This topic covers drugs for complications of cirrhosis, gallbladder and cholestatic disease, and pancreatic insufficiency, plus the principles of dosing when the liver is failing.

Hepatic encephalopathy (HE) — ammonia and other gut-derived toxins bypass the damaged liver and reach the brain.

• Lactulose is a nonabsorbable sugar. Colonic bacteria break it into acids, which lower colonic pH. Ammonia (NH₃) is converted to ammonium (NH₄⁺), which cannot be absorbed and is excreted; the osmotic laxative effect speeds its removal
• Rifaximin is a minimally absorbed antibiotic that reduces ammonia-producing gut bacteria

Portal hypertension and ascites

• Nonselective beta blockers (carvedilol, propranolol, nadolol) lower cardiac output (beta-1) and cause splanchnic vasoconstriction (beta-2 blockade) → lower portal pressure; carvedilol also has alpha-1 blockade
• Octreotide (somatostatin analog) and vasopressin/terlipressin constrict splanchnic vessels → lower portal blood flow during variceal bleeding
• Spironolactone blocks aldosterone, which is high in cirrhosis → natriuresis; furosemide is added
• Albumin expands plasma volume after large-volume paracentesis, in spontaneous bacterial peritonitis (SBP), and in hepatorenal syndrome

Cholestasis and gallstones

• Ursodiol (ursodeoxycholic acid) replaces toxic bile acids and lowers cholesterol saturation of bile → dissolves small cholesterol stones; first-line for primary biliary cholangitis
• Cholestyramine (bile acid sequestrant) binds bile acids in the gut → relieves cholestatic itching

Pancreatic insufficiency

• Pancrelipase supplies lipase, protease, and amylase to digest fat, protein, and starch. Enteric-coated beads protect enzymes from stomach acid and release them in the duodenum — they must mix with food

Drug handling in liver disease — reduced metabolism (especially CYP450), less albumin (more free drug), portosystemic shunting (less first-pass metabolism → higher levels of oral drugs), and brain sensitivity (HE) all increase drug effects.

Lactulose: bloating, flatulence, cramping; excessive doses → diarrhea, dehydration, hypokalemia, hypernatremia — which can themselves worsen HE. Very sweet taste.

Rifaximin: nausea, peripheral edema, dizziness; rarely C. difficile infection.

Nonselective beta blockers: bradycardia, hypotension, fatigue, bronchospasm, masked hypoglycemia; in refractory ascites may worsen kidney perfusion.

Octreotide: hypoglycemia or hyperglycemia, bradycardia, conduction changes, gallstones, abdominal cramps, injection-site pain.

Vasopressin and terlipressin: ischemia (cardiac, mesenteric, digital), hypertension, hyponatremia, fluid overload; terlipressin — respiratory failure (higher risk with volume overload or ACLF grade 3), abdominal pain, diarrhea.

Spironolactone: hyperkalemia, gynecomastia, hyponatremia, kidney injury. Furosemide: hypokalemia, hyponatremia, volume depletion, kidney injury, ototoxicity with rapid IV doses.

Albumin: circulatory overload, pulmonary edema, rare allergic reactions.

Ursodiol: diarrhea, abdominal discomfort.

Cholestyramine: constipation, bloating, reduced absorption of fat-soluble vitamins (A, D, E, K) and of many drugs.

Pancrelipase: abdominal pain, nausea, hyperuricemia, mouth irritation if beads are chewed or held in the mouth, and fibrosing colonopathy (colonic stricture) at very high doses — usually above 2,500 lipase units/kg per meal or 10,000 lipase units/kg per day. Made from pig pancreas.

Lactulose: caution in diabetes (contains some free sugars); galactosemia (low-galactose diets); avoid other laxatives that make stool assessment unreliable.

Nonselective beta blockers: asthma, severe bradycardia or heart block; reduce or stop in refractory ascites with systolic BP below 90 mmHg, serum sodium below 130 mEq/L (mmol/L), or acute kidney injury; do not stop abruptly unless ordered (boxed warning for propranolol and nadolol — angina and MI on abrupt withdrawal).

Terlipressin: contraindicated with SpO₂ below 90% or worsening respiratory symptoms; assess volume status first — avoid with volume overload or ACLF grade 3 unless benefit outweighs risk; caution with ischemic heart or vascular disease.

Spironolactone: avoid potassium supplements, ACE inhibitors, ARBs, and trimethoprim unless closely monitored; hold with hyperkalemia or rising creatinine.

