Download Hypertension Present - KSU Faculty Member websites

Hypertension
cardiovascular disease
characterized by
elevation of blood
pressure above
arbitrary values
considered “normal”
for people of similar
racial and
environmental
background
Done by
Imene Abderrazak Nalouti
‘9860257’
Supervised by
Dr. Rafiq Abou-Shabaan
P
Prroojjeecctt::
H
Hoossppiittaall 22 TTrraaiinniinngg C
Coouurrssee
22000000 ((S
Seem
meesstteerr IIX
X))
Page 1 of 37
Hypertension
I have great pleasure to express my heartfelt thanks and
gratitude to all those who have contributed to this little work.
The guidelines of Dr. Rafiq Abu Shabaan (Supervisor) and
Dr. Dana Salaam (Assistant Supervisor) out of their
career rich in this field were very useful in the making.
A special gratitude to the New Medical Center Hospital and
all the doctors and staff members that helped me out.
The project is only a drop of tears of joy, which is falling to
the vast and extensive field of literature. I can not claim cent
percent perfection for my effort. I do admit the errors and
omissions. Kindly forget and forgive.
Imene Abderrazak Nalouti
Abu Dhabi
January 15, 2001
Page 2 of 37
Hypertension
index
Page No.
Topic
Introduction
Definitions
Pathogenesis of HTN
Causes of secondary hypertension
Clinical clues suggesting a secondary form of HBP from initial hypertensive data
base
7. Resistant hypertension : Definition, causes
9. Hypertensive data base
10 Treatment/goal
11 Categories on Antihypertensive drugs
12 Stepped care regimens for the treatment of hypertension
13 The principle of “stepped care” therapy of hypertension
14
Classes of drugs used in the treatment
Diuretics
15
Beta- Adrenergic:
16
Angiotensin+ Calcium channel antagonists
17
Alpha II Agonistic/Vasodilators
18
Peripheral adrenergic neuron blockers
19 New anti-hypertensive drug classes/conclusions
20 Guidelines for selecting drug treatment of hypertension
21 Demographics And Anti-hypertensive Drugs
22 Mortality and CHD and Antihypertensive Therapy94
23 Characteristics of the ideal antihypertensive drug:
24 Differential antihypertensive therapy in specific clinical situation
25 Combination Antihypertensive Therapy : Selected Drugs
26 Efficacy of Monotherapy
27 The antihypertensive agents
28 Study case 1
Study case 2
Study case 3
Study case 4
1.
2.
3.
4.
6.
Study case 5
Gratitude
Page 3 of 37
Hypertension
Introduction
HTN is one of the major risk factors for coronary heart disease (CHD), cerebrovascular
accident (CVA), chronic renal failure (CRF), and congestive heart failure (CHF) in the USA.
CHD is the leading cause of death in US accounting for more than 600,000 deaths/ year
(1death/min).
HTN is part of a heterogeneous condition that is best described as an atherosclerotic
syndrome with genetic and acquired structural and metabolic disorders including the
following:
1.
2.
3.
4.
5.
6.
7.
Dyslipidemia
Insulin resistance & impaired glucose tolerance
Central obesity
Hyper uricemia
Renal function abnormalities (sodium, water uric acid)
Abnormalities of vascular and cardiac smooth muscle growth (structural
component).
Membranopathy and abnormal cellular cation transport
In understanding of the physiology and pathophysiology of the blood, vessels show that its
endothelial function plays an important role in end-organ-damage. Attention should be
directed at promoting vascular health in order to achieve optimal reduction in end-organ
damage.
Individualization of treatment is recommended based on the subsets
of hypertension approach, which is based upon:
1.
2.
3.
4.
5.
6.
7.
8.
Pathophysiology
Hemodynamics
Risk factor reduction and end-organ damage reduction
Concomitant medical disease or problems
Demographics
Quality of life and adverse effects of treatment
Compliance with therapy
Total health care cost
The primary goal in the treatment of essential HTN is to reduce all end-organ damages, not
simple to reduce blood pressure. TTN is associated with an increased risk of cerebrovascular,
cardiovascular and renal morbidity and mortality.
Page 4 of 37
Hypertension
Definitions
Blood pressure is the amount of force required for the heart to circulate the blood through
the body.
The systolic blood pressure represents the peak of the blood pressure curve and reflects
the maximal blood pressure during ventricular systole (i.e. when the ventricles are
contracting. The diastolic blood pressure represents the trough of the blood pressure curve
and reflects the minimal pressure in the vasculature at the end of ventricular diastole (i.e.
when the ventricles are filling with blood). Ideal blood pressure is 120/80 mm Hg.
Hypertension is simply defined as a cardiovascular disease characterized by elevation of
blood pressure above arbitrary values considered “normal” for people of similar racial and
environmental background. Since HTN affects organs of the body and causes their damage, it
is considered as a cardiovascular disease.
