GI Flashcards
Gastroesophageal Reflux Disease (GERD):
-Pathophysiology
-S/Sx
-Alarm symptoms
-Diagnosis
-TX
Pathophysiology: acidic gastric contents normally prevented from backflow into esophagus via protective ring of muscle fibers called lower esophageal sphincter (LES), but in GERD, reduced LES pressure causes backflow
S/Sx: heartburn (daytime or nocturnal), hypersalivation, regurgitation of acidic contents
-Less common: epigastric pain, nausea, cough, sore throat, hoarseness, chest pain
Alarm symptoms: odynophargia (painful swallowing), dysphagia. frequent N/V, hematemesis, black or bloody stools, unintentional weight loss
Diagnosis: based on pt-reported symptoms, frequency (>/=2 times/week), and risk factors (ex. family hx, diet/eating habits, sleep position)
TX:
-Lifestyle modifications: weight loss, elevate head of bed w/ foam wedges or blocks, avoid eating high fat meals within 2-3 hours of bedtime, avoid foods/beverages that trigger reflux (ex. caffeine, chocolate, acidic/spicy food, carbonated beverages)
-TX if NO alarm symptoms: OTC antacids or H2RAs if infrequent heartburn (<2 times/week), PPIs for 8 weeks if frequent or severe symptoms (can increase to BID if partial response or if nocturnal symptoms present)
-Refer to HCP if no response to lifestyle modifications +/- two weeks of OTC TX
-Maintenance: PPI low-dose (first line), alternatives: H2RA if NO erosive esophagitis and relieve symptoms (helpful in AM reflux that is stimulated by histamine), NOT recommended: metocloprmaide or sucralfate
-Vonoprazan: new TX –> place in therapy NOT established
Drugs that worsen GERD symptoms
-ASA/NSAIDs
-Bisphosphonates
-Dabigatran
-Estrogen products,
-Fish oil products, iron supplements
-Nicotine replacement therapy
Antacids:
-Drugs/Brands
-MOA
-ROA
-Dosing
-Administration considerations
-AVEs
-Warnings
Drugs: calcium carbonate (Tums), calcium carbonate/magnesium (Mylanta Supreme), calcium carbonate/simethicone (Maalax Advanced Maximum Strength), magnesium hydroxide (Milk of Magnesia), magnesium/aluminum (Mag-Al), magensium/aluminum/simethicone (Mylanta Maximum Strength), sodium bicarbonate/ASA/citric acid (Alka-Seltzer)
-Maalox = “Ma”gnesium + “Al”uminum + hydr”ox”ide
MOA: neutralize gastric acid (producing salt and water), increasing gastric pH
ROA: PO (chewables, suspensions, tablets, capsules)
Dosing: varies per product (4-6 tablets/day)
Administration:
-Provide relief within minutes, but duratoin of relief short (30-60 minutes)
-Calcium-containing antacids preferred in pregnancy
-Alka-Seltzer: contains >500mg Na (can worsen edema in HF or cirrhosis), bleed risk w/ ASA if taken often
AVEs: unpleasant taste
-Calcium: constipation, bloating, belching
-Aluminum: constipation, hypophosphatemia
-Magnesium: loose stools (use w/ aluminum may counter-balance)
Warnings (aluminum and magnesium): can accumulate w/ severe renal dysfunction (NOT recommended if CrCl <30), risk of bleeding w/ ASA containing product
Histamine-2 Receptor Antagonists (H2RAs):
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-AVEs
-Warnings
Drugs: famotidine (Pepcid AC, Zantac 360), famotidine/calcium carbonate/magnesium hydroxide (Pepcid Complete), famotidine/ibuprofen (Duexis), cimetidine (Tagamet HB), nizatidine
MOA: reversibly inhibit H2 receptors on gastric parietal cells, decreasing gastric acid secretion
ROA: PO, injection (famotidine)
Administration:
-Decrease dose when CrCl <60 (famotidine) or <50 (nizatidine) or <30 (cimetidine)
-Onset of relief: within 60 minutes, duration: 4-10 hours
-To relieve symptoms, take PRN; to prevent symptoms: take PRN 30-60 minutes before food or beverages that cause heartburn
-Maybe used in pregnancy when clinically indicated
-Cimetidine can increased SCr w/o causing renal impairment
-Avoid cimetidine due to DDIs and AVEs
AVEs: HA, agitation/vomiting in children <1 yo, tachyphylaxis (if used on scheduled basis)
-Cimetidine (high doses): gynecomastia, impotence
Warnings: confusion (usually reversible; risk factors: elderly, severely ill, renal impairment), vitamin B12 deficiency w/ prolonged use >/=2 years
-Famotidine: ECG changes (QT prolongation) w/ renal dysfunction
Proton Pump Inhibitors (PPIs):
-Drugs/Brands
-MOA
-ROA
-Timing and which ones to take with meals
Drugs: dexlansoprazole (Dexilant), esomeprazole (Nexium, Nexium 24HR, Nexium I.V.), esomeprazole/naproxen (Vimovo), lansoprazole (Prevacid, Prevacid SoluTab, Prevacid 24HR), omeprazole (Prilosec, Prilosec OTC), omeprazole/sodium bicarbonate (Konvomep, Zegerid), omeprazole/ASA (Yosprala), pantoprazole (Protonix), rabeprazole (Aciphex)
MOA: irreversibly bind to gastric H+/K+-ATPase pump in parietal cells, blocking gastric acid secretion
ROA: PO, injection (esomeprazole, pantoprazole), ODT (lansoprazole, pantoprazole)
Timing/Meals:
-60 minutes before breakfast: esomeprazole, omeprazole/sodium bicarbonate
-Before breakfast, time NOT specified: lansoprazole, omeprazole
