Parietal cell

Omeprazole was one of the first proton pump inhibitors bought onto the market in the late 1980’s, they appear to be the drug of choice for most gastric related disorders (Der, 2003) Omeprazole is the author’s drug of choice and it will be demonstrated through a drug framework. This drug has particular interest because of the gastroenterology nursing environment the author works in.

Discussion based around the drug framework will include, structure, formulation, indications for use, pharmacodynamic effect, pharmacokinetic effects, contraindications, adverse reaction, interactions with other drugs and lastly monitoring, ethical and legal issues relating to Omeprazole. Omeprazole is the generic name given to the drug, it is also commonly known as Losec (trade name). Omeprazole is used mainly for the treatment of gastro esophageal reflux disease (gord), duodenal and gastric ulcers, acid related dyspepsia which is more commonly know as heartburn (Biddle, 2003).

The literature also states that Omeprazole is used in the treatment or eradication of H. pylori, a bacterium that can weaken the lining of the stomach and lead to ulceration. The appearance of Omeprazole is an off white coloured crystalline powder which is freely soluble in ethanol, methanol and partially soluble in water. The active ingredient comes from a chemical class named benzimidazole and is broken down as: 5-methoxy-2-[[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl] sulfinyl]-1H- benzimidazole, this compound inhibits gastric secretion. The empirical formula of Omeprazole is C17H19N3O3S, it has a molecular weight of 345.

42 and has a structural formula displayed below: [pic](Rxlist. com, 2007) In New Zealand Omeprazole is available in four formulations. Omeprazole oral suspension for use with nasogastric tubes and patients with swallowing difficulties. Omeprazole delayed release capsules with enteric coated granules, available in 10mg, 20mg, and 40mg doses. Omeprazole 40mg powder and H20 solvent for intravenous therapy and Omeprazole 40mg for continuous intravenous infusion. It should be noted here, that Losec was funded by pharmac in New Zealand and is the most common name referred by the public of the drug Omeprazole.

However Dr Reddy is now funded in New Zealand and Omeprazole is simply now known as Omeprazole. Pharmacodynamics is the effect Omeprazole has on the body and how the drug achieves this process, (Bryant, Knights, Salerno, 2003). Omeprazole is what as know as a proton pump inhibitor, proton pump inhibitors block the final stage in gastric acid secretion and disrupts the chemical binding process in the parietal cells in the gastric mucosa (stomach), which in turn disrupts acid production. Simply, Omeprazole binds to hydrogen-potassium adenosine triphosphate (H+, K+ -ATPase) to block acid formation.

However the process in which this occurs is much more complex. To understand this process it is important to explain acid secretion and how a proton pump inhibitor functions in the acid secretion process. As mentioned in the latter acid secretion takes place in the gastric parietal cells in the stomach by an enzyme system (proton pump). This then catalyses the exchange of intracellular hydrogen for extra cellular potassium (K+). Hydrochloric acid (HCL) (major component of gastric acid) is stimulated by three excitatory G-coupled proteins receptor pathways, gastrin receptors which are stimulated by the G cells found in the stomach antrum.

Muscarinic (M? , M? ) receptors which are found on the parietal cells which are stimulated by acetylcholine which is released from neurons in the parietal cells and lastly Histamine receptors which is secreted from enterochromaffin cells. (Taylor, Reid, 2001). Proton pump inhibitors are weak bases and enter the parietal cells via blood and diffuse into the acidic environment of secretary cannaliculi of the parietal cells. Because of the surplus of H+ ion (protonation) Omeprazole is then confined, when adequate amounts are bound to the in the H+, K+ -ATPase system the proton pump is blocked. (Bryant, Knights, Salerno, 2003).

Pharmacokinetics refers to what effect Omeprazole has on the body. (Bryant, Knights Salerno, 2003). This process is broken down into the following categories: absorption, distribution, metabolism and excretion. Omeprazole is weak base and is better absorbed in an alkaline environment, therefore oral Omeprazole is absorbed in the small intestine (3 to 6 hours). It bypasses absorption in the stomach because of its form in which it is produced. (Enteric coated granules), this is because Omeprazole is so acid labile. Omeprazole is not affected by the presence or absence of food. (AstraZeneca, 2006).

The ph is determined by the level of the pKa, Omeprazole has a pKa of 8. 8. This determines the ph which 50% is ionized and 50% is unionized. Omeprazole is classed as first pass metabolism which occurs in the liver and establishes the bioavailability. The bioavailability of oral Omeprazole is 35% after a single dose, it is increased with consecutive daily doses to 60%. Bioavailability is increased with repeated doses because it is better absorbed in an alkaline environment (AstraZeneca, 2006). However intravenous Omeprazole has a 100% bioavailability and an immediate effect of decreased gastric acid.

The volume of distribution of Omeprazole is 0. 3 L/Kg, therefore it can be classed as lipid soluble. Omeprazole is highly protein bound at 95%. This represents that only 5% is free or active (AstraZeneca, 2006). The total plasma clearance rate of Omeprazole is 0. 3 – 0. 6L/min and elimination half life is approximately 40 minutes or 30-90 minutes after consecutive repeated doses. Elimination half life refers to the amount of time for the blood or plasma to fall by half (Bryant, Knights, Salerno, 2003). Omeprazole displays what is known as first order kinetics, the amount of plasma is proportional to its elimination rate (Kelly, 2005).

