farmaco gastro

Pharmacological Groups for Ulcer Pathology

Overview of Ulcer Pathology Medications

• The discussion focuses on various pharmacological groups, particularly those relevant to ulcer pathology, including gastroesophageal reflux disease (GERD), gastritis, and peptic ulcers. The importance of understanding these medications is emphasized.

Proton Pump Inhibitors (PPIs)

• PPIs are highlighted as the most potent agents in blocking acid production, crucial for managing ulcer pathology. They can inhibit 80-95% of hydrochloric acid secretion. Examples include omeprazole, esomeprazole, pantoprazole, and rabeprazole.

• These medications irreversibly block the proton-potassium pump in parietal cells, making them highly effective in reducing gastric acidity. This irreversible action is a key feature of their mechanism.

H2 Receptor Antagonists

• H2 receptor antagonists serve as alternatives to PPIs but are less potent; they block histamine receptors on parietal cells which also contribute to acid secretion. Common examples include ranitidine, famotidine, and cimetidine.

• Histamine acts as an agonist that increases acid production through a secondary messenger system involving cyclic AMP; thus blocking it reduces acid secretion but not as effectively as PPIs do.

Muscarinic Antagonists

• Muscarinic antagonists like atropine can reduce acid production by blocking acetylcholine receptors (M3) on parietal cells; however, their use is limited due to non-specific effects and the need for high doses which may lead to adverse effects.

• Due to these limitations, muscarinic antagonists are not commonly used in treating ulcer pathology compared to PPIs and H2 blockers.

Role of Antibiotics and Bismuth Compounds

• Helicobacter pylori plays a significant role in ulcer pathogenesis; therefore antibiotics such as amoxicillin, clarithromycin, tetracycline, and metronidazole are essential components of treatment regimens alongside anti-ulcer medications.

• Bismuth compounds like bismuth subsalicylate increase mucus and bicarbonate secretion while providing protective effects against H. pylori infection by forming a gel-like substance that protects gastric mucosa from damage caused by acids or bacteria.

Cytoprotective Agents

• Sucralfate is identified as a key cytoprotective agent that forms a viscous polymer upon contact with gastric acid; this polymer helps protect damaged areas in the gastric mucosa for up to six hours after administration. It reacts with acidic pH levels to provide its protective effect against ulcers.

Neutralizing Acids with Antacids

• Antacids neutralize stomach acids directly through chemical reactions producing salts and carbon dioxide; common antacids include magnesium sulfate and aluminum hydroxide often combined in formulations like Maalox or Mylanta for symptomatic relief post-meals rather than before meals unlike other treatments such as PPIs or sucralfate which are taken beforehand for optimal efficacy against acidity issues related to ulcers or GERD symptoms.

Anti-Acids and Their Mechanisms

Overview of Anti-Acids

• Anti-acids like hydroxaluminum and magnesium hydroxide are administered post-meals for effective acid neutralization. Magnesium provides rapid effects, while aluminum offers a longer-lasting impact.

• The combination of these anti-acids prevents side effects such as diarrhea (from magnesium) and constipation (from aluminum), ensuring balanced gastrointestinal function.

Adverse Effects of Specific Medications

• Surclar Fato contains sucrose and aluminum hydroxide, leading to constipation as a common adverse effect.

• Bismutol can cause melena, resulting in darkened stools due to its interaction with the digestive system.

Pharmacological Groups Related to Acid Production

• Key pharmacological groups include proton pump inhibitors (PPIs), H2 antagonists, cytoprotective agents like sucralfate and bismuth compounds, and antibiotics targeting Helicobacter pylori.

Risks Associated with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• NSAIDs are gastrotoxic; caution is advised especially for older adults with a history of peptic ulcer disease since they inhibit prostaglandin production which protects the gastric lining.

Understanding Proton Pump Inhibitors vs. H2 Antagonists

Differences Between Drug Classes

• Proton pump inhibitors (PPIs), such as omeprazole, are more potent than H2 antagonists like ranitidine. PPIs block 80% to 95% of acid production by inhibiting both basal and stimulated secretion.

Mechanisms of Action

• Basal acid secretion occurs during fasting or between meals, while stimulated secretion happens upon food intake. PPIs effectively inhibit both types.