-Without regards to meals: dexlansoprazole, pantoprazole tablets, rabeprazole tablets
-30 minutes before meal: pantoprazole oral suspension, rabeprazole capsule sprinkles
Proton Pump Inhibitors (PPIs):
-Administration considerations (besides timing and before or without regards to meals)
-AVEs
-Warnings
Administration:
-Onset of action: 1-3 hours; duration of action: >24 hours for most PPIs
-May be used in pregnancy when clinically indicated
-Do NOT crush, cut, or chew
-Dexlansoprazole, esomeprazole, lansoprazole, omeprazole, rabeprazole: capsules can be opened, mixed in applesauce, and swallowed immediately (w/o chewing)
-Suspension compounding kits available that contain-pre-measured powdered drug, suspension liquid w/ flavoring, and mixing tools
-Zegerid 20mg and 40mg have same Na bicarbonate content (1,100mg): do NOT substitute two 20mg capsules for 40mg due to wice the amount of Na (caution in HF, cirrhosis
AVEs: generally well tolerated (HA, abdominal pain, nausea, diarrhea)
Warnings:
-C.difficle-associated diarrhea (CDAD), hypomagnesemia, vitamin B12 deficiency with prolonged use (>/=2 years), osteoporosis-related bone fractures w/ high doses or long-term (>/=1 year) use, acute interstitial nephritis (hypersensitivity rxn), cutaneous and systemic lupus erythematosus
-IV Protonix: thrombophlebitis, severe skin rxns (SJS/TEN)
-PPIs may diminish efficacy of clopidogrel (do NOT use w/ omeprazole and esomeprazole; lesss risk w/ pantoprazole or rabeprazole)
Metoclopramide:
-Brand
-MOA
-ROA
-Administration considerations
-TX
Brand: Reglan, Gimoti
MOA: dopamine antagonist; at higher doses, inhibits 5-HT receptors in chemoreceptor zone of CNS; enhances response to ACh in upper GI tract, causing increased motility, accelerated gastric emptying, and increased LES tone
ROA: PO, injection, nasal solution
Administration:
-Take before meals and at bedtime
-CrCl <60mL/min: decrease dose by 50%
TX: CINV, PUD
-NOT recommended in guidelines for GERD
Metoclopramide:
-AVEs
-Warnings
-CIs
-BBWs
-DDIs
AVEs: drowsiness, restlessness, fatigue, HTN, pro-arrhythmic, diarrhea
Warnings: EPS (including acute dystonia), parkinsonian-like symptoms, rare neurolpetic malignant syndrome (NMS), depression, suicidal ideation
-Avoid use in PD
-Reduce reduce in renal impairment to avoid CNS/EPS AVEs
CIs: GI obstruction, perforation, or hemorrhage, hx of seizures, pheochromocytoma, use in combo w/ other drugs likely to increase EPS
BBW: can cause tardive dyskinesia (serious movement disorder, often irreversible) –> increased risk in high dsoes, long-term TX (>12 weeks), and in elderly pts
DDIs:
-Do NOT use in pts receving medications for PD (antagonistic effects)
-Do NOT use in combo w/ antipsychotics, droperidol, or promethazine
-When in combo w/ SSRIs, SNRIs, or TCAs, monitor for EPS, NMS, serotonin snydrome
Drugs that require an acidic gut (decreased absorption w/ antacids, H2RAs, and PPIs)
- Antiretrovirals: rilpivirine (NNRTI), atazanavir (PPI)
- Antivirals: ledipasvir, velpatasvir/sofosbuvir
- Azole antifungals: Sporanox (itraconazole capsules), ketoconazole, posaconazole oral suspension*
- Cephalosporins (PO): cefuroxime, cefpodoxime
- Iron products
- Risedronate DR
- Tyrosine kinase inhibitors: dasatanib, erlotinib, pazopanib
- = Absorption decreased by H2RAs and PPIs only
Oral drugs/drug classes that antacids bind
- Antiretrovirals (INSTIs): bictegravir, dolutegravir, elvitegravir, rlategravir
- Bisphosphonates
- Isoniazid
- Levothyroxine
- Mycophenolate
- Quinolones
- Sotalol
- Steroids (especially budesonide)
- Tetracyclines
DDIs with antacids, H2RAs, and PPIs
Many interactions between other medications
-Some drugs require acidic gut for absorption including EC or DR to dissolve and release drug prematurely (antacids due to short duration can often be seperated)
-Completely avoid w/ H2RAs and PPIs: dastinib, pazopanib, DR risedronate (Atelvia)
-Complely avoid w/ PPIs: erlotinib, rilpivirine, velpatasivr/sofosbuvir (Epclusa)
Antacids: refer to flashcard with drugs that antacids bind
H2RAs:
-Caution w/ CNS depressants (especially in elderly; risk of delirium, dementia, cognitive impairment; lower doses in renal impairment)
-Do NOT use famotidine w/ highest risk QT-prolonging drugs
-Cimetidine: inhibitor of CYP450 enzymes (3A4, 1A2, 2C19): avoid w/ dofetillide and cuation w/ many other drugs (ex. CCBs, clopidogrel, phenytoin, SSRIs, theophylline, warfarin)
PPIs:
-ALL inhibit CYP2C19: most weak, but omeprazole and esomeprazole are moderate (do NOT use w/ clopidogrel); can increase levels of citalopram, phenytoin, tacrolimus, voriconazole, and warfarin
-PPIs can inhibit renal elimination of methotrexate, leading to increased serum levels
Peptic Ulcer Disease (PUD): Helicobacter pylori
1. H. plyori is a ______-shaped gram _______ bacteria that produces a ______(gastric/duodenal) ulcer where the pain is _________(better/worse) with eating.
- How to diagnose H. pylori?