The main area of metabolism for Omeprazole is the liver through the cytochrome P-450 system (CYP-450). The specific enzymes that catalyze it are CYP-450 2C19 and CYP-450 3A4. Associated metabolites which are a product of metabolism include sulphone, sulphide and hydroxyl-Omeprazole. , these all do not affect acid secretion and are secreted in the urine (80%) and faeces (20%). (AstraZeneca, 2006, Bryant, Knights, Salerno, 2003). The organ involved in secretion of Omeprazole is the kidneys, because it is highly protein bound and is lipid soluble it occurs via the tubular secretion process.

(Bryant, Knights, Salerno, 2003). Age and other factors such as disease can sometimes have an effect of the excretion or bioavailability of a drug. The literature found no significant studies in a pediatric setting. However it was found that dosage did not need to be altered in the elderly. Moreover individuals with poor liver function the plasma clearance was increased and rates where found to be unchanged in individuals with impaired renal function (AstraZeneca, 2006, RxList. com, 2007). Contraindications of Omeprazole include excluding malignancy in a patient as this may mask signs and symptoms.

Also precaution with lactating mothers or pregnancy is advised. Omeprazole should also be avoided if there is a known hypersensitivity (Mims, 2007). There is no solid evidence in the literature that Omeprazole has been related to any serious undesirable adverse reactions, in humans. However gastric carcinoid tumours in long term treatment of Omeprazole were established in studies on rats (Up-To-Date, 2007). Moreover there are numerous reversible potential side effects that have been reported in humans. These include (1 – 10%) headache, dizziness, rash, diarrhea, abdominal pain, nausea, vomiting, and constipation.

Rare or less common (less than 1%) bullous eruptions, chest pain and hepatitis to name a few (AstraZeneca, 2006, Up-To-Date, 2007, Mims, 2007). It is noted that there was no literature found on phamacodynamic reactions. It could be argued this is because of the direct effect Omeprazole has on the proton pump. Omeprazole exhibits potential pharmacokinetic interaction with other drugs. Ketoconazole or itraconazole is affected by Omeprazole as it influences it absorption process due to the effect of changing gastric ph. As previously mentioned Omeprazole is metabolized using the CYP-450 system as does many other drugs.

Diazepam, phenytoin and warfarin are examples of this, when used in combination with Omeprazole it can prolong the elimination process. AstraZeneca a pharmaceutical company recommends a dose reduction and close monitoring when combined with Omeprazole. Nursing assessment is at the forefront of practice when commencing new medications. The monitoring involved with starting Omeprazole include, assessing there condition before and after starting Omeprazole. Assessing for adverse reactions and educating the patient on the drug therapy. Omeprazole has been shown that it affects different ethnic populations.

The Asian population commonly is slower at metabolizing via the CYP-450 2C19 system therefore plasma concentrations and half life of Omeprazole is higher (RxList. com, 2007). The pharmacoeconomics of proton pump inhibitors are proved to be a cost effective solution when analyzing such things as Doctor visits, hospilisation and endoscopic procedures (Der, 2003) It was found in the literature that for legal reasons the trade name ‘Losec’ (as Omeprazole it is commonly known in New Zealand) was to be changed due to the likeness of another common antidiuretic ‘Lasix’.

The likeness of the names was high risk for medical error (Faber, Azzugnuuni, DiRommana, Vanhaverbeek, 1990). In conclusion Omeprazole appears to be a favored proton pump inhibitor that is cost effective in today pharmaceutical market. It has little adverse affect and uses a relatively simple enzyme process within the body. With ongoing education to the patient Omeprazole appears to be a safe measure in treating acid related disorders. Total Mark = 84% REFERENCES AstraZeneca (2006). LOSEC Intravenous. [Product data sheet].

New South Wales, Australia. AstraZeneca (2006). LOSEC: Omeprazole magnesium delayed released tablets. [Product monograph]. Ontario, Canada. Biddle, W. , (2003) Gastrosphageal Reflux Disease: Current Treatment Approaches. Gastroenterology Nursing, 26(6) pg, 228 – 236. Bryant, B. , Knights, K. , Salerno, E. (2003) Pharmacology for health professionals. Australia: Mosby CMP Medica. (2007). Mims New Etihcals. Auckland. Der, G. (2003) An overview of Proton Pump Inhibitors. Gastroenterology Nursing, 26(5) pg 182-190.

Faber, J. , Azzugnuuni, S. , DiRommana, M. , Vanhaverbeek, N. (1990) Fatal confusion between Lasix and Losec, Lancet 6:338, p56-57. Kell, P. (2005). Phar4macodynamics [NURX 416 Nursing – applied pharmacology 2008 course notes]. Christchurch, New Zealand: University of Otago. Prilosec Side Effects & Drug Interactions. RxList. com (2007). Retrieved on 05. 03. 08 Taylor, M. , Reide, P. (2001) Mosby’s Crash Course in Pharmacology. Australia: Mosby. Up-To-Date. (2007). Omeprazole: Drug information. Lexi-Comp.

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