Departments of the foot in Latin

circulatory disorders: often – drop in blood pressure (in some cases pronounced, up to collapse and loss of consciousness).

Pharmacological Effects

Tizanidine is a centrally acting muscle relaxant. Its main site of action is in the spinal cord. By stimulating presynaptic alpha₂receptors, it inhibits the release of excitatory amino acids that stimulate the N-methyl-D-aspartate (NMDA) receptors. As a result, polysynaptic excitation transmission at the level of the intermediate neurons of the spinal cord is inhibited. Since this mechanism is responsible for the excessive muscle tension, muscle tension is reduced after inhibition. In addition to its myorelaxant properties, tizanidine also exhibits a central, moderately pronounced analgesic effect.

Sirdalud® is effective in both acute painful muscle spasms and chronic spasticity of spinal and cerebral origin. It reduces spasticity and clonic spasms, reducing resistance to passive movements and increasing the volume of active movements.

The myorelaxing effect (measured with the Ashworth scale and the pendulum test) and the side effects (decrease in heart rate and blood pressure) of Sirdalud® depend on the plasma concentration of the drug.

pharmacokinetics

Absorption. Tizanidine is rapidly and almost completely absorbed. T_Max in the plasma lies 1 hour after administration of the drug. Due to the important hepatic first-pass metabolism, the average bioavailability is approximately 34 %. C_Max of tizanidine is 12.3 and 15.6 ng/mL after a single and multiple dose of 4 mg, respectively.

Distribution. The middle V_ss after intravenous administration of tizanidine is 2.6 l/kg. Binding to plasma proteins is 30 %.

Metabolism. Tisanidine has been shown to be rapidly and extensively (about 95% %) metabolised in the liver. in vitro it has been shown that tizanidine is primarily metabolised by the isoenzyme CYP1A2. The metabolites are inactive.

Excretion. The middle T_1/2 of tizanidine from systemic blood flow is 2-4 hours. The drug is excreted mainly through the kidneys (about 70 % of the dose) in the form of metabolites, of which about 4.5 % are unchanged.

effect of food. Concomitant intake with food does not affect the pharmacokinetics of tizanidine. Although C_Max although increased by a third when the tablet is taken after a meal, this is not considered clinically significant. No significant effect on absorbance (AUC) was observed.

Tizanidine in the dose range of 1 to 20 mg has linear pharmacokinetics.

Details of pharmacokinetics in different patient groups

Patients with impaired renal function. In patients with renal impairment (creatinine Cl ≤25 mL/min), the maximum mean plasma concentration is 2-fold higher than in healthy subjects, the final T_1/2 reaches 14 hours, resulting in an increased (approximately 6-fold) systemic bioavailability of tizanidine (as measured by AUC).

Patients with impaired liver function. No specific studies have been conducted in this patient category. Tizanidine is primarily metabolised in the liver by the cytochrome CYP1A2; therefore, hepatic impairment may result in increased systemic exposure.