Sprial-shaped; gram negative; duodenal; better (food helps create protective coating around edge of intestine)
Diagnosis: urea breath test (UBT) - detects gas (CO2) produced by bacteria; fecal antigen test –> D/C PPIs, ABxs, and bismuth two weeks prior to testing to avoid false negatives
H. pylori regimens: Bismuth Quadruple Therapy - state the drugs/dose/frequency, duration of TX, when to use, alternatives, and applicable CIs
Drugs: bismuth subsalicylate 300mg QID + metronidazole 250-500mg QID + tetracycline 500mg QID + PPI BID
Duration: 10-14 days
Use: first line, espeically when resistance to clarithromycin high (>/=15%), previous macrolide exposure, PCN allergy, or triple therapy failure if previously done
Alternatives: Pylera (bismuth 420mg + metronidazole 375mg + tetracycline 375mg - 3 separate capsules) QID + PPI BID; if pt cannot tolerate PPI, substitute H2RA
CIs: alcohol w/ metronidazole, pregnancy or children <8 yo w/ tetracycline, salicyclate allergy w/ bismuth
H. pylori regimens: Concomitant Therapy - state the drugs/dose/frequency, duration of TX, when to use, alternatives, and applicable CIs
Drugs: azithromycin 1000mg BID + clarithromycin 500mg BID + metronidazole 500mg BID + PPI BID
-Duration: 10-14 days
-Use: only if local clarithromycin are low (<15%) and NO previous exposure to macrolide (preferred over clarithromycin triple therapy if previous macrolide exposure)
-Alternatives: tinidazole may be substituted for metronidazole
H. pylori regimens: Clarithromycin Triple Therapy - state the drugs/dose/frequency, duration of TX, when to use, alternatives, and applicable CIs
Drugs: amoxicillin 1000mg BID + clarithromycin 500mg BID + PPI BID (or esomeprazole QD)
-Duration: 14 days
-Use: only if local clarithromycin are low (<15%) and NO previous exposure to macrolide
-Alternatives: Prevpac (amoxicillin + clarithromycin + lansoprazole - one blister card divided into BID), Omeclamox-Pak (amoxicilin + clarithromycin + omeprazole); in PCN allergy: replace amoxicillin w/ metronidazole 500mg TID or use quadruple therapy
NSAID-induced PUD:
1. NSAIDs can cause a _______ (gastric/duodenal) ulcer where the pain is _________(better/worse) with eating due to the inhibition of __________ that is protective.
- Which NSAIDs have less GI AVEs?
- Risk Factors
- Prevention
- TX
- Gastric ulcer; worse; COX-1
- Celecoxib (COX-2 selective); somewhat COX-2 selective: meloxicam, nabumetone, diclofenac, etodolac
- Age >60 yo, hx of PUD (including H. pylori), high-doses NSAIDs, using > 1 NSAID, concomitant use of medications (steroids, anticoagulants, SSRIs, SNRIs)
- Prevention: On non-selective NSAID w/ higher GI risk (ex. hx of ulcers): add PPI (alternative: misoprostol)
-Combination products: naproxen/esomeprazole (Vimovo), ibuprofen/famotidine (Duexis), diclofenac/misoprostol (Arthrotec)
-If possible avoid, NSAIDs - TX:
-D/C NSAID
-PPI x 8 weeks (alternative: high dose H2RAs, sucralfate)
Misoprostol:
-Brand
-MOA
-ROA
-TX
-AVEs
-BBW
Brand: Cytotec
MOA: prostaglandin E1 analog that replaces gastro-protective prostaglandins removed by NSAIDs
ROA: PO
TX: prevention of NSAID-induced PUD
AVEs: diarrhea, abdominal pain
-Use of psyllium can help decreased diarrhea
BBW:
-Abortifacient: do NOT use in females unless using effective contraceptive measures, warn pts to NOT give this drug to others
-Arthrotec (misoprostol/diclofenac): increased risk of GI events (bleeding, ulceration) and CV disease
Sucralfate:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs
-Warnings
-DDIs
Brand: Carafate
MOA: sucrose-sulfate-aluminum complex that interacts w/ albumin and fibrinogen to form physical barrier over an open ulcer, allowing it to heal
ROA: PO
Administration:
-Take before meals
-Drink adequate fluids and use laxatives PRN for constipation
AVEs: constipation (aluminum component)
Warnings: caution in renal impairment - aluminum can accumulate
DDIs: difficult to use due to binding interactions (seperate antacids by 30 minutes and take other drugs 2 hours before or 4 hours after)
Constipation:
-Define
-Medical conditions that cause constipation
-Non-pharmacological
Constipation: less than three bowel movements per week or difficulty passing stools (ex. strianing, lumpy/hard stools, pushing for longer than 10 minutes)
Medical conditions that cause constipation: IBS-C, anal disorders (fissures, fistulae, rectal prolapse), MS, cerebrovascular events, PD, pregnancy, spinal cord tumors, DM, hypothyroidism
-IBS-C: chronic or recurrent abdominal discomfort relieved through defacation
Non-pharm:
-Increase fluid intake (64 oz QD recommended)
-LImit caffine and alcohol intake to avoid dehydration
-Increase physical exercise
-Fiberous foods, whole grain products, bran, fruits, vegetables
Drugs that cause constipation
-Antidiarrheals, colesevelam, opioids
-Cation-containing drugs: antacids w/ Al or Ca, iron, sucralfate
-Select antihypertensives: clonidine, non-DHP CCBs (especially verapamil)
-Anticholinergics: antihistamines, antispasmodics (baclofen),
phenothiazines (prochlorperazine), TCAs, incontinence drusg (oxybutynin)
Constipation:
-When to TX w/ OTC
-OTC options
OTC TX: most OTCs can be tried for IBS-C, chronic idiopathic constipation (CIC), or opioid-induced constipatoin (OIC) –> if NOT resolved wtihin 7 days, refer to HCP
-Alarm symptoms for referral: weight loss, GI bleeding
OTC options: for longer-acting, take at night to have a BM in the morning
1. Bulk-forming (ex. soluble fiber, psyllium) and dietary fiber - first line in most cases
- Osmotics (ex. PEG) - monotherapy or with fiber
- Stimulants (ex. senna, bisacodyl) - stool softenor can be given if stool is hard
