GI Flashcards
autonomic GI physiology: review
-Digestive tract lined with smooth muscle
-Parasympathetic nervous system- Stimulates gut muscle contraction
-Sympathetic nervous system- Inhibits gut muscle contraction
GI disorders
-dyspepsia
-PUD
-GERD, (motility disorder)
-GI bleeding
-constipation, diarrhea, nausea, vomiting
-gastroparesis, irritable bowel syndrome (motility disorders)
-inflammatory bowel disease- Ulcerative colitis, Crohn’s disease
dyspepsia
-aka heartburn, indigestion – epigastric discomfort following meals.
-Often associated w/ impaired digestion and excessive stomach acidity
-Tx with antacids and low dose H2 blockers
PUD
-Inflamed lesions or ulcers of mucosa and underlying tissue of upper gi tract
-Ulcers – damage to mucous membrane that normally protects the esophagus, stomach and duodenum from gastric acid and pepsin
-Damage can be from excessive acid production, bile acid reflux, advanced age, ischemia, inhibition of prostaglandin synthesis (ASA, NSAIDs), prolonged use of glucocorticoids and H. pylori infection
-H. pylori induced gastritis precedes dvp of peptic ulcers in most indv. Found in gi tract of almost all pts w/ duodenal ulcers and 80% of pts w/ gastric ulcers
-risk- weight, age, smoking, alcohol, elderly
-Tx - reduce gastric acidity (H2 blockers and PPI), abx vs. H. Pylori and cytoprotective agents
GERD
-characterized by esophagitis and reflux of gastric acid into the esophagus. Associated w/ excessive secretion of gastric acid and decreased pressure in lower esophageal sphincter
-Tx with H2 blockers, proton pump inhibitors and prokinetic agents. Antacids for mild symptoms and immediate relief
-Non-pharmacological measures – avoid certain foods and medications, avoid bedtime snacks, elevate upper body during sleep, smoking cessation, weight reduction , avoid tight clothes
meds that worsen GERD
-Anticholinergics
-Aspirin
-Barbiturates
-Bisphosphonates
-CCBs
-Estrogen
-Iron
-Nicotine
-Nitrates
-NSAIDs
-Potassium Chloride
-Progesterone
-Theophylline
GI bleeds: upper
-Upper GI bleed – can be PUD, esophageal varices, Mallory-Weiss tears and hemorrhagic cystitis
-Tx- volume resuscitation, endoscopic therapy, surgery and/or pharmacologic therapy with PPIs or octreotide depending on type of UGIB
-Stress ulcer prophylaxis is most commonly done with H2 receptor blockers, but can also use PPIs or sucralfate (not really used now)
GI bleeds: lower
-in small or large intestine
-Usually secondary to hemorrhoids, cancer or diverticular disease, so management aimed at underlying cause
-Tx may include endoscopic cauterization or surgery
-Topical hemorrhoid creams and suppositories (usually a steroid with anesthetic) are used for LGIB due to hemorrhoids
constipation
-Can be acute or chronic
-Can control w/ increase in dietary fiber, adequate fluid intake, regular exercise
-Fruits, vegetables and whole grain foods add bulk to the diet
-Various types of laxatives available
diarrhea
-Characterized by increase in number and liquidity of stools
-May have various underlying causes (underlying disease, viral, bacterial, drugs, foods)
-May be mild or life threatening
-Most cases are mild and self limiting
-If fever and systemic Sx are absent – can be controlled w/ dietary restriction (BRATTY diet) and fluid and electrolyte replacement. Antidiarrheals may be given as adjunct treatment.
nausea and vomiting
-Vomiting (emesis) – physiologic response to presence of irritating and potentially harmful substances in the gut or blood stream
-Can also result from vestibular stimulation (motion sickness) or psychologic stimuli such as fear, dread, anxiety, sights and odors
-Often preceded by nausea
-Various types of anti-nausea and antiemetics available
GI motility disorders
-acute gastroparesis – delay in gastric emptying time. Typically seen in pts recovering from surgery, trauma or abdominal infections
-Chronic gastroparesis – seen in pts w/ neuropathies that affect the stomach (DM)
-Tx both forms with prokinetic agents (increase gi motility)
-EXTREMELY PAINFUL
-Irritable bowel syndrome – common, non-inflammatory disorder characterized by abnormal bowel movements. May cause diarrhea, constipation or both.
