GI Flashcards
gerd
- Decreased Lower Esophageal Sphincter (LES) Pressure
- Food: • Fatty meals, onions, garlic, pepper/spearmint, chocolate, coffee, cola, tea, chili peppers • Substances: • Nicotine, alcohol • Pharmacologic agents • Anticholinergics • Barbiturates • Estrogens
- Alleviate symptoms • Decrease frequency of recurrence disease • Promote healing of mucosal injury • Prevent complications
GERD Tx
- Lifestyle Modification: loss weight, smaller meals, avoid laying down for three hours after eating, elevate HOB, whole food diet, smoking and alcohol cessation, avoid tight clothing
- Pharmacologic: Antacids, H2-receptor antagonists, and proton pump inhibitors
- Surgical • Laparoscopic fundoplication (Nissen fundoplication), endoscopic therapies
Antacids
- Agents: magnesium, aluminum, and calcium-based products (often combined); e.g. simethicone (Maalox®) provides gastric hydrochloric acid neutralization and increase in gastric PH
- Immediate, symptomatic relief , short duration of action,
- Adverse Effects: constipation (Ca > Al), diarrhea (Mg)
Antacid drug interactions
- Drug Interactions: Direct binding to tetracyclines, fluoroquinolones, decreased absorption of ferrous sulfate •
- Use with caution in patients with renal impairment: Accumulates in renal disease (Al > Mg), hypophosphatemia (Al > Ca)
H2 Receptor Antagonists
-Agents: cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®)
Inhibition of histamine2 -receptors in gastric parietal cells decreasing gastric acid production
-Symptomatic improvement in ~60% patients after 12 weeks with standard doses
H2 Receptor Antagonists: s/e
- Adverse Effects: constipation, diarrhea, dizziness, headache, thrombocytopenia (transient)
- Rare Effects: CNS symptoms in those over 50 years of age or those with renal or hepatic dysfunction; may be associated with vitamin B12 deficiency with long term use
H2 Receptor Antagonists:
- Drug Interactions: Inhibition of drugs metabolized by CYP1A2, 2D6, 3A4 (cimetidine, famotidine, and nizatidine do not interact with CYP450)
- Requires dose adjustment for moderate to severe renal insufficiency/failure
Proton Pump Inhibitors (PPIs)
- Agents: omeprazole (Prilosec®), esomeprazole (Nexium®), lansoprazole (Prevacid®), deslansoprazole (Dexilant®), pantoprazole (Protonix®), rabeprazole (Aciphex®)
- H+/K+-ATPase enzyme inhibition in gastric parietal cells (final acid production step) resulting in profound and long-lasting anti-secretory effect
- Need to take 15-30 min before meals;
PPI S.E & Drug interactions
- Drug Interactions: ketoconazole, CYP2C19 substrates such as clopidogrel (omeprazole, esomeprazole > other PPIs)
- Increased risk for infections, GI and non-GI related (clostridium difficile, gastroenteritis)
Peptic Ulcer Disease
- Disruption of normal mucosal defense and healing mechanism leads to ulcer formation (5mm ulcer or larger and extends into the muscularis mucosa)
- Symptoms: headache, dizziness, somnolence, diarrhea, constipation, nausea, magnesium, vitamin B12 deficiency
- Three common forms of PUD: Helicobacter Pylor (H. pylori)-positive, nonsteroidal anti-inflammatory drug (NSAID) induced, and stress-related mucosal damage (SRMD)
PUD Tx
- Pharm agents are symptomatic relief (does not cure), address underlying cause, agent(s) dependent on etiology e.g. NSAID-induced, stop NSAID, most uncomplicated ulcers heal w/standard H2RA, PPI, or sucralfate
- H. pylori-associated use antimicrobial and antiulcer agents
- PPI-based three-drug regimen • First course 10-14 days (minimum of seven days); second course required • PPI-based three-drug regimen with different antibiotics or use four-drug regimen
PUD: Sucralfate (carafate)
- forms ulcer-adherent complex with proteinaceous exudate at ulcer site, protecting against further acid exposure •
- AE: constipation, seizures, aluminum accumulation/toxicity (ARF/CRF/dialysis patients), hypophosphatemia, gastric bezoar formation (rare) • –
- Interactions: reduced bioavailability of fluoroquinolones, phenytoin, digoxin, amitriptyline, warfarin, ketoconazole
PUD: Bismuth preparation
-Bismuth subsalicylate and bismuth subcitrate potassium; does not inhibit or neutralize; has a local gastroprotective effect and stimulates endogenous prostaglandins, use with caution in elderly, tongue and stools can become black
Tx for N/V
