Esomeprazole

Esomeprazole is a medication that reduces stomach ache. It is primarily used to treat stomach
related illness such as GORD, Zollinger Ellison syndrome and ulcer diseases. The chirality of the drug
conforms to an S- isomer of omeprazole developed through racemic synthesis and mixture of a single
isomer (S- isomer) forming the first proton-pump inhibitor designed to treat acid-based diseases. Also, it
comes in tablets, capsule, oral liquid and injection. The essay is focused on the principles of
pharmacokinetics and pharmacodynamics that are essential in the safe application and therapeutic
management of esomeprazole medicine to patients.
Pharmacokinetics describes how drugs are affected by organisms consuming it. The process
occurs in four principles which they are absorption, distribution, metabolism and excretion. Clinical
pharmacokinetics aims to applying pharmacokinetic principles to efficient therapeutic management of
drugs in a single patient. It aims to improve the efficacy and decreasing the toxicity of a patient’s drug
therapy.
Firstly absorption, it involves all the processes of entry of Esomeprazole in the blood circulation. It
is rapidly absorbed with peak plasma (C max) concentration within one and half hours (Tmax) upon
administration through the mouth. The Cmax is a non-static coefficient that increases or reduces
proportionally in reflecting the dose. For example, at 20 to 40 mg increases the plasma concentration. In
essence, an increase from 20 to 40 mg of administration, increase the bioavailability to 90% compared
to a 40% single dose. The absorption coefficient and the mean exposure of the Esomeprazole, therefore,
undergo a considerable increase from initial 4.3225 mol *hour/L initially on day one to 11.203
mol*hour/L on the fifth day when an individual is administered a 40mg daily. According to Bennett
(2019), any food intake after administration of the Esomeprazole reduces its net charge. For instance, at
a 40mg net 43-53% reduction can be realized. Therefore, individuals are consequently advised to take
esomeprazole capsules one hour before any meal.
Secondly distribution, it is chiefly bound to the plasma protein s. approximately over 97 % of the
plasm proteins link at constant concertation of 2-20*mol/L. the volumes of distributions predominantly
vary depending on the health status and rate of patients in the individuals.
Thirdly metabolism, the metabolism of Esomeprazole occurs in the liver by P450 (CYP) enzyme
cytochrome. Consequently, esomeprazole metabolites take advantage of the absence of antisecretory
activities to increasing the inhibition processes. In essence, Metabolites such as hydroxyl and desmethyl
depends upon isoenzyme CYP2C1 and acts a principle major part of metabolism for Esomeprazole. The
remaining part of Esomeprazole depends upon CYP3A4 which from the secondary sulphone metabolite.
The two enzymes have a distinct feature. For instance, CYP2C19 shows polymorphism during the
metabolism of Esomeprazole. Individuals without isoenzyme CYP2C19 are termed as poor metabolizers,
and examples are the Asians. According to Hong and Park (2019), Complete metabolism of the
Esomeprazole requires a steady ratio approximated to 2. It is therefore evident that at an equimolar
dose, the metabolism of S and R isomers of Esomeprazole occur differently depending on the phase.
Furthermore, due to cytochrome, the higher plasma levels are achieved on S- isomer than R-isomer
esomeprazole.
Finally, execration which involves removing the drug substances in the body. According to
underwood (2019), the excretion occurs through the urine and accounts to less than one per cent by the
total volume of the parent drug during administration. Usually, the elimination of the Esomeprazole is
approximated between one to one and a half hour in the plasma. Furthermore, an approximated 80 %
of inactive metabolites are extracted by the in the urine and faeces.
Despite the extensive treatment of stomach and oesophagal diseases, it has many side effects. It
causes conditions such as heartburn, H.pylori infections, kidney damage, severe diarrhoea, increased
risk of osteoporosis, can cause cutaneous and systematic lupus erythematosus( C & SLE) which can
increases chances of rashes on the skin and nose (Cook et al., 2016). Prolong usage can also cause gland
polyps on the lining of the stomach that can cause cancer. Furthermore, prolonged use can cause
atrophic gastritis accompanied by weight loss, nausea, low blood levels, allergic reactions and deficiency
of vitamin B12 in the body.

Pharmacodynamics studies the relationships between drug concentration and sites over which
the drug acts, the biochemical and the physiological effects of the drug on the host. The host species can
be any living species such as human beings or any other animal under investigation. According to Mills
(2016), pharmacodynamics emphasizes on dose-response interrelationships. Therefore, a consent
analysis of the effect and drug concentration can be generalized by the interrelationships: L+R ⇋LR
Where; L- is drug or (ligand), R- the receptor and LR- receptor complex of the ligand.
The pharmacodynamics of Esomeprazole includes formal methods such as the mechanism of actions
and antisecretory.
Mechanism of actions involves inhibition of the proton pump that suppressing gastric acid from
being secreted. It acts by suppressing H+/K+ and ATPase at the parietal gastric cells. Generally, after
protonation, both S- and R- isomers are converted into compact parietal cells that form an active
inhibitor (achiral sulphenamide). Esomeprazole acts on the specific proton pumps by actively blocking,
the ending steps of H+ production, gastric acid secretions.
Antisecretory activity involves determining the effect of Esomeprazole on the intra-gastric pH. At
ingenious administration esomeprazole, the parameters such as percentage time, pH, coefficients of
variation and median of pH are known. For instance, Hypergastrinemia, a condition induced by PPI
(proton pump inhibitor, can lead to free bound of dyspepsia and hyperacidity to the ECLin the parietal
cells. Esomeprazole has a net effect of increasing the gastrin and the CgA. According to park (2019),
Esomeprazole increases the suppression of the gastrin. Any experimental set-up shows a decrease in
gastric levels. Esomeprazole, therefore, blocks gastrin or CCK2 receptors on cells of ECL., in essence, the
administration of Esomeprazole abolishes the effect of hypergastrinemia on the ECL cells. The process
of the Esomeprazole, therefore, leads to a net decline in the levels of gastrin.
References:

Cook, E. K., Satake, N., Sykes, B. W., Bennett, E. L., & Mills, P. C. (2016). Pharmacokinetics of

Esomeprazole following intravenous and oral administration in healthy dogs. Veterinary

Medicine: Research and Reports, 7, 123.

Dean, L. (2019). Esomeprazole Therapy and CYP2C19 Genotype. In Medical Genetics Summaries

[Internet]. National Center for Biotechnology Information (US).

Kim, D., Park, M. S., Yoo, B. W., Hong, T., Park, S. J. & Kim, C. O. (2019). The safety, pharmacodynamics,

and pharmacokinetics of immediate-release formulation containing Esomeprazole 20

mg/sodium bicarbonate 800 mg in the healthy adult male. Drug Design, Development and

Therapy, 13, 3151.

Sykes, B. W., Underwood, C., & Mills, P. C. (2017). The effects of dose and diet on the

pharmacodynamics of Esomeprazole in the horse. Equine veterinary journal, 49(5), 637-642