GERD and PUD Flashcards
Gastric acid secretion is Modulated by what 3 pathways which activate their respective receptors__ __ __
paracrine (histamine), neuroendocrine (Ach), and endocrine (gastrin)
(H2, M3, CCK2).
what limits extent of acid secretion?
Somatostatin-secreting D cells and prostaglandins
what is the lifestyle characteristics that increase symptoms
High fat meals Increase in frequency of symptoms Calorically dense meals Increase in esophageal acid exposure Tobacco Increase in frequency of symptoms
what does not change symptoms of GERD?
alcohol intake and caffeine
what are the 4 mechanisms of GERD
Decreased Lower Esophageal Sphincter Pressure
Prolonged Esophageal Clearance
Mucosal Resistance
Delayed Gastric Emptying Time
what is the normal fxn of LES
Tonic, contracted state, relaxing to permit free passage of food into stomach
what are transient LES relaxations
not assoc with swallowing, Mechanism unclear, possible causes: esophageal distention, vomiting, belching, retching
what is responsible for 65% of reflux in GERD
transient LES relaxations
what meds can cause decreased LES? lots
Anticholinergics Barbituates Benzodiazepines Caffeine Dihydropyridine Ca2+ channel blockers Dopamine Estrogen Ethanol Isoproterenol Narcotics Nicotine Nitrates Phentolamine Progesterone theophylline
foods that decrease LES
Fatty meals Peppermint/spearmint Chocolate Caffinated drinks: Coffee Cola tea Garlic Onions Chili peppers
50% GERD patients have
prolonged acid clearance
Esophagus normally cleared by
peristalsis
what does increased saliva do?
(stimulated by swallowing) provides bicarbonate buffer
decreased saliva is associated with 4
Age
Sjogren’s syndrome
Xerostomia
Sleep
mucous secretion in the esophagus does what?
function to protect esophagus Bicarbonate neutralizes acidic reflux
what foods irritate the mucosa?
Spicy food
Citrus juice
Tomato juice
Coffee
without mucous in esoph what might happen?
After repeat exposure, H+ ions diffuse into mucosa causing cellular acidification and necrosis
what meds irritate the mucosa?
Alendronate***(drink a full glass of water then stay upright for 30 min) Aspirin Iron NSAIDS Quinidine Potassium chloride
what Factors increase gastric volume/decrease gastric emptying
smoking and high fat meals
what is the cause of post prandial reflux
delayed gastric emptying time
what causes GERD in infants?
delayed gastric emptying time
Defects in antral motility
Complications: failure to thrive, pulmonary aspiration
8 life-style factors of GERD
Exercise Weight-lifting Cycling Sit-ups Smoking Obesity High-fat meals Supine body position Tight fitting clothing Pregnancy Stress
what are 4 typical symptoms of GERD
Heartburn (pyrosis)
Hypersalivation
Belching
Regurgitation
what are 6 atypical symptoms of GERD
Non-allergic asthma Chronic cough Hoarseness Pharyngitis Chest pain Dental erosion
what is primary for diagnosing GERD
endoscopy and 24 hr amb pH monitoring
what are 4 complications of GERD
Esophagitis, stricture, barretts esoph and adenocarcinoma of esoph
what has symptoms of Continual pain Dysphagia Odynophagia Bleeding Unexplained weight loss Choking
adenocarc of esoph
how do you suppress gastric acid production? 3
Antacids after meals and at bedtime
H2 histamine receptor antagonist
Covalent inhibitors of the H+, K+ -ATPase of the parietal cell (PPIs)
what is part of promotility therapy?
Metoclopramide (dopamine antagonist)
Bethanechol (cholinergic agent)
what does elevating the head of the bed do for GERD?
increases esophageal clearance
Dietary modifications for GERD - 5
- Avoid foods that lower esophageal sphincter pressure (fats, chocolate, ETOH, peppermint & spearmint)
- Avoids foods that have instant effect on the esophageal mucosa (spicy foods, OJ, tomato juice, coffee)
- Include protein-rich foods, augments lower esophageal sphincter pressure
- Eat small meals and avoid eating prior to sleeping-decrease gastric volume.
- Loose weight-reduces symptoms.
what is Ulcers extending deep into the muscularis mucosa of the stomach
PUD
what are 3 common forms of PUD?
