Peptic ulcers, GERD, and Zollinger-Ellison syndrome are all improved by inhibiting stomach acid secretion. 

Stomach acid secretion can be decreased by the use of H2 antagonists, proton pump inhibitors, and antacids.  Recall that in peptic ulcers it is also important to give antibiotics against H. pylori.

Sodium Bicarbonate (Alka Seltzer, baking soda)

Calcium Carbonate (Tums)

Magnesium and aluminum hydroxide (Mylanta)

Sodium bicarbonate, an antacid also known as Alka Seltzer, reacts with HCl to produce NaCl and carbon dioxide.  the CO2 results in gastric distention and belching.

Additionally, the absorption of unreacted bicarb can promote metabolic alkalosis at high doses.

Calcium carbonate is an antacid, also known as Tums, which reacts with HCl to form CaCl2 and carbon dioxide.  The carbon dioxide causes gastric distention and belching. 

Also, similar to sodium bicarbonate, calcium carbonate can cause metabolic alkalosis at high doses.

Like all other antacids, including calcium carbonate etc., sodium bicarbonate decreases the acidity of the stomach environment.  This can interfere with the oral bioavailability of some drugs.  For example, remember that itraconazole (the antifungal that blocks ergosterol synthesis) requires an acidic environment!

Also recall that acidic drugs like aspirin are best absorbed in low pH, then become ionized in the more basic ECF.  If the stomach is more basic, the relative amount of aspirin absorbed becomes less!

This is the combination of ranitidine (H2 antagonist) and bismuth (a mild antibiotic) into a citrate salt.  It is used to treat H. pylori infection, often being combined with a second antibiotic such as clarithromycin.

Recall: H. pylori is strongly associated with almost all peptic ulcers, especially duodenal!

Omeprazole is a proton pump inhibitor.  It acts by irreversibly inhibiting the H+/K+ ATPase of the parietal cells. The cells must therefore synthesize new proton pumps.  It is activated by acidic stomach environments, providing a built-in negative feedback loop.  Because the H+/K+ ATPase is the final common pathway for all stimulators of acid secretion, PPIs are able to very powerfully inhibits acid release, much more so than the H2 antagonists. 

All PPIs end in "_prazole" and are drugs of choice in reflux esophagitis and peptic ulcers.

Esomeprazole has the most powerful acid suppressant action.  It can be used if patients present with resistant symptoms.

ESomeprazole is "extra strong" omeprazole

Proton pump inhibitor 2x daily (or ranitidine bismuth citrate)

Amoxicillin
Clarithromycin

This treatment is effective at eradicating H. pylori in over 90% of cases.  If it is unsuccessful, repeat the course, but use metronidazole instead of clarithromycin.

Misoprostol is a prostaglandin E analogue that activates PGE1 and 2 receptors of gastric epithelial cells and stimulates the formation of mucous and bicarbonate.  It also inhibits parietal cell secretion of HCl (the more important effect of misoprostol).  This HCl inhibition occurs because the PGE receptors of the parietal cells is a Gi protein bound receptor, which inhibits adenylyl cyclase and therefore cAMP production... (counters the acid-promoting effects of histamine, which acts through cAMP)

It is mainly used for the prevention of NSAID induced ulcers (not for the treatment of) in patients on long term NSAID therapy.

Sucralfate is a sulfated polysaccharide that adheres to necrotic tissue of peptic ulcers, thereby acting as a barrier to acid and pepsin, protecting the ulcer and helping in the healing process.

(sucra reminds me of the word 'sucre' in french meaning sugar.  Think sugar coating = sucralfate coats the ulcer)

The bismuth compounds, bismuth subsalicylate and bismuth subcytrate, can produce dark stools.

They also cause constipation and are therefore also included in some treatments of travelers or episodic diarrhea!

Recall, bismuth compounds exert antibacterial activity!

Gastroparesis is 'delayed gastric emptying'.  Therefore, pharmacological agents that are able to stimulate movement of the GIT and emptying of the stomach are useful in treatment of this disorder.  The drugs used are:

Metoclopromide
Domperidone
Erythromycin

Metoclopramide and domperidone are D2 receptor antagonists.  In the gut, dopamine receptors typically cause a blockade of Ach effects.  Therefore, relieving this blockade promotes an increase in Ach-driven motility.  This increased motility is only in the esophagus and stomach, not in the small intestine or colon.

Also remember that D2 receptors are located in the chemoreceptor trigger zone, so these drugs are also powerful antiemetics!

Metoclopramide is a D2 antagonist capable of crossing the BBB.  It is used to promote gastric motility, for example in cases of diabetic gastroparesis.  It can produce extrapyramidal effects like tardive dyskinesias.  It also promotes prolactin release and can lead to galactorrhea and gynecomastia, as well as sexual dysfunction.

