GASTRO PHARM Flashcards
1
Q
Mention Proton Pump Inhibitors (PPIs)
A
- Omeprazole
- Esomeprazole
- Pantoprazole (most gastro-specific)
- Lansoprazole, dexlansoprazole (have the highest bioavailability and achieve the highest plasma levels)
- Rabeprazole (due to a higher pKa than other PPIs, rabeprazole remains unionized in the acidic environment of the gastric lumen. This unionized form is absorbed faster, which is why rabeprazole has a slightly faster onset of action)
2
Q
Proton Pump Inhibitors (PPIs) Adverse Effects
A
- Gastrointestinal
- Nausea, diarrhea, abdominal pain, flatulence
- ↑ Risk of C. difficile infection
- Reactive hypergastrinemia
- ↓ Absorption of iron and vitamin B12
- ↓ Absorption of calcium and magnesium → ↑ risk of osteoporosis in long-term use→ ↑ risk of fractures in elderly individuals (because the gastric environment becomes less acidic, dietary calcium remains bound to oxalate, resulting in reduced absorption in the duodenum and jejunum)
- Neurological
- Lightheadedness, headaches
- Possibly increased risk of developing cognitive impairment/dementia (individuals over the age of 75)
- Others
- Exanthema
- Visual disturbances (rare) (primarily seen with IV administration)
- ↑ Risk of pneumonia (particularly in the 30 days after starting therapy; possibly due to aspiration of gastric content containing a larger number of bacteria than usual following suppression of gastric acid)
- In rare cases, acute interstitial nephritis
3
Q
Proton Pump Inhibitors Interactions
A
- Although several drug interactions are suspected, those with omeprazole and esomeprazole have proven to be of clinical significance, mainly in CYP2C19-mediated interactions:
- Clopidogrel → ↓ activation
- Warfarin, phenprocoumon → ↓ clearance
- Phenytoin, carbamazepine → ↓ clearance
- Nifedipine → ↑ absorption, ↓ clearance
- Diazepam → ↓ clearance
4
Q
Mention Histamine-2 Blockers
A
- Ranitidine
- Cimetidine
- Famotidine
- Nizatidine
5
Q
Histamine-2 Blockers Mechanism
A
Ranitidine, Cimetidine, Famotidine, Nizatidine
- Target → histamine H2 receptors
- Location of H2 receptors
- Gastric parietal cells (oxyntic cells)
- Vascular smooth muscle
- Neutrophils
- Central nervous system
- Heart
- Uterus
- Histamine effects on H2 receptors
- Increased gastric acid secretion
- Positive inotropism and enhanced automaticity
- Smooth muscle relaxation leading to vasodilatation
- Effects
- Competitive, reversible antagonism of histamine H2 receptors (Gs protein-coupled receptor) on parietal cells → ↓ adenylyl cyclase activity → ↓ cAMP levels → ↓ protein kinase A activity → ↓ phosphorylation and activation of H+/K+ ATPase → ↓ gastric acid (H+) secretion
6
Q
Histamine H2 Blockers Clinical Use
A
Ranitidine, Cimetidine, Famotidine, Nizatidine
- Anaphylactic shock (together with H1 antihistamines)
- Symptomatic treatment of peptic ulcers → reduce the production of hydrochloric acid (less effective than PPIs)
- Gastroesophageal reflux disease (GERD)
- Gastritis
- Zollinger-Ellison syndrome
7
Q
Cimetidine Adverse Effects
A
Histamine H2 Blocker
- Antiandrogenic effect (via release of prolactin) → erectile dysfunction, gynecomastia, low libido in men
- Inhibition of cytochrome P450 (CYP2C19) → various drugs interactions, e.g., clopidogrel
- Headaches, dizziness, confusion due to its ability to cross the blood-brain barrier
- Can cross the placenta (but is considered safe)
- Reduces renal creatinine excretion (along with ranitidine)
8
Q
Histamine H2 Blockers Adverse Effects
A
Ranitidine, Cimetidine, Famotidine, Nizatidine
- Almost all side effects are caused by cimetidine; side effects in other H2 blockers are rare.
