Pharm - treatment of GERD and PUD CIS- Waller Flashcards
Proton-Pump Inhibitors (PPIs)
- list
Dexlansoprazole (Dexilant) Esomeprazole (Nexium) Lansoprazole (Prevacid) Omeprazole (Prilosec, Zegerid) Pantoprazole (Protonix) Rabeprazole (Aciphex)
H2-Receptor Antagonists (H2RAs)- list
Cimetidine (Tagamet)
Famotidine (Pepcid)
Nizatidine (Axid)
Ranitidine (Zantac)
Antacids
- list
Sodium bicarbonate (Alka Seltzer) Calcium carbonate (Tums, Os-Cal) Magnesium hydroxide/aluminum hydroxide (Mylanta, Maalox)
Agents Which Provide Mucosal Protection- list
Bismuth subcitrate
Bismuth subsalicylate (Pepto-Bismol)
Misoprostol
Sucralfate (Carafate)
Antibiotic Treatment of Helicobacter pylori Infection
- list
PPI or H2RA combined with two or more antibiotics Amoxicillin Clarithromycin Metronidazole Tetracycline
PPIs- MOA, PK, ADRS
Agents: dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
MOA: covalently bind H+/K+-ATPase, irreversibly inactivating the enzyme.
PK:
Inactive pro-drug, delayed-release, acid resistant, enteric coated – to protect acid labile drug from destruction
Administer on an empty stomach; 30 minutes before meals
ADRs:
Diarrhea, headache, abdominal pain (1-5%)
Clostridium difficile (2-3x risk)
↓ vitamin B12 absorption, ↑ risk of nosocomial pneumonia, modest ↑ risk of hip fracture
H2-Receptor Antagonists (H2RAs)- MOA, PK, ADRs
Agents: cimetidine, famotidine, nizatidine, ranitidine
MOA: competitive inhibition at parietal cell H2-receptors.
PK:
Duration of action dependent on dose used
ADRs:
Diarrhea, headache, fatigue, myalgia (< 3%)
Mental status changes (ICU patients, elderly, renal or hepatic impairment)
Nosocomial pneumonia, rare blood dyscrasias, bradycardia/hypotension (rapid IV infusion)
PPIs vs. H2RAs
PPI DDIs:
Decreased acidity may alter drug absorption (ketoconazole, itraconazole, digoxin, atazanavir)
Extensive CYP P450 metabolism (2C19 & 3A4)
Clinically significant interactions rare (short t1/2)
Omeprazole may inhibit metabolism of warfarin (↑ INR), diazepam, phenytoin….
H2RAs DDIs:
CYP1A2, 2C9, 2D6, 3A4 (cimetidine»_space;> ranitidine)
Theophylline, warfarin, phenytoin, lidocaine (↑ levels)
PPIs and Clopidogrel
Clopidogrel (pro-drug) requires activation by CYP2C19 for anti-platelet activity
PPIs could ↓ activation = ↓ anti-platelet activity
Especially omeprazole, esomeprazole, lansoprazole, dexlansoprazole
If co-administration required, pantoprazole or rabeprazole preferred
amtacid use and side effects
Mg has laxative effects
Al causes constipation
Antacids combining Al and Mg are used to lower stomach acid w/o producing undesirable constipation or diarrhea
Clinical Pharmacology – GERD
PPIs
Greater efficacy for ERD and NERD, esophageal complications, and extra-esophageal manifestations
H2RAs
Used intermittently for infrequent heartburn or dyspepsia
Recommendations:
Mild, intermittent symptoms – antacid or H2RA as needed
NERD – antacid or H2RA (PPI may be required)
Erosive esophagitis – PPI x 8 weeks
Lifestyle Modification in GERD
Unlikely to control symptoms in most patients.
Recommend in target populations:
overweight- weight loss
lying down- head of bed elevation
nocturnal- avoid meals 2-3 hours before bedtime
tobacco- smoking cessation
relief after trigger avoidance– quit eating those foods
Clinical Pharmacology – PUD
PPIs
Greater symptom relief & faster ulcer healing
H2RAs
Replaced by PPIs but still used occasionally for duodenal ulcers (nocturnal acid inhibition)
Recommendations:
Duodenal ulcer – H2RA or PPI x 4 weeks
Gastric ulcer – PPI x 8 weeks
Prevention of re-bleeding – PPI
Clinical Pharmacology – NSAID Ulcers
Discontinue ASA or NSAID (faster healing)
PPIs
Preferred if ASA or NSAID continued
H2RAs
May be used if ASA or NSAID discontinued
Treatment of H. pylori
Antibiotics Amoxicillin Clarithromycin Metronidazole Tetracyclines Two or three antibiotics + PPI
14-day triple therapy (all BID): PPI, clarithromycin, amoxicillin or metronidazole
14-day quadruple therapy: PPI or H2RA (BID), Tetracycline, Metronidazole, Bismuth subsalicylate (all QID)
Adverse Drug Reactions in H pylori treatment
Mild side effects to drug regimens common
Significant side effects reported in 5-20%
Clarithromycin: GI upset, diarrhea, altered taste
Amoxicillin: GI upset, headache, diarrhea
Metronidazole: metallic taste, intolerance to alcohol
Tetracycline: GI upset, photosensitivity
Self-treatment of GERD is fine in the absence of what?
alarm symptoms- bleeding, trouble swallowing, anemia,
severe or frequent heartburnt, more than 2 days/ week more than 3 months
extraesophageal- asthma, cough, laryngitis
Persistent symtoms despite appropriate therapy
Creates physical barrier at base of erosions
sucralfate and bismuth
Inhibits 30S bacterial ribosome
tetracycline
Prostaglandin analog
misoprostol
reacts with HCl forming CO2 and CaCl2
Calcium Carbonate
H2-receptor antagonist
famotidine
You recommend an agent (to a GERD patient) which is generally well tolerated but may have a low incidence of headache and diarrhea. What is this drug’s likely mechanism of action?
choices: Creates physical barrier at base of erosions H2-receptor antagonist Inhibits 30S bacterial ribosome Prostaglandin analog Reacts with HCl forming CO2 and CaCl2
H2-receptor antagonist
heartburn drugs that may impact warfarin’s CYP metabolism?
PPIs and H2RAs
most likely: Omeprazole and cimetidine
PPIs less likely to inhibit CYP
Pantoprazole or rebprazole
when do we dose adjust PPIs?
with hepatic impairment, but not renal impairment
pt with frequent heartburn, difficulty swallowing, moderate esophagitis, an esophageal stricture, and no evidence of Barrett metaplasia
Should we give antacids vs H2RAs vs. PPIs?
PPI is appropriate - most effective and goodo for esophageal copmlications and extra-esophageal manifestations
why do we use delayed-release PPIs?
so they are not destroyed by the acid of the stomach and can reach their site of action
drug that inhibits H+/K+ ATPase as continuous IV infusion?
PPI
e.g. pantoprazole
In PUD, if an NSAID must be continued, is a PPI or H2RA preferred?
PPI; an H2RA will not be as effective
what drugs are not recommended for aspirin allergy?
Busmuth subsalicylate
drug that is not compatible with alcohol?
metronidazole
