Term
| Describe the contribution of NSAIDs and H. pylori to the development of PUD |
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Definition
H. pylori (as well as acid, pepsin) is an aggressive factor contributing to the etiology of PUD, GERD
Prostaglandin (as well as HCO3-, mucous secretion) is a protective factor
- prostaglandins inhibit acid production, stimulate mucous & bicarb secretion, and stimulate vasodilation in gastric mucosa
- NSAIDS (non-selective COX-1/2 inhibitors - e.g. aspiring, not tylenol) inhibit prostaglandin synthesis
- (excess EtOH and smoking also contribute to the etiology of PUD, GERD)
Treatment of PUD:
- reduce aggressive factors (maintain stomach pH>4, eradicate H. pylori infxn)
- increase protective factors |
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Term
H2 Histamine Receptor antagonists
List:
a) the four H2 receptor antagonists now available for treatment,
b) their mechanism of action,
c) their equal efficacy but differences in potency;
d) their over-the-counter availability, and
e) their few side effects. |
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Definition
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid)
inhibit basal, food-stimulated, and nocturnal acid secretion
reduce the volume, H+ conc of gastric secretions
The four H2 antagonists are equally efficacious but differ in potency.
Adverse SE are infrequent and mild
- All agents that inhibit gastric acid secretion may alter the rate of absorption of certain drugs secondary to changes in gastric pH. |
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Term
| Distinguish the H2 histamine receptor antagonist drugs from the classic antihistamines (H1 blockers). |
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Definition
Gastrin, ACh stimulate histamine release from (ECL) cells
Histamine activates H2 subtype of receptor on parietal cells and stimulates proton pump
H2 blockers competitively inhibit histamine-mediated acid secretion and also blunt the response to gastrin and ACh - highly selective
- Classic antihistamines, H1 receptor blockers, do not inhibit acid secretion. |
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Term
| Describe the potential for drug-drug interactions resulting from cimetidine inhibition of cytochrome P450. |
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Definition
| *Cimetidine inhibits the activity of cyt P450* -> slows the metabolism of many drugs. If drug interactions are to be avoided, choose an H2 blocker other than cimetidine. |
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Term
| Describe the mechanism of action of proton pump inhibitors (PPIs) and the reason for their delayed-release formulation. Describe their superior efficacy in reducing gastric acid compared to other classes of drugs |
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Definition
Inhibit H+,K+-ATPase
Enteric coating - release of prodrug in SI - chemically stable, lipid soluble, devoid of inhibitory activity
Neutral weak base absorbed, carrier by bloodstream to parietal cells in stomach -> secretory canaliculi -> acid pH -> protonation and trapping of drug near proton pump
Generally well tolerated
- SE: nausea, diarrhea, abdominal colic, headache, dizziness, skin rash
- possible rebound hyperacidity upon discontinuation
- these drugs inhibit cyt P450
- omeprazole may reduce the metabolism of phenytoin, warfarin, diazepam
- b/c drug has such a short 1/2 life, the inhibition isn't really present |
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Term
| List the drugs used and the strategy applied for combination therapy for eradication of H. pylori infection related to PUD |
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Definition
Triple Therapy (14 days)
- PPI (BID)
- Clarithromycin (BID) (or metronidazole)
- Amoxicillin (BID) (or metronidazole)
Quadruple Therapy (14 days)
- PPI (BID)
- Tetracycline (QID)
- Metronidazole (TID/QID)
- Pepto-Bismol (QID)
- less expensive, but there are compliance issues
Prevpak - packaged in one dose (convenient), but more expensive
- Prevacid (Lansoprazole) PPI
- Clarythromycin
- Amoxicillin
After 14 day therapy is complete:
- Wait one week, with PPI held (PPI can cause false (+) on stool antigen test)
- Stool antigen test
- Most sensitive
If taking PPI for GERD, cut dose in half if in another country to prevent traveler's diarrhea (stomach acid protects against it) |
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Term
| Describe the basic ingredients in common combination antacid preparations (aluminum hydroxide, magnesium hydroxide, etc.) and their general properties. Describe the proper role of antacid therapy in the treatment of PUD and GERD. Describe common drawbacks to antacid therapy |
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Definition
Aluminum hydroxides - *constipation*
Magnesium hydroxides - *diarrhea*
Calcium carbonate - gas and acid reflux
Sodium bicarbonate - gas, systemic absorption
Simethicone - surfactant
Gaviscon - alginic acid - floating gel
Combinations of aluminum and magnesium hydroxides are the most popular
- *the combination minimizes disturbance of bowel motility*
Prescribe according to neutralizing equivalents
1 hr and 3 hr after a meal and at bedtime
Adverse effects include changes in bowel motility, alkalosis
Significant effects on the absorption of other drugs
*Do not take antacids within 1-2 hr of other drugs* |
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Term
| Describe the effects of mucosal protective agents: Pepto-Bismol (bismuth subsalicylate), sucralfate and misoprostol and their role as adjuncts in the therapy of PUD and GERD. |
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Definition
Pepto-Bismol (bismuth subsalicylate)
- Enhances secretion of mucus and HCO3-
- Inhibits pepsin activity
- Chelates with proteins at the base of ulcers and forms a protective barrier against acid and pepsin
- May inhibit H. pylori
- An effective adjunct for treatment and prophylaxis of duodenal and gastric ulcers, GERD, and diarrhea.