-Tx includes prokinetics, anticholinergics, anti-diarrheals and laxatives
inflammatory bowel disease
-Ulcerative colitis – inflammation usually limited to colon and rectum
-Crohn’s disease – inflammation can occur anywhere in gi tract
-Sx include abdominal cramping, vomiting, diarrhea.
-Tx includes glucocorticoids, aminosalicylates, immunosuppressants, antibiotics and immunomodulator drugs
pancreatic disease
-focus on supplementing pancreatic enzymes
drugs that decrease or neutralize gastric acid secretion
-Antacids
-H2-receptor antagonists
-Proton Pump inhibitors
normal gastric acid secretion
-3 areas of secretion in gastric mucosa
-Cardiac gland area: secretes mucus and pepsinogen
-Parietal area: secretes hydrogen ion, pepsinogen and bicarbonate
-Pyloric gland area – secretes gastrin and mucus
-Factors mediating gastric acid secretion
-Cephalic-vagal axis, gastric distension, local mucosal chemical receptors, different food content
antacids
-MOA – Chemically neutralize stomach acid. Increase pH of stomach from 1-2 to over 3, thus relieving the pain of dyspepsia and aiding in digestion. Can be used to treat hyperacidity, gastritis, acid indigestion and dyspepsia.
-Not really used anymore for PUD and GERD b/c need to take large doses at frequent intervals
-cations: aluminum, magnesium, calcium, (sodium)
-anions: hydroxide, carbonate, bicarbonate, citrate,
-Al (Amphogel)
-Mg (Milk of Magnesium)
-Al+Mg (Gelusil, Mylanta, Maalox, Rolaids)
-Ca (Tums)
-*Na (Alka Seltzer, baking soda) rarely used b/c it absorbed too well -> dont give to pts with HTN
-Al, Ca, Mg are poorly absorbed from the G.I.T. , absorption: Na>Ca>Mg>Al
antacids: Ca
-Calcium; CaCO3 (Tums)
-Can also be used to treat hyperphosphatemia, osteoporosis
-Contraindicated in hypercalcemia, renal calculi and hypophosphatemia
-ADRs: h/a, constipation, acid rebound with high doses, metabolic alkalosis, increase Ca, decrease PO4, belching
-DDIs – decreased absorption of iron
antacids: Aluminum
-Al(OH)3 Amphogel
-Also used for hyperphosphatemia
-Caution in CHF, renal failure, edema, cirrhosis
-ADRs: constipation, chalky taste, stomach cramps, fecal impaction, decrease PO4
-if you give to elderly (already constipated) -> potential for fecal impaction
antacids: magnesium
-Mg(OH)2 – Milk of Magnesia
-Also used as a laxative
-Caution in CNS depression, impaired renal function (esp. if CrCl<30ml/min)
-ADRs: hypotension, cramping, diarrhea, gas formation, muscle weakness
-DDIs: digoxin!, lithium
antacids: Drug interactions
-in general space out antiacid use from other meds - so many interactions
-!!1. decrease bioavailability (direct effect via adsorption)
-Al - phenothiazines, digoxin, tetracyclines, flouroquinolones, steroids
-Ca - Fe, coumadin, phenothiazine, tetracyclines, flouroquinolones, warfarin
-Mg- coumadin, digoxin, tetracyclines, floroquinolones
-!!2. alkalinization of urine - changes kinetics
-salicylates, phenobarbital
Simethicone
Available alone (Phazyme) or in combination with antacids for relief of gas
-gasx
H2 receptor blockers
-MOA – similar structure to histamine. Bind to H2 receptors on the parietal cells and inhibit the meal stimulating secretion and basal secretion of gastric acid -> causes reduction in volume and concentration of gastric acid -> decreases pepsin production by blocking the conversion of pepsinogen to pepsin
-Indications include: dyspepsia, PUD and GERD, stress ulcer prophylaxis and combined with H1 blockers for allergic rxns
-Also used for prevention and tx of dyspepsia: Use OTC formulations (lower strength)
-Should be taken 30-60 mins prior to meal
-Well absorbed PO, even though short half life can be dosed once daily or BID b/c of longer DOA (12 hours)
-For PUD and GERD, QD-bid regimen raises the pH > 4 for 13 hours per day
-HS dosing assures acid secretion suppressed all night
-first pass effect -> higher dose may be needed
H2 receptor blockers DDI and ADRs
-DDI – Cimetidine is P450 enzyme inhibitor - blocks metabolism of BDZ, salicylates, phenytoin, warfarin.
