Side effects of aluminum

Constipation, decreased bioavailability of tetracyclines, hypophosphatemia

Side effects of magnesium

Laxation (think MgSo4) even if aluminum is present; at high doses Mg prevails

Side effects of CaCO3

Lead to CO2 production

What are the three receptors found on the parietal cell?

H2 , muscarinic (Ach), gastrin

Mechanism of action for H2 antagonists?

Reversible, competitive inhibition at the H2 receptor.

Among the H2 receptor antagonist, which has the best bioavailability?

Cimetidine

Among the H2-R antagonist which has the greatest potency?

Famotidine

Among the H2-R antagonists, which two have the longer duration of therapeutic effect and why?

Rantidine and famotidine. Although the have the same half life of 3 hours, they have a high therapeutic index so can be used in relatively large doses.

What else can increase acid secretion and how does this affect H2 antagonists’ effects?

Food, gastrin, vagal – greatest effect will be on basal secretion (when all these other guys aren’t in the picture)

Mechanism of action: sucralfate

In the presence of acid, it polymerizes into a viscous material that adeheres to epithelium and ulcer craters (understandably, antacids affect this)

Side effects of sucralfate:

b/c it contains Al ion it can produce constipation, hypophosphatemia (in those w/ poor renal fxn)

Mechanism of action: Misoprostil

as an analogue of PGE1, it inhibits adenylate cyclase in the parital cell and inhibits acid secretion; may have some protective effects as an analog of PGs

Side effects: misoprostil

crampy abdominal pain, diarrhea

CI: misoprostil

pregnant women as it cause uterine contraction

Mechanism of action: Colloidal bismuth

Retards H+ diffusion to mucosa and is bactericidal to h. pylori so effective ulcer healing occurs

Mechanism of action: Esomeprazole

The final common step in H+ secretion is H/K ATPase. Inhibition of it is effective b/c it forms a drug-S-S-enzyme complex

Plasma T1/2: esomeprazole

1hr

How long is acid secretion inhibited by esomeprazole?

8 – 24 hrs (we think it is concentrated inparietal cell)

Adverse effects of PPIs:

Possible interference w/ liver enzyme fxn, increased colonization of stomach or upper GI, headaches, flatulence, respiratory infections, sinusitis, and over longer term stimulation of gastrin secretion

Uses: esomeprazole

Duodenal ulcer, esophageal reflux, hypersecretory tumors, ZE syndrome

Minimal

Which heals an ulcer quickest? Antacids, H2 recptor antag, esomeprazole, or sucralfate?

Esomeprazole

T or F: esomeprazole and H2 antagonists help eradicate Hpylori

False. They do nothing.

How is H. pylori acquired?

Non sanitary water or living conditions and also NSAIDs

What is targeted in tx of esophageal reflux?

Remove dietary influences, decrease acidity, and dec volume of gastric contents.

Which drugs could you use (in addn to diet adjustment) to tx exophageal reflux?

Esomeprazole &  H2-R antagonists (to decrease acidity), prokinetic agents (to get the food out of stomach quickly)

Prokinetic drugs are:

domperidone, tegaserod, Metoclompramide

prokinetic drugs "Dump The Meal"

What are the 5HT receptors found on vagal afferents that are responsible for vomiting?

5HT3

What are the 5HT receptors found on cholinergic fibers of vagus in gut that increase Ach and stimulates motility?

5HT4

What is the main concern for metaclopromide?

Because it includes dopaminergic responses, we are afraid of tardive dyskinesia and hyperprolactinemia.

Mechanism of action: domperidone

5HT4 agonist -> inc Ach -> inc GI motility

Mechanism of action: metaclopramide

5HT4 agonist to promotes LES pressure and gastric emptying; 5HT3 antagonist (at high doses); dopamine antagonist (antiemetic in CNS)

Side effect profile of domperidone

As it doesn’t enter the CNS, it has fewer side effects. Can cause hyperprolactinemia (pituitary outside of BBB), dry mouth, diarrhea, and possibly cardiac arrythmias

Mechanism of action: Tegaserod

5HT4 selective partial agonist with promotile activity

Side effect: Tegaserod 

Diarrhea (over stimulation)

Used for: Tegaserod

Irritable bowel syndrome (sometimes constipation is involved)

Mechanism of action: Alosteron

5HT3 selective antagonist more potent than odansteron; inhibits mobility and decreases pain

Mechanism of action: ondansteron

5HT3 antagonist; blocks emesis from cytotoxic agents

Used for: ondansteron

Cancer chemotherapy, irradiation, anesthetics used in OR anti-emetic

What type of laxative is bisacodyl?

Stimulant laxative that promote accumulation of fluid and electrolytes in the lumen

Mechanism of action: bisacodyl

Promote accumulation of fluid and electrolytes, reduce tone of circular muscles, augment peristaltic pattern

What type of laxative is methylcellulose and what is its mechanism of action?

Bulk forming laxative – an undigested polymer that adds their mass and that of absorbed water to colonic contents thereby softening stools and promoting colonic motility

What type of laxative is MgSO4 and how does it work?

Saline laxative. Poorly absorbed so exerts osmotic effect.

When is MgSO4 used?

To empty bowel before procedures and to help expel dead, dying, or stunned parasites after chemotherapy

What is the anti-diarrheal agents used?

Loperamide and diphenoxylate

Mechanism of action: diphenoxylate

Increase tone of circular muscles and segmenting contractions, reduces peristaltic pattern of contractions and slow transit time