Week 10: Pharmacotherapy (Emetics + UGIB)

Where is the vomiting center located, and what inputs does it receive?

brainstem (nucleus tractus solitarius); receives input from the chemoreceptor trigger zone (CTZ), GI tract via vagus nerve, and visual/vestibular systems

Why are multiple antiemetic drug classes effective for nausea and vomiting?

multiple receptors and pathways regulate emesis, including serotonin (5-HT3), dopamine (D2), histamine (H1), and muscarinic receptors

What are common causes of nausea/vomiting in hospitalized patients?

PONV, cannabis hyperemesis, drug adverse effects, gastroenteritis, gastroparesis, cyclic vomiting syndrome, and dehydration

What fluid and electrolyte abnormalities occur with prolonged vomiting?

hypovolemia, hypo/hypernatremia, hypokalemia, and metabolic alkalosis

Why does vomiting cause metabolic alkalosis?

Loss of gastric H+ increases pH. Urine Cl−

What complications can result from electrolyte imbalances?

arrhythmias, seizures, confusion, weakness, hypotension, and neuromuscular abnormalities

Which medications should be considered for temporary holding during severe vomiting/dehydration?

ACEIs/ARBs, diuretics, SGLT2 inhibitors, NSAIDs, metformin, sulfonylureas, antihypertensives, and narrow-therapeutic-index drugs

Why are these medications concerning during dehydration?

AKI risk (ACEIs/ARBs, NSAIDs, SGLT2i), hypovolemia (diuretics), hypoglycemia (sulfonylureas), hypotension, and toxicity (lithium/digoxin)

How should essential medications be managed when oral intake is impaired?

assess indication, risk of interruption, duration of action, and alternative routes (IV, feeding tube, rectal)

What alternatives should be considered for anticoagulants and antiepileptics?

Anticoagulants: consider parenteral bridging based on risk

Antiepileptics: use enteral or IV alternatives when needed to prevent seizures

How should insulin and transplant medications be managed during vomiting?

Insulin may still be required despite NPO status

Maintain transplant immunosuppression using alternative routes; consult transplant team

Which home medications should be held in the dehydrated 44-year-old patient with elevated SCr?

empagliflozin and spironolactone due to dehydration, hypovolemia, and AKI concerns

Which medications should be continued or substituted in this patient?

Prioritize lamotrigine for seizure prevention (IR via tube or alternative IV AED if needed)

Resume fluoxetine when feasible; assess retitration needs

Major antiemetic classes and examples?

5-HT3: ondansetron

D2: metoclopramide/prochlorperazine

H1: meclizine/promethazine

Anticholinergic: scopolamine

Steroid: dexamethasone

What other drug classes can be used as antiemetics?

NK1 antagonists, benzodiazepines, and certain antipsychotics (especially in oncology)

Ondansetron MOA and major adverse effects?

5-HT3 antagonist; headache, constipation, fatigue, dizziness, and QTc prolongation

Metoclopramide MOA and major adverse effects?

D2 antagonist/prokinetic; sedation, EPS, hyperprolactinemia, fluid retention, and depression/suicidality concerns

Prochlorperazine MOA and major adverse effects?

D2 antagonist; sedation, constipation, urinary retention, EPS, NMS, and QTc prolongation

Dexamethasone MOA and major adverse effects?

anti-inflammatory effects and reduced serotonin signaling; hyperglycemia, hypokalemia, and immunosuppression

What are the major adverse effects of meclizine and promethazine?

Meclizine: sedation, dry mouth, drowsiness

Promethazine: sedation, hypotension, anticholinergic effects, EPS, QTc prolongation, and extravasation

Scopolamine MOA and major adverse effects?

muscarinic antagonist; dizziness, dry mouth, blurred vision, confusion/delirium, and urinary retention

What formulations are available for ondansetron, and what is its QTc concern?

IV, PO tablet/liquid, ODT, oral film. QTc prolongation approximately 7-27 msec

What formulations and clinical pearls are important for metoclopramide?

IV, PO, ODT, rectal

Prokinetic; monitor EPS, depression/suicidality, and fluid retention (especially CHF)

What formulations and clinical pearls apply to prochlorperazine and dexamethasone?

Prochlorperazine: PO, injection, rectal; EPS and QTc risk

Dexamethasone: PO/injection; monitor hyperglycemia and immunosuppression

What are important clinical pearls for meclizine, promethazine, and scopolamine?

