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Diuretics
These also fall into two main groups: thiazides and loop diuretics (Table 19.4). Thiazides are very effective first-line agents in uncomplicated essential hypertension, as shown in the ALLHAT trial. However, they do have side effects, including glucose intolerance, and have been linked to the development of hyperosmolar hyperglycemic state (HHS; see Chapter 12). In patients with an eGFR < 60 mL/ min/1.73 m 2 they are rarely effective in producing a diuresis and more potent loop diuretics are required. Diuretics act in synergy with RAS-blocking agents.
β-Blockers
These drugs reduce cardiac output, slow heart rate and reduce renin release in the kidney (Table 19.5). They are of proven benefit in angina, post-MI and in heart failure. Non-cardioselective β-blockers can worsen bronchospasm and are contraindicated in people with asthma. They can also blunt some symptoms of hypoglycemia and exacerbate symptomatic peripheral vascular disease. For these reasons only cardioselective β-blockers should be used in diabetes. β-Blockers are associated with the development of glucose intolerance and type 2 diabetes and are no longer first-line therapy in the latest British Hypertension Society Guidelines.
Other agents
α-Blocking drugs were associated with more heart failure in the ALLHAT study and should not be used as monotherapy. They may be helpful in men with prostatic symptoms by improving urine flow.
Centrally acting drugs are limited to patients who cannot tolerate first-line agents. However, they have problems with drowsiness, postural hypotension and depression. Methyldopa is completely safe in pregnancy and is useful as an alternative to contraindicated agents such as RAS blockers.
Combination therapy
The UKPDS showed that most patients require three or more agents to achieve what would be regarded now as the modest target of 144/82 mmHg. Current data from the Diabetes Audit in the UK show that approximately 30% of people with diabetes had a recorded blood pressure ≤ 135/ ≤ 75 mmHg in 2007 – 8 which is similar to data from the USA (28 – 36% of treated people with type 2 diabetes had a blood pressure < 130/80). Even in clinical trials the current target for diabetes is challenging; < 30% of the 5137 diabetic patients in the ASCOT-BPLA trial achieved a blood pressure < 130/80 mmHg.
Current British Hypertension Society recommendations are for either an RAS or calcium channel-blocking agent or thiazide as first line, with the addition of another class if target is not reached (Figure 19.5). Other guidelines still include β-blockers as first line. Most suggest titration of dose of each class to the maximum effective tolerated level before adding another agent, although this does run the risk of more side effects. In order to reduce the numbers of tablets, combination medications have been developed (such as RAS blockers and diuretics, β-blockers and diuretics) in an attempt to improve compliance.
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Rudy Bilous MD, FRCP, Professor of Clinical Medicine, Newcastle University, Honorary Consultant Endocrinologist, South Tees Foundation Trust, Middlesbrough, UK Richard Donnelly MD, PHD, FRCP, FRACP, Head, School of Graduate Entry Medicine and Health, University of Nottingham, Honorary Consultant Physician, Derby Hospitals NHS Foundation Trust, Derby, UK
A John Wiley & Sons, Ltd., Publication This edition first published 2010, © 2010 by Rudy Bilous and Richard Donnelly. Previous editions: 1992, 1999, 2004
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