Gastrointestinal Pharmacology Flashcards
______ can occur in areas of upper GI tract that are exposed to stomach acid and pepsin
Peptic ulcer
Most common sites of peptic ulcers?
- duodenum
- stomach
- lower esophagus
What condition occurs when corrosive action of gastric acid and pepsin overcome mucosal defense mechanism?
Peptic ulceration
Peptic ulceration can occur if there is an excess production of ______ or if there’s a breakdown of _____ defense mechanisms
acids; mucosal defense mechanisms
What are two common causes of ulcers?
1) H. pylori
2) NSAID’s
Proton pumps move H+ and Cl- from the ____ cell and into the lumen of the ____
parietal cell; stomach lumen
True or False: Neural and endocrine mechanism regulate acid secretion
True
Gastrin is made by the stomach and small intestines in response to ____ and intake of ____
gastrin; food
___ binds to the muscarinic receptor of the parietal cell while gastrin binds to gastrin receptor. Following this ___ binds to H2 receptor.
histamine
What is the primary defense that is used by the stomach to protect itself against harsh environments?
Mucosal barrier
Mucus is made and secreted by ___. It is made up of glycoproteins, water, electrolytes, and HCO3
goblet cells
The mucus adheres to _____ cells, protecting them from erosive actions of acid and pepsin
epithelial cells
The integrity of the mucus barrier depends on what three factors?
1) Blood flow to mucosa
2) Ability of mucosal cells to reproduce
3) Prostaglandins (PGEE)
_____ is a prostaglandin analog that is available for prevention of NSAID-induced ulcers
Misoprostol
Under normal conditions, there is a balance between ___ and ___ (defense factors).
What is one condition in which this balance is disrupted, leading to excess acid production?
acid/pepsin; mucus
Zollinger Ellison Syndrome
True or False: In stress or NSAID-induced ulcers, the ability to maintain mucus barrier becomes compromised
True
True or False: Peptic ulceration commonly occurs when corrosive action of gastric acid and pepsin overcome mucosal defense mechanisms
True
Three causes of peptic ulcer disease?
1) Excess acid production
2) H. pylori
3) Breakdown of mucosal defense mechanisms
How is H. pylori eradicated?
Antimicrobials eradicate H. pylori and decrease chance for recurrence
How does H. pylori lead to spontaneous development of ulcers?
Weakens mucus defense system
What class of drugs are considered to be the classic antacids?
Neutralizing agents
What two drug classes inhibit acid secretion?
1) H2 histamine antagonist
2) PPI
What two drugs enhance the defense factors?
- Sulcralfate
- Misoprostol
True or False: Anti-microbials are used to eradicate H. pylori
True
____ are inorganic bases that neutralized HCl to form salts and water
Neutralizing Agents
What are the four neutralizing agents?
1) Sodium Bicarbonate
2) Calcium Carbonate
3) Magnesium Hydroxide
4) Aluminum Hydroxide
What two neutralizing agents produce CO2 (which can lead to distension) and can cause metabolic alkalosis?
Calcium Carbonate and Sodium Bicarbonate
Which neutralizing agent has rapid onset, but short duration of action?
Sodium Bicarbonate
____ is ok for occassional symptomatic relief of heartburn and mild gastritis, but NOT for treatment of peptic ulcer disease
Sodium Bicarbonate
In patients with high calcium intake or poor renal who are taking Calcium Carbonate, ____ Syndrome can occur
Milk Alkali Syndrome?
Features of Milk Alkali Syndrome?
Alkalosis
Hypercalcemia
Kidney Stones
Renal Damage
True or False: Calcium Carbonate can lead to acid rebound (increase in acid secretion after effects wear off)
True
True or False: Calcium Carbonate is appropriate for long-term management of peptic ulcers
False - calcium carbonate is NOT appropriate for longer term management of peptic ulcers. However, it is OKAY for occasional or low dose usage
Which three neutralizing agents have the potential for drug interactions with calcium, leading to formation of insoluble complexes?
Calcium Carbonate Magnesium Hydroxide
Aluminum Hydroxide
What three drugs can lead Calcium Carbonate and MgOH to form insoluble complexes and lead to decreases effectiveness of other drugs?
1) Digitalis glycosides
2) Tetracyclines
3) Phenytoin
Which two neutralizing agents are unlikely to lead to systemic alkalosis?
AlOH and MgOH
___ is most common side effect when MgCl2 is used alone as antacids
How can this effect be minimized?
Diarrhea
- Mg salts in combination with other agents that have constipating actions (AlOH)
In patients with poor renal function, use of _____ may lead to hypermagnesemia
Magnesium OH
True or False: Aluminum Hydroxide tend to cause constipation
True
- Can be minimized by using it combination with Mg2+ salts
The aluminum in AlOH forms an insoluble salt with ___, leading to reduced absorption of ___ within and, ultimately, _____
phosphate; hypophosphatemia
What type of adverse systemic effects can occur in patients who are taking AlOH and have impaired RENAL function?
