ASCIPRAM 10

Indications

• Depressive illness
• Generalized anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder
• Social anxiety disorder

Mechanism of action

Escitalopram enhances serotonergic activity by binding to the primary binding site on the serotonin transporter (SERT), preventing the re-uptake of serotonin into the presynaptic neuron. It also acts as an allosteric serotonin re-uptake inhibitor, binding to a secondary allosteric site on SERT to more effectively inhibit serotonin re-uptake, leading to elevated extracellular serotonin levels. This sustained increase eventually desensitizes 5-HT1A auto-receptors, which is critical for the full clinical effect of SSRIs.

Pharmacodynamics

As a selective serotonin re-uptake inhibitor, escitalopram increases serotonin levels in neuronal synapses, leading to an antidepressant effect. Compared to other SSRIs, escitalopram has a relatively quick onset of action due to its potency. The drug has been associated with potential adverse effects such as abnormal bleeding and serotonin syndrome, particularly when used with other serotonergic drugs. Abrupt discontinuation may lead to withdrawal symptoms, necessitating a gradual tapering of the dose.

Pharmacokinetics

Escitalopram is well absorbed after oral administration, with peak plasma concentrations typically reached within 4-6 hours. It has a volume of distribution of approximately 12 L/kg and is highly protein-bound. The drug undergoes extensive hepatic metabolism, primarily via the cytochrome P450 enzyme CYP2C19, and has a half-life of about 27-32 hours, allowing for once-daily dosing. Renal impairment does not significantly affect the pharmacokinetics of escitalopram, but caution is advised in hepatic impairment.

Contra-indications

• QT-interval prolongation
• concurrent use of monoamine oxidase inhibitors (MAOIs)
• hypersensitivity to escitalopram or any of its excipients

Adverse effects

• nausea
• somnolence
• insomnia
• dry mouth
• sweating
• dizziness
• sexual dysfunction
• increased risk of bleeding
• serotonin syndrome

Interactions

• moclobemide + escitalopram: Moderate (increases exposure)
• other serotonergic drugs (risk of serotonin syndrome)
• anticoagulants (increased risk of bleeding)

Precautions

• use with caution in patients with a history of seizures
• monitor for signs of serotonin syndrome
• gradual tapering recommended to avoid discontinuation syndrome
• consider risks in patients with hepatic impairment

Pregnancy

Escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data suggest potential risks including fetal cardiac defects.

Breast-feeding

Present in breast milk; use with caution and consider alternative treatments if necessary.

Storage

Store at room temperature, away from moisture and heat. Keep container tightly closed.

Formulations

• Citalopram 40 mg/ml oral drops, sugar-free
• Citalopram 10 mg tablets
• Citalopram 20 mg tablets
• Citalopram 40 mg tablets

Indications

• Management of hyperoxaluria
• Prevention of calcium oxalate kidney stones
• Assessment of metabolic disorders related to oxalate

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Oxalate primarily functions as a metabolic byproduct in various pathways. It is involved in the superpathway of glycolysis and the tricarboxylic acid (TCA) cycle. In plants, oxalate can play a part in regulating calcium levels and can affect the solubility of calcium and other minerals, influencing mineral absorption. In humans, high levels of oxalate can lead to the formation of insoluble calcium oxalate crystals, contributing to kidney stone formation.

Pharmacodynamics

Oxalate interacts with calcium in the body, leading to the formation of calcium oxalate, which is poorly soluble. This property is critical in the context of kidney stone formation, as elevated oxalate levels can increase the risk of crystallization and subsequent stone development. The balance of oxalate in the body is influenced by dietary intake, metabolic processes, and renal excretion.

Pharmacokinetics

Oxalate is absorbed from the gastrointestinal tract and is also produced endogenously. Once in the bloodstream, it is primarily excreted by the kidneys. The renal clearance of oxalate is significant, and reduced kidney function can lead to elevated serum and urine oxalate levels, increasing the risk for stone formation. Factors such as hydration, dietary oxalate, and calcium intake can influence oxalate metabolism and excretion.

Pregnancy

There is no specific information available regarding the use of oxalate during pregnancy.

Breast-feeding

There is no specific information available regarding the use of oxalate during breastfeeding.

Storage

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

Formulations

• {'formulation': 'Oxalate salt', 'description': 'Used in various formulations, particularly in laboratory and industrial applications.'}

Mechanism of action

Escitalopram, like other selective serotonin re-uptake inhibitors, enhances serotonergic activity by binding to the orthosteric (i.e. primary) binding site on the serotonin transporter (SERT), the same site to which endogenous 5-HT binds, and thus prevents the re-uptake of serotonin into the presynaptic neuron. Escitalopram, along with [paroxetine], is also considered an allosteric serotonin re-uptake inhibitor - it binds to a secondary allosteric site on the SERT molecule to more strongly inhibit 5-HT re-uptake. Its combination of orthosteric and allosteric activity on SERT allows for greater extracellular 5-HT levels, a faster onset of action, and greater efficacy as compared to other SSRIs. The sustained elevation of synaptic 5-HT eventually causes desensitization of 5-HT_1A auto-receptors, which normally shut down endogenous 5-HT release in the presence of excess 5-HT - this desensitization may be necessary for the full clinical effect of SSRIs and may be responsible for their typically prolonged onset of action. Escitalopram has shown little-to-no binding affinity at a number of other receptors, such as histamine and muscarinic receptors, and minor activity at these off-targets may explain some of its adverse effects. The mechanism of antidepressant action of escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT).

Pharmacodynamics

Escitalopram belongs to a class of medications called selective serotonin re-uptake inhibitors (SSRIs). These agents cause an increase in serotonin levels in neuronal synapses by preventing the re-uptake of serotonin (5-HT) into the presynaptic terminals of serotonergic neurons. As compared to other SSRIs, it appears to have a relatively quick onset of effect due to its potency. SSRIs as a class have been associated with abnormal bleeding, particularly in patients receiving concomitant therapy with other medications affecting hemostasis, and with the development of serotonin syndrome. Use escitalopram with caution in patients with a higher-than-baseline risk of bleeding and in patients receiving concomitant therapy with other serotonergic drugs. Escitalopram may also cause a discontinuation syndrome with abrupt removal of the drug, and should be slowly tapered if discontinuation of therapy is warranted.