- Stool softenors (ex. docusate)
- Lubricants (ex. mineral oil)
Constipation OTC TX: -What is preferred in: iron-induced or hard stool, opioid-induced constipation, pregnancy, fast relief needed
Iron-induced/hard stool: stool softenor or bulk-forming
OIC: stimulant or osmotic laxative
Pregnany: fiber
Fast relief:
-Adults: bisacodyl or glycerin (more gentle) suppository
-Children: glycerin suppository
Bulk-forming Drugs:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CI
Drugs: psyllium (Metamucil), calcium polycarbophil (FiberCon), methylcellulose (Citrucel), wheat dextrin (Benefiber)
MOA: absorb water into intestine, adding bulk to the stool to increase peristalsis and decrease stool transit time
ROA: PO
Administration:
-Onset of action: 12-72 hours
-Adequate fluids required: caution if fluid restricted (ex. HF), if difficulty swallowing (ex. PD), or at risk for fecal impaction (ex. intestinal ulcerations, stenosis)
-Calcium is a polyvalient cation: seperate calcium polycarphobil from select drugs to prevent binding interactions
-Sugar-free options available
-Take 2 hours before/after other drugs
TX: constipation
-Psyllium: moderately improves cholesterol and blood glucose levels
-May be able to use for diarrhea to soak up water with fiber (for constipation, this is why you drink with water to mush stool)
AVEs: flatulence, abdominal cramping, bloating, bowel obstruction if strictures present, choking (if powder forms and NOT taken with enough liquid)
CI: fecal impaction and GI obstruction (psyllium)
Osmotic Laxatives:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Drugs: magnesium hydroxide (Milk of Magnesia), magnesium citrate, magnesium sulfate, polyethylene glycol (MiraLax, GaviLax, GlycoLax), glycerin (Fleet Liquid Glycerin Supp, Pedia-Lax), lactulose (Constulose, Enulose, Generlac, Kristalose), sodium phosphates (Fleet Enema), sorbitol
MOA: contain large ions or molecules that are poorly absorbed that draw liquid into bowel lumen through osmosis which distends the colon and increases peristalsis
ROA: PO (magnesium products, PEG, lactulose, sorbitol
-PR (sorbitol, sodium phosphates, glycerin)
Administration:
-Onset of action: 30 minutes to 96 hours (PO - PEG: 24-96 hours, Milk of magnesia - 30min-6 hours), 5-30 minutes (PR)
-Glycerin suppositories have quick relief for children
TX: constipation, hepatic encephalopathy (lactulose)
AVEs: electrolyte imbalance, abdominal cramping, abdominal distention, flatulence, dehydration, rectal irritation (suppository)
CI: anuria (sorbitol), low galactose diet (lactulose), GI obstruction (MiraLax), severe renal impairment (magnesium-containing products)
Stimulant Laxatives:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-Warnings
Drugs: senna (Ex-Lax, Senokot, w/ docusate - Senna S, Senokot S, Senna Plus), bisacodyl (Dulcolax, Fleet Bisacodyl)
MOA: directly stimulate neurons in colon, causing peristaltic activity
ROA: PO, PR (Dulcolax)
Administration:
-Onset of action: 6-12 hours (PO), 15-60 minutes (PR)
-Take PO products at bedtime to induce bowel movement during morning
-Can give 30 minutes after meal to enhance peristalsis
TX: constipation, opioid-induced constipation
AVEs: abdominal cramping, electrolyte imbalance, rectal irritation (suppository)
Warnings: avoid use w/ stomach pain, N/V, or sudden change in bowel movements that last > 2 weeks
Emollients (Stool Softenors):
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Drugs: docusate sodium (Colace), docusate calcium, docusate potassium, w/ senna (Senna S, Senokot S, Senna Plus)
MOA: reduce surface tension of stool, allowing more water to mix with water to soften fecal mass and allow easier defecation
ROA: PO, PR
Administration:
-Onset of action: 12-72 hours (PO), 2-15 minutes (PR)
-Do NOT take docusate and mineral oil together (increases absorption of mineral oil)
TX: constipation when stool hard or dry
-Preferred when straining should be avoided (ex. postpartum, post-MI, anal fissues, hemorrhoids)
AVEs: abdominal cramping, throat irritation (liquid)
CIs: abdominal pain, N/V, use w/ mineral oil, OTC use >1 week
Mineral oil:
-Drug class
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Drug class: lubricant
MOA:* coat bowel and stool with waterproof film to keep moisture in stool*
ROA: PO, PR
Administration:
-Onset of action: 6-8 hours (PO), 2-15 minutes (PR)
-Take multivitamin at different time due to malabsorption of fat-soluble vitamins
-Do NOT take docusate and mineral oil together (docusate increases absorption of mineral oil)
-PO formulation generally NOT recommended due to safety concerns (ex. risk of aspiration, lipid pneumonitis)
TX: constipation
AVEs: abdominal cramping, nausea, incontinence, rectal discharge
CIs: age <6 yo, pregnancy, bedridden pts, elderly, use >1 week, difficulty swallowingDrug class: lubricant
Lubiprostone:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
Brand: Amitiza
MOA: chloride channel activator in gut, increasing fluid secretion and peristalsis
ROA: PO
Administration:
-Take with food and water to decrease nausea
-Consider alternative TX with methadone (decreases lubiprostone effects)
TX: chronic idiopathic constipation (CIC), IBS-C in adult women, OIC
AVEs: nausea, diarrhea, abdominal pain, abdominal distention, HA
CI: mechanical bowel obstruction
Guanylate Cyclase C Agonists:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-CIs
-BBWs
Drugs: linaclotide (Linzess), plecanatide (Trulance)
MOA: increase Cl and bicarbonate secretion into lumen of intestines, increasing speed of GI transit and reducing abdominal pain