- SE:
- Black tarry stools- most of bismuth is eliminated in the feces
- Blackened tongue with long-term use
Sucralfate (Carafate)
- forms sticky, viscous gel that adheres to gastric epithelial cells protecting them from acid and pepsin
- 1 hr before meals and at bedtime promotes healing
Misoprostol (Cytotec)
- Slowly metabolized analog of PGE1
- Stimulates mucus and HCO3- production
- Causes diarrhea in 30% of patients
- Primarily used for patients who must use NSAIDs |
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Term
| List the recognized indications for laxative treatment |
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Definition
Excessive reabsorption of water causes constipation
Intestinal motility dictates the time available for reabsorption of water and solutes.
Increased motility leads to diarrhea; decreased motility can cause constipation.
Decreased motility is an important component of nausea and vomiting and increased GI motility is a significant property of some antiemetic agents. |
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Term
| Describe laxative abuse by the general public |
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Definition
Overuse of laxative -> thorough evacuation
Requires several days to accumulate bulk
Lag in defecation is interpreted as continued constipation
Take more laxative - vicious cycle
If continued, bowel becomes unresponsive |
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Term
| Describe (by class) the different kinds of laxatives in terms of their mechanism of action, latency, and intensity of laxative effect. |
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Definition
*Dietary fiber and bulk-forming laxatives* (safest for long-term use)
- bran, psyllium, methylcellulose
Osmotic laxatives
- Polyethylene glycol-electrolyte solutions (Colyte, Golytely) are the drug of choice for bowel preparation for colonoscopy, barium enema, or colorectal surgery.
- Magnesium Oxide - Milk of Magnesia
- Lactulose: for hepatic encephalopathy
Stimulant laxatives (bisocadyl, Dulcolax, etc.)
Surfactant Stool Softeners: Docusates
Type 2 Chloride Channel (CLC-2) Activator: Lubiprostone
- Increases Cl- secretion into SI
- Increases intestinal motility
- Shortens transit time
- No loss of efficacy with continued use
- Delays gastric emptying; can produce nausea
Constipation can occur secondary to Opioid Agonists (Analgesics) = decreased intestinal motility via mu opioid receptors |
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Term
| List the three main opioid agonists used for nonspecific treatment of diarrhea and briefly describe their mechanism of action. |
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Definition
Loperamide (Imodium)
Diphenoxylate (Lomotil) + atropine
Diphenoxin (Motofen) + atropine
Act at mu receptors in GI tract to decrease motility
*poor CNS penetration, less abuse liability* |
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Term
| Describe why atropine sulfate is combined with diphenoxylate and difenoxin preparations. |
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Definition
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Term
| Describe peripherally active opioid receptor antagonists and their specialized uses in treatment of constipation induced by opioid agonists in the treatment of pain. |
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Definition
Methylnaltrexone: for patients receiving palliative care (SQ every 2 days)
Alvimopan: decrease post-operative ileus in patients who have had bowel resection- limited to 7 days due to risk of CV toxicity |
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Term
| Recognize the properties and uses of Pepto-Bismol and octreotide for the treatment of diarrhea. |
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Definition
Pepto-Bismol - OTC, used for self-limiting diarrhea
Octreotide - NOT used for traveler's diarrhea or self-limiting diarrhea; more serious
somatostatin analog
for severe diarrhea, tumors, AIDs
IV or SQ |
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Term
| List the receptors that are the targets of antiemetic agents. |
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Definition
5-HT3 receptors (CTZ)
- located at several sites involved in the vomiting reflex including the CTZ
- Antagonists of these receptors are very effective inhibitors of emesis even to chemotherapeutic agents
- anesthesia-induced N&V
- Most effective when combined with corticosteroid therapy (short-term): dexamethasone
- Ondansetron (Zofran)
D2 Dopamine Receptor Antagonists (CTZ)
- Metoclopramide (Reglan)
- not as effective as 5HT3 antagonists, so not used as much
Antihistamines agents (H1 Blockers)
- Promethazine (Phenergan)
- Dimenhydrinate (Dramamine)
- Diphenhydramine (Benadryl)
- Meclizine (Antivert)
Antimuscarinic Agent
- Scopolamine - patch for motion sickness |
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Term
| List the most commonly used antiemetic agents by drug class. |
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Definition
See "List the receptors that are the targets of antiemetic agents."
