GI Exam 1

Acid Reflux/Peptic Disease

Proton Pump Inhibitors

Omeprazole(GERD, Esophagitis, Heartburn), Esomeprazole, Lansoprazole, Dexlansoprazole, Pantoprazole, Rabeprazole(H. Pylori - associated Peptic Ulcers)

PPI MoA

Block the final stage of gastric acid production, suppress gastric acid due to all sources; Inhibit growth of H. pylori; Prodrug that is activated by acid in the canaliculus then it attaches irreversibly to the proton pump

AE: Abdominal pain, constipation, flatulence & nausea; risk of carcinoid tumors & Vitamin B12 deficiency\*

Drug Interactions CYP2C19 (Disulfiram, Phenytoin & Clopidogrel), decreased bioavailability of Ketoconazole, ampicillin esters & iron salts

PPI IV Formulations

Esomeprazole, Lansoprazole, Pantoprazole

Lansoprazole & Pantoprazole

Pregnancy Category B and can be used in children who have GERD

H2 Blockers Antagonists

Cimetidine, Ranitidine, Famotidine, Nizatidine

Indication: Nocturnal Acid, Gastric/Duodenal Ulcers, un-complicated GERD, prevent stress-induced ulcers

H2 Antag. MoA

Competitive Inhibition of H2 receptors; reduces ability of acetylcholine & gastrin to stimulate acid secretion

CI: Dose must be adjusted in renally impaired patients

Best taken 30 minutes before a meal

Cimetidine AE

Galactorrhea, Gynecomastia, reduced sperm count/impotence due to increased prolactin release

Inhibits CYP1A2, CYP2C9, and CYP2D6

Ranitidine, Famotidine, Nizatidine AE

Nausea, diarrhea, headaches, drowsiness & fatigue

Note: all three are pregnancy category B

Prostaglandin (PGE1) Analogue

Misoprostol

Inhibits parietal cells; enhance bicarbonate secretion, mucus production & blood flow within gastric mucosa

Indication: NSAID-induced gastric & duodenal ulcers

AE: Diarrhea, may exacerbate inflammatory bowel disease

Contraindication: Pregnancy

Antacids

Aluminum Hydroxide, Magnesium Hydroxide, Sodium Bicarbonate, Calcium Carbonate

Antacids MoA

Neutralize stomach acid to form water and salts

Antacids AE

Al: Constipation, hypophosphatemia (weakness & anorexia)

Mg: Diarrhea. CI: Kidney disease

Na: Fluid retention. CI: Hypertension & Hypervolemia

Sucralfate MoA

Forms viscous gel at low pH; protects gastric luminal surface from degradation by acid & pepsin

AE: Constipation

Colloidal Bismuth

Stimulates secretion of bicarbonate & prostaglandin; inhibits growth of H. pylori & forms barrier to protect from ulcers

Diarrhea

Opioid Agonists

Diphenoxylate, Loperamide

Diarrhea, Traveler’s Diarrhea

OA MoA

Inhibit GI motility, decrease secretion & absorption secondary to stimulating the inhibitor opioid receptors, allowing for water/nutrients & electrolytes to be absorbed

OA AE

Diphenoxylate: CNS effects, risk of addiction & abuse; constipation, anti-cholinergic effects

Note: Rapidly metabolized to active metabolite (Difenoxin) after administration; more potent than morphine

Loperamide: CNS depression. CI: Children age

Bile Acid Sequestrants

Cholestyramine(Bile-acid induced Diarrhea & mild antibiotic induced Diarrhea), Colestipol, Colesevelam (Bile-acid induced Diarrhea)

BAS MoA

Binds and forms complexes with bile acids & bacterial toxins, facilitating their excretion

AE: Steatorrhea & depletion of fat soluble vitamins (ADEK)

Bulk Forming Agents

Carboxymethylcellulose, Calcium Polycarbophil

Indication: Mild chronic diarrhea with irritable bowel syndrome

BFA MoA

Hydrophilic, resistant to enzymatic break-down within GI tract, absorb water & increase stool bulk

AE: May also bind nutrients and other drugs within GI, decreasing their absorption

Somatostatin Analogue

Octreotide

Indication: Chemotherapy-induced Diarrhea, HIV-associated Diarrhea & Diabetic-associated Diarrhea; Dumping Syndrom in post-gastric surgery

MoA: Inhibition of hormone secretion (serotonin, gastrin, VIP, insulin, etc.)