- Cimetidine
- Antiandrogenic effect (via release of prolactin) → erectile dysfunction, gynecomastia, low libido in men
- Inhibition of cytochrome P450 (CYP2C19) → various drugs interactions, e.g., clopidogrel
- Headaches, dizziness, confusion due to its ability to cross the blood-brain barrier
- Can cross the placenta (but is considered safe)
- Reduces renal creatinine excretion (along with ranitidine)
9
Q
Magnesium Hydroxide
A
Antacid
Mechanism:
- Acid neutralization mainly alonside acid suppression for rapid symptom relief
Adverse Effects:
- Hpokalemia
- Excessive bloating and belching are common (may be minimized if combined with simethicone)
- Diarrhea (antacids containing magnesium may cause diarrhea)
- Hyporeflexia
- Hypotension
- Cardiac arrest
Drug interactions
- Elevation of gastric/urinary pH or delay of gastric emptying can affect absorption, bioavailability, and/or urinary excretion of other drugs (antacids raise the gastric pH and/or form insoluble complexes with oral medications. Patients should be asked to wait at least 2 hours after the last antacid dose before taking other oral medications)
10
Q
Calcium Carbonate
A
Antacid
Mechanism:
- Acid neutralization mainly alonside acid suppression for rapid symptom relief
Adverse Effects:
- Hpokalemia
- Excessive bloating and belching are common (may be minimized if combined with simethicone)
- Hypercalcemia (can cause milk-alkali syndrome)
- Acid rebound
Drug interactions
- Elevation of gastric/urinary pH or delay of gastric emptying can affect absorption, bioavailability, and/or urinary excretion of other drugs (antacids raise the gastric pH and/or form insoluble complexes with oral medications. Patients should be asked to wait at least 2 hours after the last antacid dose before taking other oral medications)
- Can undergo chelation reactions with certain drugs (e.g., tetracycline), decreasing their effectiveness
11
Q
Mention Antacids
A
- Calcium carbonate
- Magnesium hydroxide
- Aluminum hydroxide
- Magnesium hydroxide/aluminum hydroxide combination
- Aluminum hydroxide/magnesium trisilicate
12
Q
Aluminum Hydroxide
A
Antacid
Mechanism:
- Acid neutralization mainly alonside acid suppression for rapid symptom relief
Adverse Effects:
- Hpokalemia
- Excessive bloating and belching are common (may be minimized if combined with simethicone)
- Constipation (antacids containing aluminum may cause costipation)
- Hypophosphatemia
- Osteodystrophy,
- Proximal muscle weakness
- Seizures
Drug interactions
- Elevation of gastric/urinary pH or delay of gastric emptying can affect absorption, bioavailability, and/or urinary excretion of other drugs (antacids raise the gastric pH and/or form insoluble complexes with oral medications. Patients should be asked to wait at least 2 hours after the last antacid dose before taking other oral medications)
13
Q
Bismuth
A
Mechanism:
- Binds to the surface of an ulcer → physical protection from acids → gastric HCO3- secretion restores mucosal pH gradient
Clinical Use:
- Ulcer therapy, traveler’s diarrhea caused by ETEC, H pylori quadruple therapy
14
Q
Sucralfate
A
Mechanism:
- Sucrose sulfate-aluminum complex that reacts with HCl in an acidic environment to create a protective barrier over the gastric/duodenal mucosa
- Acts as an acid buffer and promotes HCO3 production
- Should not be taken simultaneously with a PPI or H2 blocker
Clinical Use:
- Ulcer therapy, traveler’s diarrhea caused by ETEC
15
Q
Misoprostol
A
Mechanism:
- Prostaglandin E1 (PGE1) analog
- Increase producrion and secretion of gastric mucous barrier
- Decrease acid production
Clinical Use:
- Medical abortion
- Cervical ripening
- Induction of labor (off-label)
- Prophylaxis of NSAID-induced gastric ulcers (contraindicated during pregnancy)
Adverse Effects:
- May cause diarrhea
- Increase uterine tone
16
Q
Octreotide
A
- Mechanism:
- Long-acting somatostatin analog
- Inhibits secretion of various splanchnic vasodilatory hormones (causes splanchnic vasocontriction by stimulating somatostatin receptor and decrease splanchnic vasodilates (VIP, glucagon)
- Inhibits gastrin, secretin, CCK, GIP, VIP
- Decrease fluid secretion and GI motility
- Clinical Use:
- Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors.
- Adverse Effects:
- Nausea, cramps, steatorrhea.
- Increase risk of cholelithiasis due to CCK inhibition
17
Q
Mention 5-Aminosalicylic Acid Derivatives (5-ASAs)
A
- Mesalamine
- Sulfasalazine
- Olsalazine (compound of two 5-ASA molecules)
18
Q
Sulfasalazine
A
5-Aminosalicylic Acid Derivative (5-ASAs)
- Mechanism:
- 5-ASA bound to sulfapyridine as a carrier (sulfasalazine)
- 5-ASA → antiinflammatory, immunosuppressive
- Sulfapyridine → antibacterial
- Can be administered orally, as suppositories, or as enemas
- 5-ASA bound to sulfapyridine as a carrier (sulfasalazine)
- Clinical Use:
- Ulcerative colitis
- Colitis component of Crohn disease
- Side Effects:
- Most of the side effects are caused by the sulfapyridine component of sulfasalazine.
- GI irritation → nausea, diarrhea
- Headache, fatigue, malaise, depression
- Megaloblastic anemia and folate deficiency due to interference with dihydropteroate synthase
- Immune thrombocytopenia
- Transient oligospermia
- Sulfa drug → allergic reactions, sulfonamide toxicity
- Drug interactions:
- Coadministration of nephrotoxic drugs (e.g. NSAIDs, aminoglycosides, lithium) → ↑ risk of renal impairment
19
Q
Olsalazine
A
5-Aminosalicylic Acid Derivative (5-ASAs)
- Mechanism:
- Compound of two 5-ASA moleculres
- 5-ASA → antiinflammatory, immunosuppressive
- Can be administered orally, as suppositories, or as enemas
- Clinical Use:
- Ulcerative colitis
- Colitis component of Crohn disease
- Side Effects:
- GI irritation → nausea, diarrhea
- Drug interactions:
- Coadministration of nephrotoxic drugs (e.g. NSAIDs, aminoglycosides, lithium) → ↑ risk of renal impairment
20
Q
Mesalamine
A
5-Aminosalicylic Acid Derivative (5-ASAs)
- Mechanism:
- 5-ASA alone
- 5-ASA → antiinflammatory, immunosuppressive
- Can be administered orally, as suppositories, or as enemas
- Clinical Use:
- Ulcerative colitis
- Colitis component of Crohn disease
- Side Effects:
- GI irritation → nausea, diarrhea
- In rare cases → peripheral neuropathy, myocarditis or pericarditis, myelosuppression
- Drug interactions:
- Coadministration of nephrotoxic drugs (e.g. NSAIDs, aminoglycosides, lithium) → ↑ risk of renal impairment
21
Q
Diphenoxylate
A
- Mechanism:
- μ-receptor agonist
- Inhibits acetylcholine release from myenteric plexus neurons, decreasing activity of the intestinal smooth muscles and slowing peristalsis. Transit time within the intestine is prolonged, allowing for increased water absorption.
