Acid Blockers & H. Pylori Tx Flashcards
1
Q
Acid Secretion
Physiology
A
-
Parietal cells ⇒ H+ into lumen via H+/K+ ATPase
- ⊕ by gastrin, ACh, histamine
-
Dietary peptides:
- ⊕ Antral G-cells ⇒ gastrin → blood → fundus
- Gastrin ⇒ ⊕ Enterochromaffin (ECL) cells ⇒ histamine
- ⊕ Parietal cells ⇒ H+
- ⊕ Antral G-cells ⇒ gastrin → blood → fundus
-
ACh from PNS
- ⊕ ECL cells ⇒ histamine
- ⊕ Parietal cells ⇒ H+
- ⊕ Antral G-cells ⇒ gastrin
- ⊗ Antral D-cells ⇒ somatostatin
- Normally acts to ⊗ gastrin release from G-cells
2
Q
Acid Secretion
Modulation
A
- Luminal H+ ⇒ ⊕ antral D-cells ⇒ somatostatin ⇒ ⊗ gastrin secretion from G-cells
- Proteins and fats ⇒ ⊕ duodenal L-cells ⇒ CCK ⇒ ⊕ antral D-cells → secrete somatostatin
3
Q
Histamine H2 Receptor Antagonists
Drugs, MOA, Pharmacokinetics
A
Cimetidine, Famotidine, Ranitidine
-
Mechanism of Action:
- Competitive inhibitor @ H2 receptors on parietal cells
- ↓ Pepsin release
-
Pharmacokinetics:
- T½ 2-3 hrs but duration of action is much longer
- Administered 1-2x/day
- ⊗ meal-stimulated & basal secretion
- Esp. effective vs nocturnal secretion (dependent on histamine)
4
Q
Histamine H2 Receptor Antagonists
Indications
A
- Gastroesophageal reflux disease (GERD)
- Laryngopharyngeal reflux (LPR)
-
Peptic ulcer disease
- 1-2x/day for 6-8 wks, usu. @ night on empty stomach to suppress nocturnal secretion
- Tx for H. pylori to prevent relapse after stopping mono tx
-
Dyspepsia
- Given 30 mins before a meal
-
Stress-related gastritis
- Occurs in critically ill pts d/t impaired mucosal defenses caused by poor perfusion
- Not as effective for erosive esophagitis (PPI preferred)
5
Q
Stress-related Ulcers
Risk Factors
A
- Mechanical ventilation
- Coagulopathy
- TBI
- Major burn
- ICU pts w/:
- Multiple traumas
- Sepsis
- Acute renal failure
6
Q
Histamine H2 Receptor Antagonists
Adverse Effects & Interactions
A
Cimetidine has unique AE & interactions:
-
Anti-androgenic effects
- ♀ ⇒ galactorrhea, amenorrhea
- ♂ ⇒ gynecomastia
- Potent ⊗ of several cyp450 isozymes ⇒ numerous drug interactions
7
Q
Proton Pump Inhibitors
Drugs, MOA, Pharmacokinetics
A
- Lansoprazole, Omeprazole, Esomeprazole
- Acid-labile prodrugs ⇒ given as enteric coated tablets
- Uncharged form → parietal cell cytoplasm → acidic canaliculus → active sulfenamide form
- Forms covalent disulfide link w/ luminal cysteinyl in proton pump of parietal cell
- Rxn depends on conformational ∆ of active H+/K+-ATPase pump
- Food ⇒ ⊕ proton pumps ⇒ PPIs should be taken 30-60 min prior to meals
-
Irreversible inhibition ⇒ H+ secretion inhibited for an extended time past T½
- PPI’s suppress H+ secretion better and for a longer time than H2 blockers
8
Q
PPIs
Indications
A
-
Peptic ulcer disease
- Slightly more effective than H2 blockers
- Many pts will relapse if not tx for H. pylori
- NSAID-associated ulcers
- Gastroesophageal reflux disease (GERD)
- Laryngopharyngeal reflux (LPR)
- Zollinger-Ellison syndrome 2/2 gastrin-secreting tumors
-
Stress-related gastritis
- Occurs in critically ill pts d/t impaired mucosal defenses 2/2 poor perfusion
- Immediate release omeprazole maybe preferred in pts w/ NG tube, but otherwise H2 antagonists are preferred
- Most pts take PO but IV admin allows ↑ [drug] to enter parietal cell w/o degradation
- Used in pts unable to take PO meds that require profound acid suppression
9
Q
Immediate-Release
Omeprazole
A
- Contains sodium bicarb ⇒ protects uncoated drug from degradation by gastric acid
