Dyclowell-P

Indications

• Pain and inflammation in musculoskeletal disorders
• Rheumatic disease
• Osteoarthritis of the knee
• Postoperative pain
• Control of anterior segment inflammation following ophthalmic surgery

Dosage

Children: For paediatric dosing, please refer to the BNF for Children as specific dosages are not provided in this text.

Adults: For topical application, apply 3–4 times a day to the affected area. For injection, 75 mg may be administered intravenously, then 75 mg after 4–6 hours if required, up to a maximum of 150 mg per day for no more than 2 days.

Mechanism of action

Diclofenac sodium primarily acts as a selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). By blocking these enzymes, diclofenac decreases the production of prostaglandins, which are mediators of inflammation and pain. This mechanism leads to reduced inflammatory responses and alleviation of pain.

Pharmacodynamics

The pharmacological effects of diclofenac include anti-inflammatory, analgesic, and antipyretic properties. The onset of action is typically within a few hours following administration, with peak effects seen within 1 to 2 hours. The duration of analgesia can vary depending on the formulation and dosage used.

Pharmacokinetics

Diclofenac is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolized in the liver to active metabolites and has a half-life of approximately 1 to 2 hours. The drug is primarily excreted in the urine, with both unchanged drug and metabolites being eliminated. Food can affect the absorption, so it is often recommended to take it on an empty stomach.

Contra-indications

• History of hypersensitivity to diclofenac or other NSAIDs
• Active gastrointestinal ulceration
• History of recurrent gastrointestinal bleeding
• History of cerebrovascular bleeding
• Severe renal impairment
• Severe hepatic impairment
• Dehydration
• Hypovolaemia
• History of asthma precipitated by NSAIDs
• History of gastro-intestinal perforation related to previous NSAID therapy
• History of confirmed or suspected hemorrhagic diathesis

Adverse effects

• Gastrointestinal discomfort
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Headache
• Dizziness
• Rash
• Tinnitus
• Elevated liver enzymes
• Renal impairment
• Fluid retention
• Increased blood pressure

Interactions

• Increased risk of gastrointestinal bleeding when used with other NSAIDs or anticoagulants
• Caution with diuretics due to potential for renal impairment
• May enhance the effects of anticoagulants like warfarin
• Caution with antihypertensive medications due to potential for reduced efficacy

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor renal function in patients with pre-existing renal impairment
• Long-term use may affect female fertility, reversible upon discontinuation
• Use with caution during pregnancy, especially in the third trimester

Pregnancy

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

Breast-feeding

Use with caution; amount in milk is generally too small to be harmful.

Storage

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

Formulations

• Diclofenac sodium 1% gel
• Diclofenac sodium 75 mg injection
• Diclofenac sodium eye drops 0.1% (Voltarol Ophtha)

Indications

• Pain and inflammation in musculoskeletal disorders
• Rheumatic diseases
• Acute gout
• Postoperative pain

Dosage

Children: For children aged 9–13 years (body weight 35 kg and above), up to 2 mg/kg daily in 3 divided doses; maximum 100 mg per day. For children aged 14–17 years, 75–100 mg daily in 2–3 divided doses.

Adults: 75–150 mg daily in 2–3 divided doses.

Mechanism of action

Diclofenac potassium works primarily by inhibiting the cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. This inhibition decreases the synthesis of prostaglandins, which are mediators involved in inflammation, pain, and fever. This action results in reduced inflammation and pain sensation in affected tissues.

Pharmacodynamics

The analgesic effects of diclofenac potassium are evident within a few hours after administration. It shows a dose-dependent response in reducing pain and inflammation, making it effective for managing acute pain and inflammatory conditions. The drug can also have a beneficial effect on reducing fever.

Pharmacokinetics

Diclofenac potassium is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring within 1-2 hours after oral administration. It has a half-life of approximately 1-2 hours, but its anti-inflammatory effects can last longer due to its active metabolites. The drug is extensively metabolized in the liver, and its metabolites are excreted primarily in the urine.