Domperidone (the other D2 antagonist used in promoting gastric motility) does not cross the BBB and so does not have these adverse effects.

Remember: one of the side effects of erythromycin is that it directly stimulates motilin receptors in the GI smooth muscle.  This promotes the migrating motor complex!

unfortunately, tolerance rapidly develops.

5-HT3 antagonists are the "_setrons", such as Ondansetron.  They are the drugs of first choice in chemotherapy-induced emesis (along with the neurokinin receptor antagonist, Aprepitant). 

They are not very effective at preventing motion sickness.

Aprepitant is an antiemetic drug.  It is a neurokinin receptor antagonist.  It blocks the influence of substance P at NK-1 receptors at the Nucleus Tractus Solitarius.

Like the 5-HT3 antagonist Ondansetron, it is also a drug of first choice in the treatment of chemotherapy-induced N&V.

Drugs that block the vestibular nuclei are effective in the treatment of motion sickness.  These drugs are the first generation H1-antagonists and the antimuscarinic drugs.

H1 antagonists include meclizine, diphenhydramine, and dimenhydrinate.

The antimuscarinic used is Scopolamine

5-HT3 antagonists (Ondansetron)

Neurokinin receptor antagonists (Aprepitant)

D2 antagonists

Dronabinol

Glucocorticoids

Opioids are used in irritable bowel syndrome and travelers diarrhea.  They decrease intestinal peristalsis.

they are CONTRAINDICATED in patients with ulcerative colitis, crohn's disease, and chronic constipation.

Loperamide and diphenoxylate are opioids used in the treatment of irritable bowel syndrome and traveler's diarrhea.

They are contraindicated in cases of ulcerative colitis, Crohn's disease, and chronic constipation.

Aluminum hydroxide and magnesium hydroxide are often given together.  Al hydroxide causes constipation.  Mg hydroxide causes diarrhea.  by giving both together, these effects are balanced out.

alumINum hydroxide causes constipation, where all the feces stay IN the bowels.

-OR-

A comes before M, as C comes before D, so aluminum hydroxide causes constipation and magnesium hydroxide causes diarrhea.

Proton pump inhibitors (omeprazole) have an acid resistant coating that is dissolved only once it reaches the more alkaline enviroment of the small intestine.  The drug is then absorbed into circulation, enters the parietal cells (pH 7.4), and is excreted into the lumen (pH 1).  Because of the strong acidic pH of the lumen, the drug gets protonated.  The protonated form of the drug is active and binds a cysteine residue on the proton pump, inhibiting its H+/K+ ATPase.  This proton pump is permanently inactivated and the cell must synthesize a new pump. 

Recall: you must give the drug about one hour before a meal, because this will allow the drug to reach the parietal cells when they are activated.

Hypertensives (because it can lead to increased Na+ absorption, leading to fluid retention/ increased blood pressure)

The vestibular apparatus and cerebellum have M and H1 receptors, which are responsible for motion sickness.  This explains why drugs like first generation H1 antagonists (dimenhydrinate etc.) are beneficial here, as they block both H1 and M receptors. 

It also explains why other classes of drugs like ondansetron (5-HT3) and D2 antagonists are ineffective against motion sickness.

Cimetidine is an H2 receptor antagonist.  It has more adverse effects than the other H2 antagonists.  These include:

1) CYP450 inhibition

2) Androgen receptor inhibition leading to Gynecomastia and sexual dysfunction

3) Headaches

Ondansetron (5HT3)

Aprepitant (NeurokininR)

Glucocorticoids in combination with above

Cannabinoids (Dronabinol) when others not effective

The salt laxatives act in the small intestine.  They can stimulate defecation within 1 hour.

CONTRAINDICATED in patients with renal insufficiency because magnesium toxicity or hyperphosphatemia may occur!

The plant extract laxatives (cascara and senna) act in the colon.  They are hydrolyzed by bacteria in the colon and stimulate colon motility!

'cascara' is like a shell in spanish. Sienna is a brown color.  A brown shell = poop, which is formed in the colon.  haha...
So cascara and senna make you go #2 by acting on the colon

The CRTZ contains M1, D2, and 5-HT3 receptors.  This explains why ondansetron (5HT3 antagonist) and metoclopromide (D2, 5HT3 antagonist) are useful in chemically induced nausea.

Recall, H1 and M1 receptors are found in the vestibular nuclei and cerebellum, explaining the benefit of first gen. H1 antagonists in motion sickness!

(1,2,3 my dad hates the CRTZ = M1, D2, 5HT3)