Drugs used in peptic ulcer disease Flashcards
What are the common causes of peptic ulcer disease?
1) Helicobacter pylori (H. pylori) infection
2) Non-steroidal Anti-inflammatory Drugs (NSAIDs)
3) Critical illness (stress-related mucosal damage)
What is the mechanism by which helicobacter pylori bacteria causes peptic ulcer disease?
The H.pylori catalyzes urea, and then ammonia produced, ammonia, ammonia will erodes the mucous barrier and causes epithelial damage, H.pylori produces cytotoxins and mucolytic enzymes
What is the mechanism by which NSAID induces peptic ulcer disease?
- NSAID are weak acids and they are not ionized at gastric pH, H+ ions will be liberated and cause cellular damage
- They can diffuse freely across the mucus barrier into the gastric epithelial cells
- In addition to that NSAID inhibits the cyclooxygenase activity and thus decreases the prostaglandins production resulting in a (reduction in gastric and mucosal blood flow, decreased mucus and bicarbonate secretion, decreased cellular repair and replication)
What is the zollinger-ellison syndrome?
- Characterized by gastric acid hypersecretion and recurrent peptic ulcers that results from a gastrin-producing tumor
- ZES is suspected in patients with multiple ulcers and recurrent Peptic ulcer disease which is often accompanied with esophagitis or ulcer complications
- Excessive acid production can overwhelm the lower esophageal sphincter, causing it to open and allowing acid to reflux into the esophagus. As a result, the patient may have both GERD and multiple recurrent ulcers
What are the features of gastric ulcer?
- Pain does not follow a consistent pattern (it is not predictable)
- Food can sometime cause pain
- Nausea, vomiting, anorexia, and weight loss are commoner in gastric ulcer compared to duodenal ulcers
What are the presentations of duodenal ulcers?
- The pain is more likely to follow a consistent pattern (compared to gastric ulcer)
- Food often relieves the pain, with the pain returning 1-3 hours after eating (Food relieves the pain in duodenal ulcers because it neutralizes and buffers gastric acid before it reaches the duodenum)
- Nocturnal gastric pain often occurs (pain during sleep)
What are the non-pharmacological treatment of peptic ulcer?
1) Eliminate psychological stress
2) Stop smoking
3) Stop the use of NSAID or use better alternatives like (acetaminophen or a nonacetylated salicylate “salsalate”)
4) Avoid food or beverages that can cause dyspepsia or exacerbate ulcer symptoms (like spicy food, caffeine and alcohol)
What are the pharmacological treatment of peptic ulcer disease?
1) For H.pylori our main goal is to eradicate the H.pylori, heal the ulcer, and ultimately cure the disease (via the use of antibiotics and anti-secretory agents “like PPI, and sometimes bismuth preparations”
2) For NSAID-induced peptic ulcer or non-H.pylori peptic ulcer our goal becomes to heal the ulcer as quickly as possible (Can use PPIs, H2-receptor antagonists, or sucralfate, Antacids are not used as monotherapy to heal peptic ulcers, however Misoprostol can be used to reduce the risk of NSAID-induced PUD)
return to slide 11 and slide 10 notes
What are the different drugs used in peptic ulcer disease?
1) Proton pump inhibitors
2) Potassium-competitive acid blockers (P-CABs)
3) H2-Receptor antagonists
4) Synthetic prostaglandin-E1 (Misoprostol)
5) Bismuth preparations (antimicrobial)
6) Sucralfate (Ulcer-adherent complex)
7) Antacids
What are the different treatment of H.pylori-positive ulcers?
1) Triple therapy (Amoxicillin, + Clarithromycin, + PPI)
2) Bismuth-based quadruple therapy (Tetracyclin, + metronidazole, bismuth subsalicylate and PPI)
3) Sequential therapy (day 1-5 “PPI + Amoxicillin”, day 6-10 “Clarithromycin + metronidazole)
4) Levofloxacin-Based Triple Therapy (Amoxicillin + levofloxacin + PPI)
What is the mechanism of action of proton pump inhibitors?
1) It blocks the acid secretion by inhibiting the gastric H+/K+ ATP found in the secretory surface of the gastric parietal cells
- This will result in a long-lasting anti-secretory effect that can maintain gastric pH levels above 4
What are the different proton pump inhibitor drugs?
- Peazole family
1) Omeprazole
2) Esomeprazole “Nexium”
3) Lansoprazole
4) Dexlansoprazole (prevacid)
5) Pantoprazole
6) Rabeprazole
What are the side effects of proton pump inhibitors?
