Pharmacology Application Paper
Medication Used in the Treatment of Peptic Ulcer Disease
Peptic ulcer disease (PUD) is a condition whereby painful sores or ulcers develop on the lining of the stomach and or duodenum. Treatment of PUD is dependent on the cause. PUD is mainly caused by a bacterium called Helicobacter pylori and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs).
Medications used include:
Antibiotics that kill Helicobacter pylori. Examples are amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and tinidazole (Arcangelo et al., 2016). These antibiotics are administered according to the antibiotic susceptibility tests to test for resistance. The antibiotics are combined with proton pump inhibitors to reduce acidity in the stomach. They are given for two weeks.
Proton pump inhibitors (PPIs). They reduce gastric acid production by blocking the action of parietal cells (Arcangelo et al., 2016). PPIs include omeprazole, rabeprazole, lansoprazole, esomeprazole and pantoprazole. Their trade names include Prilosec, Aciphex, Prevacid, Nexium, and Protonix respectively. Long term use of PPIs may increase the risk of spine and hip fractures; hence, PPIs are combined with calcium supplements.
Histamine antagonists (H 2 blockers). They decrease the amount of gastric acid production in the gastrointestinal system, hence relieving pain and enhancing the healing of the ulcer. The H2 receptor antagonists include cimetidine, ranitidine, nizatidine, and famotidine (Arcangelo et al., 2016).
Antacids are also used since they neutralize the acidic nature of the stomach, providing rapid relief of pain, but they do not heal the ulcer. However, they are associated with constipation and diarrhea.
Cytoprotective agents are also administered. They protect the lining of the stomach from the effects of acid (Arcangelo et al., 2016). They include sucralfate and misoprostol, and their trade names are carafate and cytotec, respectively.
The most common drug used in my setting is pantoprazole (Protonix). This paper shall be based on this drug in the treatment of PUD. The primary treatment for PUD is a triple therapy of PPI+ clarithromycin + amoxicillin/ metronidazole for fourteen days. Amoxicillin is preferred due to its few side effects.
Pathophysiology of PUD
Peptic ulcers are disruptions of the gastric or duodenal mucosa that may extend to the muscularis mucosa (Shell, 2021). Gastric and duodenal mucosa have some protective mechanisms. They include secretion of mucous that lines their mucosa to protect it from irritation by acid. Their mucosa is covered by a surfactant that is lipid-like; it forms a gel layer that is impermeable to acid and pepsin enzymes. Some cells of the gastric and duodenal mucosa secrete bicarbonates that neutralize the acid (Shell, 2021). Moreover, the epitheliums of the stomach and duodenum have a high regenerative power. There are also many tight junctions between the epithelial cells. Some prostaglandins, such as PGE, increase the production of mucous and bicarbonates, therefore protecting the mucosa.
In case of injury of the mucosa and the acid penetrates, ion pumps in the basolateral membrane of the epithelial cells play a role in reducing the effects of the injury (Shell, 2021). The ion pumps regulate the intracellular pH by pumping out excess hydrogen ions. Moreover, mucosal blood flow removes the acid in the injured cells and provides bicarbonates through the bicarbonate buffer system.
In normal situations, there is a homeostatic balance between gastric acid secretion and gastroduodenal defense mechanisms. When this balance is disrupted, either by injury or infection, peptic ulcers develop. Factors such as NSAIDs, H. pylori infection, alcohol ingestion, pepsin enzyme, bile salts, and acid aggravate the destruction of mucosal defense mechanisms (Shell, 2021). They cause an influx of hydrogen ions into the epithelial cells.
Helicobacter pylori, a gram-negative spirochete, is linked to inflammation of the gastric mucosa (gastritis). This contributes to the primary peptic ulcer disease. H. pylori is able to produce urease. Urease alkalinizes its microenvironment, hence making the organism survive in harsh acidic conditions (Shell, 2021). H. pylori burrow into the gastric mucosa in a corkscrew manner, causing inflammation. This inflammation disrupts the balance between defense mechanisms and the aggregative factors, leading to the formation of peptic ulcers.
Apart from inflammation, H. pylori infection causes increased levels of gastrin and pepsinogen and reduced levels of somatostatin. This increases acid exposure to the duodenum, causing duodenal ulcers. Duodenal ulcers cause impaired bicarbonate secretion by the duodenum. There is an imbalance since more acid is secreted and less bicarbonate is produced, consequently lowering the duodenal pH. Low duodenal pH results in gastric metaplasia (Shell, 2021). H. pylori colonizes the areas of gastric metaplasia, hence causing duodenal ulcers.