Antacids & H2RAs (see GERD) • Antihistamine/Anticholinergic Drugs • 5-HT3 Receptor Antagonists • Corticosteroids • Phenothiazines • Substance P/Neurokinin 1 Receptor Antagonists • Cannabinoids • Atypical Antipsychotics • Butyrophenones • Metoclopramide
5-HT3 receptor antagonists
- Agents: ondansetron (Zofran®), dolasetron (Anzemet®), granisetron (Kytril®), palonosetron (Aloxi®), ramosetron (international), tropisetron (international) • MOA: —
- Serotonin (5HT3 ) receptor blockade in CNS chemoreceptor trigger zone and presynaptic on sensory vagal fibers in gut wall
Corticosteroids for N.V
-Agents: dexamethasone (Decadron®), prednisone (Deltasone®), prednisolone (Orapred®), methylprednisolone (Medrol®, Solumedrol®)
Phenothiazines for N/V
- Promethazine (Phenergan®), prochlorperazine (Compazine®), chlorpromazine (Thorazine®)
- MOA: Dopamine receptor inhibition in CNS chemoreceptor trigger zone
Substance P/Neurokinin 1 receptor antagonists
- Aprepitant (Emend®), fosaprepitant (Emend® IV), rolapitant (Varubi®), netupitant/palonosetron (Akynzeo®)
- MOA: Selective substance P/neurokinin 1 receptor antagonist in CNS chemoreceptor trigger zone
- Used for acute N&V mediated by serotonin and substance P (substance P primary mediator of delayed N&V), chemo induced N&V, multi-antiemetic drug combinations for highly emetogenic chemotherapy regimens
- Interactions: oral contraceptives (decreased efficacy), warfarin (decreased INR), dexamethasone (increased concentrations)
Butyrophenones for N/V
- Haloperidol (Haldol®), droperidol (Inapsine®)
- MOA: Dopamine receptor inhibition in CNS chemoreceptor trigger zone
- Postoperative N/V • Haloperidol NOT first-line for uncomplicated N/V
Cannabinoids for N/V
- Dronabinol (Marinol®), nabilone (Cesamet®)
- MOA: cannabinoid receptor 1 (CB1) in CNS neural tissues
- Chemotherapy induced N/V; not first-line
- Appetite stimulation
Atypical antipsychotics for N/V
- Olanzapine (Zyprexa®)
- MOA: Combination neurotransmitter (dopamine, serotonin, adrenergic, histamine, etc.) inhibition
- Postoperative N/V , not first-line
Metoclopramide (reglan) for N/V
- Dopamine blockade in chemoreceptor trigger zone, increases lower esophageal sphincter tone, prokinetic aids in gastric emptying, accelerates small bowel transit
- Useful as antiemetic in patients with diabetic gastroparesis
- AE: tardive dyskinesia, fluid retention, acute dystonic reactions, hallucinations (rare), akathisia, parkinsonian-like symptom
Antimotility agents for diarrhea
- Diphenoxylate/atropine (Lomotil®), loperamide (Imodium A-D®), opium tincture, paregoric, dicyclomine (Bentyl®), hyoscyamine (Levsin®)
- MOA: Prolong intestinal transit time, fecal volume decreased
Adsorbents and Bulk agents for diarrhea
- Attapulgite (Kaopectate®), polycarbophil (FiberCon®), psyllium (Metamucil®), methylcellulose (Citrucel®), guar gum (Benefiber®)
- MOA: Absorbs H2O in gut to form viscous liquid bulk
Antisecretory agents for diarrhea
-Agents: octreotide (Sandostatin®, Sandostatin LAR®); used for secretory diarrhea, refractory GI bleed
Interactions: Multiple due to effects on GI tract blood perfusion and drug absorption
-MOA: endogenous somatostatin analog which decreases mesenteric blood flow
-Monitor/Prevent dehydration especially for symptoms > 48 hours
Emollients for constipation
- Agents: docusate sodium (Colace®), docusate calcium (Kaopectate®)
- MOA: Surfactant that facilitates mixing of aqueous and fatty materials within the intestinal tract
- Increases intestinal H2O & electrolyte secretion, peak effect 1-3 days
Cathartics: constipation
- Agents: magnesium hydroxide (Milk of Magnesia®), magnesium citrate, sodium phosphate derivatives (Fleet®), tap water enema
- AE: Dehydration & electrolyte disturbances with improper use, magnesium or phosphorus accumulation in renal failure
Antidepressants for IBS
- Amitriptyline (Elavil®, TCA), duloxetine (Cymbalta®, SSNRI)
- Modulates perception of visceral pain, alters GI transit time, treats underlying comorbidities
- Diarrhea-predominant IBS with mod-severe abdominal pain
Tegaserod (Zelnorm): IBS
- Partial 5-HT4 agonist that modulates the enteric nervous system
- Short-term, intermittent of IBS constipation in women (12 week limit)
Alosetron (Lotronex): IBS
- Selective 5-HT3 antagonist that modulates enteric nervous system
- Diarrhea due to excessive 5-HT3 receptor stimulation
- Women with symptoms > 6 months not relieved by conventional therapy
- AE: Abdominal pain, nausea, headache
- Black Box Warning for serious GI events