Helicobacter pylori associated
NSAID induced
Stress related mucosal damage
what has the following symptoms?Epigastric pain, often worse at night
Pain typically 1-3 hrs after meal and may be relieved by eating
Pain can be episodic
Duodenal ulcers
what has the following symptoms?Epigastric pain, often worse with food
Associated symptoms: heartburn, belching, bloating, nausea, anorexia
gastric ulcers
h. pylori causes the majority of what type of ulcer
Duodenal
NSAID causes the majority of what type of ulcer
Gastric
what diet is associated with PUD
In high concentrations, alcohol associated with acute gastric mucosal damage, upper GI bleed
Smoking: unclear mechanism, impairs healing, higher death rates
what is a gram-negative rod that colonizes the mucus on the luminal surface of the gastric epithelium
Causes inflammatory gastritis
May be linked to PUD, gastric lymphoma and adenocarcinoma
h.pylori
what are 3 transmission of h.pylori?
Fecal-oral
Oral-oral
Iatrogenic
what is the MOA of antacids? it does 3 things
neutralize acid to raise intragastric pH
Decreased activation of pepsinogen
Increased LES pressure
what are the benefits of antacids?
rapid onset
what are the disadvantages of antacids?
short duration
what Adds viscous layer which acts as barrier to reflux in antacids>
alginic acid (Gaviscon)
what are the Gi ADR of antacids?
diarrhea or constipation
Diarrhea: magnesium
Constipation: aluminum
Gas: calcium, sodium bicarbonate
what can sodium bicarb do with in antacids? so what should you avoid?
Sodium bicarbonate products can cause fluid overload in pts. with CHF, renal failure, cirrhosis, pregnancy, or any salt-restricted diet; avoid in anyone taking supplemental calcium or with renal dysfunction
how does antacids affect drugs?
alter gastric pH, increase urinary pH, adsorbing medications, physical barrier to absorption, form insoluble complexes
what drugs to antacids affect?
Clincally significant:
Abx: quinolone, isoniazid, tetracycline
Ferrous sulfate, quinidine, sulfonylurea
Patients using medications >___ days should be evaluated for Risk of Barrett’s esophagus/
Risk of upper GI pathology
14
Patients excessively using antacids
considered more significant disease
If potential for drug interactions, separate dosages of antacids and drug by at least __ hours
2
what is the MOA of H2 receptor antagonists?
reversibly inhibit histamine-2 receptors on parietal cells
what are 2 uses of H2 antagonists?
On-demand therapy for intermittent mild to moderate GERD symptoms
Preventive dosing before exercise/meals
what is Less effective than PPIs in healing erosive esophagitis
H2-receptor antagonists
what are 3 H2 antagonists that she wants us to know?
Rantitidine, cimetidine, famotidine
H2 receptor antagonists are rapidly & well absorbed after what
oral admin
when is the pk time H2 antagonists work>
1-2 hrs
A large part of H2 antagonists are ___ in the urine and therefore may need a____ w/renal impairment.
excreted unchanged, reduction in dosage
what are the ADRs of H2 antagonists
Well tolerated
HA, somnolence, fatigue, dizziness, constipation or diarrhea
Thrombocytopenia: rare, reversible
what drug interactions does cimetidine have?
Inhibition of metabolism of warfarin, phenytoin, nifedipine, propranolol
what drugs need an Acidic environment required for absorption, so you would not use with H2 receptor antagonist
Ketoconazole, itraconazole, ferrous sulfate
what is true about combining antacids and H2receptor antagonist?
more effective than antacid tx alone
___eliminate symptoms and heal esophagitis more frequently and rapidly than other drugs
PPIs
what is Shown to normalize impaired quality of life caused by GERD
PPIs
when should PPIs be taken?
Before meals
5 prototypes of PPIs
Omeprazole (Prilosec) Lansoprazole (Prevacid) Esomeprazole (Nexium) Pantoprazole (Protonix) Rabeprazole (Aciphex
what is the MOA of PPIs?
Inhibit the action of the H+,K+ -ATPase
what do PPIs need to work?
acidic env
how long does it take to synthesize new H+,K+ -ATPase molecules
18hrs
what are ADRs of PPIs?
Generally uncommon
N/D/C
HA, dizziness, somnolence
if you take PPIs what might you have higher incidence of getting?
community-acquired pneumonia
Clinical significance unclear
Pts with asthma, COPD, immunocompromised, young or elderly may be at risk
what PPIs are metabolized by P450 enzymes
Omeprazole, lansoprazole, esomeprazole and pantoprazole
rabeprazole metabolized thru
nonenzymatic reduction pathway
Omeprazole and esomeprazole reduce metabolism of
Diazepam
Phenytoin
warfarin
what 3 things do promotility agents do?