- In addition, the anticholinergic effects also results in decreased secretion from the intestinal epithelia, further reducing stool volume and increasing fecal consistency.
- Inhibits propulsive peristalsis, increases sphincter tone, and inhibits intestinal fluid secretion
- Only available as a combination drug with atropine to prevent misuse (atropine has no antidiarrheal effect, but will cause tachycardia when greater amounts of diphenoxylate are taken. This leads to severe discomfort and is intended to prevent misuse)
- Clinical Use:
- Diarrhea
- Adverse Effects:
- Constipation, nausea.
- May produce central effects and toxicity at high doses.
22
Q
Loperamide
A
- Mechanism:
- μ-receptor agonist
- Inhibits acetylcholine release from myenteric plexus neurons, decreasing activity of the intestinal smooth muscles and slowing peristalsis. Transit time within the intestine is prolonged, allowing for increased water absorption.
- In addition, the anticholinergic effects also results in decreased secretion from the intestinal epithelia, further reducing stool volume and increasing fecal consistency.
- Inhibits propulsive peristalsis, increases sphincter tone, and inhibits intestinal fluid secretion
- Poor CNS penetration (low addictive potential due to lack of central opioid effects)
- Undergues high first pass metabolism and does not cross the blood brain barrier
Clinical Use:
- Diarrhea
Adverse Effects:
- Constipation, nausea.
23
Q
Mention Serotonin Receptor Antagonists
(5-HT3 Antagonists)
A
- Ondansetron
- Granisetron
- Dolasetron
- Palonosetron
24
Q
Palonosetron
A
Serotonin receptor antagonist (5-HT3 antagonists)
- Mechanism:
- 5-HT3 antagonist (centrally and peripherally)
- Strong central antiemetic effect at the area postrema
- Peripheral antiemetic effect via inhibition of the vagus nerve
- Clinical Use:
- Chemotherapy-induced vomiting, radiation-induced vomiting, and postoperative nausea and vomiting (PONV)
- Adverse Effects:
- Headaches
- Constipation or diarrhea
- QT interval prolongation (torsades de pointes)
- Increase in liver enzymes
- Serotonin syndrome
25
Q
Dolasetron
A
Serotonin receptor antagonist (5-HT3 antagonists)
- Mechanism:
- 5-HT3 antagonist (centrally and peripherally)
- Strong central antiemetic effect at the area postrema
- Peripheral antiemetic effect via inhibition of the vagus nerve
- Clinical Use:
- Chemotherapy-induced vomiting, radiation-induced vomiting, and postoperative nausea and vomiting (PONV)
- Adverse Effects:
- Headaches
- Constipation or diarrhea
- QT interval prolongation (torsades de pointes)
- Increase in liver enzymes
- Serotonin syndrome
26
Q
Granisetron
A
Serotonin receptor antagonist (5-HT3 antagonists)
- Mechanism:
- 5-HT3 antagonist (centrally and peripherally)
- Strong central antiemetic effect at the area postrema
- Peripheral antiemetic effect via inhibition of the vagus nerve
- Clinical Use:
- Chemotherapy-induced vomiting, radiation-induced vomiting, and postoperative nausea and vomiting (PONV)
- Adverse Effects:
- Headaches
- Constipation or diarrhea
- QT interval prolongation (torsades de pointes)
- Increase in liver enzymes
- Serotonin syndrome
27
Q
Ondansetron
A
Serotonin receptor antagonist (5-HT3 antagonists)
- Mechanism:
- 5-HT3 antagonist (centrally and peripherally)
- Strong central antiemetic effect at the area postrema
- Peripheral antiemetic effect via inhibition of the vagus nerve
- Clinical Use:
- Commonly used for generalized nausea.
- Chemotherapy-induced vomiting, radiation-induced vomiting, and postoperative nausea and vomiting (PONV)
- Adverse Effects:
- Headaches
- Constipation or diarrhea
- QT interval prolongation (torsades de pointes)
- Increase in liver enzymes
- Serotonin syndrome
28
Q
Prochlorperazine Mechanism
A
Dopamine receptor antagonist
- D1 and D2 antagonist
- Central antiemetic effect at the area postrema
- Exerts an antipsychotic effect through blockade of the mesolimbic D1 and D2 receptors.
- Exerts an anticholinergic effect (e.g., constipation, blurry vision) through blockade of cholinergic receptors and alpha-adrenergic antagonism (e.g., sedation, hypotension).
29
Q
Domperidone Mechanism
A
Dopamine receptor antagonist
- D2 antagonist
- Central antiemetic effect at the area postrema
- Prokinetic effect
30
Q
Metoclopramide Mechanism
A
Dopamine receptor antagonist
- D2 antagonist, serotonin receptor antagonist (as a D2 antagonist and serotonin receptor antagonist, metoclopramide exerts two complementary antiemetic effects)
- Dopamine receptors are found in the brain as well as throughout the gastrointestinal tract. The prokinetic activity of metoclopramide is mediated by D2 receptor antagonist activity and 5-HT4 receptor agonist activity.
