A Textbook of Clinical Pharmacology and Therapeutics

280 NEPHROLOGICAL AND RELATED ASPECTS
DRUGS FOR PROSTATIC OBSTRUCTION
Prostatic obstruction is often managed surgically. Symptoms
of benign prostatic hypertrophy may be improved by a 5αreductase
inhibitor (e.g. finasteride, Chapters 41 and 48) or by
an α 1-adrenoceptor antagonist (e.g. doxazosin, Chapter 28).
Tamsulosin, an α 1-adrenoceptor antagonist selective for the
α 1A-adrenoceptor subtype, produces less postural hypotension
than non-selective α 1-adrenoceptor antagonists. Hormonal
manipulation with anti-androgens and analogues of luteinizing
hormone-releasing hormone (LHRH) is valuable in
patients with prostatic cancer (Chapter 48).
ERECTILE DYSFUNCTION
Erectile failure has several organic, as well as numerous psychological,
causes. Replacement therapy with testosterone,
given by skin patch, is effective in cases caused by proven
androgen deficiency. Nitric oxide is involved in erectile function
both as a vascular endothelium-derived mediator and as a
non-adrenergic non-cholinergic neurotransmitter. This has led
to the development of type V phosphodiesterase inhibitors as
oral agents to treat erectile dysfunction. Sildenafil (Viagra)
was the first of these to be introduced, there are several other
longer-acting agents in this class currently. These drugs are
discussed in Chapter 41.
Case history
A 35-year-old woman has proteinuria (3 g/24 hours) and
progressive renal impairment (current serum creatinine
220 μmol/L) in the setting of insulin-dependent diabetes
mellitus. In addition to insulin, she takes captopril regularly
and buys ibuprofen over the counter to take as needed for
migraine. She develops progressive oedema which does not
respond to oral furosemide in increasing doses of up to
250 mg/day. Amiloride (10 mg daily) is added without benefit
and metolazone (5 mg daily) is started. She loses 3 kg
over the next three days. One week later, she is admitted to
hospital having collapsed at home. She is conscious but
severely ill. Her blood pressure is 90/60 mmHg, heart rate is
86 beats/minute and regular, and she has residual peripheral
oedema, but the jugular venous pressure is not raised.
Serum urea is 55 mmol/L, creatinine is 350 μmol/L, K � is
6.8 mmol/L, glucose is 5.6 mmol/L and albumin is 3.0 g/dL.
Urinalysis shows 4� protein. An ECG shows tall peaked Twaves
and broad QRS complexes.
Question
Decide whether each of the following statements is true or
false.
(a) Insulin should be withheld until the patient’s
metabolic state has improved.
(b) Metolazone should be stopped.
(c) The furosemide dose should be increased in view of
the persistent oedema.
(d) Ibuprofen could have contributed to the
hyperkalaemia.
(e) Captopril should be withheld.
Answer
(a) False
(b) True
(c) False
(d) True
(e) True
Comment
Although highly effective in causing diuresis in patients
with resistant oedema, combination diuretic treatment
with loop, K � -sparing and thiazide diuretics can cause
acute prerenal renal failure with a disproportionate
increase in serum urea compared to creatinine. Resistance
to furosemide may be related to the combination of
reduced GFR plus albuminuria. The combination of an
NSAID, captopril and amiloride is extremely dangerous,
especially in diabetics, and will have contributed to the
severe hyperkalaemia. The NSAID may also have led to
reduced glomerular filtration. Glucose with insulin would
be appropriate to lower the plasma K � .
Case history
A 73-year-old man has a long history of hypertension and of
osteoarthritis. Three months ago he had a myocardial infarction,
since when he has been progressively oedematous and
dyspnoeic, initially only on exertion but more recently also
on lying flat. He continues to take co-amilozide for his
hypertension and naproxen for his osteoarthritis. The blood
pressure is 164/94 mmHg and there are signs of fluid overload
with generalized oedema and markedly elevated jugular
venous pressure. Serum creatinine is 138 μmol/L and K � is
5.0 mmol/L. Why would it be hazardous to commence
furosemide in addition to his present treatment? What alternative
strategy could be considered?
Comment
The patient may go into prerenal renal failure with the
addition of the loop diuretic to the two more distal diuretics
he is already taking in the co-amilozide combination.
The NSAID he is taking makes this more likely, and also
makes it more probable that his serum potassium level
(which is already high) will become dangerously elevated.
It would be appropriate to consider hospital admission,
stopping naproxen (perhaps substituting paracetamol for
pain if necessary), stopping the co-amilozide and cautiously
instituting an ACE inhibitor (which could improve his prognosis
from his heart failure as described in Chapter 31) followed
by introduction of furosemide with close monitoring
of blood pressure, signs of fluid overload and serum creatinine
and potassium levels over the next few days.
FURTHER READING
Brater DC. Pharmacology of diuretics. American Journal of Medical
Science 2000; 319: 38–50.
Clark BA, Brown RS. Potassium homeostasis and hyperkalemic syndromes.
Endocrinology and Metabolism Clinics of North America 1995;
24: 573–91.