Table 1
Classification of adult blood pressure
Classification
Normal blood pressure
High normal blood pressure
Mild hypertension
Moderate hypertension
Severe hypertension
Classification
Normal blood pressure
Borderline isolated systolic
Isolated systolic hypertension
Diastolic Blood Pressure
< 80mm Hg
85 to 89
90 to 104
105 to 114
>115
Systolic Blood Pressure
(when diastolic BP < 90)
< 140mm Hg
> 140 to 159
> 160
The morbidity and mortality that is associated with hypertension increase linearly with higher
systolic and diastolic blood pressure. Even mild elevations in blood pressure are associated
with substantial health risks.
As a result, the World Health Organization (WHO) defines high blood pressure as a systolic
blood pressure greater than 140 mmHg and/or a diastolic blood pressure greater than 90
mmHg. A decrease in blood pressure, regardless of cause, decreases morbidity and
mortality. Treatment can be in a pharmacological and non-pharmacological approach or a
combination of both.
Since blood pressure can be highly labile, a single abnormally high blood pressure
measurement is of little significance in predicting long term cardiovascular risk.
“Office hypertension” is used to describe the phenomenon that is noted when a patient’s
blood pressure is increased during a clinic visit despite being somewhat lower at other times.
“Accelerated hypertension” is defined as a recent substantial increase in diastolic blood
pressure that is usually greater than 130mm/Hg. Papilledema (oedema of the optic disk) and
other end organ damages are not characteristics of accelerated hypertension “Malignant
hypertension” is defined as accelerated hypertension that is accompanied by severe
retinopathy, renal failure and a rapidly deteriorating clinical course. Malignant hypertension is
a hypertensive emergency.
Page 5 of 37
Hypertension
In practice, diastolic blood pressures are generally quite responsive to therapeutic
interventions, unlike systolic blood pressure, which is hard to control. This tells us that the
selection of an appropriate drug, dose and regimen is critical. The thiazide diuretics are
currently considered the drugs of choice when combined with non-drug interventions. 85% of
patients are adequately and safely managed.
Blood Pressure Measurements
Blood pressures should be measured according to established standardized techniques
because the results of blood pressure measurements vary with the technique that is used. A
recommended technique for blood pressure measurement is described below.
Proper technique for blood pressure measurement
1. The patient should be comfortable in a sitting or lying position for 3 to 5 minutes.
The arm should be free of tight clothing.
2. Determine equality of pulses and use the right arm if both pulses are equal.
3. The blood pressure cuff should be the correct size for the patient’s arm and
wrapped snugly. The bladder of the cuff should be centered over the brachial
artery about one inch above the anti cubital space. The arm should be at the level
of the heart.
4. Determine the systolic blood pressure by palpation (i.e. pump the cuff slowly until
radial pulse is no longer palpated which approximates systolic blood pressure).
5. After 1 minute, rapidly inflate the cuff to ~ 30 mm/Hg above the estimated systolic
blood pressure previously determined.
6. Deflate the cuff at a rate of 2 to 3 mm/Hg per second listening to the korotkoff
sounds and noting phase I and V (if possibly IV).
Pathogenesis Of HTN
Etiology
The vast majority (85 – 90%) of individuals with hypertension have essential or primary HTN ,
which has not established cause. Secondary causes of high blood pressure can be identified
only in about 6 to 10% of hypertensive patients.
Since secondary HTN affects only a small percentage of patients, thorough diagnostic
evaluations to uncover secondary causes of HTN should be reserved for patients at high risk
for secondary hypertension
Page 6 of 37
Hypertension
Pathophysiology
Arterial blood pressure is regulated by a number of variables. Simply stated using basic
hydrodynamic laws, mean arterial pressure (MAP) equals cardiac output (CO) times total
peripheral resistance (TPR):
MAP = CO X TPR
MAP is the average blood pressure in the arterial tree throughout the entire cardiac cycle that
includes both systole and diastole. Since the heart is in diastole for a longer time period than
systole, the MAP can be determined either mathematically by integrating the area under the
blood pressure curve, or approximated clinically by adding one third the value of the pulse
pressure (i.e. the difference between the systolic and diastolic pressure) to the diastolic
pressure. A normal MAP usually is less than 105 to 110mm/Hg.
Causes of secondary hypertension
1. Renal disease (such as)
a. Renoparenchymal disease
b. Renovascular disease
2. Coarcatation of the Aorta
3. Primary Aldosteronism
4. Cushings syndrome
5. Phaeochromocytoma
6. Drug Induced
a. Oral contraceptives
b. Anorectics
c. Alcohol
d. Thyroid hormone excess
e. Adrenocorticosteroids
f. Non-steroidal anti-inflammatory drugs
7. Increased intra cranial pressure
Blood pressure is usually maintained within a relatively constant range despite wide variations
in cardiac demand. When the cardiac output increases, a compensatory mechanism initiates
a decrease in peripheral resistance, like wise an increase in peripheral vascular resistance
results in a compensatory decrease in cardiac output. The blood pressure changes when
compensatory mechanisms are inadequate to offset an imbalance in one of these two
variables.