- Central antiemetic effect at the area postrema
- Peripheral antiemetic effect in the gastrointestinal tract (prokinetic effect); causes increase in:
- Resting tone of the lower esophageal sphincter
- Duodenal and jejunal motility
- Gastric contractions
- Together with decreased pylorus sphincter activity allows food to pass more quickly through the stomach and the small intestine
- No influence on colon motility
- Increase resting tone, contractility, LES tone, motility, promotes gastric emptying.
31
Q
Metoclopramide Interactions
A
Dopamine receptor antagonist
- Do not combine metoclopramide with antipsychotics because this increases the risk of dyskinesia!
- Antidote → biperiden (anticholinergic agent)
- Avoid combination with digoxin and antidiabetic drugs.
- Contraindicated in patients with suspected small bowel obstruction
32
Q
Domperidone Adverse Effects
A
D2 receptor antagonist
- Gastrointestinal
- Diarrhea
- Pain
- Hyperprolactinema
- Domperidone, in contrast to metoclopramide and prochlorperazine, crosses the blood-brain-barrier only minimally, hence neurological side effects are limited
- May cause cardiac arrhythmias (the lowest possible effective dose should be administered in order to avoid cardiac side effects. Domperidone has fewer early side effects than metoclopramide because of its peripheral effect)
33
Q
Prochloperazine Adverse Effects
A
D2 receptor antagonist
- Anticholinergic effect (e.g., constipation, blurry vision) through blockade of cholinergic receptors
- Alpha-adrenergic antagonism (e.g., sedation, hypotension).
- Hyperprolactinema
- Neurological
- Depression
- Fatigue
- Drowsiness
- Restlessness
- Lowering of seizure threshold
- Overdose leads to reversible extrapyramidal syndrome (e.g., dystonia, parkinsonism, tardive dyskinesia, and akathisia) and neuroleptic malignant syndrome
- Avoid combination with digoxin and antidiabetic drugs.
- Contraindicated in patients with suspected small bowel obstruction
34
Q
Metoclopramide Adverse Effects
A
Dopamine receptor antagonist
- Gastrointestinal
- Diarrhea
- Pain
- Hyperprolactinema
- Neurological
- Depression
- Fatigue
- Drowsiness
- Restlessness
- Lowering of seizure threshold
- Overdose leads to reversible extrapyramidal syndrome (e.g., dystonia, parkinsonism, tardive dyskinesia, and akathisia) and neuroleptic malignant syndrome
- Do not combine metoclopramide with antipsychotics because this increases the risk of dyskinesia!
- Antidote → biperiden (anticholinergic agent)
- Avoid combination with digoxin and antidiabetic drugs.
- Contraindicated in patients with suspected small bowel obstruction
35
Q
Prochlorperazine Clinical Use
A
Dopamine receptor antagonist
- Antipsychotic agent
- Hyperemesis gravidarum
36
Q
Domperidone Clinical Use
A
Dopamine receptor antagonist
- Nausea and vomiting
- Gastrointestinal motility disorders
37
Q
Metoclopramide Clinical Use
A
Dopamine receptor antagonist
- Prokinetic effect used to treat diabetic and postsurgery gastroparesis (delayed gastric emptying)
- Gastric lavage
- Hyperemesis gravidarum
- Persistent GERD
38
Q
Mention Antiemetics
A
-
Dopamine receptor antagonists
- Prochlorperazine
- Metoclopramide
- Domperidone
-
Serotonin receptor antagonists
- (5-HT3 antagonists)
- Ondansetron
- Granisetron
- Dolasetron
- Palonosetron
-
Anticholinergic agents
- Scopolamine
-
Antihistamines
- Meclizine
- Dimenhydrinate
- Diphenhydramine
- Doxylamine
- Promethazine
-
Neurokinin receptor antagonists
- Aprepitant
- Fosaprepitant
39
Q
Orlistat
A
- Mechanism:
- Reversibly inhibits gastric and pancreatic lipase, resulting in a decrease in fat breakdown and absorption
- Should be taken with meals containing fat
- Clinical Use:
- Weight loss in obese patients
- Side Effects:
- Numerous gastrointestinal side effects
- Abdominal pain
- Diarrhea, steatorrhea
- Increased bowel urgency and movements
- Flatulence
- Malabsorption of fat-soluble vitamins
- Numerous gastrointestinal side effects
40
Q
Metion Cation-Exchange Medications
A
- Sodium polystyrene sulfonate
- Sodium zirconium cyclosilicate
- Patiromer
41
Q
Patiromer
A
Cation-Exchange Polymer
- Mechanism:
- Releases calcium ions, which are exchanged for potassium in the colon.
- It has a higher efficacy than sodium polystyrene sulfonate and fewer adverse effects.
