Stoetling Chapter 35 GI motiliy Flashcards
Chapter 35 ANTACIDS AND GASTROINTESTINAL MOTILITY DRUGS
Oral Antacids
- Antacids are drugs that neutralize hydrogen ions from gastric contents or decrease the secretion of hydrogen chloride into the stomach.
- In current practice, the oral antacids used most often are salts of magnesium, calcium, and aluminum; the hydrogen ions in stomach acid react with the base, forming a stable compound.
- As hydrogen ions are consumed, the pH of the stomach contents increases.
- The best known example would be sodium bicarbonate, which, in the stomach, combines with hydrochloric acid (HCl) to produce sodium chloride (NaCl), water (H2O), and carbon dioxide (CO2).
- _______(1) results in a prompt and rapid antacid action, so much so that the pH is raised to the point that the stomach’s pH is neutral, which can lead to acid rebound.
- _______(2) (or magnesium oxide, which in an aqueous medium as found in the stomach promptly forms magnesium oxide) also produces prompt neutralization of gastric acid but is not associated with significant acid rebound.
- A prominent _______(3) is characteristic of magnesium hydroxide.
- _______(4), CaCO3, is also used as an antacid.
- The plasma concentration of _______(5) is increased transiently. Symptomatic hypercalcemia may occur in patients with renal disease.
- The administration of calcium carbonate–containing antacids may result in _______(6).
- Even small amounts of calcium carbonate–containing antacids evoke _______(7) of hydrogen ions (acid rebound).
- The release of CO2 in the stomach may cause _______(8) . Constipation is minimized by including magnesium oxide with calcium carbonate
- Sodium bicarbonate
- Magnesium hydroxide
- laxative effect (osmotic diarrhea)
- Calcium carbonate
- calcium
- hypophosphatemia
- the release (or neutralization)
- eructation and flatulence
Aluminum hydroxide
- Side effects of Al(OH)3 include _______(1).
- _______(2) in patients undergoing hemodialysis have been attributed to intoxication with aluminum.
- A number of neurodegenerative diseases are associated with the administration of Al(OH)3
- Aluminum compounds, in contrast to other antacids, cause _______(3) and marked constipation and, therefore, are occasionally prescribed for patients with chronic diarrhea for its _______(4); however, _______(5) may result.
Sodium citrate (Na3C6H5O7) is a nonparticulate antacid.
- There are no prospective studies that demonstrate that oral antacids decrease the risk of aspiration pneumonitis in patients having an anesthetic, but it is common practice to administer sodium citrate to pregnant patients and to nonpregnant patients who are at risk for aspirating and are undergoing an _______(6).
- Sodium citrate is preferred over other oral antacids because it is less likely to cause a foreign body reaction if aspirated and its mixing with gastric fluid is more complete and more rapid than that of particulate antacids.
- hypomagnesemia, hypophosphatemia, anemia, and constipation.
- Seizures and encephalopathy
- slowing of gastric emptying
- constipating effect
- hypophosphatemia
- anesthetic
Complications of Antacid Therapy
- The increase in gastric volume and in pH resulting from antacid use has been associated with adverse events.
- Chronic alkalinization of gastric fluid has been associated with _______(1) overgrowth in the _______(2) and small intestine.
- The use of antacids also can result in _______(3) — predisposes patients to UTI
- _______(4) is a side effect that is unique to calcium-containing antacids.
- The _______(5) Syndrome
- Characterized by hypercalcemia, increased blood urea nitrogen and plasma creatinine concentrations, and systemic alkalosis, as reflected by an above-normal plasma pH
- Phosphorus depletion can occur in patients who ingest large doses of aluminum salts
1, bacterial
2. duodenum
3. metabolic alkalosis
4. Acid rebound
5. Milk-Alkali
Drug Interactions
- Gastric alkalinization increases gastric emptying, resulting in a faster delivery of drugs into the small intestine.
- There are many drugs whose absorption is enhanced by antacids.