Efficacy Comparison

• Ranitidine blocks about 70% of acid production but primarily affects basal secretion rather than stimulated secretion from food intake.

Pharmacokinetics and Interactions

Metabolism Considerations

• PPIs irreversibly block the proton pump, whereas ranitidine's action is reversible and competitive, explaining its lower potency compared to PPIs.

Citocromo P450 Interaction

• Both anti-acids inhibit cytochrome P450 enzymes affecting hepatic metabolism; renal elimination must be monitored in cases of renal insufficiency.

Drug Interactions: Omeprazole and Clopidogrel

Important Drug Combinations

• Omeprazole is a prodrug requiring stomach acid for activation; it interacts with cytochrome enzymes that also activate clopidogrel—an antiplatelet medication—potentially reducing its efficacy when combined.

Absorption Issues with Other Medications

• Anti-acids may interfere with the absorption of certain antibiotics like tetracyclines and iron supplements by altering stomach acidity levels necessary for optimal absorption.

Adverse Reactions and Efficacy of Acid-Reducing Medications

Adverse Reactions to Lomeprazole and Ranitidine

• Lomeprazole is generally well-tolerated, but can cause headaches, nausea, vomiting, diarrhea, and long-term use may impair calcium absorption, increasing fracture risk in older adults.

• Chronic use of medications like ranitidine can lead to hepatotoxicity, nausea, vomiting, and gynecomastia due to its androgen receptor antagonism.

Mechanisms of Action and Dosage

• Simetidine acts as an androgen receptor antagonist similar to spironolactone; however, ranitidine does not have this effect. Standard dosage for lomeprazole is 20 mg every 12 hours on an empty stomach.

• Ranitidine's standard dose is 150 mg but can be administered twice daily. Proton pump inhibitors (PPIs), such as esomeprazole (an isomer of lomeprazole), offer superior potency and bioavailability.

Bioavailability Considerations

• The bioavailability of lomeprazole reaches about 50%, significantly reduced when taken with food; thus it should be taken at least one hour before meals.

• Esomeprazole has a higher bioavailability of up to 80%. Lomeprazole inhibits cytochrome P450 enzymes leading to potential drug interactions.

Drug Interactions and Alternatives

• Pantoprazole and rabeprazole do not inhibit cytochrome P450 enzymes, reducing the risk of drug interactions compared to other PPIs.

• Famotidine is noted for being significantly more potent than ranitidine but is less commonly used in practice.

Helicobacter Pylori Treatment Strategies

Importance of Combination Therapy

• Treating ulcers caused by Helicobacter pylori requires more than just acid-reducing medications; symptoms may improve temporarily without addressing the underlying infection.

• A standard triple therapy includes omeprazole (20 mg every 12 hours), clarithromycin (500 mg every 12 hours), and amoxicillin (1 g every 12 hours), administered for two weeks to reduce resistance.

Quadruple Therapy Options

• Quadruple therapy known as BOM includes bismuth subsalicylate (anti-acid against H. pylori), omeprazole, metronidazole (250 mg four times daily), and tetracycline also given four times daily for two weeks.

Clinical Implications

• Effective eradication therapies are crucial since H. pylori infections are linked with gastritis, ulcers, cancer risks including adenocarcinoma and gastric lymphoma.

Cytoprotective Agents: Sucralfate

Mechanism of Action

• Sucralfate acts as a cytoprotective agent by forming a viscous polymer that adheres to gastric mucosal defects when activated in acidic pH environments.

Protective Effects of Sucralfate and Prokinetic Medications

Protective Effects of Sucralfate

• Sucralfate provides protective effects for up to six hours, administered before meals two to three times daily based on symptoms.

• Contains aluminum, which can lead to constipation by decreasing intestinal motility.

Introduction to Prokinetic Drugs

• Prokinetic drugs enhance motility in the esophagus, stomach, and intestines, increasing peristalsis.

• Acetylcholine and serotonin stimulate gastrointestinal motility, while dopamine inhibits it.

Agonists of Serotonin Receptors

• Prokinetics include agonists of serotonin receptors, particularly 5HT4.

• Serotonin is derived from tryptophan metabolism; its agonists promote intestinal motility.

Specific Prokinetic Medications

• Tegaserod is a prokinetic drug acting as a 5HT4 receptor agonist, used for irritable bowel syndrome (IBS), especially with constipation-related pain and distension.