- Clinical Use:
- Nonurgent lowering of K+ (onset of action at∼ 2 hours; peak effect at ∼ 6 hours)
- Adverse Effects:
- Gastrointestinal upset
- Hypokalemia
42
Q
Sodium Zirconium Cyclosilicate
A
Cation-exchange resin
- Mechanism:
- Resins release sodium ions, which are exchanged for potassium, thereby enhancing enteral K+ elimination
- Clinical Use:
- Nonurgent lowering of K+ (onset of action at∼ 2 hours; peak effect at ∼ 6 hours)
- Adverse Effects:
- Gastrointestinal upset
- Hypokalemia
43
Q
Sodium Polystyrene Sulfonate
A
Cation-exchange resin
- Mechanism:
- Resins release sodium ions, which are exchanged for potassium, thereby enhancing enteral K+ elimination
- Clinical Use:
- Nonurgent lowering of K+ (onset of action at∼ 2 hours; peak effect at ∼ 6 hours)
- Adverse Effects:
- Gastrointestinal upset
- Hypokalemia
44
Q
Mention Osmotic Laxatives
A
- Polyethylene glycol (PEG)
- Glycerin
- Magnesium hydroxide
- Magnesium citrate
- Lactulose
- Sorbitol
45
Q
Polyethylene glycol (PEG)
A
Osmotic Laxative
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Polyethylene glycol (PEG) → very effective and well-tolerated (best initial treatment
- Adverse Effects:
- Diarrhea
- Dehydration
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
46
Q
Glycerin
A
Osmotic Laxative
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Adverse Effects:
- Diarrhea
- Dehydration
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
47
Q
Magnesium Citrate
A
Osmotic Laxative
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Adverse Effects:
- Diarrhea
- Dehydration
- Magnesium salts → hypernatremia, hypermagnesemia (due to partial reabsorption)
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
48
Q
Magnesium Hydroxide
A
Osmotic Laxative
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Adverse Effects:
- Diarrhea
- Dehydration
- Magnesium salts → hypernatremia, hypermagnesemia (due to partial reabsorption)
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
49
Q
Lactulose
A
Osmotic Laxative
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Lactulose is degraded by intestinal microbiota into lactic acid and acetic acid:
- Induces nitrogen (NH4+) excretion
- Used in the treatment of hepatic encephalopathy
- Adverse Effects:
- Diarrhea
- Dehydration
- Lactulose and sorbitol → severe flatulence (due to degradation by intestinal bacteria)
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
50
Q
Sorbitol
A
Osmotic Laxative
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Adverse Effects:
- Diarrhea
- Dehydration
- Lactulose and sorbitol → severe flatulence (due to degradation by intestinal bacteria)
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
51
Q
Osmotic Laxatives
A
Polyethylene glycol (PEG), Glycerin, Magnesium hydroxide, Magnesium citrate, Lactulose, Sorbitol
- Mechanism:
- Increase of osmotic pressure draws water into the intestinal lumen → stimulation of intestinal motility
- Lactulose is degraded by intestinal microbiota into lactic acid and acetic acid:
- Induces nitrogen (NH4+) excretion
- Used in the treatment of hepatic encephalopathy
- Polyethylene glycol (PEG) → very effective and well-tolerated (best initial treatment
- Adverse Effects:
- Diarrhea
- Dehydration
- Magnesium salts → hypernatremia, hypermagnesemia (due to partial reabsorption)
- Lactulose and sorbitol → severe flatulence (due to degradation by intestinal bacteria)
- Osmotic laxative misuse is frequently seen in patients with bulimia nervosa
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
52
Q
Mention Stimulant Laxatives/Secretory Laxatives
A
- Senna
- Bisacodyl
- Castor oil
53
Q
Senna
A
Stimulant Laxatives/Secretory Laxative
- Mechanism:
- Stimulation of nitric oxide-mediated epithelial cell secretion of electrolytes into the colonic lumen
- Myenteric neuronal depolarization → colon contractions
- Adverse Effects:
- For short-term use only
- Diarrhea → stimulant laxatives may result in severe water and potassium loss.
- Senna may result in melanosis coli (brownish discoloration of the colonic mucosa due to cell wall apoptosis is precipitated by active anthraquinone compounds)
54
Q
Bisacodyl
A
Stimulant Laxatives/Secretory Laxative
- Mechanism:
- Stimulation of nitric oxide-mediated epithelial cell secretion of electrolytes into the colonic lumen
- Myenteric neuronal depolarization → colon contractions
- Adverse Effects:
- For short-term use only
- Diarrhea → stimulant laxatives may result in severe water and potassium loss.
- Overuse of bisacodyl can lead to metabolic alkalosis.
55
Q
Castor Oil
A
Stimulant Laxatives/Secretory Laxative
- Mechanism:
- Stimulation of nitric oxide-mediated epithelial cell secretion of electrolytes into the colonic lumen
- Myenteric neuronal depolarization → colon contractions
- Adverse Effects:
- For short-term use only
- Diarrhea → stimulant laxatives may result in severe water and potassium loss.
56
Q
Stimulant Laxatives/Secretory Laxatives
A
Senna
Bisacodyl
Castor oil
Mechanism:
Stimulation of nitric oxide-mediated epithelial cell secretion of electrolytes into the colonic lumen
Myenteric neuronal depolarization → colon contractions
Adverse Effects:
For short-term use only
Diarrhea → stimulant laxatives may result in severe water and potassium loss.
Overuse of bisacodyl can lead to metabolic alkalosis.
