STEPTRACKERPHARMACOLOGY | GASTROINTESTINAL | HIGH-YIELD REVIEW

Antiemetics, Motility, Laxatives & IBD Drugs

Nausea has several receptor triggers; motility drugs speed or slow the gut; laxatives work by bulk, osmosis or stimulation; IBD drugs suppress mucosal inflammation.

FOCUS ON
Antiemetics: ondansetron (5-HT₃; chemotherapy, postoperative; QT prolongation, constipation, headache); metoclopramide (D2 antagonist + prokinetic; gastroparesis; tardive dyskinesia, dystonia, ↑ prolactin; avoid in obstruction, Parkinson); prochlorperazine, promethazine (D2/H1); aprepitant (NK1); dexamethasone; scopolamine, meclizine (motion sickness); dronabinol (cannabinoid). Prokinetic: erythromycin (motilin agonist). Antidiarrheals: loperamide (peripheral μ; no CNS), diphenoxylate + atropine. Laxatives: bulk (psyllium), osmotic (PEG, lactulose — also hepatic encephalopathy, magnesium), stimulant (senna, bisacodyl), stool softener (docusate), secretory (lubiprostone — ClC-2; linaclotide — guanylyl cyclase C), methylnaltrexone/naloxegol (peripheral μ antagonists — opioid constipation). IBD: 5-ASA (mesalamine; sulfasalazine → sulfapyridine: oligospermia, hemolysis, agranulocytosis), steroids (budesonide), thiopurines, methotrexate, anti-TNF (infliximab, adalimumab — TB reactivation), vedolizumab (α4β7), ustekinumab, JAK inhibitors.
DRUG
MECHANISM
USE
ADVERSE · NOTES
Ondansetron · granisetron
5-HT₃ antagonist (vagal afferents, CTZ)
Chemotherapy, postoperative, pregnancy nausea
QT prolongation, headache, constipation
Metoclopramide
D2 antagonist (CTZ) + ↑ ACh release in gut
Diabetic gastroparesis, GERD, nausea, migraine
Tardive dyskinesia, dystonia, parkinsonism, hyperprolactinemia, NMS
Prochlorperazine · promethazine
D2 (and H1, muscarinic) antagonists
Nausea, migraine (prochlorperazine)
Sedation, dystonia; promethazine tissue necrosis if extravasated
Aprepitant · fosaprepitant
NK1 (substance P) antagonist
Delayed chemotherapy-induced nausea
CYP3A4 interactions
Meclizine · dimenhydrinate · scopolamine
H1 / muscarinic antagonists (vestibular)
Motion sickness, vertigo
Sedation, anticholinergic effects
Dronabinol · nabilone
CB1 agonists
Chemotherapy nausea, AIDS anorexia
Euphoria, dizziness
Erythromycin
Motilin receptor agonist
Gastroparesis, before endoscopy for upper GI bleed
QT, tachyphylaxis
Loperamide · diphenoxylate
μ agonists in gut (minimal CNS)
Noninfectious diarrhea
Avoid in bloody/invasive diarrhea, C. difficile; loperamide overdose → QT/arrhythmia
Osmotic laxatives
PEG, lactulose, MgSO₄/citrate — draw water into lumen
Constipation, bowel prep; lactulose for hepatic encephalopathy (traps NH₄⁺)
Bloating, electrolyte shifts
Stimulant laxatives
Senna, bisacodyl → ↑ motility and secretion
Opioid constipation, bowel prep
Cramps; melanosis coli (senna)
Lubiprostone · linaclotide · plecanatide
ClC-2 activator · guanylyl cyclase C agonists → ↑ Cl⁻ secretion
Chronic idiopathic constipation, IBS-C
Diarrhea
Methylnaltrexone · naloxegol · alvimopan
Peripheral μ antagonists
Opioid-induced constipation, postoperative ileus
Analgesia preserved
Mesalamine · sulfasalazine
5-ASA → local ↓ prostaglandins, leukotrienes
Ulcerative colitis (induction, maintenance); sulfasalazine also RA
Sulfasalazine: oligospermia, rash, hemolysis (G6PD), folate ↓, agranulocytosis
Infliximab · adalimumab · vedolizumab · ustekinumab
Anti-TNF · anti-α4β7 integrin (gut-selective) · anti-IL-12/23
Moderate–severe Crohn and UC
Anti-TNF: TB/HBV reactivation (screen), infections, lymphoma

Mechanism — the vomiting center's inputs

Chemoreceptor trigger zoneD2, 5-HT₃, NK1 (blood toxins)
Vestibular systemH1, M1 (motion)
Gut vagal afferents5-HT₃ (chemotherapy)
Vomiting center (medulla)
→
Pick the drug that blocks the active input

Laxative classes

CLASS
EXAMPLE
ONSET
Bulk
Psyllium
1–3 days
Osmotic
PEG, lactulose
1–2 days
Stimulant
Senna, bisacodyl
6–12 h
Saline
Mg citrate
0.5–3 h

How it's tested

COMMON CONFUSIONMetoclopramide speeds the stomach but is a dopamine blocker — it causes extrapyramidal symptoms and worsens Parkinson disease (use domperidone where available).
THE TRAPAntimotility agents in C. difficile or bloody diarrhea can precipitate toxic megacolon.
YOUR APPROACHCause of nausea → receptor → drug. Constipation → bulk/osmotic first, stimulant for opioids, peripheral μ blocker if refractory.

If you see… think…

Involuntary lip-smacking after months of a GI drug → metoclopramide tardive dyskinesia
Chemotherapy nausea, prolonged QT → ondansetron
Delayed chemotherapy nausea, substance P → aprepitant
Hepatic encephalopathy laxative → lactulose
Opioid constipation without reversing analgesia → methylnaltrexone
Oligospermia in a man with UC → sulfasalazine
Positive TB test needed before IBD biologic → anti-TNF
Gut-selective integrin antibody → vedolizumab
Brown-black colon mucosa on colonoscopy → chronic anthraquinone (senna) use
Motion sickness patch → scopolamine