ROA: PO
Administration:
-Swallow Linzess capsules whole –> if needed, can open the capsule and mix contents w/ applesauce or room temperature water and swallow immediately
-Trulance tablets can be crushed
TX: CIC, IBS-C
AVEs: diarrhea, abdominal pain, flatulence
CI: age <6 yo, mechanical GI obstruction
BBW: do NOT use in pediatric pts (high risk of dehydration and death)
Peripherally-Acting Mu-Opioid Receptor Antagonists (PAMORAs):
-Drugs/Brands
-ROA
-Administration considerations
-TX
-CIs
-BBW
Drugs: alvimopan (Entereg), methylnaltrexone (Relistor), naloxegol (Movantik), naldemedine (Symproic)
ROA: PO
Administration (alvimopan): maximum 15 doses in 7 day span
TX: hospitalized surgery pts to decrease risk of post-operative ileus (alvimopan), OIC (methylnaltrexone, naloxegol, naldemedine)
CI (alvimopan): therapeutic doses of opioids >7 consecutive days immediately prior to use
BBW (alvimopan): potential risk of MI w/ long-term use (available only for short-term inpatient use w/ REMS program)
Prucalopride:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CI
-Monitoring
Brand: Motegrity
MOA: 5-HT4 receptor agonist to release ACh causing muscle contractions and increasing GI motility
ROA: PO
TX: chronic idiopathic constipation (CIC)
AVEs: diarrhea, HA, nausea, abdominal pain
Warnings: suicidal ideation
CI: GI obstruction, GI perforation, ileus, severe inflammatory conditions of GI tract (Crohn’s disease, ulcerative colitis, toxic megacolon)
Monitoring: worsening of depression or emergence of suicidal thoughts, rectal bleeding, blood in stool, severe abdominal pain
Laxatives for Whole Bowel Irrigation (Colonoscopy Prep):
-Drugs/Brands
-Administration considerations
-AVes
-Warnings
-CIs
-BBW
Drugs: polyethylene glycol-electrolyte solution (Colyte, GoLytely, NuLytely, GaviLyte-G, GaviLyte-N, MoviPrep, Plenvu), sodium phosphates (OsmoPrep), sodium sulfate, potassim sulfate, and magenesium sulfate (Suprep Bowel Prep Kit), sodium picosulfate, magnesium oxide, and citric acid (Clenpiq)
Administration:
-Onset of action 1-6 hours
-Bowel prep regimens typically require doses the evening before colonoscopy and the morning of colonoscopy to completely evacuate the bowel
-Clear liquid diet is required the day prior to colonoscopy and can include: water, clear broth (beef or chicken), juices w/o pulp, soda, coffee, or tea (w/o milk or cream), clear gelatin (w/o fruit pieces), popsicles (w/o fruit pieces or cream)
-DO NOT consume the following: solid or semi-solid foods, anything w/ red or blue/purple food coloring, milk, cream, tomato, orange or grapefruit juice, alcoholic beverages, cream soups
AVEs: abdominal discomfort, bloating, N/V
Warnings: arrhythmias, electrolyte abnormalities, seizures
CIs: ileus, GI obstruction, gastric retention, bowel perforation, toxic colitis, toxic megacolon
-OsmoPrep: acute phosphate nephropathy, gastric bypass or stapling surgery
-Clenpiq: severe renal impairment
BBW (OsmoPrep): nephropathy
Diarrhea:
-Define
-Causes
-Non-pharmacotherapy
-Drug TX
Diarrhea: increase in number of bowel movements or stools that are more watery and loose than normal
Causes: most cases are viral, some bacterial (E. coli most common, IBS-D (idiopathic diarrhea associated w/ chronic or recurring abdominal discomfort relieved by defecation)
Non-pharmacotherapy:
-Fluid and electrolyte replacement especially in children or older adults
-Oral rehydration solutions (ORS) - ex. Pedialyte, Enfamil Enfalyte
-Alternative: Gatorade
Drug TX:
-Viral infections often resolved w/o TX
-Non-infectious diarrhea symptomatic relief (OTC): bismuth subsalicylate or loperamide –> refer if age <6 months, pregnancy, high fever (>101F), severe abdominal pain or blood in stool
-RX: diphenoxylate/atropine, dicyclomine (anticholinergic - helps w/ cramping), eluxadoline
-IBS-D when other TX has failed: eluxadoline (Viberzi), rifaximin (costly), alosetron (women only)
Drugs that cause diarrhea
GI drugs:
-Antacids containing magnesium
-Drugs for constipation (laxatives)
-Misoprostol
-Prokinetic drugs (ex. metoclopramide, cisapride)
Others:
-Acetylcholinesterase inhibitors (ex. donepezil)
-Antidiabetics (ex. metformin, GLP-1a)
-Antineoplastics (ex. irinotecan, capecitabine, fluorouracil, MTX, TKIs)
-Colchicine
-Mycophenolate, Roflumilast
Bismuth subsalicylate:
-Brand
-MOA
-ROA
-AVes
-Warnings
-CIs
Brand: Pepto-Bismol
MOA: anti-diarrheal
ROA: PO
AVEs: black tongue/stool (temporary and harmless), salicyclate toxicity (if used excessively: tinnitus, metabolic acidosis), nausea, abdominal pain
-Can cause increased risk of bleeding when used w/ anticoagulants, antiplatelets, or NSAIDs
Warnings: children and teenagers who are recovering from the flu, chickenpox, or other viral infections should NOT use this drug due to risk of Reye’s Syndrome
CIs: salicyclate allergy, taking other salicyclates (ex. ASA), GI ulcer, bleeding problems, black/bloody stool
Loperamide:
-Brand
-MOA
-ROA
-Dosing
-Administration considerations
-AVEs
-CIs
-BBW
Brand: Imodium A-D, Anti-Diarrheal, Diamode
MOA: anti-diarrheal
ROA: PO
Dosing: 4mg PO after first loose stool then 2mg after each subsequent loose stool (max: 8mg/day for self-care or 16mg/day under healthcare supervision)
Administration:
-For self-TX, do NOT use >48 hours
-Loperamide can be abused as it causes mild opioid-like “high” in large quantities
-*FDA requires use of blister packs *or other single-dose packaging for tablets/capsules and number of doses per package to be no more than 48mg (24 tablets/capsules)
AVEs: constipation, abdominal cramping, nausea, QT prolongation