- Normally, the high acidity of your stomach, with a pH of 1 to 2, protects it from most bacteria as it is strong enough to even corrode metal. However, when you use these drugs, the pH increases to around 4, creating a more favorable environment for bacteria and making you more prone to stomach infections
1) Increased risk of clostridium difficile infections
2) Increases the risk of acquiring community-acquired pneumonia
- Long-term adverse effects (>1year)
3) Hypomagnesemia (acid are essential for the absorption of magnesium in the intestines)
4) Bone fractures
5) Vitamin B12 deficiency
What are the information that must be known by the patient before giving a PPI?
1) Take a PPI 30 to 60 minutes before a meal (mainly breakfast)
If a second dose is needed, take prior to the evening meal
2) Onset of relief is 2 to 3 hours and the duration of relief is 12 to 24 hours
- When taking PPIs, the recommended duration is a maximum of four weeks to avoid long-term complications. If you need to use them continuously throughout your life, it is advised to take them only three times, with each course lasting four weeks followed by a break.
What are the risks associated with the long-term use of PPI?
1) Fractures
2) Infections (C.difficle, and pneumonia)
3) Hypomagnesemia
4) Vitamin B12 deficiency
What is the mechanism of action of potassium-competitive acid blockers (P-CABs)?
- They are drugs that binds to potassium ions reversibly, blocking the H+/K+ ATPase enzyme, preventing the production of acid
- They have a fast onset of action and a dose-dependent effect on acid production
What are the examples of potassium-competitive acid blocker drugs?
1) Fexuprazan
2) Vonoprazan (treats gastroduodenal ulcers, reflux esophagitis, and it can be combined with antibiotics for the eradication of H.pylori)
What is the mechanism of action of H2-receptor antagonists?
They are competitive inhibitors of histamine at the H2 receptors found in the gastric parietal cells, which will inhibit the secretion of acids
What are the example of drugs that acts as a H2-receptor antagonists?
1) Cimetidine
2) Famotidine
3) Nizatidine
4) Ranitidine (Zantac)
- Must inform the patient to take it once a day preferably at bed time, the onset of relief occurs after 30-45 minutes and lasts for 4-10 hours
What is an example of drug that is a prostaglandin-E1 analog?
Misoprostol
What is the mechanism of action of misoprostol?
- It is a synthetic prostaglandin E1 analog, which replaces the protective prostaglandins which are decreased due to NSAID (for instance)
- It inhibits the basal and nocturnal acid secretion by direct action on the parietal cells
- It enhances the natural gastromucosal defense mechanisms and its healing by increasing the production of gastric mucus and mucousal secretion of bicarbonate
What is the adverse effect of misoprostol?
1) Diarrhea
2) Abdominal pain
3) Headache
4) Nausea/vomiting
5) Flatulence
6) Hypophosphatemia
7) Dysmenorrhea
-8) It can cause abortion (as PG stimulate uterine contrations)
What is a bismuth preparation and what is its mechanism of action?
Bismuth exhibits a antimicrobial activity against bacterial and viral GI pathogens
What is an example of bismuth preparation drugs?
1) Bismuth subsalicylate
2) Bismuth subcitrate potassium
What are the adverse effects of bismuth preparations?
1) Fecal discoloration
2) Tounge discoloration
3) Neurotoxicity
What is the mechanism of action of sucralfate?
- It forms an ulcer-adherent complex at the ulcer site protecting it from further injury of the stomach acid
What are the adverse effects of sucralfate?
1) Constipation
2) Hyperglycemia (in diabetic patients)
3) Aluminum toxicity (in patients with chronic renal failure or on dialysis)
- Must be taken on an empty stomach
What is the mechanism of action of antacids?
They are drugs that neutralizes the HCl in the stomach, increasing the gastric pH
What are examples of drugs that are antacids?
1) Magnesium hydroxide
2) Aluminum hydroxide
3) Calcium carbonate
What are the adverse effects of antacids?
1) Diarrhea (with magnesium hydroxide)
2) Constipation (with aluminum hydroxide and calcium carbonate)
3) Alterations in the metabolism of minerals
4) Acid-base disturbance
What is an important notice when taking antacids?
- Antacids can decrease the levels of numerous other drugs including tetracyclines, digoxin, iron supplements, fluroquinolones, and ketoconazole and thus, Patients should separate antacids and other medications by at least 2 hours
- Onset of relief is less than 5 minutes and duration of relief is 20 to 30 minutes
What are the different regimens for the eradication of H.pylori?
