving cytochrome P450 enzymes. The elimination half-life ranges from 1 to 4 hours, with renal excretion of metabolites as the primary route of elimination.

Adverse effects

• Nausea and vomiting
• Liver injury
• Renal damage
• Hypersensitivity reactions
• Flushing
• Hypotension
• Anorectal erythema
• Angioedema
• Agranulocytosis
• Thrombocytopenia
• Leukopenia
• Severe cutaneous adverse reactions (SCARs)

Interactions

• Increased risk of methaemoglobinaemia with topical prilocaine
• Increased risk of methaemoglobinaemia with topical anaesthetics
• Increased anticoagulant effect with coumarins
• Increased risk of hepatotoxicity with imatinib
• Decreased exposure with rifampicin
• Decreased exposure with pitolisant

Precautions

• Monitor patients with liver disease or heavy alcohol use for increased risk of hepatotoxicity
• Adjust doses in patients taking enzyme-inducing antiepileptic medications
• Use caution in patients with renal impairment
• Clinical judgement is required for dose adjustment in weight-based dosing

Pregnancy

Paracetamol is generally considered safe to use during pregnancy for pain and fever relief, but should be used at the lowest effective dose for the shortest duration necessary.

Breast-feeding

Paracetamol is excreted in breast milk in small amounts and is considered safe for use while breastfeeding.

Storage

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

Formulations

• Oral tablets (500 mg)
• Oral suspension (120 mg/5 mL, 500 mg/5 mL)
• Rectal suppositories (various strengths)
• Intravenous infusion (various strengths)

Indications

• Muscle spasms
• Musculoskeletal pain
• Pain associated with acute musculoskeletal conditions

Dosage

Children: Refer to the BNF for Children for appropriate dosing information for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines, as dosages may vary based on individual patient needs and clinical context.

Mechanism of action

The mechanism of action of methocarbamol is thought to depend on its central nervous system depressant activity, which may involve blocking spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways, and prolonging the refractory period of muscle cells. It does not directly affect muscle contractions or nerve fibers, acting instead within the CNS to produce its muscle relaxant effects.

Pharmacodynamics

Methocarbamol has been demonstrated to block spinal polysynaptic reflexes and decrease nerve transmission in both spinal and supraspinal pathways. It prolongs the refractory period of muscle cells, contributing to its muscle relaxant effects. While its exact pharmacodynamics are not fully understood, the CNS depressant effects are a significant aspect of its therapeutic action. Additionally, methocarbamol has shown effectiveness in preventing convulsions in animal studies following electric shock.

Pharmacokinetics

Methocarbamol is well absorbed following oral administration, with peak plasma concentrations typically occurring within 1 to 2 hours. It is metabolized in the liver, with metabolites excreted primarily via the urine. The half-life of methocarbamol can vary, but it generally ranges from about 1 to 2 hours. The drug's effects can be influenced by factors such as age, liver function, and concomitant medications.

Contra-indications

• Active peptic ulceration
• Local infection (with intrathecal use)
• Systemic infection (with intrathecal use)

Adverse effects

• Drowsiness
• Dizziness
• Confusion
• Dry mouth
• Constipation
• Diarrhea
• Depression
• Insomnia
• Chills
• Dyspnea
• Fever
• Hypersalivation
• Asthenia
• Appetite decreased

Interactions

• Alcohol (enhanced drowsiness)
• Other CNS depressants (may enhance sedative effects)

Precautions

• Use with caution in patients with cerebrovascular disease
• Diabetes
• Epilepsy
• History of peptic ulcer
• Elderly patients
• Malnutrition
• Coagulation disorders (increased risk of post-surgical complications)

Pregnancy

Safety during pregnancy has not been established; use only if clearly needed and after careful consideration of risks and benefits.

Breast-feeding

It is not known if methocarbamol is excreted in human milk; caution is advised.

Storage

Store below 25°C. Protect from light. Keep out of reach of children.