CIs: acute dysentery (bloody diarrhea and high fever - drug stops gut which is trying to get rid of toxin), pseudomebranous colitis (C. difficle), bacterial enterocolitis caused by invasive organsisms (toxigenic E. coli, Salmonella, Shigella), abdominal pain w/o diarrhea, acute ulcerative colitis
BBW: Torsades de pointes, cardiac arrest and sudden death w/ doses higher than recommended, children < 2 yo (risk of toxic megacolon)
Diphenoxylate/atropine:
-Brand
-MOA
-ROA
-Administration considerations
-AVEs
-CIs
Brand: Lomotil
MOA: anti-diarrheal
-Atropine: discourages abuse
ROA: PO
Administration:
-Control schedule: CV
-Liquid formulatoin is recommended in children <13 yo
AVEs: mild euphoria due to diphenoxylate, possible anticholinergic effects (from atropine - mild at recommended doses)
CI: risk of respiratory and CNS depression (do NOT use if <2 yo of age or <6 yo for tablets), diarrhea caused by endotoxin-producing bacteria or pseudomembranous colitis (C. difficile), obstructive jaundice
Dicyclomine:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CI
Brand: Bentyl
MOA: antispasmodic
ROA: PO
TX: diarrhea
AVEs: dizziness, dry mouth, nausea, blurred vision, somnolence, weakness, nervousness
Warnings: anticholinergic (caution in pts >/=65 yo, Beers Criteria), caution in mild-moderate ulcerative colitis (can cause toxic megacolon or paralytic ileus)
CI: GI obstruction, severe UC, reflux esophagitis, acute hemorrhage w/ CV instability, obstructive uropathy, narrow-angle glaucoma, myasthenia gravis, breastfeeding women, infants <6 months
Eluxadoline:
-Brand
-MOA
-ROA
-TX
-AVEs
-Warnings
-CIs
Brand: Viberzi
MOA: peripherally-acting mixed mu-opioid receptor agonist
ROA: PO
TX: IBS-D
AVEs: constipation, nausea, abdominal pain
Warnings: CNS depression
CIs: pts w/o gallbladder, biliary duct obstruction, sphincter of Oddi dsyfunction/disease, pancreatitic disease (hx of pancreatitis), alcoholism, or >3 alcoholic drinks/day, severe hepatic impairment (Child Pugh Class C), hx of severe constipation, GI obstruction
Monitoring: s/sx of pancreatitis or sphincter of Oddi spasm (ex. adbdominal pain that radiates to the back or shoulder, N/V), LFTs
Inflammatory Bowel Disease (IBD):
-Define
-Differences from IBS
-Ulcerative colitis (UC): define and discuss types (distal, proctitis, mild, moderate, severe, and fulminant)
-Crohn’s disease (CD): define
-UC vs. CD: diarrhea, fistulas/strictures, location, depth, pattern
-Diagnosis
IBD: group of inflammatory conditions of colon and small intestine that is chronic, intermittent with flares and remissions
Differences from IBS:
-IBS does NOT have inflammation and is not as serious of a condition
-Classic symptom of IBD: bloody diarrhea
Ulcerative colitis (UC): mucosal inflammation confined to rectum and colon w/ superficial ulcerations
-Distal disease: when UC limited to descending colon and rectum
-Proctitis: inflammation limited to rectum
-Classified as mild, moderate (>4 stools/day), severe (>/=6 bloody stools w/ evidence of toxicity), or fulminant (>10 stools/day and severe symptoms)
Crohn’s disease (CD): deep, transmural (through bowel wall) inflammatoin that can affect any part of GI tract (most commonly: ileum and colon)
UC vs. CD:
-Diarrhea: bloody (UC, CD), or non-bloody (CD)
-Fistulas/strictures: commo in CD, but not UC
-Location: entire GI tract (especially ileum and colon - CD), colon (especially rectum - UC)
-Depth: transumral (CD), superficial (UC)
-Pattern: non-continuous “cobblestone” appearance (CD), continuous (UC)
Diagonosis: colonoscopy with tissue biopsy
-Rule out other conditions
Inflammatory Bowel Disease (IBD):
-Non-pharmacological TX
-Diet: eating smaller, more frequent meals; low fat and dairy diet; fiberous foods; drink plenty of water (avoid alcohol, caffeinated, and carbonated beverages); avoid foods with sorbitol and lactose
-Vitamin supplementation to prevent defeciences: B12, folate, vitamin D, calcium, iron, zinc
-Smoking: shown to worsen CD, but may be protective in UC
-Probiotics: Lactobacillus or Bifidobacterium infantis can reduce abdominal pain, bloating, urgency, constipatoin, or diarrhea in some pts
-Natural products (limited evidence): fish oils, pepermints (oils or teas), chamomile, horehound, wheatgrass
Inflammatory Bowel Disease (IBD):
-General TX
-TX for mild, moderate, and severe
General TX:
-Induce remission/for acute exacerbations: short-course steroids (IV or PO) that should be tapered over 8-12 weeks once remission achieved
-Maitenance of remission: biologics in moderate or severe UC or CD; for mild, up to three months of therapy with budesonide for CD and mesalamine for UC
CD:
-Mild disease of ileium and/or right colon: PO budesonide for </=3 months, then D/C or change to a thiopurine or methotrexate
-Moderate/severe (preferred): anti-TNF agents (certolizumab, adaliumumab, or infliximab) w/ or w/o MTX or thiopurine, IL receptor antagonist, integrin receptor antagonist
-Moderate/severe (alternative): janus kinase inhibitor, integrin receptor antagonist
UC:
-Mild disease: mesalamine (5-ASA) –> in distal, rectal preferred; in extensive, rectal +/- PO
-Moderate/severe (preferred): anti-TNF agent (golimumab, adalimumab, infliximab) w/ or w/o thiopurine, IL receptor antagonist, integrin receptor antagonist
-Moderate/severe (alternative): janus kinase inhibitor, oral sphingosine-1-phosphate receptor modulator
Steroids in inflammatory bowel disease (IBD):
1. PO budesonide with the brand ________ is used for CD for ________(induction/maintenance/both) and with the brand _______ is used for UC for _________(induction/maintenance/both). Budesonide is a major CYP_____ substrate.