• IBS predominantly affects women under 50; Tegaserod differs from alosetron, which is a 5HT3 receptor antagonist that reduces peristalsis.

Alosetron's Role in IBS

• Alosetron decreases peristalsis and is used when diarrhea predominates in IBS cases but has significant adverse effects like QT interval prolongation leading to ventricular arrhythmias.

Other Prokinetics: Metoclopramide and Domperidone

• Metoclopramide and domperidone are antidopaminergic prokinetics that block dopamine receptors to increase gastrointestinal motility.

• By inhibiting dopamine's action on cholinergic transmission, these medications enhance acetylcholine's effect on peristalsis.

Antidopaminergic Mechanism and Side Effects

• Antidopaminergics also have antiemetic properties due to dopamine's role in vomiting reflexes.

• Notable antidopaminergics include metoclopramide (which penetrates the blood-brain barrier causing extrapyramidal side effects like parkinsonism), while domperidone does not significantly affect the central nervous system.

Clinical Applications of Metoclopramide

• Metoclopramide is effective for gastroesophageal reflux disease (GERD), particularly when regurgitation is prevalent.

Prokinetics and Laxatives in Pharmacology

Prokinetic Agents

• Cisapride: A prokinetic drug that acts on serotonin receptors, specifically as a 5HT4 agonist. It enhances cholinergic transmission, contrasting with dopamine's inhibitory effects.

• Macrolides: Antibiotics like erythromycin that inhibit protein synthesis but also mimic motilin's action, stimulating peristalsis. They are used in diabetic gastroparesis and paralytic ileus.

• Erythromycin Dosage: Administered at 250 mg every 8 hours orally for its prokinetic effect by simulating motilin action.

Laxatives Overview

• Types of Laxatives: Various groups exist; constipation is common in adults and children. Non-pharmacological measures should be prioritized before medication.

• Dietary Considerations: Emphasizes the importance of dietary fiber to manage constipation effectively, recommending whole fruits over juices to maintain fiber content.

Dietary Fiber Sources

• High-Fiber Foods: Fruits such as prunes, raisins, apples (with skin), and pears are rich in fiber. Vegetables like broccoli and spinach also contribute significantly.

• Grains for Fiber: Wheat bran is highlighted as having the highest fiber content among grains, essential for effective bowel function.

Types of Laxatives Explained

• Bulk Forming Laxatives: These laxatives absorb water in the intestine to form a mass that stimulates peristalsis through mechanoreceptors activation.

• Examples of Bulk Formers: Psyllium seeds, methylcellulose, and wheat bran are noted for their high fiber content and effectiveness in promoting bowel movements.

Other Laxative Categories

• Softeners/Emollients: Agents like docusate sodium or calcium soften stool by breaking surface tension, allowing water absorption into hard stools.

• Osmotic Laxatives Mechanism: These increase water secretion into the intestines. Polyethylene glycol is identified as the most potent osmotic laxative used often before colonoscopies.

• Lactulose Use Cases: Effective for functional constipation and irritable bowel syndrome; it’s also preferred for patients with cirrhosis due to its osmotic properties.

• Alternative Osmotic Agents: Sorbitol serves as a cost-effective alternative to lactulose while maintaining similar efficacy; magnesium sulfate can induce diarrhea by increasing peristalsis.

Laxantes e Antidiarreicos: Mecanismos de Acción

Laxantes Irritadores de la Mucosa

• Los laxantes irritadores de la mucosa generan un efecto irritativo en la pared intestinal, aumentando así la peristalsis.

• Este grupo incluye laxantes como el bisacodilo y las antraquinonas (ej. senna), que bloquean la absorción de electrolitos, favoreciendo la retención de agua y ablandando las heces.

• Se recomienda iniciar con laxantes formadores de masa, luego osmóticos y finalmente los irritadores para un tratamiento efectivo del estreñimiento.

Antidiarreicos: Mecanismos y Tipos

Opiáceos como Antidiarreicos

• Los opiáceos, como la codeína y loperamida, disminuyen el peristaltismo intestinal, actuando a través de receptores MU y DELTA.

• La activación de los receptores MU en el intestino reduce la actividad motora al inhibir la producción de AMPcíclico mediante una proteína G inhibitoria.