- Accelerated anti-secretory action may be d/t activation of proton pumps by rapid neutralization of intragastric H+ by sodium bicarb
10
Q
PPIs
Adverse Effects
A
- Generally well-tolerated
- Lack of acidic environment in stomach ⇒ poor absorption of some nutrients
- Ex. calcium ⇒ some ↑ in hip fractures reported
- ↑ Clostridium difficile
- Possible link w/ PNA
- Long-term use ⇒ fundic gland polyposis of stomach
- CKD
11
Q
Rebound Acid Secretion
A
Seen when stopping after long term use of PPIs
↓ Gastric H+ ⇒ disinhibition of G cells ⇒ ↑ gastrin ⇒ bound acid secretion
12
Q
PPIs
Drug Interactions
A
- Extensively metabolized by the cytochrome p450 system (cyp2C19; cyp3A4)
- 2C19 polymorphism ⇒ slower clearance
- Standards doses of the PPI’s take differences into account, so most pts achieve a therapeutic effect
- Omeprazole may inhibit metabolism of warfarin, diazepam, phenytoin, and carbamazepine
-
Clopidrogel prodrug needs cyp450 activation to active form
- Competition ⇒ ↓ efficacy & ↑ risk of MI
13
Q
Gastric Antacids
A
Aluminum and magnesium hydroxides, calcium carbonate, sodium bicarbonate
- MOA: Neutralizes acid
-
Indications:
- Acid indigestion
- PUD (hard to dose properly)
-
Calcium carbonate also used as a calcium supplement
- Calcium citrate absorbed better in pts on PPI’s
-
Adverse Effects:
- Aluminum ⇒ constipation and magnesium ⇒ diarrhea, usually administered together (Maalox, Mylanta)
-
Calcium carbonate and sodium bicarbonate ⇒ transient metabolic alkalosis
- CO2 liberated can cause flatulence
14
Q
Maalox
A
- Aluminum hydroxide + Magnesium hydroxide
- Contains Simethicone
- Anti-foaming agent ⇒ ↓ surface tension of gas bubbles ⇒ combines into larger bubbles that pass more easily ⇒ ↑ rate of exit
15
Q
Rolaids
A
Calcium-carbonate antacid
Also used as a calcium supplementa
16
Q
Alka-Seltzer
A
Citric acid + sodium bicarbonate antacid
- Compounds react → CO2 ⇒ flatulence
- Enough sodium bicarb ingested for H+ neutralization
18
Q
Bismuth Subsalicylate
A
Mucosal protective agent
-
Bismuth effects:
- Anti-secretory ⇒ ⊕ absorption of fluids and electrolytes across intestinal wall
- Anti-inflammatory ⇒ hydrolyzed to salicylic acid ⇒ ⊗ prostaglandin synthesis (responsible for inflammation and hypermotility)
- Antimicrobial ⇒ binds toxins secreted by E. coli, other bactericidal properties
- Relieves nausea and abdominal cramps
-
Pepto-Bismol
- Contains clay ⇒ ? benefits in diarrhea
-
Kaopectate
- Contains bismuth @ higher concentrations
-
Adverse effects:
-
Dark stools and black staining of the tongue
- Drug + bacterial sulfides in the GI tract → bismuth sulfide (cause)
- Contains salicylate ⇒ same warnings as ASA for children & pts allergic to ASA
-
Dark stools and black staining of the tongue
19
Q
Helicobacter pylori
Overview
A
- Gram ⊖ helical shaped rod
- Enters GI tract via oral route
- Attaches to adhesion molecules on surface of gastric epithelial cells
- Able to exist in an acidic environment d/t urease production
- Protects bacteria by: Urea → ammonia ⇒ buffers H+ → ammonium hydroxide
- Urease, ammonia & factors produced by H. pylori ⇒ damages epithelial lining
-
↑ acid secretion via two mechanisms:
- Urease ⇒ ↑ pH ⇒ ⊕ G-cells to release gastrin
- ↑ Gastrin ⇒ proliferation of parietal cells & ↑ acid secretion
- Inflammation damages D-cells ⇒ ↓ somatostatin (normally ⊗ gastrin secretion from G-cells)
- Urease ⇒ ↑ pH ⇒ ⊕ G-cells to release gastrin
