ETR-MR

Indications

• Osteoarthritis
• Rheumatoid arthritis
• Acute pain
• Gouty arthritis
• Chronic pain conditions

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines, as they vary based on condition and patient characteristics.

Mechanism of action

Etoricoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, an important mediator in the inflammatory process. By inhibiting COX-2, etoricoxib decreases the production of prostaglandins, which are responsible for pain, fever, and inflammation. This selective inhibition provides analgesic and anti-inflammatory effects while minimizing gastrointestinal side effects associated with non-selective NSAIDs.

Pharmacodynamics

Etoricoxib exhibits anti-inflammatory, analgesic, and antipyretic properties. Its selective action on COX-2 reduces inflammatory mediators in tissues, leading to decreased inflammation and pain relief. The drug's efficacy in managing conditions such as arthritis is attributed to its ability to target inflammatory pathways specifically.

Pharmacokinetics

Etoricoxib is well absorbed following oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has an extensive volume of distribution and is highly protein-bound (approximately 92%). The drug undergoes hepatic metabolism primarily via cytochrome P450 2C9, producing metabolites that are excreted in urine. The elimination half-life is approximately 22 hours, allowing for once-daily dosing in most cases.

Contra-indications

• Hypersensitivity to etericoxib or any of its components
• Active peptic ulcer disease
• Severe heart failure
• History of gastrointestinal bleeding or perforation related to NSAIDs
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Cardiovascular events such as myocardial infarction or stroke
• Gastrointestinal effects including nausea, diarrhea, and abdominal pain
• Renal effects including decreased renal function
• Hepatic effects including elevated liver enzymes
• Skin reactions such as rash or pruritus
• Hypertension

Interactions

• Anticoagulants such as warfarin - increased risk of bleeding
• Other NSAIDs - increased risk of gastrointestinal side effects
• Diuretics - may diminish the antihypertensive effect
• ACE inhibitors - may reduce effects and increase renal impairment risk
• Lithium - may increase lithium levels

Precautions

• Monitor blood pressure regularly, especially in patients with hypertension
• Use with caution in patients with a history of cardiovascular disease
• Assess renal function prior to initiation and during therapy
• Use with caution in elderly patients due to increased risk of adverse effects

Pregnancy

Etericoxib is generally not recommended during pregnancy, especially in the third trimester, as it may cause harm to the fetus.

Breast-feeding

It is not known if etericoxib is excreted in human breast milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, protected from light and moisture. Keep out of reach of children.

Formulations

• Oral tablets of various strengths

Indications

• Muscle spasms
• Rheumatic pain
• Traumatic pain
• Spastic sequelae of hemiparesis
• Parkinson's disease-related symptoms
• Acute and chronic lumbar and sciatic pain
• Cervico-brachial neuralgia
• Persistent torticollis
• Post-traumatic and post-operative pain

Dosage

Children: Refer to the BNF for Children for paediatric dosing guidance.

Adults: Refer to the BNF for detailed dosing recommendations.

Mechanism of action

Thiocolchicoside selectively binds to GABA-A receptors, activating GABA inhibitory pathways and acting as a muscle relaxant. It also has an affinity for glycine receptors and partially inhibits nicotinic acetylcholine receptors, contributing to its muscle relaxant properties. The drug is noted for its potential convulsant activity, necessitating caution in individuals susceptible to seizures.

Pharmacodynamics

Thiocolchicoside functions primarily as a muscle relaxant through its action on GABA-A receptors, preventing muscle contractions and providing relief from painful muscle spasms. It exhibits competitive antagonistic properties at GABA receptors and shows significant effects on glycine and nicotinic acetylcholine receptors. It is effective in alleviating symptoms associated with central and reflex muscle contractures, as well as conditions like spastic hemiparesis and neurodyslectic syndrome.

Pharmacokinetics

The specific pharmacokinetic profile of thiocolchicoside, including absorption, distribution, metabolism, and excretion details, is not provided. For optimal therapeutic management, refer to established guidelines and consult pharmacokinetic resources.

Contra-indications

• Hypersensitivity to thiocolchicoside or any of its components
• History of seizures or epilepsy
• Severe renal impairment

Adverse effects

• Drowsiness
• Dizziness
• Gastrointestinal disturbances (nausea, vomiting)
• Allergic reactions (skin rash, urticaria)
• Muscle weakness
• Severe hypotension
• Convulsions in predisposed individuals

Interactions

• CNS depressants (e.g., alcohol, benzodiazepines) may enhance sedative effects
• Antiepileptic drugs may reduce the effectiveness of thiocolchicoside
• Other muscle relaxants may increase the risk of adverse effects

Precautions

• Use with caution in patients with hepatic impairment
• Monitor patients for signs of seizures
• Caution in elderly patients or those with a history of falls
• Not recommended for use in children unless prescribed by a specialist

Pregnancy

There are limited data on the use of thiocolchicoside during pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether thiocolchicoside is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Tablets
• Injectable solution

Mechanism of action

Thiocolchicoside, is a synthetic sulfur derivative of colchicoside, a naturally occurring glucoside contained in the Colchicum autumnale plant. Thiocolchicoside has a selective and potent affinity for g-aminobutyric acid A (GABA-A) receptors and acts on muscular contractures by activating the GABA inhibitory pathways thereby behaving as a potent muscle relaxant. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. GABAergic neurons are involved in myorelaxation, anxiolytic treatment, sedation, and anesthetics. GABA can also modulate heart rate and blood pressure. It also has an affinity for the inhibitory glycine receptors (i.e., have glycomimetic and GABA mimetic activity), therefore acts as a muscle relaxant. Glycine is an inhibitory neurotransmitter and acts as an allosteric regulator of NMDA (N-methyl-D-aspartate) receptors. It is involved in the processing of motor and sensory data, thereby regulating movement, vision, and audition. Inhibitory neurotransmitter in spinal cord, allosteric regulator of NMDA receptors. In one study, thiocolchicoside inhibited the function of recombinant human strychnine-sensitive glycine receptors composed of the alpha1 subunit with a potency (median inhibitory concentration of 47 microM) lower than that apparent with recombinant GABA(A) receptors. The drug also inhibited the function of human nicotinic acetylcholine receptors made of the alpha4 and beta2 subunits, however, this effect was partial and moreover only apparent at high concentrations. Thiocolchicoside demonstrated no effect on the function of 5-HT(3A) serotonin receptors.

Pharmacodynamics

Thiocholchicoside is a muscle relaxing agent that works through selective binding to the GABA-A receptor. It prevents muscle contractions by activating the GABA inhibitory motor pathway. This medication acts as a competitive GABA receptor antagonist and inhibits glycine receptors with similar potency as nicotinic acetylcholine receptors. It has powerful convulsant activity and should not be used in individuals at risk for seizures. Used in combination with glafenine and meprobamate to tranquilize patients undergoing hysterosalpingography. In the treatment of painful muscle spasms. Thiocolchicoside acts both in contractures with a central cause and in contractures of reflex type, rheumatic and traumatic. It also alleviates symptoms of spastic sequelae of hemiparesis, Parkinson's disease and iatrogenic Parkinson symptoms, particularly neurodyslectic syndrome. Some other conditions that may benefit from this medication are acute and chronic lumbar and sciatic pain, cervico-brachial neuralgia, persistent torticollis, post-traumatic and post-operative pain.