Myopathies, Dementia, Seizures, and Osteodystrophy
Antacid mixtures are the result of ____ and ____.
Why is this combination so valuable?
AlOH and MgOH
- Combination minimizes the side effects of individual agents
True or False: Both MgOH and AlOH are NOT well absorbed and can lead to build up of toxic levels of Mg and Al, respectively, in patients with renal insufficiency
True
Which class of drugs is currently used for SYMPTOMATIC relief of heartburn, gastritis, and peptic ulcer disease?
Neutralizing Agents
Which two agents inhibit acid secretion?
1) H2 antagonists
2) Omeprazole, Pantoprazole
____ are a class of drugs that reduce the amount of acid secreted in response to histamine, vagal stimulation, acetylcholine, and gastrin
H2 - histamine antagonists
True or False: Omeprazole is used for the acute treatment and prevention of relapses in peptic ulcer disease
False - H2 (histamine antagonist) are used for acute treatment and prevention of relapses in peptic ulcer diseas
Which acid secretion inhibitor is used to treat Zollinger Ellison Syndrome and reflux-esophagitis?
Histamine (H2) Antagonists
Name three common Histamine Antagonists:
1) Cimetidine
2) Famotidine
3) Nizatidine
Which of the H2 antagonists can lead to gynecomastia in men? Why does this occur?
Cimetidine
(has anti-androgen effects - only at CHRONIC and HIGH doses!)
True or False: An active H2-R is needed for gastrin and neuronal PS stimulation of acid secretion
True
Which Acid Secretion Inhibitor inhibits P450 and, therefore, has many DDI?
Cimedtidine
What drug class does omeprazole belong to?
PPI (proton pump inhibitors)
True or False: Esomeprazole (and other PPI’s) are very effective in reducing most types of acid secretion and may also have some activity against H. pylori
True
___ are inactive prodrugs that are converted to active metabolites that covalently interact with proton pump
PPI’s (such as Omeprazole)
Five uses of PPI’s?
1) GERD
2) Peptic Ulcer Disease
3) Zollinger Ellison Syndrome
4) Preventing stress and NSAID induced ulcers
The main problem in ___ drugs is that the marked inhibition of acid secretion can lead to microbial over growth of upper GI with chronic use
PPI’s (like omeprazole)
How are PPI’s administered? activated?
Administers as: inactive prodrugs
Activated by: protonation
Where are PPI’s activated?
Parietal cell canaliculus
True or False: Proton pump inhibitors reversible activate H/K ATPase
False - Proton Pump Inhibitors IRREVERSIBLY INACTIVATES H/K ATPase
True or False: PPI work immediately
False - they take 3-7 days to reach full acid-inhibiting potential
When should PPI’s ideally be taken?
1 hour before meal
Which drug class is associated with increased risk of bone fractures in females?
A. PPI’s
B. H2 Antagonists
C. Neutralizing Agents
A. PPI’s
Three primary clinical uses for PPI’s?
1) GERD
2) Peptic Ulcer Disease
3) Zollinger Ellison Syndrome
What is the first line of treatment for excess acid production, as in Zollinger Ellison Syndrome?
A. PPI’s
B. Neutralizing Agents
C. Magnesium OH
A. PPI’s
___ and ___ are the strongest inhibitors of CYP2C19
Omeprazole and Esomeprazole
Which PPI has the least effect on CYP2C19?
Pantoprazole
True or False: Clopidogreal requires activation by CYP2C19
True
Inhibition of hepatic drug metabolizing enzymes and decreased gastric acidity are side effects of ___
PPI’s
What three agents enhance defense factors (cytoprotective agents)?
Sucralfate
Misoprostol
____ is an aluminum salt that polymerizes to form a sticky material that binds to exposed proteins in ulcer, forming a protective barrier
Sucralfate
___ is a PGE1 analogue that increases mucus production and reduces acid secretion
Misoprostol
True or False: Sucralfate is used to prevent NSAID induced ulceration
False - Misoprostol is used to prevent NSAID induced ulcerations
Which cytoprotective agents should NOT be given to expecting mothers? Why?
Misoprostol, a cytoprotective agent, should NOT be given to expecting mothers because it can induce uterine contractions and abortion
Which five microbial gents are effective against H. pylori?
1) Metronidazole
2) Amoxicillin
3) Tetracyclines
4) Calrithromycin
5) Colloidal Bismuth
Triple therapy has been used to treat H.pylori and includes a ____, in conjunction with ___ and either Amoxicillin, a tetracycline, or clarithromycin
bismuth salt, metronidazole, tetracycline/clarithromycin
Three major effects of chronic laxative use?