Contra-indications

• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• History of recurrent gastrointestinal haemorrhage
• Cerebrovascular disorders
• History of hypersensitivity to aspirin or any other NSAID
• Severe cardiac impairment
• Severe hepatic impairment
• Severe renal impairment
• History of allergic disorders

Adverse effects

• Diarrhoea
• Gastrointestinal disturbances
• Headache
• Insomnia
• Malaise
• Acute gout pain
• Palpitations
• Skin reactions
• Vertigo
• Angioedema
• Decreased appetite
• Dyspepsia
• Hypertension
• Nephritis
• Neutropenia
• Photosensitivity
• Severe cutaneous adverse reactions
• Syncope
• Tachycardia
• Thrombocytopenia
• Tinnitus
• Blurred vision

Interactions

• Increased risk of gastrointestinal bleeding with other NSAIDs
• Caution with anticoagulants due to potential increased bleeding risk
• Caution with antihypertensives as NSAIDs may reduce their efficacy
• Caution with diuretics due to potential renal impairment

Precautions

• Caution in patients with dehydration
• Caution in elderly patients due to increased risk of serious side effects
• Caution in patients with a history of cardiovascular disease
• Use with caution in patients with renal impairment
• Monitor for signs of gastrointestinal bleeding

Pregnancy

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

Breast-feeding

Use with caution during breastfeeding; no specific information available.

Storage

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

Formulations

• Oral tablets
• Oral suspension

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

• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Acute pain
• Dysmenorrhea
• Postoperative pain
• Inflammatory conditions

Dosage

Children: For children, the dosage must be determined based on weight and the specific indication. It is essential to refer

Adults: The usual oral dose for adults is 50 mg taken two to three times daily, with a maximum daily dose of 150 mg. In specific cases, doses may vary based on the condition being treated and the patient's response.

Mechanism of action

Diclofenac inhibits cyclooxygenase-1 and -2 (COX-1 and COX-2), enzymes responsible for the conversion of arachidonic acid to prostaglandins. This inhibition reduces the levels of prostaglandins G2, leading to decreased inflammation, pain, and fever. Prostaglandin E2 (PGE2), a primary mediator of nociception, is suppressed, which lowers pain sensitivity and peripheral sensitization via G-protein coupled receptors.

Pharmacodynamics

Diclofenac reduces inflammation and nociceptive pain while also exhibiting antipyretic effects. Its action can increase the risk of gastrointestinal ulceration due to the inhibition of protective mucus secretion in the stomach, which is a common side effect of NSAIDs.

Pharmacokinetics

Diclofenac is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a high volume of distribution and is extensively metabolized in the liver, primarily by cytochrome P450 enzymes. The elimination half-life is approximately 1 to 2 hours, with metabolites excreted in urine. Its pharmacokinetics can be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Untreated local infection

Adverse effects

• Gastrointestinal ulceration
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Rash

Interactions

• Ciclosporin: Unknown (increases concentration)
• Iron chelators: Unknown (increases exposure)
• Deferiprone: Unknown (increases exposure)

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor renal function in long-term use
• Consider cardiovascular risks in patients with pre-existing conditions

Pregnancy

Manufacturer advises to avoid unless essential.

Breast-feeding

Manufacturer advises to avoid unless essential.

Storage

Store below 25°C. Protect from light and moisture.

Formulations

• Diclofenac 50 mg oral tablet
• Diclofenac 100 mg extended-release oral tablet
• Diclofenac 75 mg injection
• Diclofenac 1% gel

Indications

• Used as a disintegrant in tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

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

Formulations

• Powder
• Granules

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 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

• 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

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Suspensions

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Mechanism of action

Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G₂ which is the precursor to other PGs. These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac. PGE₂ is the primary PG involved in modulation of nociception. It mediates peripheral sensitization through a variety of effects. PGE₂ activates the G_q-coupled EP₁ receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE₂ also activates the EP₄ receptor, coupled to G_s, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE₂ act via EP₃ to increase sensitivity to bradykinin and via EP₂ to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP₂ receptor which couples to G_s. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI₂ is known to play a role via its G_s-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain. PGI₂ and PGE₂ contribute to acute inflammation via their IP and EP₂ receptors. Similarly to β adrenergic receptors these are G_s-coupled and mediate vasodilation through the AC/PKA pathway. PGE₂ also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury. PGD₂ plays a role in the activation of endothelial cell release of cytokines through its DP₁ receptor. PGI₂ and PGE₂ modulate T-helper cell activation and differentiation through IP, EP₂, and EP₄ receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation. PGE₂ can cross the blood-brain barrier and act on excitatory G_q EP₃ receptors on thermoregulatory neurons in the hypothalamus. This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE₂ thereby reducing the activity of these neurons. Diclofenac has pharmacologic actions similar to those of other prototypical NSAIAs. The drug exhibits anti-inflammatory, analgesic, and antipyretic activity. The exact mechanisms have not been c

Pharmacodynamics

Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever. It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.

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

It has very good absorptive properties.