dubam

Uses

Ethyl salicylate is a salicylate indicated in the treatment of sports related pain.

Glycol salicylate is a salicylate used to treat mild to moderate muscle pain.

This drug is only recommended for topical usages for the relief of muscular and rheumatic pain in human and animals .

Methyl nicotinate is a methyl ester of niacin used to treat muscle and joint pain.

Indicated for the temporary relief of aches and pains in muscles, tendons, and joints.

Methyl salicylate is a topical counter-irritant used for the symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons.

Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine.

dubam is also used to associated treatment for these conditions: Arthritis, Back Pain Lower Back, Fibromyalgia Syndrome, Rheumatism, Soreness, Muscle, SprainsBack Pain Lower Back, Chilblains, Contusions, Joint Pain, Pain caused by Fracture Bone, Soreness, Muscle, Sprains, Stiff ShoulderGeneralized joint pain, Localized muscle pain, Soreness, MuscleAcute Muscle Pain, Arthritis, Back Pain Lower Back, Backache, Contusions, Joint Pain, Ligament pain, Muscle Inflammation, Muscle Injuries, Muscle Strain, Muscle swelling, Pain, Pain of the Bone and Bones, Pain, Nerve, Partial-Onset Seizures, Postherpetic Neuralgia, Soreness, Muscle, Sprains, Tendon pain, Minor aches, Muscle, joint pains

How dubam works

Similar to other salicylates. Salicylates and other analgesics and anti-inflammatory drugs, particularly the non-steroidal anti-inflammatory drugs (NSAID) mainly used in rheumatology, inhibit cyclooxygenase, therefore reducing prostaglandin synthesis .

While the mechanism of action of methyl nicotinate and other topically-administered nicotinic acid esters is not clear, it is thought that methyl nicotinate promotes the release of prostaglandin D2 that is strictly locally-acting due to its short half-life . It was demonstrated in human subjects that the local cutaneous vascular response to methyl nicotinic was suppressed by inhibitors of prostaglandin biosynthesis, indicating that the effect of methyl nicotinate on vascular smooth muscles may be mediated by the release of local prostaglandins . Prostaglandins released from the skin and blood vessels induce cutaneous vasodilation .

Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves . This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2.

Toxicity

Acute ingestion of > 150 mg/kg of salicylates may result in severe toxicity. Salicylate tablets may form stomach bezoars, prolonging absorption of the drug and toxicity. Chronic toxicity can occur after several days or more of high therapeutic doses; it is common, often undiagnosed, and often more serious than acute toxicity. Chronic toxicity is likely to occur in elderly patients .

Treatment for salicylate poisoning consists of activated charcoal and alkaline diuresis with extra KCl .

Unless contraindicated (eg, by altered mental status), activated charcoal is administered as soon as possible and, if bowel sounds are active and there is adequate gastrointestinal motility, may be repeated every 4 hours until charcoal appears in the stool .

After volume and electrolyte abnormalities are corrected and maintained, alkaline diuresis can be used to increase urine pH, ideally to ≥ 8. Alkaline diuresis is advised for patients with any symptoms of poisoning and should not be delayed until salicylate levels are determined. This process is usually safe and greatly increases the rate of salicylate excretion. Because hypokalemia can interfere with alkaline diuresis, patients are often given a solution composed of 1 L of 5% D/W, 3 50-mEq ampules of NaHCO3, and 40 mEq of KCl at 1.5 to 2 times the maintenance IV fluid rate. Serum potassium levels are monitored. Due to the fact that fluid overload can lead to the occurrence of pulmonary edema, patients are monitored for respiratory findings .

Drugs that increase urinary HCO3 (eg, acetazolamide) must be avoided because they worsen metabolic acidosis and decrease blood pH. Drugs that decrease respiratory drive should be avoided when possible because they may impair hyperventilation and respiratory alkalosis, decreasing blood pH .

The acute subcutaneous LD50 of structurally-related nicotinamide and nicotinic acid in rats were 1.68 and 5.0 g/kg bw, respectively . In humans, oral ingestion of 3-9 g of nicotinic acid per day resulted in "niacin hepatitis", gout, and impaired glucose intolerance within a short period of time .

Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination .

Volume of Distribution

According to the animal studies, nicotinic acid is mainly concentrated in the liver, kidneys, and adipose tissue .

After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier.

Elimination Route

Salicylate absorption follows first-order kinetics with an absorption half-life ranging from 5 to 16 minutes .

The presence of methyl group facilitates the penetration of methyl nicotinate through the skin with good lipophilicity, allowing rapid absorption following topical administration . In vitro, about 80-90% of the polar compounds methyl nicotinate rapidly penetrated the skin . It was demonstrated in excised skin of hairless mice that methyl nicotinate can effectively bypass the stratum corneum layer of the skin . In humans, nicotinic acid and nicotinamide were shown to be rapidly absorbed from the stomach and intestine via a sodium carrier-mediated mechanism at low concentrations .

Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100% .

Half Life

The serum half-life of Aspirin, a similar salicylate, is 20 min .

In vitro, the half-life of methyl nicotinate in the dermis was 3 to 10 minutes .

The plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication.

Clearance

No pharmacokinetic data available.

Elimination Route

Salicylates are generally excreted .

Following epicutaneous administration of small radiolabelled dose of methyl nicotinate in human volunteers, approximately 15% of the dose was recovered in the urine within 108 hours after treatment . The excretion of nicotinic acid mainly takes place in the kidneys .

Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%).

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