GI and Antiemetic Drugs Flashcards
What four common medical conditions involve the GI tract?
Peptic ulcers/GERD
Chemotherapy-induced emesis
Diarrhea
Constipation
What are some causes of peptic ulcer disease?
Gram-negative H. Pylori infection NSAID use Increased HCl secretion Inadequate mucosal defense against gastric acid Tumors
What is Zollinger-Ellison syndrome?
A condition in which there is increased production of gastrin. Usually, a small tumor (gastrinoma) in the pancreas or small intestine produces the high levels of gastrin in the blood. Gastrin increases secretion of gastric acid.
What are some treatment options for peptic ulcer disease?
Eradicate H. Pylori infection
Reduce gastric acid secretion
Protect gastric mucosa
How would an H. Pylori infection be documented?
Biopsy
Serologic tests
Urea breath tests
How would an H. Pylori infection be treated?
Triple therapy
- PPI
- Metronidazole or amoxicillin
- Clarithromycin
Quadruple therapy
- Bismuth subsalicylate
- Metronidazole
- Tetracycline
- PPI
What endogenous compounds stimulate gastric acid secretion?
ACh
Histamine
Gastrin
They activate protein kinases, which stimulate the proton pump.
Name some H2 receptor antagonists.
Cimetidine (prototype), ranitidine, famotidine, and nizatidine (the ones that end in “-tidine”)
What are H2 receptor antagonists used for?
Healing duodenal and gastric ulcers
True or false: recurrence of ulcers after stopping H2 receptor antagonist treatment is low.
False. Recurrence is 60-100%
When would an H2 receptor antagonist be given as an IV infusion?
To prevent and manage acute stress ulcers.
True or false: H2 antagonists can be used to treat GERD.
True; however, their onset is delayed (45 min)
True or false: antacids should be used as a long-term treatment for GERD.
False. Although antacids quickly and efficiently neutralize secreted acid, their action is only temporary.
Although cimetidine is the prototype H2 receptor antaognist, it has two notable drawbacks. What are they?
Acts as inhibitor of CP450, slowing metabolism of and potentiating actions of several drugs (warfarin, dizepam, phenytoin, carbamazepine, imipramine)
Acts as nonsteroidal anti-adrenergic drug
What advantage(s) does ranitidine have over cimetidine?
Longer-acting
5-10x more potent
What advantage(s) does famotidine have over cimetidine?
20-50x more potent
What advantage(s) does nizatidine have over the other H2 receptor antagonists?
It is eliminated principally by the kidneys (as opposed to the liver). Its bioavailability is nearly 100% due to little first-pass metabolism.
What are some adverse effects of cimetidine?
HA
Dizziness
Diarrhea
Muscular pain
Which drugs are PPIs?
The ones ending in “-prazole.”
Which PPIs are available OTC?
Omeprazole
Lansoprazole
True or false: PPIs are prodrugs with an acid-resistant enteric coating.
True.
True or false: PPIs are the preferred drugs for stress ulcer treatment.
True.
For what GI conditions are PPIs approved?
Stress ulcer treatment
GERD
True or false: PPIs increase the risk of bleeding from NSAID ulcers.
False. They decrease the risk.
Should PPIs be taken with or without food?
PPIs should be taken 30-60 minutes before a meal.
What is one serious potential adverse effect of long-term PPI use?
Hip, wrist, and spine fractures
Where does prostaglandin E come from and what are its effects?
It is secreted by the gastric mucosa, and it inhibits the secretion of HCl and stimulates secretion of mucus and bicarbonate.
What drug is a stable analog of protaglandin E, and for what condition is it approved?
Misoprostol; it is approved for prevention of NSAID-caused gastric ulcers.
In what condition would misoprostol be contraindicated?
Pregnancy due to uterine contractions.
Which antacids are commonly used?
Aluminum hydroxide
Magnesium hydroxide
Calcium carbonate
Which of the commonly-used antacids may also be used in the treatment of osteoporosis?