Senna may result in melanosis coli (brownish discoloration of the colonic mucosa due to cell wall apoptosis is precipitated by active anthraquinone compounds)
57
Q
Mention Emollient (Surfactant) Stool Softener
A
- Docusate
58
Q
Docusate
A
Emollient (Surfactant) Stool Softener
- Mechanism:
- Emulsification (i.e., integration of water and fat) of stool → softening of stool → easier passage through the intestinal tract
- Adverse Effects:
- Diarrhea
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
- Bloating, cramping
59
Q
Emollient (Surfactant) Stool Softener
A
Docusate
- Mechanism:
- Emulsification (i.e., integration of water and fat) of stool → softening of stool → easier passage through the intestinal tract
- Adverse Effects:
- Diarrhea
- Overuse of osmotic laxatives can lead to metabolic alkalosis.
- Bloating, cramping
60
Q
Mention Bulk-Forming Laxatives
A
- Methylcellulose
- Psyllium husks (outer coating of the seed of the Plantago ovata plant)
- Polycarbophil
- Fiber supplement
- Pectin
61
Q
Methylcellulose
A
Bulk-Forming Laxative
- Mechanism:
- Chemical compound derived from cellulose
- Bulk-forming laxatives are indigestible, not systemically absorbed
- Soluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall → stimulation of peristalsis
- Adverse Effects:
- Bloating
- Worsening constipation or ileus if the patient doesn’t take enough water with doses
62
Q
Psyllium Husks
A
Bulk-Forming Laxative
- Mechanism:
- Outer coating of the seed of the Plantago ovata plant
- Bulk-forming laxatives are indigestible, not systemically absorbed
- Soluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall → stimulation of peristalsis
- Adverse Effects:
- Bloating
- Worsening constipation or ileus if the patient doesn’t take enough water with doses
63
Q
Pectin
A
Bulk-Forming Laxative
- Mechanism:
- Bulk-forming laxatives are indigestible, not systemically absorbed
- Soluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall → stimulation of peristalsis
- Adverse Effects:
- Bloating
- Worsening constipation or ileus if the patient doesn’t take enough water with doses
64
Q
Fiber Supplement
A
Bulk-Forming Laxative
- Mechanism:
- Bulk-forming laxatives are indigestible, not systemically absorbed
- Soluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall → stimulation of peristalsis
- Adverse Effects:
- Bloating
- Worsening constipation or ileus if the patient doesn’t take enough water with doses
65
Q
Polycarbophil
A
Bulk-Forming Laxative
- Mechanism:
- Bulk-forming laxatives are indigestible, not systemically absorbed
- Soluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall → stimulation of peristalsis
- Adverse Effects:
- Bloating
- Worsening constipation or ileus if the patient doesn’t take enough water with doses
66
Q
Bulk-Forming Laxatives
A
Methylcellulose: chemical compound derived from cellulose
Psyllium husks (outer coating of the seed of the Plantago ovata plant)
Polycarbophil
Fiber supplement
Pectin
Mechanism:
Bulk-forming laxatives are indigestible, not systemically absorbed
Soluble fibers increase water absorption in the intestinal lumen → stretching of the bowel wall → stimulation of peristalsis
Adverse Effects:
Bloating
Worsening constipation or ileus if the patient doesn’t take enough water with doses
67
Q
Mention Neurokinin Receptor Antagonists
A
- Aprepitant
- Fosaprepitant
68
Q
Fosaprepitant
A
NK1 antagonist
- Mechanism:
- Inhibition of NK1 receptors in the solitary nucleus → central antiemetic effect (neurokinin receptor antagonists also inhibit substance P-induced vomiting. Substance P is a neurotransmitter of afferent neurons involved in the pharyngeal or “gag” reflex)
- Additional inhibition of substance P-induced vomiting due to antagonism
- Clinical Use:
- Chemotherapy-induced nausea and vomiting (CINV) prophylaxis (delayed phase) (in combination with 5-HT3 receptor antagonists and dexamethasone for patients receiving chemotherapy with moderate-to-high emetic risk)
- Adverse Effects:
- Hypersensitivity reactions
- Infusion site reactions
- Increased levels of other drugs (e.g., macrolides, tricyclic antidepressants, statins, opioids) due to weak CYP3A4 enzyme inhibition
69
Q
Aprepitant
A
NK1 antagonist
- Mechanism:
- Inhibition of NK1 receptors in the solitary nucleus → central antiemetic effect (neurokinin receptor antagonists also inhibit substance P-induced vomiting. Substance P is a neurotransmitter of afferent neurons involved in the pharyngeal or “gag” reflex)
- Additional inhibition of substance P-induced vomiting due to antagonism
- Clinical Use:
- Chemotherapy-induced nausea and vomiting (CINV) prophylaxis (delayed phase) (in combination with 5-HT3 receptor antagonists and dexamethasone for patients receiving chemotherapy with moderate-to-high emetic risk)
- Adverse Effects:
- Hypersensitivity reactions
- Infusion site reactions
- Increased levels of other drugs (e.g., macrolides, tricyclic antidepressants, statins, opioids) due to weak CYP3A4 enzyme inhibition
70
Q
Neurokinin Receptor Antagonists
A
Aprepitant, Fosaprepitant
- Mechanism:
- NK1 antagonist
- Inhibition of NK1 receptors in the solitary nucleus → central antiemetic effect (neurokinin receptor antagonists also inhibit substance P-induced vomiting. Substance P is a neurotransmitter of afferent neurons involved in the pharyngeal or “gag” reflex)
- Additional inhibition of substance P-induced vomiting due to antagonism
- Clinical Use:
- Chemotherapy-induced nausea and vomiting (CINV) prophylaxis (delayed phase) (in combination with 5-HT3 receptor antagonists and dexamethasone for patients receiving chemotherapy with moderate-to-high emetic risk)
- Adverse Effects:
- Hypersensitivity reactions
- Infusion site reactions
- Increased levels of other drugs (e.g., macrolides, tricyclic antidepressants, statins, opioids) due to weak CYP3A4 enzyme inhibition
71
Q
Lubiprostone
A
Chloride channel agonist
- Mechanism:
- Chloride efflux into intestinal lumen, which is followed by sodium and water
- Agonist of the CIC-2 chloride channel located on the apical membrane of the intestine, which increases chloride secretion into the intestinal lumen
- Adverse Effects:
- Headache, nausea
72
Q
Methylnaltrexone
A
- Mechanism:
- Peripherally acting μ-opiod receptor antagonist
- Quaternary ammonium derivative of naltrexone with limited ability to penetrate the blood-brain barrier. This characteristic allows the drug to be used without affecting pain relief or inducing withdrawal from other opioids.