LES incompetence, decreased esophageal clearance and delayed gastric emptying
what are metoclopramide, bethanechol, and cisapride?
promotility agents
what is contraindicated in Parkinson’s Dz, mechanical obstruction, concomitant use of other dopamine antagonists, anticholinergics, and pheochromocytoma
metoclopramide
what may increase acid production, not well tolerated due to cholinergic side-effects
bethanechol
what may cause Fatal cardiac dysrhythmia
cisapride
what is Not recommended for use except very mild cases of GERD
mucosal protectants
what is sucralfate
non-absorbable aluminum salts - mucosal protectant
what is Comparable to H2-receptor antagonist for mild esophagitis but Less effective in refractory esophagitis
sucralfate
what is the MOA of sucralfate?
When the pH is below 4, an extensive polymerization & cross-linking of sucralfate to form a sticky, viscid, yellow-white gel.
The gel adheres to epithelial cells and adheres very strongly to the base of ulcer craters.
what are 3 uses of sucralfate?
Effective at promoting healing in PUD
As a maintenance therapy–more efficacious in duodenal than gastric ulcers.
Used to prevent stress ulcers
what are More effective when administer prior to meals than after since acid is needed for activation
sucralfate and PPIs
what are 3 adrs of sucralfate?
Constipation—Al3+
Dry mouth
Abdominal discomfort
what are Drug int with sucralfate and therefore you should to what
Phenytoin Digoxin Tetracycline Ketoconazole
Fluroquinolone antibiotics
Therefore better to administer these meds 2 hours prior to sucralfate.
Improvement of symptoms with full dose PPIs usually
reverses with discontinuation of therapy
what is ineffective in GERD? 2
Full dose H2-receptor antagonist once daily not appropriate
Reduced dose PPIs
Alternate day dosing
“Weekend” therapy
Dose needed to control symptoms is appropriate dose for
maintenance
Acid suppression decreases recurrence of
esophageal strictures
Full dose PPIs lengthen time between
symptomatic relapses
what are complications of PUD
Ulceration and obstruction
what increases with NSAIDs use and PUD
perforation risk
Mortality of what ulcer perforation is higher?
gastric
what is caused by scarring or edema of duodenal bulb or pyloric channel land lead to gastric retention
obstruction
what has symptoms of Early satiety, bloating, anorexia, nausea, vomiting, weight loss that occurs over months?
obstruction
what is PAC?
PPI, amox, clarithr
what is PMC
PPI, metronidazole, and clarithr
what is PBMT
PPI, PeptoBismol, Metro, Tetra(or amox or clarithr)
what does pepto do for PUD? 5
-Cytoprotection through enhanced secretion of mucus and HCO3-.
-Inhibit pepsin activity.
-Accumulate bismuth subcitrate in craters of gastric ulcers.
-Antibacterial effects:
Reduce bacterial adherence to mucosal cells
Damage bacterial cell walls.
-Promote healing of both gastric and duodenal ulcers
what is the MOA for prostaglandin analogs? and what is an ex
Misoprostol is a synthetic analogue of prostaglandin E.
Imitates the action of endogenous prostaglandins (PGE2 and PGI2) in maintaining the integrity of the gastroduodenal mucosal barrier.
Promotes healing.
what is indication for prostaglandin analogs?
Ulcer healing
Ulcer prophylaxis w/NSAID use
what are contraindications for Pg analogs?
Hypotension
Breastfeeding
Pregnant
what is ADRs of PG analogs?
diarrhea and constipation
in PUD elim or reduce what things? 3
Psychological stress Cigarette smoking The use of NSAIDs including aspirin Consider APAP Lowering the dose Nonacetylated salicylate (salsalate) Relatively selective COX-2 inhibitors (nabumetone, etodolac) or highly-selective COX-2 inhibitors (celecoxib) Co-administration w/H2 antagonist or PPI
what are diet changes you can make for PUD?
Avoid food and beverages that cause dyspepsia or exacerbate ulcer symptoms
Spicy foods
Caffeine
ETOH
what is H pylori linked to?
PUD, gastric lymphoma, and adenocarcinoma
what are complications of H.Pylori?
Zollinger ellison syndrome, and Upper GI bleed, perforation, and obstruction
What is ZE syndrome?
Gastric acid hyper secretion and recurring ulceration from a gastrin secreting tumor
how do you treat ZE syndrom?
PPI and chemo
what presents as insidious occult blood, melana, or hematemesis?
upper GI bleed
3 ways to treat PUD
PAC, PMC, PBMT(adds pepto)