AE: GI cramps, hypothyroidism & headaches

Constipation

Cholinomimetic Agent

Bethanecol

GERD & Gastroparesis

MoA: M3 agonist

AE: Sedation, nausea, vomiting, excessive salivation & bradycardia

Bulk Forming Agent (Const)

Methylcellulose(Constipation, Hemorrhoids & Irritable Bowel Syndrome), Psyllium, Calcium Polycarbophil (Constipation)

Methylcellulose & Psyllium MoA

Ingestible hydrophilic colloids that absorb water forming a bulky soft mass that distend the colon & promotes peristalsis

AE: Bloating & constipation

Calcium Polycarbophil

Synthetic polymer of polyacrylic acid, highly hydrophilic & hydrophilicity increases with pH

Osmotic Laxatives

Magnesium salts, Sorbitol, Lactulose(Hepatic encephalopathy & constipation), Magnesium Citrate, Polyethylene Glycol (Constipation & colon cleansing (prior to colonoscopy / surgery))

Mg Salts MoA

Constipation

Rapid action, laxative with catharsis power

AE: Risk of fluid & electrolyte loss, fecal incontinence, hypomagnesemia, muscle cramps, bradycardia, fatigue & hypotension

CI: Kidney Disease / Failure

Sorbitol, Lactulose, Magnesium Citrate, Polyethylene Glycol MoA

Soluble but not absorbable compounds that increase the water secreted into the colon

Sorbitol AE

Fluid & electrolyte loss, hyperglycemia & diarrhea

Note: Pregnancy Category C

Lactulose AE

Diarrhea, flatulence & belching

Note: Pregnancy Category B

Polyethylene Glycol AE

Diarrhea, flatulence & electrolyte imbalance

Stool Softeners

Docusate Sodium, Mineral Oil, Glycerol

Docusate Sodium MoA

Decrease surface tension of stool, allows fatty & aqueous substances to mix, soften stool

AE: Diarrhea

Mineral Oil MoA

Penetrate & soften stool, interfere with water reabsorption

CI: Pregnancy

Stimulant Laxatives (Cathartics)

Bisacodyl, Senna, Cosara

Stimulant Laxatives (Cathartics) MoA

Irritates intestinal smooth muscles, stimulates peristalsis, stimulate colonic intramural plexus; produce net intestinal fluid accumulation

AE: Electrolyte imbalance, gastric irritation & cramping

Peripheral Acting Mu Opioid Receptor Antagonists (PAMORA)

Methyl Naltrexone, Alvimopan

PAMORA MoA

Opioid-induced Constipation

μ - selective antagonist, does not cross the BBB.

SQ

Chloride Channel Activators

Linaclotide, Lubiprostone

Linaclotide MoA

Chronic Constipation & Irritable Bowel Syndrome

Activates CFTR leading to chloride rich secretions & acceleration of intestinal transit

AE: Diarrhea

CI: Pediatric Patients

Note: Pregnancy Category C

Lubiprostone MoA

Prostanoid activator of colonic CFTR; weak agonist at prostaglandin receptors

AE: Nausea & Diarrhea

Serotonin 5HT4 Receptor Agonists

Tegaserod, Cisapride

5HT4 Agonists MoA

Stimulate presynaptic 5HT4R to release acetylcholine / CGRP leading to peristalsis, bowel contraction & distal bowel relaxation

Prokinetic Agents

Metoclopromide, Domperidone

Metoclopromide MoA

Nausea & Constipation

D2 (dopamine) agonist, enhance response to acetylcholine in tissues 

AE: Related to D2 inhibition

Domperidone MoA

D2 selective agonist

Does not cross BBB

GERD

Antacids

Calcium Carbonate, Magnesium Hydroxide, Aluminum Hydroxide

Aluminum Hydroxide + Magnesium Trisilicate

Antacids Notes

Mild Symptoms of GERD

Neutralize stomach pH

Does not provide prolonged relief

Not to be taken at bedtime for overnight relief; may need to be taken multiple times a day