-cimetidine causes gynecomastica, CNS (slurred speech, delerium, confusion, lethargy) -> dont give to older pts unless low dose
-ADRs - all agents in this class cause
headache, itching, dizziness. Rarely cause
blood dyscrasias and bradycardia
-Must adjust doses in renal impairment
-famotidine is least amount of DDIs
H2 receptor blockers drugs
-cimetidine (Tagamet) (B), tid-qid
-!famotidine (Pepcid)(B), qd-bid
-nizatidine (Axid)(B), qd-bid- use in psychiatric hospitals- decreases the weight gain in pts on antipsychotics
-All available PO & IV, except nizatidine in PO only
-All available generic and OTC (except nizatidine RX only)
proton pump inhibitors
-MOA – inhibits the proton pump (H+, K+-ATPase) located in the membrane of the parietal cells and blocks secretion of gastric acid
-Indications include: TREATMENT of PUD, GERD, erosive esophagitis, hypersecretory condition, Zollinger-Ellison syndrome
-Should only be used for max 8 weeks for short term tx of active disease
-may be used longer for maintenance therapy at lower dose
-Can also use to PREVENT NSAID-induced ulcers
-Kinetics - administered as inactive pro-drugs; short half life - but DOA up to 24 hours
-Can give qd-bid
-Must take 30-60 mins prior to meal so drug is available before acid pump is activated by food
-If giving QD, better to give before the dinner meal
PPI ADRs
-fairly well tolerated
-minor GI effects like diarrhea and abdominal pain
-May cause headache
-May decrease B12 absorption
-May increase risk of C. dificile diarrhea, esp. if taken with certain antibiotics
-New reports of increase risk of hip fractures with long-term use
PPIs DDIs
-Caution if given in conjunction w/ drugs that REQUIRE an acidic environment for absorption (atazanavir, ketoconazole)
-All are substrates of CYP450 system
-Omeprazole is a CYP2C19 inhibitor. Significant DDI with clopidogrel -> decrease in antiplatelet activity!!!
PPI drugs
-omeprazole* (Prilosec)(C)- Combo w/ Na bicarb (Zegerid)
-lansoprazole (Prevacid)(B)
-rabeprazole (Aciphex)(B)
-pantoprazole* (Protonix)(B) - less DDI - used in hospitals a lot
-esomeprazole (Nexium) (B)
-dexlansoprazole (Kapidex) (B)
-* Available generic
-All PPIs are available PO, Protonix and Nexium are also available as IV
cytoprotective agents: sucralfate
-(Carafate)(B) MOA – it is a viscous polymer that adheres to ulcers and epithelial cells, inhibits pepsin catalyzed hydrolysis of mucosal proteins and stimulates prostaglandin synthesis
-formation of protective barrier of GI tract- doesnt treat -> just coats
-Works best in pH 1-2.
-Used for PUD (duodenal), but less effective than H2 blockers or PPI
-May be used to prevent bleeding from stress-related gastritis.
-ADRs - rare - not absorbed, may cause constipation
-Dose: 1 gm QID (1 hr ac & hs)
-Don’t take with antacids (± 2 hr)
cytoprotective agents: misoprostol
-Misoprostol (Cytotec) (X) !