Formulations

• Tablet 10mg
• Solution for injection 10mg/20ml
• Oral liquid formulation

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 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

Dosage

Children: Refer to specific clinical guidelines for dosing in children, as no standard paediatric dosage is specified in the provided resources.

Adults: Refer to specific clinical guidelines for dosing, as no standard adult dosage is specified in the provided resources.

Mechanism of action

Ethylene glycol toxicity results from its metabolism to glycolic acid and other toxic metabolites. Glycolate accumulates in the body and is eliminated more slowly than ethylene glycol itself. The renal excretion of both compounds plays a crucial role in their elimination, accounting for a significant portion of the administered dose.

Pharmacodynamics

The pharmacodynamics of glycolate are closely tied to its role as a metabolite of ethylene glycol. Its accumulation can lead to metabolic acidosis, although minimal clinical effects have been observed at low doses. The relationship between glycolate and ethylene glycol indicates that glycolate may contribute to the overall toxic effects of ethylene glycol ingestion.

Pharmacokinetics

The pharmacokinetics of glycolate indicate that it reaches peak plasma levels between 4-6 hours after the administration of ethylene glycol. The elimination half-life of ethylene glycol is approximately 1.7 hours in rats and 3.4 hours in dogs. Glycolate is predominantly eliminated through renal excretion, with about 5% of the dose being excreted unchanged.

Pregnancy

There is limited data on the safety of glycolate in pregnancy. Caution is advised.

Breast-feeding

Data on the excretion of glycolate in human milk is not available. Caution is advised.

Storage

Store at room temperature, away from light and moisture.

Indications

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

Dosage

Children: Refer to specific dietary guidelines as maize is typically consumed as part of a balanced diet rather than as a medication.

Adults: Refer to specific dietary guidelines as maize is typically consumed as part of a balanced diet rather than as a medication.

Mechanism of action

Maize provides energy primarily through its high starch content, which is broken down into glucose during digestion. The fiber in maize can aid in digestion and promote gut health. Certain compounds in maize, such as antioxidants and phytonutrients, may also contribute to its health benefits, including anti-inflammatory and antioxidant effects.

Pharmacodynamics

The consumption of maize influences metabolic processes by serving as a significant energy source. Its complex carbohydrates provide a slow release of glucose into the bloodstream, helping to maintain stable blood sugar levels. The dietary fiber in maize promotes satiety and aids in weight management, while its phytochemical content may help in reducing chronic inflammation and the risk of certain diseases.

Pharmacokinetics

The digestion of maize begins in the mouth, where enzymes in saliva start breaking down starches. Once ingested, maize is primarily digested in the small intestine, where enzymes further break down carbohydrates into simple sugars. Absorption occurs in the small intestine, with glucose entering the bloodstream. The fiber content is not digested but passes into the large intestine, where it can be fermented by gut bacteria. The bioavailability of nutrients from maize can be influenced by its preparation and processing methods.

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

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Powder
• Granules

Indications

• 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

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 established dietary guidelines for children, as specific dosing for stearic acid is not typically defined.

Adults: Refer to established dietary guidelines and clinical recommendations for fatty acid intake, as specific dosing for stearic acid is not typically defined.

Mechanism of action

Stearic acid is metabolized in the liver and can be converted to oleic acid through a process called desaturation. It does not significantly affect cholesterol levels compared to other saturated fatty acids, as it can be converted into monounsaturated fatty acids. Stearic acid may also modulate signaling pathways involved in inflammation and metabolism.

Pharmacodynamics

Stearic acid exhibits various physiological effects, including modulation of lipid metabolism. It has been shown to influence the composition of cell membranes and can affect the fluidity and function of membranes due to its saturated structure. Stearic acid may also play a role in the regulation of gene expression related to lipid metabolism and inflammation.