- Counteracts inhibitory effect of opioids on peristalsis
- Clinical Use:
- Can alleviate opioid-induced constipation without inducing opiate-related withdrawal symptoms (limited ability to cross the blood brain barrier).
Mechanism:
Adverse Effects:
Rare (does not cause opiate withdrawal)
73
Q
Mention Sympathomimetic Weight Loss Drugs
A
- Diethylpropion
- Phentermine
- Benzphetamine
74
Q
Diethylpropion
A
Norepipnephrine Releasing Hormone
- Mechanism:
- Work by stimulating release and inhibiting reuptake of norepinephrine and to lesser extent serotonin and dopamine
- Increased sensation of satiety and subsequently reduced calorie intake
- Clinical Use:
- Sympathomimetic weight loss drug indicated for short term (< 12 weeks) treatment for obesity
- Adverse Effects:
- Can increase blood pressure and should be avoided in patients with comorbid hypertension or heart disease
75
Q
Benzphetamine
A
Norepipnephrine Releasing Hormone
- Mechanism:
- Work by stimulating release and inhibiting reuptake of norepinephrine and to lesser extent serotonin and dopamine
- Increased sensation of satiety and subsequently reduced calorie intake
- Clinical Use:
- Sympathomimetic weight loss drug indicated for short term (< 12 weeks) treatment for obesity
- Adverse Effects:
- Can increase blood pressure and should be avoided in patients with comorbid hypertension or heart disease
76
Q
Phentermine
A
Norepipnephrine Releasing Hormone
- Mechanism:
- Work by stimulating release and inhibiting reuptake of norepinephrine and to lesser extent serotonin and dopamine
- Increased sensation of satiety and subsequently reduced calorie intake
- Clinical Use:
- Sympathomimetic weight loss drug indicated for short term (< 12 weeks) treatment for obesity
- Adverse Effects:
- Can increase blood pressure and should be avoided in patients with comorbid hypertension or heart disease
77
Q
Mention Histamine H1 Blockers Used as Antiemetics
A
- Meclizine
- Dimenhydrinate
- Diphenhydramine
- Doxylamine
- Promethazine
FIRST GENERATION!
78
Q
Doxylamine
A
First Generation Histamine H1 Blocker
- Target → histamine H1 receptors
- Location of H1 receptors
- Heart
- Central nervous system
- Vascular endothelial cell surfaces
- Smooth muscles (especially bronchial and nasopharyngeal lining)
- Histamine effects on H1 receptors
- ↓ Conduction in AV node
- ↑ Activation of peripheral nociceptive receptors → ↑ pain and pruritus
- ↑ Nasal and bronchial mucus production
- ↑ Bronchiolar smooth muscle contraction (via IP3 and DAG release) → bronchoconstriction
- ↑ Capillary dilation and permeability → hypotension and edema
- Effects
- Central antiemetic effect at the area postrema and vestibular system
- Central action → sedation
- Inhibition of allergic bronchial constriction
- Inhibition of increased vascular permeability
- Competitive, reversible antagonism or inverse agonism of histamine H1 receptors (Gq protein-coupled receptor) (because H1 blockers act as competitive antagonists of histamine, they may be ineffective if histamine levels are high. Therefore, they work best if taken before contact with the allergen. In severe cases, such as anaphylaxis or angioedema, additional epinephrine is necessary to control the allergic reaction)
- Clinical Use:
- Nausea and vomiting due to vestibular causes
- Hyperemesis gravidarum
- Allergies
- Insomnia → used as sedatives (sleep aid)
- Pruritus
- Motion sickness
- Adverse Effects:
- Antihistamine effects → drowsiness and confusion (significantly less pronounced in second-generation antihistamines due to their limited CNS activity)
- Anticholinergic side effects → dry mouth, dilated pupils, blurred vision, reduced bowel sounds, urinary retention, dizziness, tinnitus (mostly with first-generation antihistamines)
- Anti-α-adrenergic effects, e.g, postural hypotension (can lead to falls), weight gain
- Headaches
- Antidote → physostigmine
79
Q
Diphenhydramine
A
First Generation Histamine H1 Blocker
- Target → histamine H1 receptors
- Location of H1 receptors
- Heart
- Central nervous system
- Vascular endothelial cell surfaces
- Smooth muscles (especially bronchial and nasopharyngeal lining)
- Histamine effects on H1 receptors
- ↓ Conduction in AV node
- ↑ Activation of peripheral nociceptive receptors → ↑ pain and pruritus
- ↑ Nasal and bronchial mucus production
- ↑ Bronchiolar smooth muscle contraction (via IP3 and DAG release) → bronchoconstriction
- ↑ Capillary dilation and permeability → hypotension and edema
- Effects
- Central antiemetic effect at the area postrema and vestibular system
- Central action → sedation
- Inhibition of allergic bronchial constriction
- Inhibition of increased vascular permeability