Efecto sobre Motilidad Intestinal

• La estimulación del receptor MU también provoca hiperpolarización del músculo liso al favorecer la salida de potasio, lo que contribuye a disminuir aún más la motilidad intestinal.

• Además de reducir motilidad, los opioides aumentan el tono del esfínter anal, siendo útiles en problemas funcionales como el síndrome del intestino irritable.

Otros Antidiarreicos

• El subsalicilato bismutol actúa disminuyendo la producción de prostaglandinas, lo que también reduce la motilidad gastrointestinal; es útil en diarreas agudas.

• El octiotride es un análogo de somatostatina que potencia efectos similares a los opioides al bloquear conductancia cálcica y aumentar hiperpolarización muscular.

Somatostatin and Its Mechanisms

Effects of Somatostatin

• Somatostatin has effects similar to mu receptors, influencing motility, secretion, and splenic flow. It reduces blood flow in the portal vein, making it useful in treating variceal hemorrhage.

• The hormone activates a tyrosine phosphatase that inhibits the phosphorylation of the epidermal growth factor receptor (EGFR), which is essential for cell division stimulation.

• By blocking EGFR activation, somatostatin is used in treating endocrine tumors such as carcinoid tumors and glucagonomas, as well as refractory diarrhea cases.

Clinical Applications

• Somatostatin decreases portal blood flow, reducing bleeding during variceal hemorrhages.

• Rasecadotril is another medication used for diarrhea; it blocks enkephalins that promote intestinal motility. It's particularly effective in severe acute diarrhea cases to prevent rapid dehydration.

Antiemetics: Mechanisms and Medications

Understanding Nausea and Vomiting

• Antiemetics are drugs that block pathways involved in nausea and vomiting by targeting various neurotransmitters at the brainstem's vomiting center.

• The vomiting center is located in the medulla oblongata; multiple afferent signals stimulate this area to induce nausea and vomiting.

Neurotransmitter Involvement

• Key areas include the chemoreceptor trigger zone (CTZ), which contains dopamine and serotonin receptors that activate the vomiting reflex.

• Other receptors involved include histamine and muscarinic receptors found throughout the gastrointestinal tract and central nervous system.

Types of Antiemetics

• Antiemetic medications primarily function by antagonizing these receptors to prevent vomiting.

• Anticholinergics: Scopolamine is noted for its antiemetic properties alongside its use for intestinal colic.

• Antihistamines: Dimenhydrinate (Gravol), an H1 antagonist, effectively blocks nausea signals from reaching the brain.

Serotonin Receptor Blockers

• Serotonin receptor antagonists like ondansetron are crucial for managing chemotherapy-induced nausea. They inhibit serotonin's action on its receptors to mitigate emesis during cancer treatments.

Antiemetic Medications and Their Mechanisms

Overview of Antidopaminergic Agents

• Antidopaminergic medications, such as metoclopramide and domperidone, serve dual purposes: they act as prokinetics and possess antiemetic effects.

• These agents work by blocking various receptors including acetylcholine, H1 histamine, serotonin 5HT3, and dopamine D2 to achieve their antiemetic effects.

Neurolépticos and Their Applications

• Neurolépticos like haloperidol and chlorpromazine are also antidopaminergic; they belong to different families but share the ability to alleviate nausea.

• Haloperidol is noted for its potential to induce secondary parkinsonism, while chlorpromazine is highlighted for its stronger antiemetic properties.

Corticosteroids in Nausea Management

• The role of corticosteroids in managing nausea is not fully understood; however, they may help reduce symptoms of nausea and vomiting.

Clinical Case: Hyperemesis Gravidarum

• In cases of severe vomiting during pregnancy (hyperemesis gravidarum), treatments include dimenhydrinate or metoclopramide. Ondansetron is contraindicated due to teratogenic risks.

• For severe refractory hyperemesis gravidarum, a combination of chlorpromazine and corticosteroids may be employed alongside non-pharmacological approaches like dietary adjustments.

Vitamin B6 as an Antiemetic

• Vitamin B6 (pyridoxine) is recognized for its antiemetic properties and is often used as a first-line treatment in hyperemesis gravidarum. It can also mitigate neuropathic side effects when combined with certain medications.