- The rate of absorption of _______(1), indomethacin, and naproxen is increased when gastric fluid pH is increased.
- Conversely, absorption of drugs that are weak bases, for example, ketoconazole, itraconazole, dipyridamole, and enoxacin, is decreased if gastric pH is >5
- Aluminum hydroxide accelerates absorption and increases bioavailability of _______(2) by an unknown mechanism.
- Antacids containing aluminum, and to a lesser extent, calcium or magnesium, interfere with the absorption of _______(3) and possibly digoxin from the gastrointestinal tract.
- salicylates
- diazepam
- tetracyclines
Histamine-Receptor Antagonists
- Histamine:
- Induces contraction of smooth muscles in the airways
- _______(1) the secretion of acid in the stomach
- Stimulates the release of neurotransmitters in the central nervous system (CNS) through three receptor subtypes:
- H1, H2, H3.
- Histamine-receptor antagonists do not inhibit release of histamine but, rather, attach to receptors and prevent responses mediated by histamine.
- H3- and H4-receptor modulators do not currently play a role in anesthetic practice
H1-Receptor Antagonists
- First-generation drugs tend to produce sedation, whereas second-generation drugs are relatively nonsedating
- H1-receptor antagonists are highly selective for H1 receptors, having little effect on H2, H3, or H4 receptors.
- First-generation H1 receptor antagonists may also activate muscarinic, cholinergic, 5-hydroxytryptamine (5-HT serotonin), or α-adrenergic receptors, whereas few of the _______(2) have any of these properties.
Pharmacokinetics
- The elimination half-life of chlorpheniramine is approximately 24 hours.
- Acrivastine is excreted mostly unchanged in the urine, as is cetirizine, the active metabolite of _______(3).
- Increases
- second-generation antagonists
- hydroxyzine
Histamine-Receptor Antagonists
Clinical Uses
- H1-receptor antagonists are among the most widely used of all medications.
- H1-receptor antagonists prevent and relieve the symptoms of _______(1) (sneezing, nasal and ocular itching, rhinorrhea, tearing, and conjunctival erythema), but they are less effective for the nasal congestion characteristic of a delayed allergic reaction.
- Depending on the H1-receptor antagonist selected and its dose, pretreatment may provide some protection against bronchospasm induced by various stimuli (histamine, exercise, cold dry air).
- In patients with chronic urticaria, H1-receptor antagonists relieve pruritus and decrease the number, size, and duration of urticarial lesions.
- _______(2) include cetirizine, fexofenadine, loratadine, desloratadine, azelastine
- _______(3) include diphenhydramine, chlorpheniramine, cyproheptadine
- Diphenhydramine
- allergic rhinoconjunctivitis
- The second-generation H1-receptor antagonists
- The first-generation H1-receptor antagonists
- Diphenhydramine
- A _______(1), an antipruritic, and an antiemetic.
- When administered alone, it modestly stimulates ventilation by augmenting the interaction of hypoxic and hypercarbic ventilatory drives.
- Use of antihistamines in the acute treatment of anaphylactic reactions is directed at blocking further histamine-mediated respiratory sequelae and other systemic complications.
- The administration of _______(2) is indicated as first-line therapy for the treatment of anaphylaxis.
- H1 and H2 antihistamines may be helpful in treating cutaneous and upper respiratory signs and symptoms of anaphylaxis and are considered second-line therapies, along with other drugs, including _______(3).
- Second-generation H1-receptor antagonists such as terfenadine, fexofenadine, and astemizole have low water solubility, and, unlike first-generation drugs, are not available for parenteral use.
- _______(4)
- H1-receptor antagonist that is the theoclate salt of diphenhydramine. Dimenhydrinate has been used to treat motion sickness as well as postoperative nausea and vomiting; inexpensive
- H1-receptor antagonists may be sold as nonprescription sleeping aids because of drug-related somnolence
- sedative
- epinephrine
- glucocorticoids
- Dimenhydrinate
H1-Receptor Antagonists
Side Effects
- _______(1)
- Adverse effects on the CNS, including somnolence, diminished alertness, slowed reaction time, and impairment of cognitive function.
