CAPSITOP GEL (Each 30g tube contains Diclofenac Diethylamine/ Capsicum Oleoresin/ Methyl Salicyclate/Levomenthol 0.025% w/w 1.160% w/w/ 1.000% w/w/ 3.000% w/w)

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

• 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

• Pruritus
• Eczema
• Acne
• Rosacea

Dosage

Children: For children aged 12-17 years, apply up to 3 grams 3-4 times a day, ensuring coverage is less than 10% of body surface area.

Adults: Apply thinly to the affected area 1-2 times a day. Maximum application should cover less than 10% of body surface area, with a total daily maximum of 12 grams.

Mechanism of action

Levomenthol primarily activates the cold-sensitive TRPM8 receptors in the skin. This stimulation leads to a feeling of coolness by inhibiting calcium ion currents in neuronal membranes. Additionally, menthol may exhibit analgesic properties through kappa-opioid receptor agonism, further contributing to its pain-relieving effects.

Pharmacodynamics

Levomenthol is a covalent organic compound that can be synthesized or extracted from peppermint and other mint oils. It induces a cooling sensation when applied topically, inhaled, or ingested, by stimulating cold-sensitive receptors located in the skin. Notably, this effect occurs without a decrease in actual skin temperature, making it useful in topical formulations for managing discomfort.

Pharmacokinetics

Levomenthol is absorbed through the skin upon topical application. Its effects are localized, and it does not significantly enter systemic circulation when used as directed. The onset of action is typically rapid, providing immediate symptomatic relief from conditions like itching and irritation.

Contra-indications

• Severe heart disease
• Severe hepatic impairment
• Glaucoma
• Urinary retention
• History of mania or arrhythmias

Adverse effects

• Drowsiness
• Dizziness
• Headache
• Nausea
• Vomiting
• Dry mouth
• Dry eyes
• Diarrhea
• Constipation
• Skin reactions
• Altered taste
• Blurred vision
• Suicidal behaviors

Interactions

• Tricyclic antidepressants
• Other central nervous system depressants

Precautions

• Avoid application to large areas of the skin
• Use caution in patients with a history of psychiatric disorders
• Caution advised for driving and skilled tasks due to potential somnolence or dizziness

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises use only if potential benefit outweighs risk.

Storage

Store in a cool, dry place, protected from light.

Formulations

• AquaSoothe 1% cream (Menthol 10 mg per 1 gram)
• AquaSoothe 2% cream (Menthol 20 mg per 1 gram)
• Arjun 0.5% cream (Menthol 5 mg per 1 gram)
• Arjun 1% cream (Menthol 10 mg per 1 gram)
• Dermacool 0.5% cream (Menthol 5 mg per 1 gram)
• Dermacool 1% cream (Menthol 10 mg per 1 gram)
• Menthoderm 0.5% cream (Menthol 5 mg per 1 gram)
• Menthoderm 1% cream (Menthol 10 mg per 1 gram)
• Menthoderm 2% cream (Menthol 20 mg per 1 gram)
• Menthoderm 5% cream (Menthol 50 mg per 1 gram)

Indications

• Topical pain relief for conditions such as osteoarthritis and neuropathic pain
• Management of postherpetic neuralgia
• Supportive treatment for muscle and joint pain
• Stimulation of digestion and appetite

Dosage

Children: Dosage for pediatric patients should be determined by a healthcare provider, taking into consideration

Adults: Topical formulations generally recommend application to the affected area, with specific dosing instructions provided by the product label. For oral supplements, follow the manufacturer's guidelines or consult a healthcare professional.

Mechanism of action

Capsaicin, the main active component in Capsicum, exerts its effects by binding to the TRPV1 (transient receptor potential vanilloid 1) receptor, which is a cation channel involved in the transmission of pain and heat sensations. This binding leads to the depolarization of sensory neurons, resulting in the release of substance P, a neuropeptide associated with pain signaling. Continuous exposure to capsaicin results in the desensitization of these receptors, leading to decreased pain perception over time.

Pharmacodynamics

The analgesic properties of Capsicum are attributed to its ability to alter the perception of pain. Capsaicin induces a sensation of warmth and pain initially, which is followed by a prolonged analgesic effect due to the depletion of substance P from the nerve endings. Additionally, Capsicum may exhibit anti-inflammatory effects through the modulation of cytokine release and inhibition of inflammatory pathways, contributing to its therapeutic applications in pain management and inflammatory conditions.

Pharmacokinetics

Capsaicin is poorly absorbed when ingested orally, but it can be effectively absorbed through the skin when applied topically. After application, it is metabolized by the liver, and its metabolites are excreted primarily through the kidneys. The onset of action for topical preparations can vary, with effects often observed within hours. The duration of action may last from several hours to days, depending on the formulation and the area of application.

Adverse effects

• Burning sensation at the site of application
• Skin irritation or rash
• Gastrointestinal upset (if ingested)
• Allergic reactions

Precautions

• Avoid contact with eyes and mucous membranes
• Use caution in patients with sensitive skin
• Consult a healthcare professional before use in patients with underlying health conditions

Pregnancy

Capsicum is generally considered unsafe during pregnancy due to potential effects on the fetus. Pregnant women should consult a healthcare provider before use.

Breast-feeding

Capsicum should be used with caution during breastfeeding as it may affect milk production or flavor.

Storage

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

Formulations

• Topical ointments or creams
• Capsules
• Powdered form for oral use

Mechanism of action

Diethylamine acts primarily as a weak base, facilitating nucleophilic substitution reactions. Its basicity allows it to accept protons, which can enhance the reactivity of other compounds in chemical processes.

