Antacid and Anti-Ulcer Pharmacology Flashcards
What types of meds are used only for short-term, temporary relief of mild pain and symptoms associated with PUD/GERD
Antacids
Classes of antacids
Low-systemic agents: aluminum salts, calcium salts, magnesium salts
High-systemic agents: sodium salts
Supplemental agents: simethicone
MOA of antacids
Combine chemically with H+ ions —> generation of byproducts like water, CO2, and Cl-
Note that they DO NOT reduce acid secretion or production, and rebound acid production is possible!
Antacids are shown to increase ____ at higher doses
LES tone
Onset, DOA, and Acid Neutralizing Capacity (ANC) of calcium carbonate antacids
Onset: rapid
DOA: long
ANC: very good
Onset, DOA, and Acid Neutralizing Capacity (ANC) of aluminum hydroxide antacids
Onset: slow
DOA: short
ANC: fair/weak
Onset, DOA, and Acid Neutralizing Capacity (ANC) of magnesium hydroxide/carbonate/trisilicate antacids
Onset: rapid
DOA: long
ANC: good
Onset, DOA, and Acid Neutralizing Capacity (ANC) of sodium bicarbonate antacids
Onset: rapid
DOA: short
ANC: fair/good
MOA of simethicone antacids
Acts as a surfactant, decreasing surface tension and aiding in expulsion of gas
Adverse effects of aluminum hydroxide antacids
Constipation
Hypophosphatemia [thus can be used as acute tx for hyperphosphatemia]
[also renal osteodystrophy and encephalopathy]
Adverse effects of magnesium antacids
Diarrhea (stool-softening/laxative-like activity)
Hypermagnesemia
Calcium antacid adverse effects
Constipation
Hypercalcemia (Milk-alkali syndrome —> nephropathy and metabolic alkalosis)
Hypophosphatemia
Calcium-based kidney stones
Adverse effects of sodium antacids
Gas/flatulence
Hypernatremia
Metabolic alkalosis
What antacids are typically paired together to reduce GI side effects?
Magnesium + Calcium antacids
[Mg causes diarrhea, Ca causes constipation — together cancels out]
There are many drug interactions with antacids — what is the rule of thumb for how to best avoid these?
Take all antacids 1-2 hours before other medications OR 2-4 hours after other medications
Classes of Anti-Ulcer agents
H2 Receptor Antagonists
Proton Pump Inhibitors
Surface Acting Agents
PGE1 Analogs
Bismuth Compounds
H2 blockers used as anti-ulcer meds
Cimetidine
Ranitidine
Famotidine
Nizatidine
[some also made with antacids included]
MOA of H2 blockers
Reversibly inhibit H2 receptors on basolateral membrane of parietal cell
T/F - H2 blockers can cause total achlorhydria
False — they do not completely stop H+ production
H2 blockers have relatively prompt onset of 0.5-2 hours and have QD to BID dosing. How much do they reduce acid production, and how long does it take for ulcer healing?
Inhibit 20-50% of acid production [depending on dose/duration]
Ulcer healing occurs in 4-8+ weeks UNLESS CAUSED BY H.PYLORI
Adverse effects of H2 blockers
Primarily GI related: nausea, diarrhea, constipation
Some CNS related: Headache
[note that these are relatively mild, transient, and infrequent; with long-term high dosing can see blood dyscrasias like neutropenia and thrombocytopenia]
______ is an H2 blocker that, with long-term high dosing, can decrease testosterone binding to its androgen receptor —> gynecomastia in men and galactorrhea in women
Cimetidine
Which H2 blocker is a prototypical inhibitor of several CYP450 enzymes, thus leading to many drug-drug interactions?
Cimetidine
[Ranitidine has ~10% of the CYP450 inhibition compared to cimetidine]
A relative contraindication to H2 blockers is pregnancy. What H2 blocker can be used if absolutely necessary?
Ranitidine (or famotidine)
Proton pump inhibitors used as anti-ulcer meds
Omeprazole Esomeprazole Lansoprazole Dexlansoprazole Pantoprazole Rabeprazole
MOA of PPIs
PPIs covalently bind to sulfhydryl groups of H/K-ATPase at parietal cell secretory sites, thereby inhibiting gastric acid secretion by irreversibly inhibiting functioning ‘-ase’ pumps
[possible to generate achlorhydria!]
Describe PPIs in terms of duration of action, degree of acid inhibition and time for ulcers to heal
Effects of PPIs last 24 hours (usually QD dosing),
Inhibit 50-90% of acid [depending on dose/frequence/duration]
Full symptom effects seen in several days (longer than H2 blockers)
Ulcerations healed in 4-8+ weeks — unless caused by H.pylori!!
Adverse effects of PPIs
GI: diarrhea, dyspepsia, nausea, CDAD — Clostridium Difficile-associated Diarrhea
CNS: headache, dizziness
Rare AEs: generalized myalgias, fatigue, myopathies
PPIs are associated with increased risk for what 3 conditions?
