A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
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DRUGS USED TO TREAT DYSLIPIDAEMIA 183<br />
reduced). The risk <strong>of</strong> muscle damage is increased if they are<br />
taken with a statin, although lipid specialists sometimes<br />
employ this combination. They can cause a variety <strong>of</strong> gastrointestinal<br />
side effects, but are usually well tolerated.<br />
Contraindications<br />
Fibrates should be used with caution, if at all, in patients with<br />
renal or hepatic impairment. They should not be used in<br />
patients with gall-bladder disease or with hypoalbuminaemia.<br />
They are contraindicated in pregnancy <strong>and</strong> in alcoholics<br />
(this is particularly important because alcohol excess<br />
causes hypertriglyceridaemia; see Table 27.1).<br />
Pharmacokinetics<br />
Bezafibrate <strong>and</strong> gemfibrozil are completely absorbed when<br />
given by mouth, highly protein bound, <strong>and</strong> excreted mainly<br />
by the kidneys.<br />
OTHER DRUGS<br />
Other drugs sometimes used by lipidologists are summarized<br />
in Table 27.2. These include nicotinic acid which needs to be<br />
administered in much larger doses than needed for its effect as<br />
a B vitamin (Chapter 35). Its main effects on lipids are distinctive,<br />
namely to increase HDL, reduce TG <strong>and</strong> reduce Lp(a).<br />
Unfortunately, it has troublesome adverse effects including<br />
flushing (mediated by release <strong>of</strong> vasodilator prostagl<strong>and</strong>in<br />
D 2 ) which is reduced by giving the dose 30 minutes after a<br />
dose <strong>of</strong> aspirin.<br />
Key points<br />
Treatment <strong>of</strong> dyslipidaemia<br />
• Treatment goals must be individualized according to<br />
absolute risk. Patients with established disease need<br />
treatment irrespective <strong>of</strong> LDL.<br />
• Dietary measures involve maintaining ideal body<br />
weight (by caloric restriction if necessary) <strong>and</strong> reducing<br />
consumption <strong>of</strong> saturated fat – both animal (e.g. red<br />
meat, dairy products) <strong>and</strong> vegetable (e.g. coconut oil) –<br />
as well as cholesterol (e.g. egg yolk).<br />
• Drug treatment is usually with a statin (taken once<br />
daily at night) which is effective, well tolerated <strong>and</strong><br />
reduces mortality. Consider the possibility <strong>of</strong> secondary<br />
dyslipidaemia.<br />
• Ezetimibe is well tolerated. It is a useful adjunct to a<br />
statin in severely dyslipidaemic patients who show an<br />
inadequate response to a statin alone, <strong>and</strong> has almost<br />
completely replaced bile acid binding resins for this<br />
indication.<br />
• Fibrates are useful as a first-line treatment in patients<br />
with primary mixed dyslipidaemias with high<br />
triglyceride concentrations, as well as high LDL (<strong>and</strong><br />
<strong>of</strong>ten low HDL). Avoid in alcoholics.<br />
• Other reversible risk factors for atheroma (e.g.<br />
smoking, hypertension) should be sought <strong>and</strong> treated.<br />
• Consideration should be given to adjunctive use <strong>of</strong><br />
aspirin as an antiplatelet/antithrombotic drug.<br />
Case history<br />
A 36-year-old male primary-school teacher was seen because<br />
<strong>of</strong> hypertension at the request <strong>of</strong> the surgeons following<br />
bilateral femoral artery bypass surgery. His father had died<br />
at the age <strong>of</strong> 32 years <strong>of</strong> a myocardial infarct, but his other<br />
relatives, including his two children, were healthy. He did<br />
not smoke or drink alcohol. He had been diagnosed as<br />
hypertensive six years previously, since which time he had<br />
been treated with slow-release nifedipine, but his serum<br />
cholesterol level had never been measured. He had been<br />
disabled by claudication for the past few years, relieved<br />
temporarily by angioplasty one year previously. There were<br />
no stigmata <strong>of</strong> dyslipidaemia, his blood pressure was<br />
150/100 mmHg <strong>and</strong> the only abnormal findings were those<br />
relating to the peripheral vascular disease <strong>and</strong> vascular surgery<br />
in his legs. Serum total cholesterol was 12.6 mmol/L,<br />
triglyceride was 1.5 mmol/L <strong>and</strong> HDL was 0.9 mmol/L. Serum<br />
creatinine <strong>and</strong> electrolytes were normal. The patient was<br />
given dietary advice <strong>and</strong> seen in clinic four weeks after discharge<br />
from hospital. He had been able to run on the games<br />
field for the first time in a year, but this had been limited by<br />
the new onset <strong>of</strong> chest pain on exertion. His cholesterol level<br />
on the diet had improved to 8.0 mmol/L. He was readmitted.<br />
Questions<br />
Decide whether each <strong>of</strong> the following statements is true or<br />
false.<br />
(a) This patient should receive a statin.<br />
(b) Coronary angiography is indicated.<br />
(c) Renal artery stenosis should be considered.<br />
(d) The target for total cholesterol should be 6.0 mmol/L.<br />
(e) Ezetimibe would be contraindicated.<br />
(f) An α 1 -blocker for his hypertension could<br />
coincidentally improve his dyslipidaemia.<br />
(g) His children should be screened for dyslipidaemia <strong>and</strong><br />
cardiovascular disease.<br />
Answer<br />
(a) True.<br />
(b) True.<br />
(c) True.<br />
(d) False.<br />
(e) False.<br />
(f) True.<br />
(g) True.<br />
Comment<br />
It was unfortunate that this young man’s dyslipidaemia was<br />
not recognized earlier. Coronary angiography revealed severe<br />
inoperable triple-vessel disease. The target total cholesterol<br />
level should be 5.0 mmol/L <strong>and</strong> was achieved with a<br />
combination <strong>of</strong> diet, a statin at night <strong>and</strong> ezetimibe in<br />
the morning. Renal artery stenosis is common in the setting <strong>of</strong><br />
peripheral vascular disease, but renal angiography was negative.<br />
This patient’s relatively mild hypertension was treated<br />
with doxazosin (a long-acting α 1 -blocker, see Chapter 28)<br />
which increases HDL, as well as lowering blood pressure. He<br />
probably has heterozygous monogenic familial hypercholesterolaemia<br />
<strong>and</strong> his children should be screened. One <strong>of</strong> his<br />
sons is hypercholesterolaemic <strong>and</strong> is currently being treated<br />
with a combination <strong>of</strong> diet <strong>and</strong> a statin.<br />
FURTHER READING<br />
Durrington PN. Dyslipidaemia. Lancet 2003; 362: 717–31.<br />
Durrington PN. Hyperlipidaemia: diagnosis <strong>and</strong> management, 3rd edn.<br />
London: Hodder Arnold, 2005.