Acid/Peptic Flashcards
How do acid/peptic disorders develop
Mucosal erosions or ulcerations arise when the caustic effects of aggressors (acid, pepsin, bile) overwhelm he defensive factors of the GI mucosa
What normally regenerates GI mucosa after injury
Mucus and bicarb secretion
prostaglandins
blood flow
What causes peptic ulcers
MC: H pylori
NSAIDs
What are the two classes of peptic disease fighting agents
agents that reduce intragastric acidity
agents that promote mucosal defense
What contributes to acid secretion
Gastrin from antral G cells, Ach from postganglionic nerves, and Histamine bind receptors (CCK-B, H2, M3) on parietal cells
Binding causes increase in calcium which stimulates protein kinase which stimulates acid secretion from H/K ATPase (proton pump)
Do the three receptors work together
They are all on the same cell (parietal cell) but if you block any of the three, they are not dependent on each other
If you block one specific one, you don’t necessarily block the acid stimulation from the others
What agents reduce intragastric acidity
Antacids
H2 blockers
PPI
What are antacids
Non-Rx meds for intermittent heartburn and dyspepsia
They are weak bases that react with gastric HCl to form a CO2 and NaCl= less acidity
Give 1 hour after a meal to neutralize gastric acid for up to 2 hours
What are some antacids
sodium bicarb: Baking soda, Alka seltzer
Calcium carbonate: tums, Os-Cal
Mag hydroxide
Aluminum hydroxide
ADE of Sodium bicarb antacids are
CO2 gastric distention and belching
Unreacted alkali is absorbed and can cause metabolic alkalosis if high dose in renal insufficiency
NaCl absorption enhances fluid retention if w/ HF, HTN, or renal insufficiency
What is the MOA of Calcium carbonate
Less soluble and reacts more slowly w/ HCl to form CO2 and CaCl
ADE of calcium carbonate are
belching
metabolic alkalosis
Excess sodium bicarb or calcium carb w/ calcium dairy= hypercalcemia, renal insufficiency, metabolic alkalosis (milk-alkali syndrome)
What is the MOA of mag/aluminum hydroxide
React slowly with Hcl to form mag chloride or aluminum chloride and water
No gas! does not cause belching
Metabolic alkalosis is not common
ADE of mag/aluminum hydroxide are
Osmotic diarrhea (unabsorbed mag)
Constipation (aluminum salts)
-Commonly used with Gelusil, Maalox, and Mylanta to minimize impact on bowel
Who should not take mag/aluminum hydroxide antacids
Renal insufficiency patients, because both are absorbed and excreted by the kidneys
Never give antacids w/in 2 hours of giving these meds (mag, alu, and Ca interfere with them)
Tetracyclines
Fluoroquinolones
Itraconazole
Iron
How do antacids affect other drugs
They can affect absorption of other meds by binding drug and:
reducing absorption -or- increasing pH so solubility of drug is altered
What are the H2 blockers
Cimetidine- least potent
Ranitidine (zantac)
Famotidine (pepcid)- most potent
Nizatidine
What is the PK of H2 blockers
Rapidly absorbed from intestine
First pass hepatic metabolism (all except nizatidine)
Do you have to dose adjust H2 blockers
Yes in mod-severe renal insufficiency (and hepatic)
Elderly 2/2 reduction in volume distribution and drug clearance
What is the MOA of H2 blockers
Competitively inhibit H2 receptors (not H1 or 3)
Suppress acid secretion
Reduce volume of gastric secretion and concentration of pepsin
Reduce acid secretion stimulated by histamine, gastrin, and cholinomimetic agents
Block histamine release from ECL gells
Diminish direct stimulation of parietal cell to release gastrin or ACh
When should you give an H2 blocker
before bed! This is when the most acid is produced
Is Rx H2 blocker better than OTC?