Kidney disease (AKI)
Bone fractures
Cardiovascular disease (MI)
Drug interactions with PPIs
Omeprazole is a prototypical PPI for CYP450 inhibition —> many drug interactions
Pregnancy is a relative contraindication to PPI use. Which drug can be used if absolutely necessary?
Lansoprazole (or pantoprazole)
—try to avoid omeprazole!!
MOA of sucralfate
Undergoes cross-linking from interaction with stomach acid —> viscous, sticky polymer which adheres to epithelial cells around ulcer’s crater — preventing acid access to ulcer sites
May also stimulate local prostaglandin and mucous production and epidermal growth factor (cytoprotective)
Does not affect pH!
Sucralfate is indicated for short-term tx of duodenal ulcers, but is also used off-label for what conditions?
Aphthous ulcers
Mucositis/stomatitis
Radiation proctitis/ulcers (enema)
Bile reflux gastropathy
Adverse effect associated with sucralfate
Constipation
[formula includes Al(OH)3 — aluminum component associated with constipation]
Relative contraindications to sucralfate
Severe renal failure (d/t aluminum component)
Drug interactions are possible with sucralfate, so what is the recommendation?
If possible, take 2-hours after other meds
[note that sucralfate is dosed QID for active ulcers, so timing can be difficult]
Which anti-ulcer med is recommended for people who also require NSAID therapy?
Misoprostol — because it has NSAID diclofenac
MOA of misoprostol
Prostaglandin E1 analog — provides protective prostaglandin to gastric mucosa and reduces gastric acid release from parietal cell
[thus provides cytoprotection by increasing mucosal defenses; standard doses reduce basal and nocturnal acid output]
Primary indication for misoprostol is prevention of NSAID-induced gastric ulceration in pts at high risk of ulcerations and complications. What are some off-label uses for misoprostol?
When given with mifepristone —> pregnancy termination
Alone for cervical ripening
Post-partum hemorrhaging
Adverse effects of misoprostol
Primarily GI: diarrhea (possibly with N/V + cramping)
CNS: headache, dizziness
Contraindications to misoprostol
Pregnancy (unless specifically for off-label use)
IBD
MOA of bismuth compounds
Originally developed as anti-diarrheal agent - most well known for its antimicrobial actions (used in combo pack for H.pylori)
Exact mechanism for PUD is not known, but as a salicylate derivative can function similar to ASA and inhibit prostaglandin synthesis
OTC vs. Rx use of bismuth compounds
OTC: used alone for reflux, indigestion, and diarrhea
Rx: used in combo with abx and acid-suppressant for H.pylori [believed to prevent microbial attachment to mucosa, possible inactivation of enterotoxins, and disruption of bacterial cell wall]
Adverse effects of Bismuth compounds
Constipation
Black/dark regularly-formed stools [know it is not GI bleed bc it is regularly formed!]
T/F: bismuth compounds are not associated with drug interactions
False, there are many drug interactions - so these should be taken 2 hours after other meds
Relative and absolute contraindications to bismuth compounds
Relative: antiplatelets and anticoagulants, severe renal failure
Absolute: GI bleeding, salicylate hypersensitivity
Combination therapy for tx of H.pylori is a MUST — what must this combination include?
At least 2 abx and an acid reducer (PPI or H2 blocker)
The American College of Gastroenterology recommends 10-14 days of a triple-drug regimen containing: a PPI, clarithromycin, and either amoxicillin or metronidazole [all BID dosing]
What is included in the more powerful quadruple therapy for H.pylori?
PPI (BID)
Metronidazole (QID)
Tetracycline (QID)
Bismuth subsalicylate (QID)
The Helidac (QID) used for H.pylori treatment includes bismuth subsalicylate 525 mg, Metronidazole 250 mg, and Tetracycline 500 mg. What must you remember to add to this regimen?
PPI or H2 antagonist
What would you give a pt with H.pylori who is allergic to penicillin?
PPI
Clarithromycin
Metronidazole
[consider quad therapy with bismuth]
What would you give a pt with H.pylori that is metronidazole-resistant?
PPI
Clarithromycin
Tetracycline
[consider quad therapy with clarithromycin and amoxicillin]
What would you give a pt with H.pylori that is resistant to Clarithromycin?
PPI
Amoxicillin or tetracycline
Metronidazole
[consider bismuth quad therapy]
How would you treat a pregnant patient with PUD without evidence of H.pylori?
Consider short course of antacids or sucralfate
[if moderate symptoms, consider ranitidine; if severe symptoms, consider lansoprazole]
How would you tx a pt w/ PUD that is considered NSAID-at risk?
If NSAIDnot required, consider acetaminophen and discontinue NSAID
If NSAID required, consider COX-2 NSAID and/or consider PPI or Misoprostol