H2 Receptor Antagonists

Famotidine, Ranitidine, Cimetidine, Nizatidine

H2 Receptor Antagonists Notes

Mild to Moderate Symptoms of GERD

Suppress acid secretion in the stomach

Headache, dizziness & mild fatigue

Useful if taken before meals that may cause heartburn

Cimetidine CI: Warfarin, Phenytoin, Propanol & Nifedipine

Proton Pump Inhibitors

Omeprazole, Lansoprazole, Rabeprazole, Esomeprazole, Pantoprazole, Dexlansoprazole, Omeprazole + Sodium Bicarbonate

Proton Pump Inhibitors Notes

Moderate & Frequent Symptoms of GERD

Turn off pumps responsible for producing acid (parietal cells)

Headache, diarrhea, dizziness, nausea, & abdominal pain; Vitamin B12 deficiency\*

Take 30-60 minutes before a meal to maximize effect; may take 3-4 days to reach maximum effect

Not to be taken on an as-needed basis

Peptic Ulcer Disease

Prostaglandin E Analogue

Misoprostol

Prevention of NSAID-induced Ulcers

AE: Abdominal cramping, dose-related diarrhea

CI: Pregnancy

Start at 200 mg BID and incease to QID if tolerated

Proton Pump Inhibitors

Omeprazole, Lansoprazole, Rabeprazole, Esomeprazole, Pantoprazole, Dexlansoprazole

Prevention of NSAID-induced Ulcers

Drug Interaction with Clopidogrel

If patient is also taking Clopidogrel, space out doses (do not take simultaneously)

H2 Receptor Antagonist

Famotidine

(limited evidence) Prevention of NSAID-induced Ulcers

Reduces risk of duodenal ulcers

Antibiotics

Amoxicillin, Tetracycline, Clarithromycin

\

Salicylate

Bismuth Subsalicylate

Aspirin Allergy

Antibiotic & Antiprotozoal

Metronidazole

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Quadruple Therapy

Bismuth Quadruple Therapy:

PPI + Bismuth + Tetracycline + Metronidazole

Active Peptic Ulcers caused by H. pylori infection

Aspirin Allergy

10-14 days

PPI once or BID + Bismuth 525 mg QID + Metronidazole 250-500mg QID + Tetracycline 500 mg QID

Concomitant Quadruple Therapy

Concomitant Quadruple Therapy: PPI + Clarithromycin + Amoxicillin + Metronidazole

10-14 days

Requires validation as first line therapy; PPI once + Clarithromycin 250-500mg BID + Amoxicillin 1000mg BID + Metronidazole 250-500mg BID

Clarithromycin Triple Therapy

Clarithromycin Triple Therapy:

PPI + Clarithromycin + Amoxicillin or Metronidazole

CI: Metronidazole in place of Amoxicillin in penicillin allergy

14 days

PPI once or BID + Clarithromycin 500mg BID + Amoxicillin 1000mg BID or Metronidazole 500mg TID

Sequential Therapy

Sequential Therapy:

PPI + Amoxicillin + Clarithromycin + Metronidazole

10 days

PPI once or BID days 1-10 + Amoxicillin 1000mg days 1-5+ Clarithromycin 250-500mg BID days 6-10 + Metronidazole 250-500mg BID days 6-10

Irritable Bowel Syndrome

Opioid Agonist

Loperamide, Diphenoxylate, Atropine Sulfate

IBS - Diarrhea

Antibiotic

Rifaximin

IBS - Diarrhea

550 mg tablets TID for 14 days

Bile Acid Sequestrant

Cholestryamine 

IBS - Diarrhea

κ & μ Opioid Agonist; Δ Opioid Antagonist

Eluxdoline

IBS - Diarrhea

AE: Abdominal Pain

CI: Sphincter of Oddi Spasm & Pancreatitis

5HT3 Antagonist

Alosetron

IBS - Diarrhea

Probiotic

Bifidobacterium infantis

IBS - Diarrhea

Bulk Forming Laxatives

Psyllium, Polycarbophil, Methylcellulose

IBS - Constipation

AE: Flatulence, distension, bloating & unpleasant taste

Increase fiber intake to 20-30g per day over a period of 1-2 weeks

Osmotic Laxatives

Polyethylene Glycol, Magnesium Hydroxide, Lactulose, Sorbitol, Mannitol

IBS - Constipation

Draws water along osmotic gradient

PG, Mg: Electrolyte imbalance (Sodium, Magnesium or Phosphorus deficiencies) & dehyrdation

