Pharmacology of PUD/GERD

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Questions and Answers

What are the mechanisms by which sodium bicarbonate acts as an antacid?

Sodium bicarbonate acts by neutralizing gastric acid, producing carbon dioxide as a by-product, which can lead to bloating and belching.

Explain the primary use of misoprostol and its contraindications.

Misoprostol is used to decrease acid secretion and promote bicarbonate and mucous secretion; it is contraindicated in pregnancy due to the risk of stimulating uterine contractions.

Describe how bismuth compounds contribute to gastrointestinal health.

Bismuth compounds coat erosions and ulcers, stimulate mucous and bicarbonate secretion, and have direct antimicrobial effects, including against H. pylori.

What are the consequences of using magnesium and aluminum hydroxide together?

Using magnesium and aluminum hydroxide together may prevent osmotic diarrhea from magnesium salts and alleviate constipation caused by aluminum salts. Signup and view all the answers

What risks are associated with sodium bicarbonate in patients with reduced renal function?

In patients with reduced renal function, sodium bicarbonate may be absorbed systemically, leading to metabolic alkalosis. Signup and view all the answers

What is the primary mechanism of action of antacids in treating GERD?

Antacids neutralize gastric acid by directly interacting with H+ ions to form salt and water. Signup and view all the answers

How do proton pump inhibitors (PPIs) like omeprazole affect the efficacy of clopidogrel?

PPIs inhibit CYP2C19, which reduces the activation of clopidogrel, potentially decreasing its antiplatelet effectiveness. Signup and view all the answers

What are some common adverse effects associated with the use of proton pump inhibitors?

Common adverse effects include diarrhea and headache. Signup and view all the answers

Discuss the mechanism by which histamine type 2 receptor antagonists reduce stomach acid secretion.

Histamine type 2 receptor antagonists work as competitive antagonists, blocking H2 receptors on parietal cells, leading to reduced acid secretion. Signup and view all the answers

What notable adverse effects are associated with the use of cimetidine, compared to other H2 blockers?

Cimetidine can cause androgen receptor antagonism, increased prolactin levels, and has numerous drug interactions. Signup and view all the answers

How do antacids stimulate prostaglandin production?

Antacids may stimulate prostaglandin production due to their alkaline nature and effect on the gastric environment. Signup and view all the answers

Explain the role of bismuth compounds in gastrointestinal treatment.

Bismuth compounds help to protect the stomach lining and may have antimicrobial properties. Signup and view all the answers

What is one consequence of the inhibition of calcium absorption by proton pump inhibitors?

Inhibition of calcium absorption can lead to an increased incidence of fractures. Signup and view all the answers

How do proton pump inhibitors (PPIs) relate to the treatment of PUD and GERD?

PPIs, such as omeprazole and esomeprazole, inhibit the gastric proton pump, reducing acid secretion and alleviating symptoms of PUD and GERD. Signup and view all the answers

What is the importance of the prodrug nature of most proton pump inhibitors?

As prodrugs, they avoid premature breakdown and ensure effective absorption at their site of action in the gastric acid environment. Signup and view all the answers

Describe a potential drug interaction involving PPIs and nutrients.

PPIs may reduce the absorption of vitamin B12 due to their suppression of gastric acidity, which is necessary for its digestion. Signup and view all the answers

How do bismuth compounds contribute to the treatment of PUD?

Bismuth compounds have a cytoprotective effect, promoting mucosal healing and inhibiting the growth of H. pylori bacteria. Signup and view all the answers

What are the implications of using promotility agents with PPIs?

Promotility agents may enhance gastric emptying and reduce symptoms of GERD when used alongside PPIs, improving overall treatment effectiveness. Signup and view all the answers

Explain the role of misoprostol in the management of PUD?

Misoprostol is a prostaglandin analog that enhances gastric mucosal protection and reduces the risk of NSAID-induced ulcers. Signup and view all the answers

What impact do proton pump inhibitors have on the absorption of ketoconazole?

PPIs can decrease the absorption of ketoconazole by reducing gastric acidity, which is necessary for its solubility. Signup and view all the answers

How is calcium absorption affected by long-term PPI use?

Chronic use of PPIs can impair calcium absorption, potentially leading to increased risk of fractures. Signup and view all the answers

Study Notes

PUD/GERD Pharmacology

The topics covered include a review of acid secretion and the pharmacology of agents used to treat peptic ulcer disease (PUD)/gastroesophageal reflux disease (GERD), and dyspepsia.
Recommended reading includes chapters 62 (sections 1-3) of "Basic and Clinical Pharmacology" (15th edition) and chapter 53 of "The Pharmacological Basis of Therapeutics" (14th edition).

Overview

The presentation discusses a review of acid secretion.
It also covers the pharmacology of agents used to treat PUD/GERD and dyspepsia.

Video #1

The video displays a diagram showcasing the various pathways and receptors involved in acid secretion within the stomach.
It highlights factors such as cholinergic nerve stimulation, histamine, gastrin, prostaglandins (PGE2), and proton pump inhibitors impacting the parietal cells.

Video #2

The second video describes the mechanism of action of proton pump inhibitors (PPIs).
It emphasizes the covalent inhibition of the H+, K+ ATPase enzyme within the parietal cell, leading to reduced acid production.
It also shows the accumulation of PPIs within the parietal cell at low pH (around 4).
The diagram shows the crucial sulfenamide reaction with cysteine residues.

Proton Pump Inhibitors - MOA

Proton pump inhibitors (PPIs) include omeprazole, esomeprazole, pantoprazole, and others.
These drugs are structurally related to H2-receptor antagonists, but lack affinity for the H2 histamine receptor.
They function by specifically and selectively inhibiting the gastric proton pump.
Most PPIs are prodrugs, requiring activation after absorption.
Various enteric-coated formulations are used to prevent the PPI from breaking down before reaching the target site.

