Question

Escitalopram with half life

27 - 32 hours

question 1

half life 27-32 hours

• Calculate how long it takes to eliminate 95% of a single dose of escitalopram from the body. Provide the range of values and the equation used.
• From the given pharmacokinetics parameter, explain which elimination model of escitalopram is likely to follow.

questionB

what is the mechanism of actions of escitalopram, and the affect escitalopram has on the structure of the target site

Identify the molecular target for escitalopram, and explain the full mechanism of action (including signalling) for escitalopram . identify the specific target receptors and structure of escitalopram and how it affect affects it target.

question C

what are thetheraputic use and adverse affects of escitalopram. Explain why this adverse effect occurs.

the pharmacokinetics of escitalopram

Answer 1

Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking the reuptake of the neurotransmitter into the presynaptic neuron.

The 5-HT (5-hydroxytryptamine, serotonin) transporter (SERT) mediates the reuptake of 5-HT from the synaptic cleft into the neuron, and inhibition of this uptake is the target of selective serotonin reuptake inhibitors (SSRIs). Escitalopram (S-citalopram) is the most selective SSRI available, whereas the other enantiomer, R-citalopram, is approximately 30-40 times less potent than the S-enantiomer. Both biochemical experiments (measurement of extracellular 5-HT in the frontal cortex of rats) and behavioural studies (using the chronic mild stress and conditioned fear stress models) demonstrate that R-citalopram appears to counteract the effect of escitalopram, and that it is a dose-dependent action. When escitalopram is administered at a specific dose, it produces a greater effect than when the same dose of the S-enantiomer is administered in combination with the R-enantiomer, i.e. when citalopram is administered. While mainly the S-enantiomer is bound to the primary binding site on the SERT, both enantiomers bind to the allosteric binding site. However, the R-enantiomer stabilises the binding of the S-enantiomer at the primary site less than the S-enantiomer. Furthermore, R-citalopram has an inhibitory effect on the association of escitalopram with the transporter, thereby possibly reducing escitalopram's effect. In summary, escitalopram appears to possess a unique mechanism of action at the 5-HT transporter protein. Furthermore, escitalopram (S-citalopram) is different from citalopram because R-citalopram counteracts the activity of the S-enantiomer.

Pharmacodynamics

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). In vitro and in vivo studies in animals suggest that escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) with minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate. Tolerance to a model of antidepressant effect in rats was not induced by longterm (up to 5 weeks) treatment with escitalopram. Escitalopram has no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), and benzodiazepine receptors. Escitalopram also does not bind to, or has low affinity for, various ion channels including Na+ , K+ , Cl- , and Ca++ channels. Antagonism of muscarinic, histaminergic, and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular side effects of other psychotropic drugs.

Pharmacokinetics

The single- and multiple-dose pharmacokinetics of escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day. Biotransformation of escitalopram is mainly hepatic, with a mean terminal half-life of about 27-32 hours. With once-daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of escitalopram in plasma in young healthy subjects was 2.2-2.5 times the plasma concentrations observed after a single dose. The tablet and the oral solution dosage forms of escitalopram oxalate are bioequivalent.

Uses

Escitalopram is used to treat depression and anxiety. It works by helping to restore the balance of a certain natural substance (serotonin) in the brain. Escitalopram belongs to a class of drugs known as selective serotonin reuptake inhibitors (SSRI). It may improve your energy level and feelings of well-being and decrease nervousness.

COMMON side effects

If experienced, these tend to have a Less Severe expression

• Diarrhea
• Difficulty Sleeping
• Dizziness
• Drowsiness
• Dry Mouth
• Excessive Sweating
• Low Energy
• Nausea
• Orgasm Problems
• Problems With Ejaculation

INFREQUENT side effects

If experienced, these tend to have a Less Severe expression

• A Stuffy And Runny Nose
• A Toothache
• Abnormal Sexual Function
• Altered Interest In Having Sexual Intercourse
• Constipation
• Decreased Appetite
• Flu-Like Symptoms
• Gas
• Indigestion
• Inflammation Of The Tissue Lining The Sinuses
• Numbness And Tingling
• Stomach Cramps
• The Inability To Have An Erection

RARE side effects

If experienced, these tend to have a Severe expression

• A Clot In The Lung
• A Condition With Muscle Tissue Breakdown Called Rhabdomyolysis
• A Decrease In The Blood Clotting Protein Prothrombin
• A Disorder With Excess Antidiuretic Hormone Called Syndrome Of Inappropriate Antidiuretic Hormone
• A Feeling Of Restlessness With Inability To Sit Still
• A Heart Attack
• A Skin Disorder With Blistering And Peeling Skin Called Stevens-Johnson Syndrome
• A Skin Disorder With Blistering And Peeling Skin Called Toxic Epidermal Necrolysis
• A Type Of Allergic Reaction Called Angioedema
• Acute Inflammation Of The Pancreas
• Aggressive Behavior
• Anemia
• Atrial Fibrillation
• Bleeding
• Bleeding Of The Stomach Or Intestines
• Blood Clot In A Deep Vein Of The Extremities
• Decreased Blood Platelets
• Extrapyramidal Disease, A Type Of Movement Disorder
• Hallucinations
• High Blood Pressure
• High Blood Sugar
• Inflammation Of The Lining Of The Stomach And Intestines
• Inflammation Of The Liver Called Hepatitis
• Kidney Failure
• Liver Failure
• Liver Tissue Death
• Low Amount Of Potassium In The Blood
• Low Amount Of Sodium In The Blood
• Low Blood Pressure
• Low Blood Sugar
• Low Levels Of A Type Of White Blood Cell Called Neutrophils
• Low Levels Of White Blood Cells
• Manic Behavior
• Mental Problems From Taking The Drug
• Muscle Tremors
• Neuroleptic Malignant Syndrome, A Reaction Characterized By Fever, Muscle Rigidity And Confusion
• Prolonged QT Interval On EKG
• Rapid Ventricular Heartbeat
• Secondary Angle-Closure Glaucoma, A Type Of Eye Disorder
• Seizures
• Serotonin Syndrome, A Type Of Disorder With High Serotonin Levels
• Slow Heartbeat
• Suicidal Thoughts
• Torsades De Pointes, A Type Of Abnormal Heart Rhythm
• Very Low Levels Of Granulocytes, A Type Of White Blood Cell

If experienced, these tend to have a Less Severe expression

• A Feeling Of General Discomfort Called Malaise
• A High Prolactin Level
• A Migraine Headache
• A Problem With Menstrual Periods
• A Skin Rash
• Abnormal Manner Of Walking
• Abnormally Long Or Heavy Periods
• Agitation
• An Increased Need To Urinate Often
• Blurred Vision
• Bronchitis
• Bruising Under The Skin
• Chest Pains Unrelated To Heart Problems
• Cough
• Cramps
• Difficulty Concentrating
• Dilated Pupils
• Double Vision
• Drug-Induced Hot Flashes
• Fever
• Heart Throbbing Or Pounding
• Heartburn
• Hematoma, A Collection Of Blood Outside Of The Blood Vessels
• High Cholesterol
• Hives
• Increased Hunger
• Inflammation Of A Vein
• Irritability
• Joint Pain
• Loss Of Muscle Coordination
• Low Energy And Weakness
• Muscle Pain
• Nosebleed
• Orthostatic Hypotension, A Form Of Low Blood Pressure
• Pain In The Jaw Area
• Pain With Menstruation
• Ringing In The Ears
• Sensation Of Spinning Or Whirling
• Stuffy Nose
• Weight Gain