Meclizine: vertigo, Beers criteria

Promethazine: extravasation risk

Scopolamine: patch every 3 days, mainly preventive; delirium risk in elderly

Why is IV promethazine associated with tissue injury, and how can it be prevented?

acidic pH (4-5.5); ensure proper IV placement, prevent leaks, and dilute IV concentration to

What should be done if promethazine extravasation occurs?

stop administration, manage/remove the line per protocol, aspirate as appropriate, apply warm compress, and elevate the site

How do domperidone and droperidol differ?

Both D2 antagonists. Domperidone acts peripherally with limited EPS and prokinetic effects; droperidol acts centrally with sedation, EPS, and dose-dependent QTc ris

Why is QTc prolongation concerning with antiemetics?

can cause torsades de pointes, a potentially fatal ventricular arrhythmia

What should be assessed before starting QTc-prolonging antiemetics?

medication list, cardiac history, baseline ECG/QTc, electrolytes (K+, Mg2+, Ca2+), renal function, and hepatic function.

What QTc values define low, intermediate, and high risk?

Low:

How should intermediate-risk QTc prolongation be managed?

maintain K+ >4 mmol/L and Mg2+ >1 mg/dL per slide; minimize QT-prolonging drugs and repeat ECG at 48 and 96 hours if ongoing therapy.

How should high-risk QTc prolongation (>500 ms) be managed?

reconsider QT-prolonging antiemetics, correct electrolytes, discontinue other QT-prolonging drugs, and use telemetry/repeat ECG monitoring

Which antiemetics have the greatest QTc concerns?

ondansetron and D2 antagonists (especially droperidol); prochlorperazine has relatively lower risk per lecture; risk increases with dose/frequency

What nonpharmacologic strategies can reduce nausea/vomiting?

inhaled isopropyl alcohol, peppermint aromatherapy, ginger, small meals, avoiding triggers, and reducing emetogenic medications

What are major risk factors for postoperative nausea and vomiting (PONV)?

female sex, age

How is PONV typically prevented or treated?

risk-based institutional protocols, often combining dexamethasone with a 5-HT3 antagonist (ondansetron/granisetron)

What characterizes cannabis hyperemesis syndrome (CHS)?

recurrent abdominal pain, persistent nausea, and vomiting associated with continued cannabis use

How is cannabis hyperemesis treated?

Acute: topical capsaicin, hot showers/baths, IV droperidol/haloperidol, or benzodiazepines

Prevention: cannabis cessation

Why are standard antiemetics often ineffective in CHS?

ondansetron and metoclopramide are often ineffective; CHS may respond better to capsaicin or dopamine antagonists

How can medications cause nausea/vomiting?

direct adverse effects (metronidazole, mycophenolate), elevated peak concentrations (IV opioids), or dose-related GI intolerance

How is medication-induced nausea/vomiting managed?

identify offending medication, reduce dose/change route/discontinue if possible; consider 5-HT3 or D2 antagonists for acute relief.

Which medication classes commonly cause nausea/vomiting?

NSAIDs, opioids, antibiotics, antidepressants (SSRIs), metformin, GLP-1 agonists, iron, and chemotherapy agents

What medications may be used for antiemetic pretreatment?

5-HT3 antagonists, corticosteroids, D2 antagonists, and sometimes diphenhydramine; common before certain chemotherapies/infusions

What is gastroenteritis, and how is associated N/V treated?

Viral/bacterial GI inflammation; oral rehydration, electrolyte replacement, and 5-HT3 antagonists. Antibiotics if indicated

What are pediatric treatment considerations for gastroenteritis?

single-dose oral ondansetron is best studied; zinc supplementation may be considered

What is gastroparesis, and what are its common causes/symptoms?

delayed gastric emptying without obstruction; associated with longstanding diabetes/cystic fibrosis

causes N/V, bloating, pain, and reduced appetite

What are the three major treatment approaches for gastroparesis?

nutrition (small meals/liquids, enteral if needed), symptom relief (metoclopramide first-line), and improved motility (metoclopramide/erythromycin)

What other treatments may be considered for refractory gastroparesis?

domperidone, gastric electrical stimulation, or surgery; 5-HT3 antagonists may provide second-line symptom relief

What is cyclic vomiting syndrome (CVS)?

recurrent episodes of severe, persistent vomiting lasting hours or longer, alternating with periods of normal health; migraine-like features

How is cyclic vomiting syndrome treated acutely and prevented?