General drug safety in cirrhosis

• Avoid NSAIDs — kidney injury, GI bleeding, diuretic resistance
• Avoid ACE inhibitors and ARBs in clients with ascites
• Acetaminophen/paracetamol: limit to about 2 g/day in cirrhosis (safer than NSAIDs at this dose)
• Avoid or minimize sedatives, benzodiazepines, and opioids — they precipitate HE; if needed, lower doses and longer intervals
• Avoid aminoglycosides (kidney injury) where alternatives exist
• Many drugs need dose reduction by Child–Pugh class; check the label
• Herbal and dietary supplements can cause liver injury — ask about all products

Cholestyramine: give other drugs at least 1 hour before or 4–6 hours after; interacts with warfarin, levothyroxine, digoxin, thiazides, and fat-soluble vitamins. Contraindicated in complete biliary obstruction.

Ursodiol: aluminum antacids and bile acid sequestrants bind it — separate doses; estrogens and clofibrate increase cholesterol stone formation.

Pancrelipase: do not crush or chew; do not mix with alkaline foods (milk, pudding) — enteric coating dissolves early; H2RAs or PPIs may be added to improve effect; porcine origin — discuss with clients who avoid pork products.

1. Airway and safety in HE: assess level of consciousness, orientation, asterixis, sleep–wake reversal; aspiration precautions; fall precautions
2. Lactulose: titrate to 2–3 soft stools/day; count and record stools; monitor potassium and sodium (normal potassium 3.5–5.0 mEq/L (mmol/L); sodium 135–145 mEq/L (mmol/L)); watch for dehydration; may be given by nasogastric tube or as a retention enema when the client cannot swallow
3. Ammonia levels do not reliably reflect HE severity — clinical assessment guides treatment
4. Beta blockers: apical pulse and blood pressure before each dose; hold per parameters (e.g., heart rate below about 55/min or systolic BP below about 90 mmHg) and report
5. Variceal bleeding: protect the airway, two large-bore IVs, restrictive transfusion (hemoglobin target about 7–8 g/dL (70–80 g/L)), start octreotide and IV antibiotics as ordered, prepare for endoscopic band ligation within 12 hours; glucose monitoring on octreotide
6. Diuretics for ascites: daily weight at the same time (target loss about 0.5 kg/day without edema, 1 kg/day with edema), abdominal girth, intake and output, Na⁺, K⁺, creatinine; sodium restriction to about 2 g (88 mmol)/day
7. Paracentesis and albumin: client voids first; after the procedure monitor BP, pulse, and the site; give albumin as ordered
8. Terlipressin: SpO₂ and respiratory status before each dose; stop and report dyspnea, hypoxemia, or signs of fluid overload
9. Pancrelipase: give at the start of each meal and snack; assess stool (number, fat, oil, odor), weight, abdominal symptoms; dose by lipase units per kg or per gram of fat per prescription; for infants, open capsules onto a small amount of acidic soft food (e.g., applesauce) and give immediately, then follow with breast milk or formula
10. Liver function tests for clients on hepatotoxic drugs: ALT, AST, bilirubin, albumin, INR

• Lactulose: take daily and adjust to 2–3 soft stools; mix with juice to improve taste; report confusion, sleepiness, constipation, or more than 4 watery stools a day
• Avoid alcohol completely; avoid NSAIDs and herbal supplements; limit acetaminophen as instructed; ask before any new medicine, including over-the-counter products
• Adequate protein is needed in cirrhosis — do not restrict protein unless told; small frequent meals and a late-evening snack
• Beta blocker: do not stop suddenly; check pulse if taught; report dizziness or fainting
• Diuretics: weigh daily; follow the sodium limit; report muscle cramps, weakness, or confusion
• Pancrelipase: take with the first bite of every meal and snack; swallow capsules whole (or sprinkle beads on applesauce and swallow without chewing); do not keep beads in the mouth; do not change brands without advice (products are not interchangeable); report persistent oily stools, abdominal pain, or weight loss
• Cholestyramine: mix powder with fluid; take other medicines 1 hour before or 4–6 hours after
• Ursodiol: may take months to work; keep follow-up imaging and blood tests

• Lactulose traps ammonia as ammonium → titrate to 2–3 soft stools/day; watch K⁺, Na⁺, dehydration
• Rifaximin is added to lactulose to prevent recurrent HE
• Carvedilol (or propranolol/nadolol) prevents variceal bleeding — check pulse and BP; do not stop abruptly
• Acute variceal bleed: octreotide + IV antibiotic (ceftriaxone) + band ligation
• Terlipressin: respiratory failure boxed warning — do not give with SpO₂ below 90%
• Ascites: spironolactone + furosemide (100:40); monitor Na⁺, K⁺, creatinine, weight
• Albumin after paracentesis above 5 L and in SBP
• Cirrhosis: no NSAIDs, acetaminophen about 2 g/day or less, avoid sedatives
• Pancrelipase with every meal and snack; swallow whole; not with milk; very high doses → fibrosing colonopathy
• Cholestyramine binds other drugs: 1 hour before or 4–6 hours after