Drugs- Treatment of GERD and PUD (Kinder) Flashcards
(46 cards)
what 3 things regulate acid secretion from parietal cells
i) Neuronal (acetylcholine, ACh), paracrine (histamine), and endocrine (gastrin) factors regulate acid secretion through receptor binding on parietal cells.
Somatostatin
produced by antral D cells inhibits gastric acid secretion.
(1) When gastric pH falls below 3, this stimulates SST release which suppresses gastrin in a negative-feedback loop.
what is the role of Prostaglandins and how are they affected by NSAID’s
(1) Prostaglandins E2 and I2 inhibit the proton pump by reducing cAMP production (EP3 receptors are GPCRs coupled to Gi on parietal cells).
(2) PGE2 and PGI2 also stimulate production of protective factors (mucus, bicarbonate) by superficial epithelial cells and enhance mucosal blood flow.
(3) Non-steroidal anti-inflammatory drugs (NSAIDs) block PG production resulting in more acid secretion, less mucus and bicarbonate production, and diminished blood flow. Thus, NSAIDs are ulcerogenic and should be avoided or dose reduced in ulcer patients.
what are the causes of GERD
transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, delayed gastric emptying, or hormonal changes due to pregnancy.
how do you treat mild intermittnet symtpoms of GERD
antacid or H2RA as needed
NERD treatment
antacid or H2RA (PPI may be required in more severe symptoms)
Erosive esophagitis treatment
PPI for 8 weeks
what are the symptoms of Peptic ulcer disease
iii) Symptoms:
burning epigastric pain,
pain occurring after meals or on an empty stomach,
nocturnal pain relieved by food intake (less common symptoms: indigestion, vomiting, heartburn).
what are the alarming symptoms of GERD
i) Alarm symptoms: bleeding, anemia, early satiety, unexplained weight loss, progressive dysphagia, recurrent vomiting, family history of GI cancer, previous esophagogastric malignancy.
treatment of duodenal ulcer
H2RA or PPI for 4 weeks
gastric ulcer treatment
PPI for 8 weeks
what are the 3 agents that reduce gastric acidity
PPI’s
H2RA
antacids
what are the agents that promote mucosal defense
bismuth compounds
misoprostol
sucralfate
“prazole”
Proton pump inhibitors
a) Dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
MOA of PPI’s
: inactive pro-drugs, lipophilic weak bases diffuse readily across lipid membranes into acidified compartments (parietal cell canaliculus) from the alkaline intestinal lumen. Rapidly becomes protonated and undergoes conversion to active form which forms a covalent disulfide bond with H+/K+-ATPase, irreversibly inactivating the enzyme.
inhibits both fasting and meal stimulated acid secretion.
i) Blocks final common pathway of acid secretion – the proton pump
ii) Inhibits 90-98% of 24 hour acid secretion in standard doses
why are PPI’s ideal drugs from PK perspective
c) PK: ideal drugs from a PK perspective as they have short serum half-lives, concentrated and activated near site of action, and have a long duration of action.
food impact on PPI’s
ii) Bioavailability – decreased ~50% by food, administer on an empty stomach at least 30 minutes before a meal (breakfast).
PPIs only inhibit actively secreting proton pumps so should preferably be given 1 hour before a meal so peak concentration coincides with max activity of proton pump.
when should you dose adjust PPI’s
hepatic insufficiency
what is the therapeutic use of PPI’s
GERD
PUD
H. pylori infection
NSAId ulcers
stress related mucosal injury
prevention of re-bleeding
Zollinger-ellison syndrome
OTC’s- for heartburn
what are the adverse drug reactions of PPI’s
i) 1-5% (only slightly increased over placebo): diarrhea, headache, abdominal pain
ii) Increased risk (2-3x) of hospital- and community-acquired Clostridium difficile
iii) Decreased vitamin B12 absorption (potentially leads to subnormal levels with prolonged therapy), modest increased risk of hip fracture, increased risk of nosocomial pneumonia, small increased risk of enteric infections.
what are the drug drug interactions of PPI’s
i) Decreased gastric acidity may alter drug absorption (ketoconazole, itraconazole, digoxin, atazanavir)
ii) All PPIs metabolized via CYP P450 enzymes (including 2C19 and 3A4) but clinically significant drug interactions are rare due to short half-lives of the PPIs.
what does omeprazole interact with
(1) Omeprazole may inhibit metabolism of warfarin, diazepam, phenytoin, and others
PPI’s and clopidogrel
(a) Clopidogrel is a pro-drug which requires activation by CYP2C19. PPIs (especially omeprazole, esomeprazole, lansoprazole, and dexlansoprazole) could reduce clopidogrel activation thus reducing anti-platelet activity. If co-administration is required, pantoprazole or rabeprazole preferred.
H2RA’s (“tidine”)
MOA
inhibition at parietal H2 receptors (highly selective) does not affect H1 or H3
blocks histamine released from ECL cells by gastrin or vagal stimulation
