Clinical Pharmacology and Therapeutics

40 EFFECTS OF DISEASE ON DRUG DISPOSITION
Case history
A 57-year-old alcoholic is admitted to hospital because of
gross ascites and peripheral oedema. He looks chronically
unwell, is jaundiced, and has spider naevi and gynaecomastia.
His liver and spleen are not palpable in the presence of
marked ascites. Serum chemistries reveal hypoalbuminuria
(20 g/L), sodium 132 mmol/L, potassium 3.5 mmol/L, creatinine
105 μmol/L, and international normalized ratio (INR) is
increased at 1.8. The patient is treated with furosemide
and his fluid intake is restricted. Over the next five days he
loses 10.5 kg, but you are called to see him because he has
become confused and unwell. On examination, he is drowsy
and has asterixis (‘liver flap’). His blood pressure is
100/54 mmHg with a postural drop. His serum potassium is
2.6 mmol/L, creatinine has increased to 138 μmol/L and the
urea concentration has increased disproportionately.
Comment
It is a mistake to try to eliminate ascites too rapidly in patients
with cirrhosis. In this case, in addition to prerenal renal failure,
the patient has developed profound hypokalaemia,
which is commonly caused by furosemide in a patient with
secondary hyperaldosteronism with a poor diet. The
hypokalaemia has precipitated hepatic encephalopathy. It
would have been better to have initiated treatment with
spironolactone to inhibit his endogenous aldosterone. Low
doses of furosemide could be added to this if increasing
doses of spironolactone up to the maximum had not produced
adequate fluid/weight loss. Great caution will be
needed in starting such treatment now that the patient’s
renal function has deteriorated, and serum potassium
levels must be monitored closely.
FURTHER READING
Carmichael DJS. Chapter 19.2 Handling of drugs in kidney disease. In:
AMA Davison, J Stewart Cameron, J-P Grunfeld, C Ponticelli,
C Van Ypersele, E Ritz and C Winearls (eds). Oxford textbook of clinical
nephrology, 3rd edn. Oxford: Oxford University Press, 2005:
2599–618.
Rowland M, Tozer TN. Disease. In: Clinical pharmacokinetics: concepts
and applications, 3rd edn. Baltimore: Williams and Wilkins, 1995:
248–66.