A hypertensive emergency
• outline the risk factors for essential and secondary hypertension;
• explain how high blood pressure may damage the body tissues;
• outline tests to clarify the causes of hypertension;
• compare the antihypertensive actions of beta-adrenoceptor antagonists, agents acting on the renin-angiotensin system and short-acting agents such as labetalol;
• explain how very high blood pressure may be treated.
Part 1
Billie is a 26-year-old computer officer in a busy organization. Her job involves hours of screen work and she also has an evening job at the offices of a supermarket chain. She originally attributed her bad headaches to the stress of doing two jobs. However, her headaches have become much more severe over the last five days and so, since she has also experienced visual disturbances, she decided to go to the accident and emergency department of her local hospital today.
On examination Billie’s blood pressure was 230/125 mmHg and she was sweaty and anxious with a heart rate of 120 beats per minute. This is extremely high for a young person and may indicate malignant hypertension or a hypertensive crisis. Billie described a family history of hypertension and admitted that her blood pressure was ‘quite high’ a year ago, when she was prescribed a beta-adrenoceptor antagonist (beta-blocker). Since it did not make her feel better, she stopped taking the beta-blocker after a few months. It emerged that the drug had made her so tired that it was difficult to continue her evening job, and she needed the extra income. Billie smokes about 10 cigarettes a day and drinks moderately, consuming the equivalent of two bottles of wine a week. Her urine sample showed a moderate albumin content but no other abnormalities.
What is the normal range of blood pressure and resting heart rate in Billie’s age group?
Blood pressure increases with age; systolic pressure usually rises faster than diastolic pressure. A normal range of blood pressure for a person in the age group 20-30 years is likely to be 110-120 mmHg systolic and 70-80 mmHg diastolic. Resting heart rate is normally 50-70 beats per minute.
List the risk factors for the development of essential hypertension. Is Billie likely to have this type of hypertension?
The cause of 90% of hypertension (essential hypertension) is unknown. Risk factors for essential hypertension include:
• family history (genetic factors)
• obesity, lack of exercise and sedentary habits
• alcohol abuse
• high salt intake
• stressful work and lifestyle.
Essential hypertension is a silent pathological process which progresses at a variable rate in different individuals, damaging tissues of the heart, brain, kidney and eye, but usually produces no symptoms. Since the condition is normally symptomless, there is likely to be a large number of undiagnosed hypertensive patients in the community.
Billie might have developed rapidly worsening essential hypertension or might have hypertension that is secondary to another condition. Her headache could possibly be associated with a recent viral infection, unconnected with her hypertension. Whatever the underlying cause, Billie’s blood pressure is very high and requires immediate treatment.
Is Billie’s alcohol consumption and smoking likely to be contributing to her blood pressure problem?
Billie drinks modestly; she is not exceeding the recommended maximum weekly intake for women. In addition there is some evidence that moderate consumption of wine, particularly red wine, can benefit the heart. Although cigarette smoking contributes to overall cardiovascular risks, it does not appear to be directly associated with hypertension, unless it is very heavy.
Which antihypertensive agents are suitable for treating young adults with hypertension?
For young people with essential hypertension, either a beta-blocker or an ACE inhibitor is recommended. For older patients, the medication of choice for hypertension is either a diuretic or calcium channel blocker.
What are the adverse effects of the beta-adrenoceptor antagonists (beta-blockers)? Is fatigue a common side effect of their use?
Beta-blockers can have a number of adverse effects. In fact, all drugs used to treat hypertension have some side effects. Beta-adrenoceptor antagonists are no exception, and Billie did not perceive that taking the β-blocker was helping her. Side effects include cold extremities, hypoglycaemia, bronchoconstriction (making them unsuitable for asthmatic hypertensive patients) and sometimes bad dreams or nightmares. Some patients taking β-blockers appear to be particularly affected by fatigue. Since hypertension is itself without symptoms, the benefits of drug treatment may not be apparent to a patient. Drug compliance can therefore be a problem.
Although the cause of essential hypertension is unknown, there are several possible secondary causes which could lead to increased blood pressure. Name three conditions which are known to cause secondary hypertension.
The conditions associated with secondary hypertension include:
• renal disease, including renal parenchymal disease, for example pyelonephritis and renal failure
• tumours of the adrenal medulla, for example phaeochromocytoma
• tumours of the adrenal cortex, for example in Cushing’s syndrome
• vascular diseases, such as stenosis of the aorta or renal artery
• pre-eclampsia (in pregnancy)
• iatrogenic disease (one caused by medication), for example oral contraceptives, corticosteroids.
What investigations could be performed to clarify the cause of Billie’s extremely high blood pressure?
When hypertension is discovered, the following tests may be recommended:
(1) blood cell count, erythrocyte sedimentation rate and plasma electrolytes
(2) blood glucose, cholesterol, urea and creatinine
(3) examination of urine (e.g. for glucose and albumin)
(4) chest X-ray (to detect ventricular hypertrophy).
The eyes should be examined for retinal changes. If stenosis of an artery is suspected, further tests, scans and angiography are carried out.
