Esomeprazole
Esomeprazole is a medication that reduces stomach ache. It is primarily used to treat stomach related illnesses 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, capsules, oral liquid, and injection. The essay focuses on the principles of pharmacokinetics and pharmacodynamics essential in the safe application and therapeutic management of esomeprazole medicine to patients.
When organisms consume drugs, they get affected through a process known as pharmacokinetics. The process occurs in four principles which they are absorption, distribution, metabolism, and excretion. Clinical pharmacokinetics aims at applying pharmacokinetic principles to the competent therapeutic management of drugs. The principles will be applied to a single patient. It aims to improve the efficacy and to decrease the toxicity of a patient’s drug therapy.
The first step is absorption. It involves all the processes of entry of Esomeprazole in the blood circulation. It is rapidly absorbed with peak plasma (Cmax) concentration within one and a 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.
Distribution is the second process. It is chiefly bound to the plasma proteins. 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.
Besides,
- esomeprazole
being the third process 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 depend upon isoenzyme CYP2C1 and acts as 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.
The final step is execration, which involves removing the drug substances in the body. According to underwood (2019), the excretion occurs through the urine and accounts for less than one percent of the parent drug’s total volume during administration. Usually, the elimination of the Esomeprazole is approximated between one to one and a half hours in the plasma. Furthermore, an approximated 80 % of inactive metabolites are extracted by the in the urine and feces.
Despite the extensive treatment of stomach and esophageal diseases, it has many side effects. It causes conditions such as heartburn, H.pylori infections, kidney damage, severe diarrhea, 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.
The 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 ECL cells; in essence, Esomeprazole’s administrationEsomeprazole 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.
Esomeprazole is an effective medicine for treating gastroesophageal diseases, through proper prescription, it can keep the inter gastric pH at a required low level. Therefore, the correct dosage of 40mg for adults and alterations of the dosage is necessary to maintain the functionality, especially in gastrointestinal prevention infections. For instance, in peptic ulcer during therapies such as endoscopic hemostatic. Furthermore, since it is a single racemate enantiomer(omeprazole), it can be considered, because of the specific ubiquitous mechanism and specialized approach of combating the secretion of the acid applied. Similarly, it has no other pharmacodynamics effects as compared to competitive medicine in the market. For example, it is not clastogenic under Vivo conditions and possesses no potentials of mutation. It also does not have any genotoxic effects on embryo-fetal relationships at the approved clinical dosage. Therefore, Esomeprazole is highly recommended for human use.
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