GI: GERD Flashcards
Types of cells in the gastric gland
Mucosal, parietal, chief, endocrine (enterochromaffin like cells, G cells, D cells)
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location & function of mucosal cells
Near the top/pit of gastric gland, mucosal cells secrete mucous and bicarb
Location & function of parietal cells
- Isthmus of gastric gland
- secrete gastric acid and IF
Parietal cells: resting vs stimulated state
Go between resting and stimulated state.
Resting state: tubovesicles in cytoplasm that contain proton pumps. Surface: receptors for gastrin, Ach, histamine
Stimulated state: TVs and PPs fuse to surface. Canaliculus surface area of cell expands to make room for more. HCl and KCl released. Hydrogen and chloride bind –> hydrochloric acid.
K+ is pumped back into cell and process continues
Location & function of chief cells
Base of gastric gland
Chief cells secrete gastric lipase and pepsin to break downlipids and proteins
Location and function of endocrine cells
Interspersed through gastric gland
- Enterochromaffin like cells (ECLs) secrete histamine
- G cells secrete gastrin
- D cells secrete somatostatin (the brakes)
chemical messengers that increase gastric acid secretion
Ach, histamine, and gastrin all increase GA secretion.
(Ach released by vagus)
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chemical messenger that inhibits gastric acid secretion
Somatostatin: binds to ECLs, G cells, and directly to parietal cells to inhibit GA secretion
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Gastric Acid Defenses
Lower esophageal sphincter tone
- Prevents acid reflux into esophagus
Gastric mucous coats the surface of the stomach
- Traps secreted bicarb
- Secreted by mucous cells
- Stimulated by PGs (PGE1 and PGE2)
Mucous creates gel-like surface. Stimulated by PGs, NSAIDs, decrease PG synthesis – hence ulcer w/overuse
Causes of / risk factors for GERD
- decreased lower esophageal sphincter tone (caffeine, chocolate, spicy foods, etc)
- decreasedesophageal clearance of gastric fluids
- decreased saliva production (iatrogenic – meds)
- Delayed gastric emptying (gastroparesis from diabetes)
- Obesity
- Pregnancy
How to treat GERD in pregnancy: lifestyle
Lifestyle modification before pharm interventions:
- Smaller meals
- Avoid eating at bedtime
- Elevate HOB
How to treat GERD in pregnancy: pharm
Pharm stepwise Tx:
- Antacids
- H2 antagonists –> Ranitidine (Zantac) has most safety data
- PPI (less safety data c/t H2Bs): Lansoprazole (Prevacid) and Pantoprazole (Protonix) have more safety data
Type of drugs used to treat GERD
PPIs, antacids, H2 blockers
Types of PPIs
- Omeprazole (Prilosec)
- Esomeprazole (Nexium)
- Pantoprazole (Protonix)
- Lansoprazole (Prevacid)
- Dexlansoprazole (Dexilant)
- Rabeprazole (Aciphex)
PPI: MOA
Prodrugs absorbed in sm intestines
Travel systematically to parietal cells
Activated by stimulated proton pumps
Irreversible disulfide bonds formed with the proton pump
Must create new proton pumps to secrete gastric acid. Why they are so effective.
PPI: dosing
Counseling: take 15-30min before bfast or biggest meal of day; Dose after dinner for nocturnal symptoms
PPIs: absorption
A: rapid, bioavailability & absorption rate decreased w/food
PPIs: half life & duration
½ life: 1.5h, 24h duration (irreversible bond)
PPIs: metabolism
M: liver via CYP2C19 and CYP3A4
PPIs: Excretion
E: inactive in urine and feces
PPIs: important drug interaction
Clopidogred (Plavix) Interaction – prodrug requiring CYP2C19 activation: potential reduce antiPLT activity; avoid PPI or RX protonix or aciphex if necessary
PPIs: ADRs
Prolonged use:
- decreased vit B12 absorption
- decreased mg (esp w/diuretics)
- increased risk bone fractures (decreased Ca absorption) Ca needs acidic environment
- increased risk C. diff & pneumonia (GA destroys c diff spores, bacteria)
Discontinuation causes rebound acid hypersecretion * -Temporary. some recommend H2B bridge.*
Short term well-tolerated
PPIs: crush or split tablets?
• Do not crush or split tablets
PPIs vs H2 blockers for esophageal GERD Sx
PPIs more efficacious
PPIs: which are most effective?