Pharmacokinetics

Stearic acid is absorbed from the gastrointestinal tract and is incorporated into chylomicrons for transport in the bloodstream. It is metabolized primarily in the liver, where it undergoes beta-oxidation to produce energy. The elimination half-life and specific metabolic pathways may vary based on dietary intake and individual metabolic differences.

Pregnancy

There are no established guidelines regarding the use of stearic acid during pregnancy. Consultation with a healthcare provider is recommended.

Breast-feeding

There is limited information available on the use of stearic acid during breastfeeding. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Keep container tightly closed.

Formulations

• Capsules
• Tablets
• Powder
• Topical ointments

Dosage

Children: Refer to specific product formulations for guidelines, as dosing can vary based on the formulation and therapeutic context.

Adults: Refer to specific product formulations for guidelines, as dosing can vary based on the formulation and therapeutic context.

Mechanism of action

Stearates, such as magnesium stearate, function primarily by reducing friction during tablet manufacturing and enhancing the flow properties of powders. They do not exert a therapeutic pharmacological action in the body but facilitate the delivery of other active substances.

Pharmacodynamics

Given that stearates are primarily excipients, they do not exhibit traditional pharmacodynamic properties as active drugs do. Their role is to optimize the formulation of drugs, enhancing physical characteristics such as texture and consistency, which indirectly affect the performance of the active ingredients.

Pharmacokinetics

Stearates are poorly absorbed in the gastrointestinal tract due to their lipid nature. When ingested, they may pass through the digestive system with minimal systemic absorption. Their primary action occurs at the site of formulation, where they assist in the dispersion and release of active ingredients rather than being metabolized or exerting effects in the body.

Pregnancy

The safety of sterate during pregnancy has not been established. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

Store in a cool, dry place away from light. 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

The mechanism of action of methocarbamol is thought to be dependant on its central nervous system depressant activity. This action may be mediated through blocking spinal polysynaptic reflexes, decreasing nerve transmission in spinal and supraspinal polysynaptic pathways, and prolonging the refractory period of muscle cells. Methocarbamol has been found to have no effect on contraction of muscle fibres, motor end plates, or nerve fibres. Precise mechanism of action has not been determined. These agents act in the central nervous system (CNS) rather than directly on skeletal muscle. Several of these medications have been shown to depress polysynaptic reflexes preferentially. The muscle relaxant effects of most of these agents may be related to their CNS depressant (sedative) effects. /Skeletal Muscle Relaxants/

Pharmacodynamics

Methacarbamol is a skeletal muscle relaxant with an unknown mechanism of action. Methacarbamol has been shown to block spinal polysynaptic reflexes, decrease nerve transmission in spinal and supraspinal polysynaptic pathways, and prolong the refractory period of muscle cells. Methocarbamol does not act as a local anesthetic upon injection. In animal studies, methocarbamol also prevents convulsions after electric shock.