1) Triple therapy
2) Bismuth-based quadruple therapy
3) Sequential therapy
4) Salvage therapy
What are the drugs of the triple therapy?
- 10-14 days (14 days preferred to increase the chance of eradication
1) Amoxicillin
2) Clarithromycin
3) PPI
- If the patient is allergic to penicillin then give metronidazole instead of amoxicillin
What is the first line treatment of H.pylori?
The triple therapy (Amoxicillin/metronidazole, PPI, clarithromycin), especially in areas where the resistance to clarithromycin is <20%
What can we add to a triple therapy of H.pylori to decrease the side effect and increase the chances of eradication?
Probiotics
What does the bismuth-based quadruple therapy contains?
- Given for 10-14 days
1) Tetracyclin
2) Metronidazole
3) Bismuth subsalicylate
4) PPI or a H2-receptor antagonist
- PYLERA (contains Tetracycline 125mg, Metronidazole 125mg, and Bismuth subcitrate potassium 140mg)
- Mnemonic: (My BiCYCLE has 4 Pedals)
My-> metronidazole
Bi-> Bismuth
Cycle-> tetraCYCLINE
Pedals-> PPI
What is the first line therapy of H.pylori in areas where clarithromycin resistance is >20%?
Bismuth-based quadruple therapy, it might also be the first line treatment in patients with penicillin allergy and those who previously has been treated with a macrolide antibiotic and also when triple-therapy fails
What is the sequential therapy?
- Newer H.pylori therapy where antibiotics are adminstered in a sequence rather than together
1) Day 1-5:
- PPI + Amoxicillin
2) Days 6-10:
- PPI + Clarithromycin + Metronidazole
- we kept the PPI but we changed the antibiotic halfway through the treatment
What does the levofloxacin-based triple therapy contain?
- Given for 10 days
1) Amoxicillin
2) Levofloxacin
3) PPI
- This regimen is an option for salvage therapy in patients who have persistent H. pylori infection
Which regimen is used in patients with a persisten H.pylori infection?
Levofloxacin-based triple therapy
- If the patient is having repeated infections of H Pylori/all the treatments failed🡪salvage therapy (used in special cases), Only in salvage therapy, we will use levofloxacin bcz the problem is it can develop resistance, that’s why this antibiotic is only used in special cases
What is the treatment of NSAID-induced ulcers?
- Discontinue the NSAID and treat using a PPI, H2-receptor antagonist or sucralfate (a medicine that forms a complex with the ulcer)
- PPI are the preferred drug as they provide the fastest symptom relief and ulcer healing
In an NSAID-Induced ulcer, what should we do if we need to continue using the NSAID?
1) Reduce the dose of the NSAID
2) Change the NSAID to (acetaminophen, a non-acetylated salicylate “salsalate”)
3) Partially selective COX-2 inhibitor like “meloxicam” or selective one like “celecoxib”
4) Use the PPi to treat the ulcer
What is the treatment that is not caused by H.pylori nor NSAIDs?
If an idiopathic peptic ulcer is confirmed treat with standard ulcer healing therapy (standard H2-receptor antagonist or sucralfate “6-8 weeks”, or a standard PPI dosage “4-weeks”)
What is the treatment of gastric acid hypersecretion (Zollinger-Ellison syndrome)?
PPI
- They are the oral drug of choice to treat ZES, given every 8-12 hours
What are the different pharmacological agents used in the treatment of GERD?
1) Antacids and alginic acid products
2) H2-receptor antagonists
3) Proton pump inhibitors
4) Promotility agents
What are the surgical interventions to treat GERD?
1) Fundoplication is used to increase the pressure of the sphincter
2)
What are some promotility drugs used?
1) Bethanechol: A parasympathomimetic that selectively stimulates muscarinic receptors, this will in turn enhance the propulsive activity leading to a increased tone and motility
- bethanechol is the only one that can have a beneficial effect on motility and a lower effect on producing acid since it mostly works on the Smooth muscle of the stomach and the intestine and has minimal effect on the parietal cells
2) Metoclopramide: It increases the GI tone by blocking the dopamine D2 receptors, which prevents the relaxation of the GIT
3) Domperidone: It is a peripheral dopamine D2-receptor antagonist which increases the motility and gastric emptying
What is an example of a gamma-amino-butyric acid B receptor agonist that inhibits the transient relaxation of the lower esophageal sphincter?
Baclofen
What is the mechanism of action of baclofen?
- It is a gamma-amino-butyric acid B receptor agonist that inhibits the transient relaxations of the lower esophageal sphincter
- Baclofen is specific to the sphincter (gamma b receptor)