Also:
Cannabinoids
- Dronabinol (Marinol)- delta 9-tetrahydrocannabinol (THC)
- chemotherapy-induced nausea and vomiting
- also an appetite stimulant |
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Term
| List the major indications for antiemetic therapy and the drug(s) of choice for each indication. |
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Definition
Motion sickness and vertigo - scopolamine
Postoperative recovery - 5HT3 antagonists
Pregnancy - B6, not much pharm treatment
Cancer Chemotherapy - 5HT3 antagonists
Migraine |
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Term
| Describe how control of nausea and vomiting resulting from cancer chemotherapy or radiation therapy usually involves a combination of antiemetic drugs and is a necessary and critical component of the therapeutic strategy. |
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Definition
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Term
| Discuss the promotility (prokinetic) properties of metaclopramide and describe the indications for its use and the advantages and potential side effects of this drug. |
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Definition
D2 Dopamine antagonist
5-HT3 antagonist
5-HT4 agonist
Facilitates ACh release
Antiemetic
*Treats gastroparesis* (common in type II DM) and GERD
- Can cause dumping syndrome, nausea
- tolerance develops quickly
Motilin & Macrolide Antibiotics
- Motilin-hormone stimulates motility
- Erythromycin, Clarithromycin, Azithromycin act on motilin receptor |
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Term
| Drugs used in blockade of gastric acid production |
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Definition
PPI: Omeprazole (PRILOSEC OTC)
H2 Histamine Receptor Antagonists: Ranitidine (ZANTAC)
Antacids, sucralfate |
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Term
| Antibiotic Treatment of H. pylori |
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Definition
PPI or H2 blocker plus a combination of one or more antibiotics
Clarithromycin (BIAXIN)
Amoxicillin (AMOXIL)
Metronidazole (FLAGYL)
Tetracycline (ACHROMYCIN) |
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Term
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Definition
| Bismuth subsalicylate (PEPTO-BISMOL) |
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Term
| Prokinetic (Pro-motility) Agent |
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Definition
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Term
| Agents Used to Treat Diarrhea |
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Definition
Opioids (Loperamide (IMODIUM))
Somatostatin Analogs |
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Term
| Agent Used to Treat Opioid-Induced Constipation |
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Definition
| Methylnaltrexone (RELISTOR) |
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Term
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Definition
Bulk-forming Agents
Stool Softeners
Polyethylene glycol-Electrolytes (COLYTE, GOLYTELY)
Lubiprostone (AMITIZA) |
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Term
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Definition
5-HT3 Antagonists (Ondansetron (ZOFRAN))
D2 Receptor Antagonists (Metoclopramide (REGLAN))
Antihistamines (Promethazine (PHENERGAN))
Antimuscarinics (Scopolamine (TRANSDERM-SCOP))
Cannabinoids |
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Term
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Definition
No structural anomalies = functional disorder; no diagnostic markers
ANTICHOLINERGICS
- Muscarinic cholinergic receptor antagonists
- Atropine-like drugs
- Dicyclomine, glycopyrrolate, propantheline, hyoscamine
- Decrease motility
- Relax intestinal smooth muscle
- Inhibit ACh-mediated release of serotonin
- Decrease secretions
- *Many side effects: dry mouth, dry eye, tachycardia, constipation*
Tricyclic Antidepressants (have effects on pain!)
- Imipramine
- Desipramine
- Amitriptyline
Doses are lower than that required to treat depression
MOA: May be anticholinergic actions and alteration of processing of visceral afferent information
Side Effects
- Anticholinergic actions
- Orthostatic hypotension
- Overdose may lead to fatality
- CV: conduction defects and arrhythmias
- CNS: seizures
5-HT3 Receptor Antagonist (reduces motility)
- Alosetron (Lotronex)
- used in cases where diarrhea is the predominant symptom
- Can cause constipation, which can be severe
- Ischemic colitis in less than 1%
- Restricted use by FDA
Lubiprostone (Cl-channel activator) for constipation predominant
Peppermint oil, probiotics |
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Term
"The Big Picture"
Histamine/H2 antagonists
NSAIDS
ACh
H. pylori
PPI
antacids
pepto bismol
Gastrin, CCK |
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Definition
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Term
Nausea & vomiting & the brain
Receptor locations
CTZ
Vestibular system
GI tract, heart
CNS |
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Definition
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