Calcium carbonate (as a calcium supplement)
Which of the antacids tends to cause diarrhea, and which tends to cause constipation?
Aluminum hydroxide tends to cause constipation; magnesium hydroxide tends to cause diarrhea.
What are some of the beneficial effects of mucosal protective agents?
Prevention of mucosal injury
Reduction of inflammation
Healing of existing ulcers
Which drug is a complex of Al(OH)₃ and sulfated sucrose?
Sucralfate.
What are the actions of sucralfate?
Stimulates prostaglandin, mucus and bicarbonate release
True or false: sucralfate may be used in conjunction with antacids.
False. It requires an acidic pH for activation; therefore it is not compatible with PPIs, H2 antagonists, or antacids since these increase gastric pH.
How does bismuth subsalicylate act as a mucosal protective agent?
Antimicrobial actions
Pepsin inhibition
Stimulation of mucus secretion
What are some common causes of emesis?
Motion sickness
Pregnancy
Hepatitis
What are some potentially serious effects of emesis?
Dehydration
Profound metabolic imbalances
Nutrient depletion
What two brainstem sites are key in the vomiting reflex?
Chemoreceptor trigger zone, in the area postrema
Vomiting center, in the lateral reticular formation of the medulla
How do chemotherapeutic agents trigger emesis?
Stimulation of D2 and 5-HT3 receptors
Color/smell
Release of serotonin from GI system, carrying signal to vomiting reflex centers
Which drugs are useful in treatment emesis caused by motion sickness?
Scopolamine and H1 receptor antagonists (dimenhydrinate, meclizine, cyclizine)
Which phenothiazine is an effective anti-emetic agent? Which emetogenic chemotherapeutic agents is it effective against?
Prochlorperzine; it is effective against low-to-moderate agents such as fluorouracil and doxorubicin.
What type of drug is useful against all grades of emetogenic therapy?
5-HT3 receptor antagonists; drugs ending in “-setron”
Which benzamide has antiemetic properties, and which receptor does it block?
Metoclopramide; D2
Which butyrophenones have antiemetic properties, and which receptor do they block?
Droperidol, haloperidol; D2
Which benzodiazepines have antiemetic properties?
Lorazepam, alprazolam; have mild antiemetic properties
Which corticosteroids have antiemetic properties?
Dexamethasone, methylprednisolone; have mild to moderate antiemetic properties
What might be the result of combining various antiemetic drugs?
Increased antiemetic activity, or decreased toxicity
What three classes of drugs are used as antidiarrheals?
Antimotility agents
Adsorbents
Drugs that modify fluid and electrolyte transport
Which antidiarrheal drugs are antimotility agents?
Loperamide & diphenoxylate (analogs of meperidine and have opioid-like actions on the gut)
Which antidiarrheal drug modifies fluid and electrolyte transport?
Bismuth subsalicylate (used for traveler’s diarrhea, decreases fluid secretion in the bowel)
What are two potential risks of laxative use?
Potential for dependency
Electrolyte imbalance
Which laxatives fall into the category of stimulant/irritant?
Senna (water and electrolyte secretion into the bowel) Bisacodyl (potent stimulator of the colon) Castor oil (increases peristalsis, uterine contraction)
Which laxatives fall into the category of bulk laxatives, and when should you be cautious in prescribing them?
Methylcellulose, psyllium seeds, and bran; take caution with immobile patients due to intestinal obstruction
Which laxatives fall into the category of saline and osmotic laxatives?
Magnesium citrate, magnesium hydroxide, and sodium phosphate (nonabsorbable salts that hold water in the intestine)
Which laxatives fall into the category of stool softener?
Docusate sodium, docusate calcium, and docusate potassium
Which laxatives fall into the category of lubricant laxatives?
Mineral oil and glycerin suppositories (act by facilitating the passage of hard stools)
Which laxative falls into the category of chloride channel activator?
Lubiprostone (works by activating chloride channels to increase fluid secretion in the intestinal lumen)
True or false: lubiprostone can be used for chronic constipation.
True; it does not appear to show tolerance or dependency.