Pharmacodynamics

The pharmacodynamic properties of diethylamine are largely related to its role as a chemical reagent rather than a pharmaceutical agent. It does not exert therapeutic effects in the same way that many drugs do but is involved in various chemical pathways as a reactant.

Pharmacokinetics

Detailed pharmacokinetic data for diethylamine is limited due to its primary use in laboratory and industrial applications rather than as a therapeutic agent. However, it is expected to be readily absorbed through mucous membranes and the skin, with potential metabolic pathways involving N-dealkylation and oxidation.

Pregnancy

There is limited data on the use of diethylamine in pregnancy. Caution is advised.

Breast-feeding

There is insufficient data on the excretion of diethylamine in human milk. Caution is advised.

Storage

Store in a cool, dry place, away from light.

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

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

Storage

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

Indications

• Antimicrobial treatment
• Antioxidant therapy
• Flavoring agent in food
• Natural preservative
• Traditional medicine applications

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Adults: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action of oleoresin varies depending on its source and the specific compounds it contains. Generally, oleoresins exhibit antimicrobial activity, which may involve the disruption of microbial cell membranes or interference with metabolic processes. Additionally, some components may have anti-inflammatory and antioxidant effects, contributing to their therapeutic potential.

Pharmacodynamics

Oleoresins exhibit a range of pharmacodynamic effects, including antimicrobial, antioxidant, and anti-inflammatory activities. The specific effects will depend on the source of the oleoresin and its chemical composition. These properties are attributed to the various phytochemicals present, such as terpenes, phenolics, and other bioactive compounds, which can modulate biological pathways and influence physiological responses.

Pharmacokinetics

The pharmacokinetics of oleoresin are not well-defined due to the complexity of its composition. Generally, the absorption and metabolism of oleoresins can vary widely based on the individual compounds they contain. Lipophilic components may be absorbed through the gastrointestinal tract and metabolized in the liver, while other components may undergo different metabolic pathways. The elimination half-life is also variable, reflecting the diverse nature of its constituents.

Pregnancy

Safety in pregnancy has not been established, consult healthcare provider.

Breast-feeding

Consult healthcare provider before use during breastfeeding.

Storage

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

Indications

• Pain management
• Inflammatory conditions such as arthritis
• Fever reduction
• Cardiovascular disease prevention

Dosage

Children: Refer to BNF for Children for age-specific dosing recommendations.

Adults: Refer to specific product guidelines or BNF for appropriate dosing recommendations based on the condition being treated.

Mechanism of action

Salicyclate exerts its effects primarily through the inhibition of cyclooxygenase enzymes (COX-1 and COX-2), which play a crucial role in the conversion of arachidonic acid to prostaglandins. By decreasing the production of these pro-inflammatory mediators, salicyclate reduces pain and inflammation. Additionally, it may modulate other signaling pathways involved in pain perception and inflammatory responses.

Pharmacodynamics

The pharmacodynamics of salicyclate involve its ability to decrease the synthesis of prostaglandins, thereby alleviating pain and reducing fever. It also has antiplatelet effects, which can contribute to its therapeutic use in certain cardiovascular conditions. The onset of analgesic effects typically occurs within 30 minutes to an hour after administration, while the anti-inflammatory effects may take longer to manifest, depending on the condition being treated.

Pharmacokinetics

Salicyclate is absorbed well from the gastrointestinal tract, with peak plasma concentrations occurring usually within 2 to 4 hours after oral administration. It is extensively metabolized in the liver, primarily via conjugation to glucuronic acid, and has a relatively short half-life. The elimination of salicyclate and its metabolites occurs primarily through the kidneys, necessitating dose adjustments in patients with renal impairment.

Contra-indications

• Hypersensitivity to salicylates
• Active peptic ulcer disease
• Severe renal impairment
• Bleeding disorders
• Asthma exacerbated by salicylates

Adverse effects

• Gastrointestinal irritation
• Nausea
• Vomiting
• Tinnitus
• Ringing in the ears
• Rash
• Headache
• Dizziness
• Acute renal failure

Interactions

• Increased risk of bleeding with anticoagulants
• Reduced effectiveness of certain antihypertensives
• Increased toxicity when combined with methotrexate
• Potential interaction with alcohol leading to increased gastrointestinal side effects

Precautions

• Use cautiously in patients with pre-existing gastrointestinal issues
• Monitor renal function in long-term use
• Consider potential for Reye's syndrome in children

Pregnancy

Use during pregnancy is generally not recommended, especially in the third trimester due to risks of fetal harm and bleeding complications during delivery.

Breast-feeding

Salicylic acid is excreted in breast milk, caution is advised.

Storage

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

Formulations

• Oral tablets
• Liquid formulations
• Topical preparations
• Rectal suppositories

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

Menthol primarily activates the cold-sensitive TRPM8 receptors in the skin. Menthol, after topical application, causes a feeling of coolness due to stimulation of 'cold' receptors by inhibiting Ca++ currents of neuronal membranes. It may also yield analgesic properties via kappa-opioid receptor agonism.

Pharmacodynamics

Menthol is a covalent organic compound made synthetically or obtained from peppermint or other mint oils. Menthol induces a cooling sensation on the skin upon inhalation, oral ingestion, or topical application by stimulating the cold-sensitive receptors expressed on the skin, without actually causing a drop in the skin temperature.