Mechanism of action

According to its FDA labeling, acetaminophen's exact mechanism of action has not been fully established - despite this, it is often categorized alongside NSAIDs (non-steroidal anti-inflammatory drugs) due to its ability to inhibit the cyclo-oxygenase (COX) pathways. It is thought to exert central actions which ultimately lead to the alleviation of pain symptoms. One theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclo-oxygenase, COX-1 and COX-2, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for eliciting pain sensations. Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX indirectly. Studies also suggest that acetaminophen selectively blocks a variant type of the COX enzyme that is unique from the known variants COX-1 and COX-2. This enzyme has been referred to as _COX-3_. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat. The exact mechanism of action of this drug is not fully understood at this time, but future research may contribute to deeper knowledge. Although further investigation is warranted, the active metabolite of acetaminophen (AM404) was shown to interact with several molecular targets, including the Ca_v3.2 calcium channel, the cannabinoid CB1 receptors, TRPV1 receptors, and Na_v1.8 and Na_v1.7 channels. Acetaminophen produces analgesia and antipyresis by a mechanism similar to that of salicylates. Unlike salicylates, however, acetaminophen does not have uricosuric activity. There is some evidence that acetaminophen has weak anti-inflammatory activity in some nonrheumatoid conditions (e.g., in patients who have had oral surgery). ... Acetaminophen lowers body temperature in patients with fever but rarely lowers normal body temperature. The drug acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. The effects of acetaminophen on cyclooxygenase activity have not been fully determined. Acetaminophen is a weak, reversible, isoform-nonspecific cyclooxygenase inhibitor at dosages of 1 g daily. The inhibitory effect of acetaminophen on cyclooxygenase-1 is limited, and the drug does not inhibit platelet function. Therapeutic doses of acetaminophen appear to have little effect on cardiovascular and respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing. Acetaminophen (N-acetyl-p-aminophenol (APAP)) is the most common antipyretic/analgesic medicine worldwide. If APAP is overdosed, its metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI), causes liver damage. However, epidemiological evidence has associated previous use of therapeutic APAP doses with the risk of chronic obstructive pulmonary disease (COPD) and asthma. The transient receptor potential ankyrin-1 (TRPA1) channel is expressed by peptidergic primary sensory neurons. Because NAPQI, like other TRPA1 activators, is an electrophilic molecule, /the researchers/ hypothesized that APAP, via NAPQI, stimulates TRPA1, thus causing airway neurogenic inflammation. NAPQI selectively excites human recombinant and native (neuroblastoma cells) TRPA1. TRPA1 activation by NAPQI releases proinflammatory neuropeptides (substance P and calcitonin gene-related peptide) from sensory nerve terminals in rodent airways, thereby causing neurogenic edema and neutrophilia. Single or repeated administration of therapeutic (15-60 mg/kg) APAP doses to mice produces detectable levels of NAPQI in the lung, and increases neutrophil numbers, myeloperoxidase

Pharmacodynamics

Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the _salicylate_ drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses. Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation. Allergic reactions are rare occurrences following acetaminophen use.

Mechanism of action

Ethylene glycol toxicity results from its metabolism to glycolic acid and other toxic metabolites. The accumulation of glycolate and the elimination kinetics of ethylene glycol and its metabolites are not well understood, so studies with male Sprague-Dawley rats and mixed breed dogs have been carried out. Ethylene glycol was administered by gavage to rats and dogs which were placed in metabolic cages for urine and blood sample collection at timed intervals. The peak plasma level of ethylene glycol occurred at 2 hr after dosing and that of glycolate between 4-6 hr. The rate of ethylene glycol elimination was somewhat faster in rats with a half-life of 1.7 hr compared to 3.4 hr in dogs. The maximum plasma level of glycolate was greater in rats although the pattern of accumulation was similar to that in dogs. Glycolate disappeared from the plasma at the same time as ethylene glycol, suggesting a slower rate of elimination of the metabolite than that of ethylene glycol. Renal excretion of ethylene glycol was an important route for its elimination accounting for 20-30% of the dose. Renal excretion of glycolate represented about 5% of the dose. Ethylene glycol induced an immediate, but short lived diuresis compared to that in control rats. Minimal clinical effects (mild acidosis with no sedation) were noted at these doses of ethylene glycol (1-2 g/kg) in both rats and dogs. The results indicate that the toxicokinetics of ethylene glycol and glycolate were similar in both species. The effect of 0.35 to 0.8 mmol/kg glycolic acid and 1.0 to 4.4 mmol/kg sodium glycolate on cyclopropane-epinephrine induced cardiac arrhythmias was examined using dogs. Doses of 0.35 to 0.5 mmol/kg glycolic acid increased the duration of arrhythmias in the 13 dogs tested, whereas doses >0.5 mmol/kg decreased or totally eliminated the arrhythmias in each of 11 dogs. Depression was observed for many of the dogs at higher doses. Sodium glycolate was much less effective in decreasing the arrhythmias, with 3 mmol/kg being required and its action being transient.

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

It has very good absorptive properties.