Lecture 10.1 – Hepatic Case Drug Handling in liver disease (safe prescribing)

Flashcards covering patient factors, drug factors, pharmacokinetics (absorption, distribution, metabolism, elimination), cholestasis effects, routes of administration, and general cautions for safe prescribing in liver disease.

What is the main purpose of the Child-Pugh Scoring System in the context of drug handling in liver disease?

It is not developed to predict drug handling; it assesses disease severity and likely outcomes.

How do BNF/SPC recommendations typically categorize medications for patients with liver disease?

The vast majority of medications are cautioned or contraindicated.

List key patient factors to consider when dosing drugs in liver disease.

Underlying diagnosis; overall severity (Child-Pugh/MELD); signs and symptoms; trends in LFTs/disease progression; overall goals for care.

List key drug factors that influence safe prescribing in liver disease.

Pharmacokinetic properties (bioavailability F, volume of distribution Vd, clearance Cl); pharmacodynamic properties; side‑effect profile; therapeutic index; route of administration.

What general approach should be taken regarding hepatotoxic medicines and half-lives?

Avoid hepatotoxic medicines; ideally use medicines with a shorter half-life; start with a small dose and titrate; monitor closely.

When should dose reduction be considered based on lab values in liver disease?

If INR/prothrombin time and bilirubin are raised or albumin is low.

What dosing strategy is recommended at initiation for liver disease patients?

Start with a small dose and increase slowly or dose as required; monitor the patient with regular review.

How does bilirubin affect pharmacokinetics in liver disease?

Absorption for highly lipophilic drugs may be reduced; biliary clearance may be reduced; enterohepatic circulation may reduce exposure; competition for protein binding sites may enhance clinical effect.

Is there a direct link between AST/ALT and drug exposure (AUC) in liver disease?

No direct link; AST/ALT can be normal in cirrhosis; cholestasis may be indicated by ALP and GGT elevations.

What cholestasis-related changes can occur to drug absorption and clearance?

Reduced protein binding; reduced absorption of lipid-soluble drugs; drugs eliminated by biliary routes may accumulate.

What happens to enterohepatic circulation in cholestasis?

Enterohepatic circulation is reduced, potentially reducing drug effectiveness (e.g., MMF).

What is the risk to drugs with extensive biliary clearance in liver disease?

They may accumulate (e.g., vinca alkaloids, doxorubicin).

How can hepatorenal syndrome affect renal function assessment like eGFR?

eGFR can be overestimated in cirrhosis; renal excretion of drugs can be affected.

Describe low extraction ratio drugs in liver disease and their management.

Clearance is less dependent on blood flow; hepatic blood flow reduction has limited effect; bioavailability is usually unaffected unless highly protein-bound; metabolism depends on liver function; reduced function → delayed elimination and longer half-life; may need dose interval adjustment (e.g., citalopram, theophylline).

Describe high extraction ratio drugs in liver disease and their management.

Clearance depends on hepatic blood flow; reduced hepatic blood flow increases bioavailability; may require dose and dose interval adjustment (e.g., propranolol, morphine, sertraline, sumatriptan).

Give two examples of low extraction ratio drugs mentioned in the notes.

Citalopram and theophylline.

Give four examples of high extraction ratio drugs mentioned in the notes.

Propranolol, morphine, sertraline, sumatriptan.

What effect does cholestasis have on protein binding and lipid-soluble drug absorption?

Bile salts compete for protein binding sites, reducing protein binding and reducing absorption of lipid-soluble drugs.

What is a potential consequence of extensive biliary clearance in liver disease?

Drugs may accumulate (e.g., vinca alkaloids, doxorubicin).

How can hepatic disease affect renal excretion estimates like eGFR?

eGFR can be overestimated due to hepatorenal syndrome; renal excretion of drugs may be affected.

Which drugs/classes can worsen encephalopathy through sedation in liver disease?

Sedation from opioids, benzodiazepines, and hypnotics can worsen encephalopathy; brain sensitivity is increased.

Which drugs increase the risk of GI mucosal damage and bleeding in liver disease?

NSAIDs, aspirin, and bisphosphonates.

Which medications can precipitate or worsen constipation and thereby worsen encephalopathy in liver disease?

Opioid analgesics, sedating antihistamines, and antimuscarinics.

What general cautions should be considered regarding clotting, fluids, and sodium in liver disease medications?

Be cautious with drugs affecting clotting (warfarin, aspirin, clopidogrel, NSAIDs); diuretics can cause fluid/electrolyte imbalance; some preparations have high sodium content; consider narrow therapeutic index and hepatotoxic/nephrotoxic risks.

What routes of administration are generally preferred and which should be avoided in liver disease?

Oral preferred; avoid modified-release and long-acting formulations; avoid IM if clotting is deranged; topical may irritate; rectal route can be used if varices/bleeding are present.

What key considerations should you review before prescribing in liver disease (checklist)?

Is the medicine highly metabolised in the liver? What is its side‑effect profile? Is there potential for renal impairment? What is the route of administration? How will you titrate to patient response?

What is a concise takeaway about drug handling in liver disease from these notes?

Treat patients with liver disease carefully by considering patient and drug factors, monitor labs and clinical status, avoid hepatotoxic meds when possible, and tailor dosing and routes to liver function and disease severity.