All PPIs equally effective
PPIs: what to do if partial response only?
adjust timing to fit Sx, consider BID
PPI onset
Takes a few days, Use antacids as bridge
PPIs vs H2Bs when maintenance Tx is needed
- Continue PPI if Sx return after Tx, erosive esophagitis, Barrett’s esophagitis
- Consider H2 if no erosive esophagitis
Omeprazole (Prilosec): available formulations
- Capsule, tablet, suspension
- QD, OTC
- Available for pedi, 5kg
(PPI)
Omeprazole (Prilosec): drug interactions
Def not w/Plavix
(PPI)
Esomeprazole (Nexium) : formulations
- Capsule, packet, injection
- QD, OTC
- Available for pedi 1-11yo
Pantoprazole (Protonix): formulations
Tablet, packet, injection
QD
(PPI)
Lansoprazole (Prevacid): formulations
- Capsule/ODT, suspension
- OTC
- Available for pedi 1-11yo
(PPI)
Dexlansoprazole (Dexilant): formulations
Capsule
QD
(PPI)
Rabeprazole (Aciphex): formulations
- Tablet, sprinkle capsules
- QD
- Available for pedi 1-11yo
Which PPI if must use w/plavix
Pantoprazole (Protonix) or Rabeprazole (Aciphex)
PPI w/relatively more safety data in pregnancy
Pantoprazole (Protonix) and Lansoprazole (Prevacid)
Most common PPI for pedi, even infants
Lansoprazole (Prevacid)
Antacids: MOA
Neutralize GA by reacting w/hydrochloric acid
Antacids: special considerations
Consider pt characteristics when Rxing, e.g, no alka seltzer for CHF, RF, low Na+ diet d/t fluid retention
Types of antacids
- Sodium Bicarbonate (Alka Seltzer)
- Calcium Carbonate (Tums)
- Magnesium hydroxide + Aluminum hydroxide (Mylanta)
Sodium Bicarbonate (Alka Seltzer): dosing
325 mg 1-4x daily prn
Calcium Carbonate (Tums): dosing
500-1000 mg Q2h prn
Magnesium hydroxide + Aluminum hydroxide (Mylanta): dosing
10-20mL (400-800mg aluminum +mg) 4x daily prn
Sodium Bicarbonate (Alka Seltzer): ADRs
Belching, metabolic alkalosis, fluid retention
Sodium Bicarbonate (Alka Seltzer): forms
NaCl, CO2 and H20
Calcium Carbonate (Tums): ADRs
Belching, hypercalcemia, metabolic alkalosis
Calcium Carbonate (Tums): forms
Forms: CaCl2, CO2 and H20
Magnesium hydroxide + Aluminum hydroxide (Mylanta): ADRs
Diarrhea (Mg), Constipation (Al), Aluminum accumulation in CKD
Combined to reduce AEs of both
Magnesium hydroxide + Aluminum hydroxide (Mylanta): forms & C/Is
- Forms: MgCL and Al2Cl3 and H20
- Not in RF!
H2 Blockers: agents
- Cimetidine (Tagamet)
- Famotidine (Pepcid)
- Ranitidine (Zantac)
- Nizatidine (Axid)
H2 Blockers: MOA
Acid inhibition via reversible H2 receptor blockade
H2 Blockers: absorption
rapid, 1-3h
H2 Blockers: 1/2 life & duration
1.1-4h (duration of effect: most 10-12h)
H2 Blockers: metabolism
10-35% via liver
H2Bs: excretion
parent drug & metabolites in kidneys
H2Bs: ADRs
Diarrhea, HA, fatigue, constipation (minor)
CNS effects (confusion, hallucinations, delirium) more in elderly
Cimetidine (Tagamet): formulation & dosing
Tablet or solution
Q12h, OTC
(H2B)
Cimetidine (Tagamet): ADRs
H2B adrs + Gynecomastia/impotence (cimetidine)
(H2B)
Cimetidine (Tagamet): drug interactions
Drug interactions: Cimetidine (CYP2C9, CYP2D6, CYP1A2) - inhibitor, may increase serum concentration
(H2B)
Famotidine (Pepcid): formulations and dosing
- Tablet, suspension, injection
- Q12h, OTC
- Pedi dosing available
Ranitidine (Zantac): formulation and dosing
- Tablet, capsule, syrup, injection
- Q12h, OTC
- Pedi dosing available
Ranitidine (Zantac): pregnancy
Has most safety data in pregnancy of H2Bs
Nizatidine (Axid): formulation and dosing
Tablet, capsule, solution
Q12h