- What is different about PO budesonide vs. other PO steroids?
- PO steroids should mostly be used for acute flares and avoided long-term. If used longer than ____ weeks, must taper to avoid withdrawl symptoms. Can use alternate day therapy (ADT) to decrased _____________ and other side effects. If long-term used required, assess _________ and consider ___________ and _________ if needed.
- Rectal steroids such as ________ and _________ are indicated for _________(UC/CD) only for _________(induction/maintenance)
- Entocort EC; both; Uceris; induction; CYP3A4 (caution w/ grapefruit)
- Undergoes extensive first-pass metabolism, resulting in decreased systemic exposure than other PO steroids
- 2 weeks; adrenal suppression; BMD; vitamin D and calicium supplementation; bisphosphonates
- hydrocortisone; budesonide; UC; induction (hydrocortisone - maybe maintenance in mild distal UC as alternative to aminosalicyclates
Mesalamine:
-Brands
-MOA
-ROA
-Administration considerations
-TX
Brand: Pentasa, Apriso, Delzico, Asacol HD, Liaida, Rowasa, Canasa
MOA: aminosalicyclate - anti-inflamamatory effect in GI tract (metabolite of sulfasalazine)
ROA:
-ER capsules: Pentasa, Apriso, Delzicol
-ER tablets: Asacol HD, Liadia
-Enema: Rowasa
-Suppository: Canasa
Administration:
-Mesalamine better tolerated than other aminosalicyclates (ex. sulfasalazine, balsalazide, olsalazine)
-Rectal mesalamine more effective than PO and rectal steroids for distal disease/proctitis in UC
-Can use PO and topical formulations together
-Asacol, Delzicol: can leave ghost tablet
-Swallow capsules/tablets whole –> do NOT crush, cehw, or break due to DR coating
-Apriso: do NOT use w/ antacids (dissolution is pH-dependent)
-Administer enemas and suppositories in evening, just before bedtime. Try not to have bowel movement until morning. Can stain surfaces including clothing and fabrics
TX: UC induction
Mesalamine:
-AVEs
-Warnings
-CIs
-Monitoring
AVEs: abdominal pain, nausea, HA, flatulence, eructation (belching), nasopharyngitis
Warnings:
-Acute intolerance syndrome (cramping, acute abdominal pain, bloody diarrhea)
-Caution in pts w/ renal or hepatic impairment
-Delayed gastric rentetion (due to pyloric stenosis) can delay release of PO products in colon
-Hypersensitivity rxns (including myocarditis, pericarditis, nephritis, hematologic abnormalities, and other internal organ damage) –> more likely w/ sulfasalazine than mesalamine
-Increased risk of blood dyscrasias in pts >65 yo
-Photosensitivity
-Apriso: contains phenylalanine –> do NOT use in PKU
-Rowasa: enema contains potassium metabisulfite (may cause allergic-type reaction)
CIs: hypersensitivity to salicyclates or aminosalicyclates
Monitoring: renal function, CBC, hepatic function, s/sx of IBD
Thiopurines:
-Drugs/Brands
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-Warnings
-BBW
-Monitoring
-DDIs
Drugs: azathioprine (Azasan, Imuran), mercaptopurine (Purixan)
MOA: immunosuppressive
ROA: PO
TX: inducation and maitenance of remission for CD and UC
Administration (mercaptopurine): take OES; avoid old terms “6-mercaptopurine” or “6-MP” - increased risk of overdose due to doses 6-fold higher than normal
AVEs: N/V/D, rash, increased LFTs
Warnings: hematologic toxicities (leukopenia, thrombocytopenia, anemia); pts with genetic deficiency of thiopurine methyltransferase (TPMT) are at increased risk for myleosuppression (consider testing before starting); GI hypersensitivity rxns (severe N/V/D, rash, fever, increased LFTs); hepatotoxicity
BBW: chronic immunosuppression increases risk of malignancy with IBD (especially lymphomas); mutagenic potential; risk of hematologic toxicities
Monitoring: LFTs, CBC (weekly for first month), renal function, s/sx of malignancy
DDIs:
-Azathioprine metabolized to mercaptopurine: do NOT use in combo
-Aminosalicyclates inhibit TPMT, caution in combination
-Allopurinol inhibits pathway for inactiavtion of azithoprine –> dose reduction required if used in combination
Drugs in CD and UC:
1. What are some considerations of sulfasalazine and balasalazide?
- __________ is an immunosuppresant that can be used in moderate/severe CD that is dosed once weekly SC or IM. ____________ is an immunosuppresant reserved for severe acute UC.