Acute: ondansetron, triptans, IV fluids, sedation/analgesia

Prevention: avoid triggers, TCAs (amitriptyline), or antiepileptics (topiramate)

How is dehydration-associated vomiting managed?

restore intravascular volume with IV fluids, preferably chloride-rich fluids when appropriate, and replace potassium to correct metabolic alkalosis

A patient is admitted to the hospital with considerable nausea and vomiting. They have been diagnosed with gastroparesis. Their QTc interval is 430 msec. Select necessary actions for treatment.

evaluate if enteral nutrition is needed while repleting fluids

give metoclopramide

consider erythromycin to help with motility

Treatment of N/V Types - Summary Chart

What structures make up the upper GI tract?

mouth through the duodenojejunal junction, above the ligament of Treitz

What is the normal stomach pH, and what stimulates gastric acid secretion?

pH ~2; gastrin stimulates acid and pepsin secretion

gastric juice contains HCl, lipase, and pepsin

What mechanisms protect the gastric mucosa from acid injury?

Pre-epithelial: mucus, bicarbonate, prostaglandins

Epithelial: tight junctions. Subepithelial: mucosal blood flow

What are the major causes of UGIB?

peptic ulcers, Mallory-Weiss tears, anastomotic ulcers, esophagitis, and variceal bleeding

What causes peptic ulcers and anastomotic ulcers?

Peptic: H. pylori, NSAIDs, excess acid

Anastomotic: ulceration at a surgical connection (e.g., Roux-en-Y bypass)

How do Mallory-Weiss tears, esophagitis, and varices cause UGIB?

Mallory-Weiss: forceful vomiting tears mucosa

Esophagitis: mucosal erosion

Varices: portal hypertension causes dilated veins to rupture.

What is the balance between aggressive and protective gastric factors?

Aggressive: acid, pepsin, H. pylori, NSAIDs

Protective: mucus, bicarbonate, prostaglandins, blood flow, and antioxidants

What are common causes and exacerbating factors for UGIB?

Causes: NSAIDs, H. pylori, surgery, stress

Exacerbating: anticoagulants, antiplatelets, alcohol, smoking, prior UGIB, reflux

How do NSAIDs cause gastric injury and bleeding?

COX-1 inhibition → ↓ protective prostaglandins; direct phospholipid damage → impaired mucosal barrier and ulcers

How does H. pylori cause peptic ulcer disease?

adheres to mucosa, forms biofilms, alters cell signaling, and causes chronic inflammation that weakens gastric defenses

What medications commonly cause pill-induced esophagitis?

doxycycline/tetracyclines, bisphosphonates, NSAIDs, potassium chloride, ferrous sulfate, and chemotherapy agents

A patient presents with an upper GI bleed (UGIB) that the care team suspects is due to a Mallory-Weiss tear. How does a MW tear happen?

forceful vomiting/retching increases intra-abdominal pressure, tearing the mucosa at the gastroesophageal junction

What would be signs of a MW tear?

hematemesis following repeated vomiting or retching; possible melena and lightheadedness

What are common signs and symptoms of UGIB?

hematemesis, melena, hematochezia (brisk bleed), abdominal pain, nausea, and lightheadedness

What laboratory findings support UGIB?

elevated BUN/BUN:Cr >30, decreased Hgb, possible CBC dilution after fluids, and positive H. pylori testing

What are the major stages of UGIB treatment without anticoagulation?

Pre-endoscopy: stabilize, NPO, hold offenders, consider PPI/RBCs/erythromycin

Endoscopy: hemostasis. Post: PPI and prevention

How does UGIB management change if the patient takes anticoagulants?

hold anticoagulants, assess reversal need, stabilize, perform endoscopy, and determine safe restart timing

What should be assessed before endoscopy in UGIB?

hemodynamics, Hgb, transfusion/reversal need, NPO status, offending medications, and adjunct therapies

What are the RBC transfusion thresholds in UGIB?

Hgb ≤7 g/dL; ≤8 g/dL with cardiovascular risk factors (CAD, prior MI/CABG, ACS)

What should be remembered about RBC transfusions and iron studies?