Proton Pump Inhibitors - PK Notes

Pharmacokinetic properties like pKa, bioavailability, half-life, maximum plasma concentration (Tmax), and dosing regimens are presented.
Relevant data are tabulated to assist with quick reference and analysis.
Drug-nutrient interactions with vitamin B12, iron, calcium, and magnesium are mentioned along with a potential impact on absorption.
These drugs are primarily metabolized by CYP2C19 and 3A4, with minimal renal clearance.
Their short plasma half-lives contrast with the extended duration of their effect due to reversible inhibition of the proton pump.
Drug interactions with clopidogrel, an antiplatelet, are discussed. These interactions can potentially reduce clopidogrel's effectiveness and increase cardiovascular risk.

Proton Pump Inhibitors - Toxicity Notes

Common adverse effects (ADRs) of PPIs are diarrhea and headache.
Long-term use may be associated with kidney dysfunction, fractures, and infections; potential reasons include calcium absorption inhibition and altered gut flora.

Histamine type 2 receptor antagonists - MOA

These drugs are competitive H2-receptor antagonists.
The primary mechanism of action involves blockade of H2 receptors on parietal cells.
They are highly selective for the H2-receptor, leading to fewer off-target effects.
They are effective in inhibiting nocturnal acid secretion.
However, they also inhibit all acid secretion.

Histamine type 2 receptor antagonists - MOA (Table)

Clinical comparisons of different histamine type 2 receptor blockers, outlining their potency, dose required for 50% acid inhibition in 10 hours, and typical dosing for various conditions like acute ulcers, GERD, and stress-related bleeding.
Common drugs like cimetidine, ranitidine, nizatidine, and famotidine are included, along with their approximate potency, the acid inhibitory dose required, and their usual dosages.

Histamine type 2 receptor antagonists - Toxicity

Overall, adverse effects are minimal with these drugs.
However, cimetidine, the first H2-blocker, has notable side effects, including androgen receptor antagonism, an increase in prolactin levels, and interference with estradiol metabolism.
Cimetidine has an unusually high number of drug interactions due to its inhibition of specific drug-metabolizing enzymes (CYP 1A2, 2C9, 2D6, and 3A4).

Antacids

Commonly used for intermittent or short-term GERD relief.
Antacids act by neutralizing stomach acid through direct reaction with H+.
Some antacids can stimulate prostaglandin production.
Typical antacids contain 3-4 times the milliequivalents (mEq) of base salts needed to neutralize stomach acid.

Antacids - specific types

Different antacid types (sodium bicarbonate, calcium carbonate, and magnesium/aluminum hydroxide) have differing properties.
- Sodium bicarbonate quickly produces carbon dioxide, which can lead to bloating and belching. It may also cause metabolic alkalosis, especially in people with compromised kidney function.
- Calcium carbonate also produces carbon dioxide, but the reaction is slower than with sodium bicarbonate.
- Magnesium/aluminum hydroxide, does not produce carbon dioxide as a byproduct, and has a lower risk of inducing metabolic alkalosis. This option may cause osmotic diarrhea, though, due to potential magnesium salts production.

Misoprostol

Misoprostol is a methyl-PGE1 analog.
It has a very short serum half-life.
This drug decreases acid secretion, promotes bicarbonate and mucous secretion, and activates PGE2 receptors.
Misoprostol can stimulate uterine contractions; thus, it is contraindicated during pregnancy and generally used with caution in women of childbearing age.

Bismuth Compounds

Bismuth compounds can coat the esophagus and stomach lining, may stimulate prostaglandin production, increase mucus and bicarbonate secretion, decrease GI secretions, and have antimicrobial effects against H. pylori.
Possible side effects include stool and tongue discoloration

Sucralfate

Sucralfate is a complex of sucrose and aluminum hydroxide.
It forms a viscous solution in water.
It is thought to coat and protect areas of the GI tract that have a high negative charge, particularly those affected by ulcers.

Promotility Agents - Dopamine Receptor Antagonists

Dopamine receptor antagonists (like metoclopramide and domperidone) inhibit cholinergic muscle stimulation, increase peristalsis, improve esophageal tone, and enhance gastric emptying.
These agents can also act as antiemetics (preventing nausea and vomiting).

Promotility Agents - Dopamine Receptor Antagonists (Adverse Effects)

Primarily CNS-related adverse effects, including restlessness, drowsiness, insomnia, anxiety, and agitation, are often more pronounced in older adults.
Long-term use might increase the risk of tardive dyskinesia and other EPS (extrapyramidal symptoms) in some cases.
Hyperprolactinemia (increased prolactin levels), galactorrhea, gynecomastia, and menstrual disturbances can also occur.
Domperidone is less likely to cross the blood-brain barrier (BBB), and therefore generally has fewer central nervous system side effects.

Promotility Agents - Other

Cisapride and prucalopride are 5-HT4 receptor agonists, generally promoting prokinetic activity.
Cisapride was removed due to rare but serious cardiac arrhythmias.
Alosetron is an 5-HT3 antagonist, used primarily as an antiemetic.
Erythromycin is a macrolide antibiotic showing prokinetic activity by mimicking motilin.

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Description

This quiz reviews the pharmacological agents used to treat peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and dyspepsia. It references chapters from 'Basic and Clinical Pharmacology' and 'The Pharmacological Basis of Therapeutics'. Enhance your understanding of acid secretion and the mechanisms of these treatments.