GI Drugs Flashcards
what do acid peptic diseases compose of
peptic ulcer (duodenal and gastric), gastroesophageal reflux, zollinger ellison syndrome (ZES)
pathologies that causes peptic ulcers
- gastric acid
- decreased mucosal resistance to acid
- H pylori infection
- NSAIDs
- concurrent use of warfarin and corticosteroids
- stress esp if older than 65
- lifestyle
- gastrinoma - gastrin secreting tumor
what do peptic disease do to the surface of GI tract
erodes and ulcerates the mucosal lining
therapeutic choices for peptic ulcer diseases and their functions
A HAM
- Antacids: neutralizes acid
- H2 antagonist and Proton Pump Inhibitor - reduces gastric acid secretion
- Antimicrobial treatments - eradicate H pylori infection
- Mucosal protective agents - augment mucosal surface defense
mechanism of gastric antacids
they are weak bases that react with gastric HCl to form water and salt –> increase in pH –> quick relief of symptoms
name the antacids
CAM
Calcium Carbonate
Aluminum Hydroxide
Magnesium Hydroxide
adverse effects of each antacids
- Calcium Carbonate –> Hypercalcemia which leads to nephrolithiasis and constipation –> fecal compaction
- Aluminum Hydroxide –> form aluMINIMUM chloride that is insoluble –> MINIMUM amount of feces –> constipation and Hypophosphatemia
- Magnesium Hydroxide –> for Mg salt which is poorly absorbed and causes diarrhea (Mg – Must go to the bathroom)
clinical correlates of antacids and drug absorption
- increases oral absorption of weak bases (quinidine)
- decreases oral absorption of weak acids (warfarin)
- decreases oral absorption of Ca, Mg, and Al molecules –> chelate tetracycline
what are some factors that enhance gastric acid secretion and via what mechanism
Histamine, Acetylcholine, and Gastrin via H+/K+ ATPase pump
what are the H2 receptor blockers
FRaNC
Famotidine
Ranitidine
Nizatidine
Cimetidine
how effective are H2 receptor blockers/mechanism
they are effective at decreasing gastric acid secretion but have no effect on gastric emptying time
of all the H2 receptor blockers, which ones are longer acting/more potent
all but cimetidine
clinical uses of H2 receptor blockers
- promote healing of duodenal and gastric ulcers
- relieve gastro esophageal reflux
- given preoperatively to prevent aspiration pneumonia
adverse effects of H2 blockers excluding cimetidine
nausea, headache, dizziness
adverse of H2 blocker cimetidine
- inhibitor of CYP450 enzymes
- antiandrogenic effects - gynecomastia, elevated prolactin levels, decreased libido
- confusion in older people
- decrease renal excretion of creatinine
since Cimetidine is a CYP450 inhibitor, what drugs does it affect
- warfarin
- procainamide
- phenytoin
- benzos
- theophylline
- imipramine
- quinidine
what are the proton pump inhibitors
PROLE PRAZOLES
- Pantoprazole
- Rabeprazole
- Omeprazole
- Lansoprazole
- Esomeprazole
mechanism of proton pump inhibitors
in parietal cells, they are converted to their active form –> reacts with cysteine on H+/K+ ATPase –> form stable covalent bond –> irreversible inactivation of enyzme
clinical uses of proton pump inhibitors
- GERD, duodenal and gastric ulcers, multiple endocrine neoplasia 1 (MEN-1), Zollinger Ellison
- together with antibiotics help with H pylori infection
- NSAIDs induced ulcers: not only inhibit proton release but also they support platelet aggregation and maintain clot integrity (hemorrhagic ulcers usage)
adverse effects of proton pump inhibitors
- omeprazole inhibits metabolism of warfarin, clopidogrel, phenytoin, diazepam, cyclosporine
- decrease bioavailability of vit B12
- acid needed for absorption of digoxin and ketocanozole so decreased absorption of them
- long term use of omeprazole –> gastric carcinoid tumor
how do you diagnose H pylori infection
- endoscopic biopsy of ulcer margin
- serology test
- urea breath test
first line antimicrobials for H pylori eradication
CAMT Clarithromycin Amoxicillin Metronidazole Tetracycline
what are the mucosal protective agents
Mucosal MoBS
Misoprostol
Bismuth Subsalicylate
Sucralfate
mechanism of sucralfate
- binds to necrotic tissue and acts as a barrier to acid
- stimulates prostacyclin synthesis
when is sucralfate ineffective and why
with use of H2 receptor blocker or PPIs or antacids because it needs an acidic environment (low pH) to be activated
mechanism of bismuth subsalicylate
binds to ulcers and forms a coating and protects it from acid and pepsin
extra effects of bismuth subsalicylate
has some antimicrobial effects against H. pylori
mechanism of misoprostol
prostaglandin analogue (eicosanoid) that decreases acid secretion, stimulates mucin and bicarb secretion
clinical use of misoprostol
prevention of gastric ulcers induced by NSAIDS
adverse effects of misoprostol
DAE
- diarrhea
- abortion
- exacerbates IBD
cause of gastroesophageal reflux
abnormal relaxation of lower esophageal sphincter which allows acids from stomach to get to the esophagus
risk factors for gastroesophageal reflux
obesity, drugs, zollinger ellison, increased BMI
treatment of gastroesophageal reflux
- nonpharmacological: lose weight, don’t drink acid rich drinks before bed, sleep with head elevated, small meals, stop smoking and drinking
- antacids: neutralize acid
- PPIs and H2 blockers
what are the prokinetic drugs
- Cholinomimetics: neostigmine, bethanechol
- 5-HT agonists: metoclopramide, cisapride
- Macrolides: erythromycin
importance of prokinetic drugs
relieve GI symptoms of abdominal discomfort, bloating, heart burn, nausea, vomiting etc
mechanism of pro kinetic activity of metoclopramide
muscarinic activity via 5-HT4 receptor agonist activity
clinical use of metoclopramide
- diabetic, post op gastroparesis, and relief of symptoms of GERD
- nausea and vomiting for those on chemo
adverse effects of metoclopramide
anti dopaminergic
- sedation
- diarrhea
- Parkinsonian effects
mechanism of cisapride and use
5-HT4 agonist that stimulates ACh –> treatment of gastroparesis, GERD, constipation
adverse effect of cisapride
cardiac effects - arrhythmias