Part 2
Very high blood pressure can affect the brain, causing visual disturbance, irritability, confusion and possibly epileptic seizures. Billie’s high blood pressure could be due to escalating essential hypertension, but in a young person it is likely to be secondary to another cause. Before an investigation begins, it is important to establish whether she is pregnant, taking prescribed medicines or is self-medicating. An examination of Billie’s eyes showed some haemorrhage and exudate in her retina, indicating severe hypertension. In patients with dangerously high blood pressure, pressure must be reduced gradually over several hours, with frequent measurements to confirm that pressure reduction is satisfactory. Once blood pressure is in the ‘safe’ range, other tests can be performed to discover a possible explanation for the severe hypertension.
X-rays, angiography and scans confirmed that Billie’s problem was renal artery stenosis, a condition most commonly seen in females of 20-50 years of age. Removal of the obstruction to renal blood flow is required to reduce blood pressure permanently, but in the short term drug treatment will be needed to lower blood pressure to an acceptable range.
Why is it necessary to find out if a young female patient is pregnant, taking prescribed medication or self-medicating?
A pregnancy test is necessary because hypertension is a feature of pre-eclampsia, a serious condition which can occur in pregnancy and which threatens the life of both mother and foetus. Also, many antihypertensive drugs are contraindicated in pregnancy. It is necessary to know whether the patient is taking prescribed medicines or is self-medicating, as some drugs, such as monoamine oxidase inhibitors (MAOIs), can interact with dietary components to cause a very rapid rise in blood pressure.
Sodium nitroprusside can be used to rapidly reduce blood pressure in hypertensive emergencies, but it is not suitable as a regular antihypertensive medication. Why is this?
Sodium nitroprusside acts via the production of NO. It is a powerful vasodilator and a potent, rapidly acting antihypertensive agent. The drug is administered by intravenous infusion but is then converted to thiocyanate in plasma. Thiocyanate toxicity can occur with continued use; consequently, sodium nitroprusside can be used only for short-term treatment.
Renal artery stenosis causes the kidney to become ischaemic. How does this result in high blood pressure?
When the lumen of the renal artery is reduced by >70%, the kidney becomes ischaemic and the renin-angiotensin system is activated. Renal ischaemia causes a reduction in glomerular function and triggers the release of renin from juxtaglomerular cells. Renin acts on angiotensinogen to produce angiotensin I, which is converted to angiotensin II by ACE. Angiotensin II is a potent vasoconstrictor that increases blood pressure. Angiotensin II also releases aldosterone, which stimulates the kidney to retain more salt and water, and so increases extracellular fluid and blood volume. An increase in blood volume results in increased blood pressure.
Surgical removal of a renal artery obstruction usually reduces blood pressure to an acceptable level and any residual hypertension can be easily managed.
Which agents would be suitable to treat hypertensive patients who have a high renin level? Give reasons for your answer.
The antihypertensive drugs which interact with the renin-angiotensin system are ACE inhibitors, angiotensin receptor antagonists and β-blocking drugs (which reduce renin secretion via antagonism at the β1-receptor on juxtaglomerular cells). This group of agents is less effective in patients who have low renin levels. It explains why agents affecting the renin-angiotensin system are less active than diuretics and calcium channel blocking drugs in lowering blood pressure in elderly people and Afro-Caribbeans, who generally have low plasma renin levels.
Hypertensive patients with normal or high renin levels can benefit from treatment with agents which affect the renin-angiotensin system.
Labetalol is a short-acting antihypertensive agent which can be used in a hypertensive emergency. What is the mechanism of action of labetalol?
Labetalol has antagonist effects at both alpha- and beta-adrenoceptors. It acts rapidly and is one of the few agents which is safe to use in pregnancy. It both reduces cardiac output and elicits peripheral vasodilation. These actions reduce peripheral resistance and result in the effective lowering of blood pressure.
Key Points
• Ninety per cent of hypertension is essential hypertension which has no symptoms and no known cause. There is a genetic component, and various lifestyle factors increase blood pressure, such as obesity and sedentary habits, stress and a high salt and alcohol consumption.
• The drug of choice in young hypertensive patients is either a β-blocker or an ACE inhibitor. Beta-blockers have several side effects, including bronchoconstriction, hyperglycaemia, bad dreams and fatigue, which may be marked in some patients. Patient compliance can therefore be a problem.
• Only 5-10% of hypertension has a known cause; in these cases, it is secondary to a condition such as a tumour of the adrenal medulla, pre-eclampsia during pregnancy, renal disease or renal artery stenosis. Removal of the primary cause, such as stenosis of the renal artery, resolves the hypertension.
• Since pre-eclampsia of pregnancy maybe a cause of escalating high blood pressure, it is necessary to carry out a pregnancy test in young female patients. Also some antihypertensive agents are teratogenic and so are unsuitable in pregnant patients. Labetalol, an alpha- and beta-adrenoceptor antagonist, is a drug which is safe for treating hypertensive pregnant patients.
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