1) Laxative dependence
2) Alterations in bowel function
3) Electrolyte imbalances
____: abnormally difficult passage of dry, hardened feces - results from decreased motility in relation to amount of water in fecal material
____: abnormally frequent passage of loose, watery feces. It can result from increased motility, excessive intestinal secretion, or decreased reabsorption of water
Constipation
Diarrhea
4 main mechanisms by which laxatives work?
1) Increase motility
2) Prevent absorption of H2O
3) Enhance secretion
4) Dissolve or lubricate fecal mass
What are the four bulk forming laxatives?
1) Dietary Fiber
2) Methylcellulose
3) Psyllium
4) Polycarbophil
___ is an insoluble, hydrophilic polyacrylic resin
Polycarbophil
Which forms stool faster: Bulk Forming Laxatives or Contact/Stimulant Laxatives?
Contact/Stimulant Laxatives (2-8 hrs)
Which laxatives mimic the effect of a well-balanced diet and is SAFEST for chronic use?
Bulk Forming Laxatives
___ laxatives absorb water and swell to form soft mass that induces peristaltic reflexes
Bulk forming laxatives
True or False: Dietary fibers is a classic bulk forming agent
True
Which class of laxatives act on intestinal mucosa to enhance secretion, INHIBIT water absorption, or induce peristalsis?
Contact/Stimulant Laxatives
Which class of laxatives is associated with laxative dependence?
Contact/Stimulant Laxatives
What are the three contact/stimulant laxatives?
1) Bisacondyl
2) Senna/sennosides
3) Phenolphthalein
___ is a contact/stimulant laxative that acts on the bowel to INHIBIT absorption of water and may stimulate peristaltic movements
Phenolphthalein
Castor Oil is hydrolyzed in the small intestines to release ____, the active agent that acts on the mucosa of the ____ to inhibit absorption of ___ and stimulates ____
ricinoleic acid; small intestine; fluid; peristaltic movements
True or False: Castor oil is associated with watery evacuation, pain, and cramping
True
True or False: Both Bulk Forming Laxatives and Osmotic Laxatives are poorly absorbed
True
How do osmotic laxatives work? How long does it take for them to have an effect?
Exert osmotic effect to hold water in intestinal tract
1-6 hours
What are the three osmotic laxatives and cathartics?
1) MgOH
2) Lactulose
3) Polyethylene Glycol
Note: MgOH is both an osmotic laxative AND a neutralizing agent
____ is a widely used osmotic laxative/cathartic, particularly to prepare bowel for diagnostic/surgical procedure
Polyethylene Glycol
___ is a poorly absorbed lubricating agent that coats and lubricates fecal mass
Mineral Oil
Risks of Mineral Oil?
Lipid Pneumonitis (aspiration)
Surface Active Agents are also known as ____
Fecal Softeners
___ is a fecal softener/surface active agent that exerts a detergent effect to break and soften fecal mass + may stimulate secretion of fluid
Docusate Sodium
True or False: Detergent effect of Docusate Sodium may increase solubility and absorption of other drugs
True
___ activates chloride channels on the intestinal brush border and, thereby, increases fluid secretion.
Used to treat chronic idiopathic constipation and IBS!!!!
Lubiprostone
Best drug for chronic idiopathic constipation and IBS in females?
Luboprostone
Prokinetic Agents increase __ motility
GI
____ is a cholinomimetic agonist that stimulates M3 receptors on muscle cells and myenteric plexus synapses
Bethanechol
____ is a prokinetic agent that can be used to treat Ogilvie’s syndrom
Neostigmine
(achetylcholinesterase Inhibitor)
Why is neostigmine better than bethanechol?
The latter just acts at a receptor, whereas neostigmine inhibits Ach breakdown
(have some neural control over when Ach is present)
____ is a prokinetic agent that constricts lower GI sphincter, promotes gastric emptying, and can be used to treat GERD or esophagitis.
It is an anti-emetic!!!!!
Metoclopramide
What condition can metoclopramide prevent?
Gastroparesis and GERD
___ can be used as an anti-mimetics and is a prokinetic agent. How is it achieved?
metoclopramide
- blocks dopamine receptors in CNS
___ is an anti-microbial agent that directly stimulates motilin receptors on GI smooth muscle and can treat DIABETIC GASTROPARESIS
Erythromycin
True or False: Methylnaltrexone and Alvimopan are selective opioid antagonists of the u-opioid receptor and cross the BBB
False - DO NOT cross BBB
Methylnaltrexone use?
-Opioid induced constipation
-Gastreparesis
Alvimopan use?
Post-op Ileus
