ETRICOX T

Indications

• Pain and inflammation in musculoskeletal disorders
• Acute gout
• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis

Dosage

Children: For children aged 16-17 years, the recommended dose is 120 mg once daily for a maximum of 8 days.

Adults: 120 mg once daily for a maximum of 8 days.

Mechanism of action

Etoricoxib selectively inhibits isoform 2 of the cyclo-oxygenase enzyme (COX-2), preventing the conversion of arachidonic acid to prostaglandins (PGs), which are mediators of inflammation and pain. This selective inhibition results in reduced inflammatory responses without significantly affecting the COX-1 pathway, which is important for maintaining gastrointestinal mucosal integrity.

Pharmacodynamics

Etoricoxib exhibits a high selectivity for COX-2, being about 106 times more selective for COX-2 than for COX-1. This selective action minimizes the gastrointestinal side effects commonly associated with non-selective NSAIDs, as COX-1 plays a protective role in the gastric mucosa. Etoricoxib provides analgesic and anti-inflammatory effects by lowering prostaglandin levels involved in the inflammatory process.

Pharmacokinetics

Etoricoxib is well-absorbed following oral administration, with peak plasma concentrations typically occurring about 1 to 2 hours after ingestion. The drug has a half-life of approximately 22 hours, allowing for once-daily dosing. It is extensively metabolized in the liver, primarily via CYP2C9 and CYP3A4 pathways, and is excreted mainly through urine as metabolites. The presence of food does not significantly affect its absorption.

Contra-indications

• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• Severe cutaneous adverse reactions (SCARs)
• Cerebrovascular disease
• Uncontrolled hypertension (persistently above 140/90 mmHg)
• Severe renal failure
• Hypersensitivity to aspirin or other NSAIDs
• Ischaemic heart disease
• Active inflammatory bowel disease

Adverse effects

• Hypertension
• Fluid retention
• Gastrointestinal discomfort
• Nausea
• Vomiting
• Headache
• Dizziness
• Chest pain
• Heart failure
• Palpitations
• Skin reactions
• Malaise
• Nephrotoxicity
• Insomnia
• Anemia
• Visual impairment
• Aseptic meningitis
• Tinnitus

Interactions

• Increased exposure when used with combined hormonal contraceptives
• Increased exposure when used with hormone replacement therapy
• May interact with other NSAIDs

Precautions

• Caution in patients with cardiac impairment
• Caution in patients with renal impairment
• Dehydration risk
• Caution in patients with allergic disorders
• May mask symptoms of infection

Pregnancy

Avoid unless the potential benefit outweighs the risk, especially during the third trimester due to risk of closure of the fetal ductus arteriosus.

Breast-feeding

Use with caution during breastfeeding; the manufacturer advises avoiding use if possible.

Storage

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

Formulations

• Modified-release tablet
• Dispersible tablet
• Oral suspension
• Oral solution

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

Like any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid.

Pharmacodynamics

Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1).

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.