Long-term use of NSAIDs results in erosion of the gastric and duodenal mucosa. NSAIDs work by reducing the synthesis of prostaglandins such as PGE, which form a protective mechanism for the mucosa (Shell, 2021). The drugs have a topical irritant effect on the mucosa, contributing to the formation of ulcers. The drugs impair the barrier properties of the mucosa and reduce mucosal blood flow. Moreover, the drug also interferes with the repair of superficial injury. All these effects cumulatively lead to erosion of the mucosa, hence the formation of ulcers.
A patient with peptic ulcer disease presents with epigastric pain, which is burning in character. The pain tends to be relieved by taking foods that buffer acidity. PUD is also characterized by early satiety and nausea. Fatty foods increase the severity of pain. Moreover, it is characterized by melena stool. PUD is diagnosed through endoscopy and x-rays. Furthermore, tests to detect H. pylori are used in its diagnosis.
Drug response in treating PUD
Pantoprazole is a proton pump inhibitor (PPI). It is under the benzimidazole group, which has an extended rate of metabolism. It has been approved by the Food and Drug Association for the treatment of PUD and other diseases like Gastro-Esophageal Reflux disease (GERD). PPIs act by irreversibly inhibiting the H+ /K+ ATP pump (Arcangelo et al., 2016). This is the final step in gastric acid production. It forms a covalent bond between hydrogen and potassium ions on the ATPase enzyme. Consequently, gastric acid production is inhibited. Its site of action is the secretory surface of the gastric parietal cells. Pantoprazole has an increased rate of degradation in acidic pH. Its effects are dose-related and lead to inhibition of both basal and stimulated parietal cells despite the stimulus. Its inhibition effect lasts for approximately 24 hours (Arcangelo et al., 2016). In this period, there is no secretion of any gastric acid. It has a rapid onset of action and maximal effects occurring between two to six hours after administration. It will be metabolized in the liver by demethylation and sulfation.
Protonix is administered either orally or intravenously. It is swallowed whole without crushing or chewing. It will generally reduce acid production, hence promoting the healing of ulcers. It also kills H. pylori, hence eradicating it. To eradicate H. pylori, is given 40mg twice daily, while to prevent peptic ulcer rebleeding, a loading dose of 80mg is administered, followed by 8mg per hour infusions. For NSAID-induced ulcers, 20-40mg of pantoprazole is administered orally daily (Arcangelo et al., 2016). It has a bioavailability of 77%.
Pantoprazole is associated with few adverse effects. They include diarrhea, headache, abdominal pain, and upper respiratory tract infections. Long-term use of pantoprazole is associated with complications such as diarrhea attributed to Clostridium difficile, bacterial vegetations in the stomach, vitamin B12 deficiency, iron, calcium, and magnesium deficiency, interstitial nephritis, bone demineralization, and reduced absorption of some drugs such as clopidogrel.
Protonix has minimal toxicity and does not require therapeutic drug monitoring. It is contraindicated in patients with a history of hypersensitivity to the drug itself or other PPIs.
Collaboration with a pharmacist
I interviewed a pharmacist called Shejal Swaly, who is the head pharmacist for ICU patients. She was very friendly. From the interview, I learned a lot about the pharmacology of Protonix. It was a very informative session that I had with her. The following are some of the things that I learned.
Pharmacokinetics refers to what the body does to the drug. The body absorbs, distributes, metabolizes, and excretes the drug. Protonix is an enteric-coated tablet. Its absorption begins after it exits the stomach. It is dose-related; therefore, its maximum plasma concentration (Cmax) and area under the curve (AUC) are directly proportional to the oral or intravenous dosage, specifically from 10- 80mg doses (Arcangelo et al., 2016). Multiple daily doses do not alter its pharmacokinetics neither does the drug pantoprazole accumulate in the body. It has a short terminal elimination half-life of 1-1.9 hours (Arcangelo et al., 2016). It is metabolized extensively in the liver. For example, in extensive metabolizers who are given a 40mg dosage, their maximum plasma concentration (Cmax) is 2.4mg/ml, while the time taken to reach maximum concentration (Tmax) is 2.4 hours, and the total AUC is 4.8mg. Hr/ml. This really demonstrates its half-life to be 1 hour. Food affects absorption with pantoprazole. Its Tmax increases significantly when given together with food. Its apparent volume of distribution is 11.0- 23.6 liters, while its total clearance is 7.6- 14 liters per hour.