- Because there is some cross-reactivity with muscarinic receptors, anticholinergic effects such as dry mouth, blurred vision, urinary retention, and impotence may be seen.
- _______(2) is common, and prolongation of the _______(3) interval on the electrocardiogram, heart block, and cardiac arrhythmias have occurred.
- Second-generation H1 antagonists
- Unlikely to produce CNS side effects such as somnolence unless the recommended doses are exceeded.
- Most second-generation H1-receptor antagonists are not removed by hemodialysis.
- Antihistamine intoxication is similar to anticholinergic poisoning and may be associated with seizures and cardiac conduction abnormalities resembling tricyclic antidepressant overdose.
- First-generation H1 antagonists
- Tachycardia
3, QTc
H2-Receptor Antagonists
- Cimetidine, ranitidine, famotidine, and nizatidine are H2-receptor antagonists that produce selective and reversible inhibition of H2 receptor–mediated secretion of hydrogen ions by parietal cells in the stomach.
- All four drugs are present in breast milk and can cross the placenta and blood–brain barrier.
- Despite the presence of H2 receptors throughout the body, inhibition of histamine binding to the receptors on gastric parietal cells is the major beneficial effect of H2-receptor antagonists.
- Pharmacokinetics
- The absorption of cimetidine, ranitidine, and famotidine is rapid after oral administration.
- Nizatidine does not undergo significant hepatic first-pass metabolism, and its bioavailability after oral administration approaches 100%
- Cimetidine is widely distributed in most organs but not fat.
- 70% of the total body content of cimetidine is found in skeletal muscles.
- Only nizatidine appears to have an _______(1) (N2-mono desmethyl-nizatidine), possessing about 60% of the activity of the parent drug.
- Decreases in the doses of all four drugs are recommended for patients with renal dysfunction.
- active metabolite
H2-Receptor Antagonists
Clinical Uses
- H2-receptor antagonists are most commonly administered for the treatment of duodenal ulcer disease associated with hypersecretion of gastric hydrogen ions.
- In the preoperative period, H2-receptor antagonists have been administered as chemoprophylaxis to increase the pH of gastric fluid before induction of anesthesia.
- ASA’s practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration state that there is evidence that H2-receptor antagonists increase gastric pH and reduce gastric volume and may be administered preoperatively to patients at increased risk for _______(1).
- H2-receptor antagonists, in contrast to antacids, have no influence on the pH of the gastric fluid that is already present in the stomach.
- aspirating
H2-Receptor Antagonists
Side Effects
- The frequency of severe side effects is low with all four H2-receptor antagonists.
- The risk for experiencing adverse side effects during treatment with an H2-receptor antagonist is increased by the presence of multiple medical illnesses, hepatic or renal dysfunction, and advanced age.
- The most common adverse side effects are _______(1).
- Changes in mental status usually occur in the elderly and tend to be associated with high doses of _______(2) administered IV, often to patients in an intensive care unit.
- _______(3) and, to a lesser extent, ranitidine increase the plasma concentrations of prolactin, which may result in galactorrhea in females and gynecomastia in males.
- Impotence and loss of libido may occur in males receiving chronic high-dose treatment with _______(4).
- Cardiac arrhythmia (sinus bradycardia, sinus arrest, sinus arrest with idioventricular escape rhythm, complete atrioventricular heart block) have been described after either oral or IV administration of H2-receptor antagonists
- Prolonged QTc interval and fatal cardiac arrest with famotidine have been reported
- _______(5) are generally associated with rapid IV administration of these drugs, most often to critically ill or older patients.
