Anti-ulcer drugs Flashcards
role of gastric acid
- digestion of proteins
- activates proenzymes
- absorption of calcium, iron, B12
- suppresses bacterial growth
stimulation of parietal cells
- ACh
- gastrin
- histamine
Ach function
- major neural stimulatory of parietal cells
- increases gastrin release
- inhibits somatostatin
gastrin function
- major endocrine regulator
- release triggered by a protein meal and gastric distention
- increases histamine release
histamine function
- major autocrine/paracrine stimulator
inhibitors of parietal cells
- somatostatin and prostaglandins
somatostatin function
- inhibitor of acid secretion by inhibiting gastrin and histamine release
prostaglandin function
- inhibit acid secretion by decreasing cAMP
- stimulation secretion of mucin and bicarbonate
- inhibited by NSAIDs
PPI MOA
- irreversibly block active H/K ATPase pumps in parietal cells
- if the pumps are inactive the drug will not work
PPI pharmacokinetics
- highly protein bound
- metabolized in the liver by P450, specifically CYP2C19 and CYP3A4
- should be taken 20-30 minutes before breakfast
PPI adverse effects
- diarrhea
- increased gastrin level: hyperplasia of ECL cells, rebound hypersecretion of acid once PPI discontinued
- risk factor for C. difficile colitis
- risk factor for hip fracture and hypomagnesmia
PPI drug interactions
- PPIs may inhibit CYP2C19 which decreases clopidogrels antiplatelet effect
- dexlansoprazole is only PPI FDA approved for concominant use with clopidogrel
- most are pregnancy B except omeprazole which is class C
common H2RB
- ranitidine (Zantac)
- famotidine (Pepcid)
HR2B MOA
- inhibit acid production by reversibly competing with histamine for binding to H2 receptors
- give at night
H2RB pharmacokinetics
- absorbed rapidly, peak concentration in 1-2 hours
- small % protein bound
H2RB drug interactions
- mainly with cimetidine
- cimetidine inhibits cytochrome P450 more so than do other agents of this class
- pregnancy class B
prostaglandin analogue MOA
- stimulates secretion of mucin and bicarbonate
- acid suppression at cellular interface is most critical effect
prostaglandin side effects
- diarrhea
- abortion risk
antacid MOA
- neutralized the acid environment
antacid side effects
- careful in chronic renal disease
- hypermagnesemia: N/V, weakness, hypocalemia, arrhythmias
- milk- alkali syndrome: hypercalemia, alkalosis, renal impairment
bismuth subsalicylate indications
- used to treat diarrhea, heartburn, and upset stomach
- used in combo with other meds (PPIs, antibiotics) to treat H. pylori induced ulcers
bismuth side effects
- black stools, people may think upper GI bleed
GERD severity stage I
- sporadic uncomplicated heartburn
- 2-3 episodes per week
- treat with lifestyle modification and antacid or H2RB as needed
GERD severity stage 2
- more frequent symptoms
- greater than 2-3 episodes per week
- PPI more effective than H2RB
GERD severity stage 3
- chronic unrelenting symptoms
- relapse off treatment
- EGD shows complications: Barrett’s, stricture, ulcers
- PPI once or twice daily: 30 minutes before breakfast and 30 before dinner
- PPI and H2RB: PPI 30 minutes before breakfast, H2RB at bedtime
PUD treatment
- mainstay of treatment are PPIs
- if H pylori present then:
- PPI twice daily for 7-14 days AND
- amoxicillin for 7-14 days AND
- clarithromycin for 7-14 days
- if allergic to penicillins then give metronidazole
risk factors for acute GI bleeds secondary to PUD
- mechanical ventilation more than 48 hours
- coagulopathy
active ulcer or bleeding
- low bp
- high HR
- low hemoglobin/ hematocrit
- increased BUN/Cr ratio
treatment for active bleeding
- endoscopic therapy is mainstay
- plus pantoprazole (protonix)
curling ulcer
- associated with severe burns and volume depletion leading to ischemia and cell necrosis diminishing the mucosal barrier
cushing ulcer
- associated with increased intracranial pressure, and theorized to increase ACh stimulation of parietal cells
risk factors for developing stress ulcers
- mechanical ventilation for more than 48 8hours and coagulopathy
treatment of ZES
- PPIs twice daily