-MOA – prostaglandin E1 analog, inhibits gastric acid secretion and promotes secretion of mucus and bicarbonate.
-Primarily used for prevention of ulcers in pts on long-term NSAID therapy. VERY EFFECTIVE. Must be given BID-QID with food for the duration of NSAID therapy.
-ADRs include N,V,D, abdominal cramping, flatulence and headache
tx of H. pylori infection
-Single drug therapy rarely effective
-Multi-drug therapy must be used
-Use either proton-pump inhibitor OR H2 blocker + two or more of the following: amoxicillin, bismuth, clarithromycin, metronidazole, tetracycline or levofloxacin
-!!!Preferred regimen: PO triple therapy for 14 days with:
-PPI BID (continue for 4-6 wks)
-Clarithromycin BID
-Amoxicillin 1 g BID OR metronidazole 500 mg BID
c dif tx recommendations
emesis!!!!!!!!!!!!!!! TEST
-Emesis initiated by a nucleus of cells in the medulla called the vomiting center
-Vomiting center activated by:
-vagal impulses from the gut via the solitary tract nucleus
-the Chemotrigger zone (CTZ)
-cerebral cortex
-vestibular apparatus
-Receptors involved in emesis
-Gut: 5-HT3, M1
-Solitary tract nucleus: 5-HT3, D2, M1, H1
-Chemotrigger zone (CTZ): 5-HT3, D2, M1
-CTZ also activated by blood-borne substances, incl chemotherapy agents
-Vestibular apparatus: M1, H1
antihistamine antiemetics
-MOA - block peripheral stimulation of the H1 receptor from the vestibular apparatus to the vomiting center and in the solitary tract nucleus. They are most effective in relieving nausea and vomiting associated with motion sickness
-dimenhydrinate (Dramamine)(B)
-diphenhydramine (Benadryl) (B)
-meclizine (Antivert) (B) – used for vertigo- hangover
-ADRs – drowsiness, headache, blurred vision, dry mouth, constipation
anticholinergic antiemetics: antispasmodics
-MOA - primarily decrease GI motility by blocking muscarinic stimulation of the gut and CTZ. Also works at STN.
-Primarily used as antispasmodics in gi disorders, esp. for irritable bowel syndrome
-hyoscyamine (Levsin) (C)
-dicyclomine (Bentyl) (B)
-hyoscyamine + atropine + phenobarbital- self limiting -decrease abuse
5HT3 receptor antagonists-antiemetics
-MOA - block 5-hydroxytryptamine (Serotonin) receptors (5-HT3 receptors are found in the gut, solitary tract nucleus and CTZ)
-ondansetron (Zofran) (B) PO, IV
-granisetron (Kytril) (B) PO, IV
-dolasetron (Anzemet) (B) PO, IV
-palonosetron (Aloxi) (B) IV only
-ADRs for all – headache, drowsiness, diarrhea and rarely bradycardia
-All are used to PREVENT chemotherapy induced nausea and vomiting
-must be given prior to or immediately following administration of chemo drug
-Other FDA indications include prevention and/or tx of post-op nausea and vomiting and prevention of radiation-induced nausea and vomiting
-These indications vary amongst the different agents
Dopamine (D2) receptor antagonists- antiemetics: phenothiazines (PTZ)
-MOA – primarily blocks dopamine (D2) receptor at the CTZ, thereby decreasing stimulation of the vomiting center, also block (D2) receptor in the solitary tract nucleus
-As a class, PTZ have antiemetic, antipsychotic, anticholinergic, antihistamine, antitussive, and sedative properties
-prochlorperazine (Compazine) (C)
-promethazine (Phenergan) (C)
-trimethobenzamide (Tigan) (C)
-ADRs - sedation, confusion, anticholinergic, orthostatic hypotension, hematologic SEs, and Extrapyramidal SEs
-Dystonia- uncontrolled movements
-dyskinesia
-these are good for people that cant keep meds down -> suppository and injectables
crohns vs UC chart