Pantoprazole absorption is rapid with a Cmax of 2.5g/ml. It is well absorbed and undergoes little first-pass effect. Its bioavailability is 77% (Arcangelo et al., 2016). Its absorption is not affected by the administration of antacids concomitantly; however, food delays absorption up to two hours or more. Despite the delayed absorption, its Cmax and AUC are not altered by food. Therefore, pantoprazole should not be taken with food; it should be taken either one hour prior to or after eating.
Pantoprazole is well distributed in the body. It is mainly found in extracellular fluid with an apparent volume of distribution of about 11-23 liters (Arcangelo et al., 2016). It is highly bound to plasma proteins, mainly albumin. Its plasma binding
It is rapidly metabolized in the liver through the cytochrome P450 system. Its metabolism is not affected by the route of administration. It is mainly metabolized by demethylation followed by sulfation in phase II reactions. This is catalyzed by CYP2C19 (Arcangelo at al., 2016). In phase I reactions, it is metabolized by oxidation catalyzed by CYP3A4. Its metabolites have no significant pharmacologic effects. In hepatic failure, dosage adjustments are necessary since its concentration increases 1.5 times compared to healthy patients.
71% of pantoprazole is excreted in the urine, while 18% is excreted in feces through the biliary system (Arcangelo at al., 2016). There is no renal elimination of unchanged drugs; hence, there are no dosage adjustments in renal failure.
Potential Drug Interactions
Pantoprazole influences the absorption of drugs that depend on gastric pH for their absorption (Rattanasuwan et al., 2020). These drugs include dasatinib, mycophenolate mofetil, ketoconazole, itraconazole, iron salts, and erlotinib, to mention a few. They require low pH for absorption. Pantoprazole reduces gastric acid, hence increasing pH and reducing the absorption of these drugs. High doses of Protonix and concomitant use of methotrexate increase and prolong the serum concentrations of methotrexate and its metabolites like hydroxy methotrexate, hence causing toxicities (Rattanasuwan et al., 2020). Pantoprazole reduces clopidogrel activation hence reducing its antiplatelet activity. Moreover, concomitant administration of pantoprazole with warfarin leads to increased INR and prothrombin time, resulting in excessive bleeding and even death (Rattanasuwan et al., 2020). Pantoprazole also reduces the antiviral activity of some antiretroviral drugs, such as atazanavir and rilpivirine. Concomitant use of Protonix and these drugs will cause the development of drug resistance. Pantoprazole also increases the toxicity of some antiviral drugs, such as saquinavir.
Protonix has several adverse reactions. It causes hypersensitivity and severe skin reactions, especially in people who have a history of hypersensitivity to PPIs. It also causes deficiencies in vitamin B12, magnesium, calcium, and iron (Rattanasuwan et al., 2020). This results in hypomagnesemia and hypocalcemia. Consequently, there are osteoporosis-related bone fractures due to the long-term use of Protonix. There is an increased risk of getting hip and spine fractures. It is also associated with acute tubulointerstitial nephritis and hepatic effects (Rattanasuwan et al., 2020). It also causes cutaneous and systemic lupus erythematous and polyps of fundic glands. It is also associated with clostridium difficile-associated diarrhea due to the development of bacterial vegetation in the stomach. The other common side effects include headaches, abdominal pain, nausea, vomiting, bloating, and joint pains (Rattanasuwan et al., 2020). It also predisposes an individual to community-acquired pneumonia.
Binding of Protonix
Protonix is highly protein-bound. It is 98% bound to albumin (Rattanasuwan et al., 2020). When it is administered together with another highly protein-bound drug, such as warfarin, its effects might increase. Warfarin is >95% protein bound. Each of the drugs will displace the other from albumin, hence increasing the free drugs in circulation. The free or unbound drug portion is the active one. The increase in unbound drugs leads to the accumulation and toxicity of the drugs. In the case of administering warfarin and Protonix together, there might be excessive bleeding or more adverse effects of Protonix. Therefore, it is not wise to administer two highly protein-bound drugs together. However, there is no direct interaction between Protonix and other drugs in terms of protein binding.