Yes, maintains greater than 50% acid inhibition x 10 hours whereas OTC provides only 6 hours of relief
What disorders benefit from H2 blockers
GERD
PUD
NUD (non-ulcer dyspepsia)
Prevention of bleeding from stress related gastritis
ADE of H2 blockers are
diarrhea, HA, fatigue, myalgias, constipation- BUT
These occur in <3% of patients! H2 blockers are VERY safe
-Nosocomial PNA in critically ill pt
Mental status changes: confusion, hallucinations, agitation (IV or pt in ICU)
Can pregnant women take H2 blockers
They cross the placenta and are secreted into breast milk so ONLY give if absolutely necessary
What is specific about Cimetidine
Inhibits binding of DHT to androgen receptors= inhibits estradiol metabolism & increases serum prolactin
Can cause gynecomastia or impotence in men or galactorrhea in women
What do H2 blockers interact with
Cimetidine: inhibits hepatic CYP450 pathways
Ranitidine: binds 4-10 times less avidly than cimetidine to CYP450
Nizatidine and Famotidine don’t really interact with CYP450
What are the PPI
Omeprazole (prilosec) Esomeprazole (nexium) Lansoprazole (prevacid) Dexlansoprazole Rabeprazole Pantoprazole (protonix)
What is the PK of PPI’s
They are inactive acid labile prodrugs; PO are delayed release and acid resistant (enteric coated) while prodrugs rapidly become protonated within canaliculus
*Rapid first pass hepatic metabolism
(really no renal clearance)
What decreases bioavailability of drug
food! by about 50%
So, give PPI 30-60 min before meal (MC breakfast)
What do PPI’s block
They inactivate actively secreting pumps, but do NOT have effects on inactive or dormant pumps
How long are PPI active
They inhibit acid for up to 24 hours (irreversible inactivation of PP)- it takes 18 hours for synthesis of new proton pump molecules
Do you need to adjust PPI doses
Yes, in patients with severe liver impairment
Where are H/K ATPase pumps found
ONLY on parietal cells
What is acid suppression from a PPI dependent on
irreversible inactivation of proton pump, not the PK of different agents
PPI’s can be used for
GERD PUD NUD prevention of stress related mucosal bleeding Gastrinoma
What are ADE of PPI’s
Diarrhea, decreased B12 release from food, HA, abd pain
Promotes absorption of iron, calcium, magnesium (monitor bone density and give calcium supplements)
Increased risk of infections, nosocomial PNA, C. Diff
What happens to Gastrin when you give a PPI
Increases 2x
transient rebound acid hypersecretion for 2-4 weeks (dyspepsia, heartburn)
What do PPI’s interact with
Decrease absorption of: Ketoconazole, digoxin
Reduce activation of: Clopidogrel
Omeprazole inhibits warfarin
Rabeprazole and Pantoprazole have no specific drug interactions
If you are taking clopidogrel what PPI do you prefer
Pantoprazole
Rabeprazole
How does the gastroduodenal mucosa protect itself from acid/pepsin effects
Mucus and epithelial tight junctions restrict back diffusion of acid/pepsin
Blood flow carries bicarb and nutrients to surface cells
Prostaglandins stimulate mucus, bicarb and blood flow
What are the mucosal protective agents
Sucralfate
Prostaglandin analogs
Bismuth
What is Sucralfate
Salt of sucrose + aluminum hydroxide
In water, it forms a viscous paste that binds ulcers for 6 hours It is negatively charged and proteins on ulcers are + charged)
This physical barrier restricts caustic damage
-ALSO: stimulates mucosal prostaglandin and bicarb secretion
What is Sucralfate used for
Prevent stress related bleeding
What are ADE of Sucralfate
Constipation (aluminum=constipation!)
*Do not use prolonged if w/ renal insufficiency
What does Sucralfate interact with
other meds; can bind and impair their absorption
What does the GI mucosa produce
Prontaglandins! Mainly E and F
What is a prostaglandin analog
Misoprostol (PGE1)
Rapidly absorbed, must admin 3-4x day (half life <30 min)
Excreted in urine
Do you need to adjust dose of misoprostol in renal insufficiency
NO!!!
How does Misoprostol work
Inhibits acid and protects mucosa
Stimulates mucus and bicarb secretion (= more blood flow)
Binds PG receptor on parietal cells= reduced histamine
Stimulate intestinal electrolyte and fluid secretion, intestinal motility, and uterine contractions
What are the clinical uses for Misoprostol
Reduces incidence of NSAID induced ulcers
ADE of Misoprostol are
Diarrhea, abdominal cramping
Stimulates uterine contraction; NO IN PREGNANCY
What are the two bismuth compounds available
Bismuth subsalicylateL non-Rx
Bismuth subcitrate potassium: Rx drug w/ flagyl&tetracycline
What happens to Bismuth subsalicylate in the body
Undergoes rapid dissociation in the stomach= absorption of salicylate
99% of bismuth appears in the stool (turns it black or grey) while salicylate is absorbed and excreted in the urine
How do Bismuth compounds work
Coats ulcers and erosions, protecting from acid and pepsin
Stimulate PG, mucus, and bicarb secretion
Subsalicylate: reduce stool frequency and liquidity in acute infectious diarrhea (inhibits PG and chloride secretion)
Directly antimicrobial against H Pylori and travelers diarrhea
What are clinical uses of bismuth compounds
Dyspepsia
Acute diarrhea
Subsalicylate: prevent travelers diarrhea
H. Pylori eradication: Used with PPI+Tetracycline+Flagyl x10-14 days (take bismuth 4x daily)
ADE of bismuth compounds are
Black stool (harmless) Darkening of tongue (harmless) High doses= salicylate toxicity Bismuth toxicity= encephalopathy (ataxia, confusion, HA, seizure)- but not with either of the drugs we learned
What do you have to monitor with a PPI and H2 blockers
CBC, electrolytes, renal and liver function tests
What do you have to monitor with Misoprostol
PREGNANCY! make sure they arent
Also, Serum phosphate
When would you treat a patient with H. Pylori
Gastric/duodenal ulcer
MALT lymphoma
after endoscopic resection of gastric cancer
uninvestigated dyspepsia
What are controversial indications to treating H Pylori
NUD GERD On NSAIDs High risk gastric cancer Unexplained Fe deficiency anemia
What are other regimens used for H Pylori
PPI + Clarithromycin + Amoxicillin/Flagyl
PPI + Bismuth + Tetracycline + Flagyl