Chloride Channel Activators

Lubiprostone, Linaclotide

IBS - Constipation

Lubi: Selectively activates type 2 chloride channels in apical (luminal) membrane of GI tract

Pregnancy Category C

Lina: Take on empty stomach

Guanylate Cyclase-C Agonist

Plecanatide

IBS - Constipation

Increases luminal chloride secretion

Avoid

Antipasmotic

Dicyclomine

IBS - Abdominal Pain

Abdominal cramping, constipation, xerostomia & dry eyes

Tricyclic Antidepressants

Amitriptyline, Nortriptyline, Desipramine

IBS - Abdominal Pain

Infectious Diarrhea

Vancomycin

Severe or non-severe Gram + Cocci infection (S. aureus)

Macrolide Antibiotic

Fidaxomicin, Azithromycin

Severe or non-severe C. difficile infection

Non-systemic, minimally absorbed into the bloodstream; Bactericidal effects

Traveler's Diarrhea (areas where Campylobacter is highly endemic)

Salicylate

Bismuth Subsalicylate

Traveler’s Diarrhea

Antibiotic

Quinolones (Antibiotic)

Norfloxacin

Levofloxacin, Ciprofloxacin

start on first day in country until 1-2 days after return

Second line: Rifaximin

Traveler’s Diarrhea

Antimotility Agent

Loperamide

Traveler’s Diarrhea

CI: Bloody Stool and/or fever

Giardiasis

Tinidazole, Nitazoxanide

Metronidazole (not FDA app. for Gia.)

Inflammatory Bowel Disease

Aminoglycoside Azo Compounds

Sulfasalazine, Balsalazide, Olsalazine

Amino Azo MoA

Ulcerative Colitis

Not absorbed, but delivered to the colon; Prodrugs that must be converted into the active form 

AE Sulfas.: Folate deficiency, nausea, vomiting, diarrhea, headaches and arthralgia

Aminoglycoside Mesalamine Compounds

Pentasa, Asacol, AprisoLialda

Amino Mesalamine MoA

Ulcerative Colitis

5-ASA inhibits inflammation; inhibits COX enzymes to reduce prostaglandin synthesis; inhibits activity of NF-kB

Corticosteroid

Prednisone, Hydrocortisone(Short-term course induction of IBD remission), Methyprednisolone, Prednisolone, Budesonide(Induction in mild to moderate Crohn's disease)

Corticosteroid MoA

Suppression of inflammation & immune system; inhibit NF-kB and phospholipase A2

AE: Osteoporosis, bone loss, fractures, hyperglycemia, hypervolemia, hypertension, increased vulnerability to infections, weight gain, thinning of skin, easy bruising, poor wound healing, may exacerbate GI bleeding

Immunosuppressants

6-Mercaptopurine, Azathioprine

6-Mer: Prodrug, metabolized by a non-enzymatic reaction to form 6 - Mercaptopurine

Aza: Inhibits purine biosynthesis

AE: Bone marrow depression & hepatotoxicity

Anti-metabolite

Methotrexate IM

Steroid Sparing & Maintenance of Crohn's Disease remission

MoA: Anti-inflammatory; interferes with action of IL-1, stimulates adenosine release to inhibit T cell activation & stimulates apoptosis of activated T lymphocytes

Anti-TNF Antibodies

Infliximab, Adalimumab, Certolizumab, Golimumab

Infliximab MoA IV

Chimeric monoclonal antibody with both murine (mice) & human amino acid sequences

Induction & Maintenance of remission in Ulcerative Colitis

AE: Flu-like infusion reaction may worsen congestive heart failure

Screening of HIV and Hepatitis C 

Adalimumab, Certolizumab, Golimumab Indications SQ

Ulcerative Colitis & Crohn's Disease

Useful if resistant to Infliximab