- Competitive, reversible antagonism or inverse agonism of histamine H1 receptors (Gq protein-coupled receptor) (because H1 blockers act as competitive antagonists of histamine, they may be ineffective if histamine levels are high. Therefore, they work best if taken before contact with the allergen. In severe cases, such as anaphylaxis or angioedema, additional epinephrine is necessary to control the allergic reaction)
- Clinical Use:
- Nausea and vomiting due to vestibular causes
- Hyperemesis gravidarum
- Allergies
- Insomnia → used as sedatives (sleep aid)
- Pruritus
- Motion sickness
- Adverse Effects:
- Antihistamine effects → drowsiness and confusion (significantly less pronounced in second-generation antihistamines due to their limited CNS activity)
- Anticholinergic side effects → dry mouth, dilated pupils, blurred vision, reduced bowel sounds, urinary retention, dizziness, tinnitus (mostly with first-generation antihistamines)
- Anti-α-adrenergic effects, e.g, postural hypotension (can lead to falls), weight gain
- Headaches
- Antidote → physostigmine
80
Q
Promethazine
A
First Generation Histamine H1 Blocker
- Target → histamine H1 receptors
- Location of H1 receptors
- Heart
- Central nervous system
- Vascular endothelial cell surfaces
- Smooth muscles (especially bronchial and nasopharyngeal lining)
- Histamine effects on H1 receptors
- ↓ Conduction in AV node
- ↑ Activation of peripheral nociceptive receptors → ↑ pain and pruritus
- ↑ Nasal and bronchial mucus production
- ↑ Bronchiolar smooth muscle contraction (via IP3 and DAG release) → bronchoconstriction
- ↑ Capillary dilation and permeability → hypotension and edema
- Effects
- Central antiemetic effect at the area postrema and vestibular system
- Central action → sedation
- Inhibition of allergic bronchial constriction
- Inhibition of increased vascular permeability
- Competitive, reversible antagonism or inverse agonism of histamine H1 receptors (Gq protein-coupled receptor) (because H1 blockers act as competitive antagonists of histamine, they may be ineffective if histamine levels are high. Therefore, they work best if taken before contact with the allergen. In severe cases, such as anaphylaxis or angioedema, additional epinephrine is necessary to control the allergic reaction)
- Clinical Use:
- Nausea and vomiting due to vestibular causes
- Hyperemesis gravidarum
- Allergies
- Insomnia → used as sedatives (sleep aid)
- Pruritus
- Motion sickness
- Adverse Effects:
- Antihistamine effects → drowsiness and confusion (significantly less pronounced in second-generation antihistamines due to their limited CNS activity)
- Anticholinergic side effects → dry mouth, dilated pupils, blurred vision, reduced bowel sounds, urinary retention, dizziness, tinnitus (mostly with first-generation antihistamines)
- Anti-α-adrenergic effects, e.g, postural hypotension (can lead to falls), weight gain
- Headaches
- Antidote → physostigmine
81
Q
Meclizine
A
First Generation Histamine H1 Blocker
- Target → histamine H1 receptors
- Location of H1 receptors
- Heart
- Central nervous system
- Vascular endothelial cell surfaces
- Smooth muscles (especially bronchial and nasopharyngeal lining)
- Histamine effects on H1 receptors
- ↓ Conduction in AV node
- ↑ Activation of peripheral nociceptive receptors → ↑ pain and pruritus
- ↑ Nasal and bronchial mucus production
- ↑ Bronchiolar smooth muscle contraction (via IP3 and DAG release) → bronchoconstriction
- ↑ Capillary dilation and permeability → hypotension and edema
- Effects
- Central antiemetic effect at the area postrema and vestibular system
- Central action → sedation
- Inhibition of allergic bronchial constriction
- Inhibition of increased vascular permeability
- Competitive, reversible antagonism or inverse agonism of histamine H1 receptors (Gq protein-coupled receptor) (because H1 blockers act as competitive antagonists of histamine, they may be ineffective if histamine levels are high. Therefore, they work best if taken before contact with the allergen. In severe cases, such as anaphylaxis or angioedema, additional epinephrine is necessary to control the allergic reaction)
- Clinical Use:
- Nausea and vomiting due to vestibular causes
- Hyperemesis gravidarum
- Allergies
- Insomnia → used as sedatives (sleep aid)
- Pruritus
- Motion sickness
- Adverse Effects:
- Antihistamine effects → drowsiness and confusion (significantly less pronounced in second-generation antihistamines due to their limited CNS activity)
- Anticholinergic side effects → dry mouth, dilated pupils, blurred vision, reduced bowel sounds, urinary retention, dizziness, tinnitus (mostly with first-generation antihistamines)
- Anti-α-adrenergic effects, e.g, postural hypotension (can lead to falls), weight gain
- Headaches
- Antidote → physostigmine
82
Q
__________ are used in delayed chemotherapy induced emesis. Can cause neutropenia.
A
NK1 antagonists
83
Q
______________ are recommended for vestibular nausea.
A
Antihistamines and anticholinergics