Pantoprazole is metabolized in the liver by CYP2C19. There are genetic differences that affect the activity of this enzyme. This drug displays genetic polymorphism. The different genotypes of this enzyme are classified into three groups: homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers (they have an elimination half-life of 3.5-10 hours and the least accumulation). Pharmacodynamics and pharmacokinetics differ among these genotypes. The lowest gastric Ph levels are indicated in the former group, while the highest levels are indicated in the latter group. These differences are replicated in the cure rates for PUD. CYP2C19 genotyping test is used to define the optimal treatment regimen for the different genotypes in the triple therapy for PUD. Moreover, the enzyme CYPP2C19 is absent in some populations. For instance, in 3% of Caucasians and African Americans and in 17-23% of Asians (Rattanasuwan et al., 2020).
Ways of improving communication between interprofessional team members
Effective communication between healthcare team members is crucial in the care of a patient. Better communication between the interprofessional team members ensures better treatment outcomes. It also creates trust with the patients, encouraging them to disclose important information that will help in the diagnosis and provision of care. However, there are many challenges associated with effective interprofessional communication, resulting in poor patient outcomes. The following are ways of improving interprofessional communication.
Employing structured communication tools will provide better clarity in communications. Some of the tools include SBAR, which stands for situation, background, assessment, and recommendation. This is a structured way of communicating among the health providers. Another structured tool is DRAW, which means diagnosis, recent changes, anticipated changes, and what to watch out for. These tools will ensure the efficient transfer of information, hence improving patient outcomes. Healthcare providers should be trained in using these standardized tools so as to improve their communication skills.
Healthcare team members should also be trained in basic communication skills. Continuous training sessions will hone their communication skills. Skills like active listening, emotional intelligence, and nonverbal cues will be developed. Providing an environment with sufficient resources to enable effective communication will also be helpful.
Moreover, creating opportunities that enhance teamwork will improve communication between the interprofessionals. These opportunities include carrying out collaborative rounds that will keep every team member informed. Other opportunities include doing pre-operative and post-operative team briefings. This will enhance communication. Also, doing team-building outdoor activities will help build relations between the healthcare team members, hence improving their communication.
Lastly, recognition and self-awareness by doing a constant assessment of the current situation of interprofessional communication. This will help us know whether there is any improvement or not. Through the assessments, we will be able to identify the individuals who are not working on their communication skills. You will also be able to identify disruptive behaviors that are contrary to achieving effective communication. The assessments will also help set up standard behaviors and procedures that will enhance communication for every department. Better, effective communication will ensure patients’ safety.
Application in practice
From my findings, I will apply the I formation gained in my practice. I have now known the dosage regimens for patients diagnosed with PUD. For treatment of PUD, I will prescribe a triple therapy of any PPI + clarithromycin + amoxicillin for 14 days. 40mg of Protonix once daily is enough for treatment. I will also replace Protonix with other PPIs in cases of extreme adverse effects.
My findings will also help me in practice in that I will be able to educate my patients. I will educate them not to take Protonix with meals but 30-60 minutes before meals to ensure maximal effects. I will also advise them of the long-term risk of osteoporosis; hence, I will also administer calcium supplements to prevent osteoporosis. I will also educate my patients on the adverse effects of using Protonix. I will also know conditions where Protonix is contraindicated; hence, I will not administer it in patients with osteoporosis, vitamin B12 deficiency, diarrhea associated with Clostridium difficile, and hypomagnesemia.
Moreover, I will be able to communicate effectively with my other healthcare team members. I will apply tools like DRAW and SBAR to ensure I pass the important information effectively. I will also attend collaborative ward rounds to promote teamwork and communication.
Arcangelo, V. P., Peterson, A. M., & Wilbur, V. (2016). Pharmacotherapeutics for advanced practice: A practical approach. LWW.
Rattanasuwan, T., Khoury, A. P., & Ebied, A. M. (2020). Proton pump inhibitors: For what and for how long? SN Comprehensive Clinical Medicine, 2(6), 719-726. https://doi.org/10.1007/s42399-020-00268-2
Shell, E. J. (2021). Pathophysiology of peptic ulcer disease. Physician Assistant Clinics, 6(4), 603-611. https://doi.org/10.1016/j.cpha.2021.05.005
We’ll write everything from scratch
The paper is called an application paper. The paper details and outline will be provided along with sources that need to be used. The majority of the paper is information that is the questions that come from asking the pharmacist. I asked a pharmacist about pharmacogenomics, and there was nothing that she could think of. So, this section would be smaller.
Where it says consult pharmacist, just get the information from sources as the outline will be followed.
Please just use the 3 sources Document for reference.
I will send a message with more information on the drugs used for Gerd and PUD. I will also send the Pharmacists name in the message. I will send this tonight when I get home.
The drug is Protonix, not Prilosec; although they are the same class PPIs, the hospital uses Protonix
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