pharm 6: antacids, H2, PPI

antacids work by increasing ______ and suppressing _____

intragastric pH

pepsin activity

(pH of 7 - no pepsin activity)

antacids will bind ______

bild salts

antacids will increase ___________(4)?

bicarb, mucosal cell regeneration, prostaglandins, and mucus

antacids include

calcium carbonate

magnesium carbonate

magnesium hydroxide

aluminum hydroxide

simethicone

calcium carbonate is also called

tums

magnesium hydroxide is called

milk of mag

simethicone relieves

gas in GI tract by a defoaming action

antacids are compared via their

acid neutralizing capacity

Duration of action of antacids

empty stomach - 20-40min

1hr after meals - up to 3hrs

systemic antacids

sodium bicarb

Nonsystemic antacids

aluminum hydroxide

magnesium hydroxide

magnesium carbonate

calcium carbonate

antacids work with ______ to form ________

gastric acid

salt and water

antacids are used in treatment of

GERD, gastric and duodenal ulcer disease

Aluminum salts AE

constipation, tissue accumulation in renal insufficiency, hypophosphatemia, osteomalacia (Al inhibits osteoblasts), encephalopathy

calcium salt AE

constipation, diarrhea

milk-alkali syndrome

rebound hyperacidity

magnesium salts AE

diarrhea

accumulation in pts with renal insufficiency

sodium bicarb AE

sodium and water retention

metabolic alkalosis (renal insuff)

magnesium/aluminum combinations AE

minor changes in bowel function

antacids decrease absorption of

fluoroquinolones, iron salts, digoxin, tetracyclines, ketoconazole

most drug interactions are minimized by administering the drug

2 hours before or after antacid

simethicone relieves

gas in the GI tract by defoaming action

simethicone used as adjunctive therapy in conditions in which

gas is a problem

simethicone is combined with _____

antacids to defoam gastric juice - does not decrease ANC requirements

Simethicone is given

40-80mg after meals and at bedtime

H2 receptor antagonists include

Cimetidine, Famotidine (Pepcid), Nizatidine, & Ranitidine

H2 antagonists block

histamine from binding H2 receptors on gastric parietal cells

H2 antagonists inhibit

gastric acid secretion

H2 somewhat reduce secretion of

intrinsic factor

H2 antagonists also inhibit

basal (fasting) and nocturnal acid secretion

acid secretion stimulated by muscarinic agonists, food, gastrin, and calcium

reduce H+ concentration

most common AE of H2 antagonists

HA, dizziness, nausea, myalgia, rash, itching, rebound hyperacidity

what are rare AE of H2 antagonists?

thrombocytopenia, neutropenia, aplastic anemia

what is the effect with IV administration

bradycardia

cimetidine will increase

serum creatinine

long-term therapy/high doses of cimetidine can lead to

decreased libido, gynecomastia, breast tenderness, altered lactation

cimetidine is a ______ inhibitor

CYP3A4 (also CYP1A2, 2C19, 2D6)

proton pump inhibitors (PPIs) include

Omeprazole, Pantoprazole, Esomeprazole, Rabeprazole, Lansoprazole

PPI will bind and ____________

irreversibly inhibit proton pump (H+/K+ ATPase in stomach)

PPI also inhibits

gastric acid secretion~

effect of PPI persists after drug disappears from plasma for

4-5 days

inactive PPi drug is activated in an

acidic environment (pH <5) in the parietal cells

PPI are metabolized to inactive metabolites in

liver ; then secreted in urine

PPIs accumulate in

acidic parietal cell

what are the most powerful inhibitors of gastric acid

PPIs

PPI indications

erosive esophagitis w GERD

erosive esophagitis maitenance

H. pylori

gastric ulcer

duodenal ulcer

ZES

AE of PPI

Nausea

Diarrhea

HA

Dizziness

Somnolence

Kidney damage

B12 deficiency

PPI increase risk of

c.diff, gastric cancer, dementia

PPI reduce concentration of drugs that require

acidic environment for absorption

omeprazole has most interactions =

inhibits 2C19 and 3A4

warfarin, phenytoin, carbamazepine, diazepam, nifedipine, digoxin, cyclosporin, clopidogrel

when are PPI preferably taken

in the morning in fasted state

PRN use of PPI is

unlikely to work; It takes time for the medication to fully inhibit the stomach's acid production

PGE2 and PGI2 synthesized by the

gastric mucosa

role of PGE and PGI is to inhibit

secretion and acid and stimulate secretion of mucus and bicarb

PG synthesis is inhibited by

aspirin/NSAIDS

prostaglandin analog includes

misoprostol

misoprostol is used to prevent

gastric ulcers caused by NSAIDS

AE of misoprostol

Diarrhea

Abdominal pain

what is the black box warning for misoprostol

abortifacient

gastric ulcer treatment includes

Sucralfate

sulcralfate adheres to

ulcerated epithelium and protects it for > 6 hours; Acts like a “band-aid”

in acidic environment, (pH < 4) sucralfate causes

extensive polymerization and cross-linking occur forming a sticky, viscid gel

sucralfate stimulates production of

epidermal growth factor and prostaglandin synthesis

sucralfate also absorbs

pepsin

AE of sucralfate

Constipation

Dry mouth

Abdominal discomfort

Hypophosphatemia

Accumulation in renal insufficiency

sucralfate is eliminated via

renal and feces

sucralfate is FDA approved for

treatment of duodenal and gastric ulcers

postone ulcer disease relapse

sucralfate is not approved for

stress ulcer prophylaxis and reflux esophagitis and gastritis

GERD treatment for mild/intermittent

antacids or low dose H2 antagonists as needed

moderate/persistent GERD

scheduled H2 antagonists

severe or erosive GERD -

PPI

treatment for H.pylori + ulcers

quadruple therapy -

1. PPI

2. bismuth subsalicylate

3. tetracycline

4. metronidazole

14 days

for NSAID induced ulcers,

discontinue NSAID if possible

start PPI or misoprostol

stress ulcers treatment

IV PPI or H2 antagonist in critically ill

antacids can provide

symptom relief within minutes

H2 antagonists are used to

decrease heartburn, nocturnal symptoms

PPIs are used for

resolution of heartburn, ulcer healing

misoprostol is used for

prevention of NSAID Ulcers

sucralfate is used for

relief of ulcer pain within days

bismuth compounds effects are attributed to

cytoprotection, inhibits pepsin activity, compound accumulates in ulcer crater

bismuth is used for

h.pylori

bismuth AE

discolors stool