~200 mg iron/unit RBC; transfusion can alter iron labs. Recheck iron studies in 2-4 weeks

How does ISTH define major bleeding?

fatal bleeding, critical-site bleeding, Hgb drop ≥2 g/dL, or transfusion of ≥2 RBC units

What is clinically relevant non-major bleeding (CRNMB)?

bleeding not meeting major criteria but requiring medical intervention, hospitalization, or face-to-face evaluation

How is warfarin-associated bleeding reversed?

Mild/moderate: hold warfarin, give vitamin K based on INR

Severe/life-threatening: 4-factor PCC + vitamin K 10 mg IV

What reverses dabigatran (Pradaxa) in life-threatening UGIB?

idarucizumab (Praxbind); consider if taken within 24 hours

not routine due to cost/limited data

What reverses apixaban or rivaroxaban in life-threatening UGIB?

4-factor PCC (e.g., Kcentra) may be considered per institutional protocol

Andexanet alfa (Andexxa) was withdrawn from the U.S. market 12/25

What is the major clinical consideration when reversing DOACs?

reserve reversal for life-threatening bleeding; consider last dose, severity, cost, and institutional protocol

Should platelet transfusions routinely reverse aspirin or P2Y12 inhibitors?

No. Guidelines recommend against routine transfusion due to limited benefit and increased mortality; give if thrombocytopenic when indicated

Should aspirin be held during UGIB?

Primary prevention: hold

Secondary prevention: generally continue; if held, restart after endoscopic hemostasis

Are IV PPIs required before endoscopy for UGIB?

Guidelines are neutral; consider if endoscopy is delayed. Do not delay endoscopy to administer PPIs

What is the high-dose IV PPI regimen, and why is it used?

80 mg IV bolus → 8 mg/hr infusion. Raises gastric pH ≥6 to stabilize clots and reduce rebleeding

Why is erythromycin used before UGIB endoscopy?

motilin receptor agonist; improves gastric emptying/visualization and may reduce repeat endoscopy

What is the recommended erythromycin dose before endoscopy?

250 mg IV over 5-30 minutes; perform endoscopy 20-90 minutes after infusion

What additional medication is used for suspected variceal bleeding?

octreotide; start empirically with UGIB when variceal bleeding is suspected, especially with cirrhosis

A patient presents to the ED reporting melena (dark, tarry stool), hematemesis (bloody vomit), and lightheadedness. They were able to drive into the hospital on their own and their blood pressure is normal and stable. The care team suspects they have an UGIB. At home they are on lisinopril, apixaban, and levetiracetam.

Current labs include: BUN/Cr of 36, Hgb of 6.9 g/dL.

What would you recommend as a first step of treatment?

RBC transfusion, early endoscopy with erythromycin, and hold apixaban/lisinopril

When should endoscopy occur after UGIB?

within 24 hours after stabilization; consider within 12 hours for high-risk patients

What are the purposes of endoscopy in UGIB?

identify bleeding source, provide hemostasis (clips, thermal therapy, injection), and classify rebleeding risk

What should be addressed after UGIB endoscopy?

PPI dose/duration, restarting anticoagulants/antiplatelets, rebleeding prevention, and H. pylori/special populations

Which Forrest classifications indicate low rebleeding risk, and how are they treated?

FIIc (flat pigmented spot), FIII (clean base); standard-dose PO PPI daily, early diet, discharge often within 1-2 day

Which Forrest classifications indicate high rebleeding risk?

FIa (spurting), FIb (oozing), FIIa (visible vessel), FIIb (adherent clot)

What is the PPI regimen for high-risk UGIB after endoscopy?

Days 1-3: 80 mg IV bolus + 8 mg/hr ×72 hours

Days 4-14: PO BID. Day 15+: PO daily

What other management considerations apply to high-risk UGIB?

clear liquid diet initially; hospital discharge often ~3 days after endoscopy

How long should PPI therapy continue after UGIB?

usually 8 weeks uncomplicated; longer/indefinite for recurrent bleeds or chronic NSAIDs/antiplatelets

What is the typical PPI duration for anastomotic ulcers?

3-6 months, depending on healing and recurrence risk

When should warfarin be restarted after UGIB?

usually 7-15 days; earlier (

What factors guide DOAC restart after UGIB?

bleeding severity, reversibility, age, thrombotic risk, rapid onset, and cardiology input

When should aspirin be restarted after UGIB?

Primary prevention: reassess need

Secondary prevention: continue or restart once endoscopic hemostasis is confirmed