- The mechanism for hypotension appears to be peripheral vasodilation
- diarrhea, headache, fatigue, and skeletal muscle pain
- cimetidine
- Cimetidine
- cimetidine
- Bradycardia and hypotension
TABLE 35.3
Side effects of H2-receptor antagonists
- Interaction with cerebral H2 receptors (_________(1), somnolence, confusion)
- Interaction with cardiac H2 receptors (bradycardia, hypotension, heart block)
- _________(2)
- Acute pancreatitis
- Increased hepatic transaminase levels
- Alcohol dehydrogenase dehydration
- Thrombocytopenia
- Agranulocytosis
- Interstitial nephritis
- Interference with drug metabolism by cytochrome P450
- headache
- Hyperprolactinemia
Proton Pump Inhibitors
- Proton pump inhibitors (PPIs) (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) are the most effective drugs available for controlling gastric acidity and volume
PPIs are more effective than H2-receptor antagonists for healing esophagitis and preventing relapse.
PPIs also appear to be more effective than H2-receptor antagonists for relieving _______(1), the cardinal feature of “gastroesophageal reflux disease.”
Omeprazole
- Omeprazole is a _______(2) that acts as a prodrug that becomes a PPI
- Omeprazole takes several days to exert its maximal inhibitory effect on gastric acid secretion
- This drug heals duodenal and possibly gastric ulcers more rapidly than do the H2-receptor antagonists.
- In patients with _______(3), treatment with omeprazole decreases the rate of bleeding and the need for surgery.
- Omeprazole is superior to H2-receptor antagonists for the treatment of reflux esophagitis and is the best pharmacologic treatment of _______(4).
- heartburn
- substituted benzimidazole
- bleeding peptic ulcers
- Zollinger-Ellison syndrome
Gastrointestinal Prokinetics
- Motility-modulating drugs exert their therapeutic effects by increasing lower esophageal sphincter tone, enhancing peristaltic contractions, and accelerating the rate of gastric emptying.
- _______(1)
- acts as a gastrointestinal prokinetic drug that increases lower esophageal sphincter tone and stimulates motility of the upper gastrointestinal tract.
- It remains the only drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of _______(2).
- Mechanism of Action
- produces selective cholinergic stimulation of the gastrointestinal tract (gastrokinetic effect) consisting of:
- (1) increased smooth muscle tension in the lower esophageal sphincter and gastric fundus
- (2) increased gastric and small intestinal motility
- (3) relaxation of the pylorus and duodenum during contraction of the stomach.
- The cholinergic stimulating effects of metoclopramide are largely restricted to smooth muscles of the proximal gastrointestinal tract and require some background cholinergic activity.
- Metoclopramide acts as a dopamine-receptor antagonist, but any effects on dopamine-induced inhibition of gastrointestinal motility are not considered to be clinically significant.
- However, metoclopramide does cross the blood–brain barrier, and within the CNS, metoclopramide inhibition of dopamine receptors can produce significant extrapyramidal side effects.
- Metoclopramide
- diabetic gastroparesis
Gastrointestinal Prokinetics
Pharmacokinetics — blah blah blah
Clinical Uses
- Clinical uses of metoclopramide include:
- (1) preoperative decrease of gastric fluid volume
- (2) production of an antiemetic effect
- (3) treatment of _______(1)
- (4) symptomatic treatment of gastroesophageal reflux
- (5) intolerance to enteral feedings in patients who are critically ill.
Preoperative Decrease in Gastric Fluid Volume
- Metoclopramide, 10 to 20 mg IV over 3 to 5 minutes administered 15 to 30 minutes before induction of anesthesia, results in increased lower esophageal sphincter tone and decreased gastric fluid volume.
- This gastric-emptying effect of metoclopramide may be of potential benefit before the induction of anesthesia in:
- (1) patients who have recently ingested solid food
- ____(2) patients
- (4) patients with diabetes mellitus and symptoms of gastroparesis
- (5) patients, especially those with a history of esophagitis (“heartburn”), suggesting lower esophageal sphincter dysfunction and gastric hypomotility.
- gastroparesis
- trauma patients
