21st March 2024

Hepatic and renal impairment

Hepatic impairment

Metabolism is the main method of elimination for many drugs. In severe liver disease, the cytochrome P-450 system is reduced but can be complex and unpredictable. Dose adjustments may need to be made particularly if the drug is metabolised in the liver.

Hypoalbuminaemia

Severe hepatic disease can lead to reduced levels of albumin which is the most abundant plasma protein. In this state, there is a decrease in plasma protein binding. The unbound drug is able to pass through the cell membrane and exert its effects on cells. Highly protein bound drugs such as doxycycline, phenytoin and prednisolone exert larger effects than usual.

Coagulopathy

Patients with severe liver function may have impaired synthesis of clotting factors. This leads to increased sensitivity to drugs such as phenindione and warfarin.

Encephalopathy

Patients with hepatic encephalopathy may have symptoms exacerbated by sedatives, opioids, constipating agents and electrolyte disturbances which can also be precipitated by diuretics.

Renal impairment

In those with renal impairment absorption, distribution, metabolism and elimination are all impaired. There is an overall increased risk of adverse drug reactions in part due to the accumulation of active metabolites and reduced secretion and resorption.

NSAIDs and COX II inhibitors should be avoided as they can lead to reduced glomerular filtration rate and acute interstitial nephritis. One should be cautious using opioids, tramadol, gabapentinoids and benzodiazepines as these may accumulate and lead to sedation and respiratory depression.

Nitrates and rate controlling antihypertensives should be used with care as may worsen renal hypoperfusion and the latter cause bradycardia. Digoxin and ACEi in settings of acute renal impairment can exacerbate hyperkalaemia. Thiazides, loop diuretics and potassium sparing diuretics can lead to electrolyte imbalances. Contrast media can have a direct tubular toxic effect, where appropriate patients should be hydrated before and after contrast.

Antihyperglycemics can accumulate leading to hypoglycaemia and metformin can lead to lactic acidosis. Low molecular weight heparin and direct oral anticoagulants may accumulate in patients with impaired renal function, leading to risk of bleeding. In patients taking warfarin, an acute rise in urea may raise INR.

References

• Bnf.nice.org.uk. 2022. Prescribing in the elderly, hepatic impairment, renal impairment, pregnancy | Medicines guidance | BNF content published by NICE. [online] Available at: <https://bnf.nice.org.uk/medicines-guidance>
• Bnf.nice.org.uk. 2022. Hypertension, epilepsy, diabetes, pregnancy and breastfeeding | Treatment summaries | BNF content published by NICE. [online] Available at: https://bnf.nice.org.uk/treatment-summaries
• Bertram Katzung, Anthony Trevor, Basic and Clinical Pharmacology, 15th edn (San Francisco, CA: McGraw Hill / Medical, 2021).