Dr.

Ahmed Al- Akydy

Assist. Prof. Pharmacology
&
Therapeutics
 Learning outcomes

 On completion of this case study, you will be able to:

1) Outline the risk factors for essential and secondary hypertension

2) Explain how high BP may damage the body tissues
3) Outline tests to clarify the causes of hypertension

4) Compare the antihypertensive actions of beta-adrenoceptor (β-

adrenoceptor) antagonists, agents acting on the renin–
angiotensin system and short-acting agents such as labetalol
5) Explain how very high BP may be treated.
 CASE
A 50-year-old man has been diagnosed with hypertension
picked up at a routine medical at work. He attends his GP
for assessment of his cardiovascular risk. He has no past
medical history of note, has a strong family history of
ischaemic heart disease (his father had a myocardial
infarction at aged 38 years) and he has a 30-year pack
history of smoking. On examination he is obese and his
blood pressure measurement is consistently >160/90
mmHg.
 Q: What are the factors that contribute to his
cardiovascular risk and how should he be managed?
 CASE STUDY
 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 BP was
230/125mmHg and she was sweaty and anxious with a heart rate of
120 beats per minute.
 CASE STUDY- continue
 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 BP was ‘quite
high’ a year ago, when she was prescribed a β-adrenoceptor
antagonist (beta-blocker). Since it did not make her feel better, she
stopped taking the β-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.
 Questions
Q1: What is the normal range of BP and resting heart rate in Billie’s age
group?
Q2: List the risk factors for the development of essential hypertension. Is
Billie likely to have this type of hypertension?
Q3: Is Billie’s alcohol consumption and smoking likely to be
contributing to her BP problem?
Q4: Which antihypertensive agents are suitable for treating young adults
with hypertension?
Q5: What are the adverse effects of the β-blockers? Is fatigue a common
side effect of their use?
Q6: Although the cause of essential hypertension is unknown, there are
several possible secondary causes which could lead to increased BP.
Name the conditions which are known to cause secondary
hypertension.
Q7: What investigations could be performed to clarify the cause of
Billie’s extremely high BP?
 CASE STUDY- continue
 Part 2
 Very high BP can affect the brain, causing visual disturbance,
irritability, confusion and possibly epileptic seizures. Billie’s high
BP 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 BP, pressure must be reduced gradually over
several hours, with frequent measurements to confirm that
 CASE STUDY- continue

 pressure reduction is satisfactory. Once BP 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 BP
permanently, but in the short term drug treatment will be needed to
lower BP to an acceptable range.
 CASE STUDY- continue
Q8: Why is it necessary to find out if a young female patient is pregnant,
taking POMs or self-medicating?

Q9: Sodium nitroprusside can be used to rapidly reduce BP in hypertensive

emergencies, but it is not suitable as a regular antihypertensive
medication. Why is this?
Q10: Renal artery stenosis causes the kidney to become ischaemic. How
does this result in high BP?
Q11: Which agents would be suitable to treat hypertensive patients who
have a high renin level? Give reasons for your answer.
Q12: Labetalol is a short-acting antihypertensive agent which can be used in
a hypertensive emergency. What is the mechanism of action of labetalol?
 Answer
 Part 1
• An1: BP increases with age; systolic pressure usually rises faster than diastolic
pressure. A normal range of BP 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.
• An2 : The cause of 90% of hypertension (essential hypertension) is unknown. Risk
factors for essential hypertension include:

1) Family history (genetic factors)

2) Obesity,

3) Lack of exercise and sedentary habits

4) Alcohol abuse
5) High salt intake

6) Stressful work and lifestyle.

 Answer - continue

• 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 BP is very high and requires immediate treatment.
 Answer- continue

• An3 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.
• An4 For young people with essential hypertension, either a β- blocker
or an ACE inhibitor is recommended. For older patients, the
medication of choice for hypertension is either a diuretic or CCBs
 Answer- continue

• An5 β-blocker 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,
hyperglycaemia, 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.
 Answer- continue
• An6 The conditions associated with secondary hypertension include:

1) Renal disease, including renal parenchymal disease, for example

pyelonephritis and renal failure
2) Tumours of the adrenal medulla, for example phaeochromocytoma

3) Tumours of the adrenal cortex, for example in Cushing’s

syndrome

4) Vascular diseases, such as stenosis of the aorta or renal artery

5) Pre-eclampsia (in pregnancy)

6) Iatrogenic disease (one caused by medication), for example oral

contraceptives, corticosteroids.
 Answer- continue
• An7 When hypertension is discovered, the following tests may be
recommended:

1) Blood cell count, ESR 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.
 Answer- continue
 Part 2

• An8 A pregnancy test is necessary because hypertension is a

feature of preeclampsia, 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 BP.
 Answer- continue
• An9: 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 IV 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.
• An10: 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.
 Answer - continue

• Renin acts on angiotensinogen to produce angiotensin I, which is

converted to angiotensin II by ACE. Angiotensin II is a potent
vasoconstrictor that increases BP. 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 BP. Surgical removal
of a renal artery obstruction usually reduces BP to an acceptable
level and any residual hypertension can be easily managed.
 Answer - continue
• An11: 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 BP 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.
 Answer - continue

• An12: 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 BP.
 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 BP, 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
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 may be a cause of escalating high
BP, 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.