- List some janus kinase inhibitors, sphingosine-1 phosphate receptor modulators, anti-TNF MABs, and interleukin receptor antagonists used for CD and UC?
- -Sulfasalazine: more AVEs due to sulfonamide compontent (CI: salicyclate allergy, sulfa allergy)
-Balasalazide: can stain teeth and tongue - Methotrexate; Cyclosporine
- Janus Kinase Inhibitors:
-UC: tofacitinib (Xeljanz), udadacitinib (Rinvoq)
-CD: upadacitinib (Rinvoq)
S1P Receptor Modulators: for UC –> ozanimod, etrasimod
Anti-TNF MABs: for moderate/severe UC or CD often in combo w/ thiopurine –> infliximab, adalimumab
Interluekin receptor antagonists: for moderate/severe disease
-UC and CD: ustekinumab (Stelara) and its biosimilar (Wezlana)
-CD: risankizumab (Skyrizi)
-UC: mirikizumab-mrkz (Omvoh)
Vedolizumab:
-Brand
-MOA
-ROA
-Administration considerations
-TX
-AVEs
-Warnings
-Monitoring
Brand: Entyvio
MOA: integrin receptor antagonist -MAB that binds to subunit of integrin molecules that inhibits interactions with adhesion molecules and preventing inflammatory cells from migrating into GI tissue
ROA: IV
Administration:
-D/C if no benefit by week 14
-Refrigerate and store in original packaging to protect from light
-Swirl during reconstitution, do NOT shake
-Cannot be used w/ other immunosuppressants
TX: induction and maitenance of remission in moderate/severe IBD
AVEs: HA, nasopharyngitis, hypersensitivity, arthralgia, antibody development
Warnings: infusion rxns, hypersensitivity rxns, infections, liver injry, PML (lower risk than w/ natalizumab)
-All immunizations must be up to date before starting: avoid live vaccines during TX
Monitoring: LFTs, s/sx of infection, hypersensitivity, neurological symptoms (for PML), routine TB screening
Natalizumab:
-Brand
-MOA
-ROA
-Dosing frequency
-Administration considerations
-TX
-AVEs
-Warnings
-BBW
Brand: Tysabri
MOA: integrin receptor antagonist -MAB that binds to subunit of integrin molecules that inhibits interactions with adhesion molecules and preventing inflammatory cells from migrating into GI tissue
ROA: IV
Dosing frequency: Q4 weeks
Administration:
-D/C if no response by 12 weeks
-Cannot be used with other immunosuppressants (if taking steroids when initiating, begin tapering when benefit is observed, stop natalizumab if pt cannot taper steroids within 6 months of initiation)
-Stable in NS only; do NOT shake
TX: induction and maitenance of remission in moderate/severe IBD
-Rarely used for CD due to risk of PML
AVEs: infusion rxns, HA, fatigue, arthralgia, nausea, rash, depression, gastroenteritis, abdominal/back pain
Warnings: herpes encephalitis and meningitis, hepatotoxicity, hypersensitivity (antibody formations), immunosuppression, infections
BBW: progressive multifocal leukoencephalopathy (PML - opportunistic viral infection of brain that leads to death or severe disability)
-Only available through REMS program
-Monitor: mental status changes, risk factors (anti-JCV antibodies, increased TX duration, and prior immunosuppressant use)
Vertigo:
-Define
-TX
-Nonpharm for motion sickness
-What is NOT effective?
Vertigo: dizziness with the sensation that environment is moving or spinning typically a condition in inner ear that affects balance
-*TX: vestibular (inner-ear) suppressants including antihistamines (ex. meclizine, dimehydrinate) and BZDs
-5-HT3 receptor antagonists are NOT useful for vertigo since they do NOT affect inner ear*
Motion Sickness:
-Define
-TX
-Nonpharm for motion sickness
-What is NOT effective?
Motion Sickness: dizziness with sensation of being off-balance and woozy due to repetitive motions
-Nonpharmacological: acupuncture bands, ginger
-Antihistamines: diphenhydramine (Benadryl), dimenhydrinate (Dramamine), meclizine (Dramamine Less Drowsy, Bonine)
-Anticholinergics: scopalamine patch - not any more effective than OTCs, but applied behind ear and lasts three days
-Promethazine: Rx only for motion sickness when antihistamines NOT effective, do NOT use in children due to risk of respiratory depression (BBW: avoid in <2 yo and strongly against >2 yo)
-Metoclopramide and 5-HT3 receptor antagonists generally NOT effective for motion sickness
-Take PO medications 30-60 minutes before needed effect
Scopolamine:
-Brand
-MOA
-ROA
-Administration considerations/counseling
-TX
-AVEs
-CIs
Brand: Transderm Scop
MOA: anticholinergic
ROA: patch
Administration/Counseling:
-Press 1 patch firmly to skin behind ear for 30 seconds at least 4 hours before effect needed, apply Q3 days PRN
-Avoid placing patch over hair or when patch is removed. Hair may be removed too
-Wash hands after applying
-Do NOT drive: high level of drowsiness, dizziness, and confusion
-Avoid alcohol while wearing patch
-Do NOT use in children
TX: motion sickness (try to avoid in elderly)
AVEs: dry mouth, CNS effects (drowsiness, dizziness, confusion - can be significant in elderly, frail), stinging of eyes and pupil dilation (if eyes are touched after handling), risk of increased IOP, tachycardia (rare), withdrawl symptoms (diaphoresis, dizziness, fatigue, HA, nausea) after D/C (can last several days)
CI: hypersensitivity to belladonna alkaloids, closed-angle glaucoma