Early in the course of essential hypertension, the heart rate and cardiac output generally are
increased and the total peripheral resistance generally is either decreased or unchanged.
When hypertension becomes long standing with increasing age, the cardiac output tends to
decrease and the total peripheral resistance tends to increase. This increased resistance is
particularly noted in the kidneys resulting in increased secretion of rennin and subsequently
increased concentrations of angiotension II. The kidney is also directly affected by the
elevated blood pressure as noted by the development of nephrosclerosis, a fall in glomerular
filtration rate, and a deterioration of overall renal function. As total peripheral resistance
progresses from arteriolar constriction, cardiac out decreases and eventually the heart
compensates with hyperfunction.
Page 7 of 37
Hypertension
Hyperfunction increases cardiac demand , which eventually may lead to cardiac
decompensation.
Sympathetic overactivity or hyperdynamic beta-adrenergic circulatory state is another
important pathophysiological variable of essential hypertension. These patients with a
hyperdynamic beta-adrenergic component to their hypertension have an increased heart rate
response to isoproterenal compared to normal subjects. During episodes of increased
sympathetic nervous system activity (such as periods of psychological stress), increases in
cardiac output, heart rate, plasma renin concentration and peripheral vascular resistance are
noted. Simultaneously, the plasma volume is decreased. Clinically, these patients are often
young, white females who complain of unusual chest pain, often associated with palpitations
and/or cardiac awareness (i.e. the patient notices his/her heart beating profoundly), these
patients often are suspected erroneously to have phaeochromocytoma.
Another commonly proposed pathophysiologic mechanism for essential hypertension involves
a disorder of sodium metabolism. Apparently the extra cellular fluid volume increases
secondary to a genetic predisposition in-patients exposed to high dietary sodium intake.
Although a normal natriuretic response would be expected in the presence of high sodium
intake, these patients maintain an inappropriate high plasma volume relative to increased
peripheral vascular resistance.
The final hemodynamic outcome is an elevated blood pressure with increased peripheral
vascular resistance and “normal” plasma volume and cardiac output.
The cause(s) and pathophysiologic processes of hypertension remain an enigma and are
multifactorial. The evidence that these three mechanisms (i.e. renin, sympathetic over activity,
sodium balance) are somehow involved in some way in the pathogenesis of essential
hypertension is considerable and provides a conceptual framework for the diagnosis and
treatment of this disease. It is clear that emphasis must be placed on detection and treatment
of hypertension in the hope of preventing morbidity and mortality while the search for the cure
continues.
Page 8 of 37
Hypertension
Table 2
Clinical clues suggesting a secondary form of HBP from initial hypertensive
data base
Corrective clause
Historical clue
Physical examination
clue
Laboratory clue
Estrogen use
Oral contraceptive use or
menopause treatment
Renovascular disease
Moderate or severe HBP
before age 25 or after 50.
Rapidly progressive HBP
Abdominal bruitsa with
both systolic and diastolic
components.
Funduscopic hemorrhages
Suppressed or stimulated
plasma rennin activity
IVP (rapid sequences)
Digital subtraction
angiography
Renoparenchymal disease
Dysuria, polyuria
frequency, nocturia
Urinary tract infections,
Renal stones (or colic)
Family history – polycystic
kidney disease
Renal disease
Edema
Proteinuria
Hematuria
Bacteriuria
Coaretation
Intermittent elaudication
Diminished or absent
femoral pulses compared
to carotids. Lower systolic
leg BP compared to arm
BP
Clonidine suppression
testb. Elevated serum
glucose. Urine
metanephrine or
vanillymandelic acid
Pheochromocytoma
Paroxysmal headaches
palpitations, sweating
dizziness and pallor
(in 30% of patients)
Nervousness, tremor,
tachycardia, orthostatic
hypotension
Hypokalemiac
Primary aldosteronism
Weakness, polyuria,
polydipsia, intermittent
paralysis
Orthostatic hypotension
Elevated serum glucose.
Elevated plasma cortisol
after suppression with
dexamethasone
Cushings
Menstrual disturbances
Moon face
Truncal obesity
Buffalo hump
Hirsutism
Violet striae
a Majority of abdominal bruits do not originate from the renal artery
b Failure of plasma catecholamines to decrease by 50% within three hours of administration of 0.3 mg Clonidine
highly suggests pheochromocytoma
c Serum K + may be normal in 25% of patients
Page 9 of 37
Hypertension
Resistant hypertension
Definition:
The patient’s DBP remains above 90mm Hg despite full doses of three appropriate antihypertensive medications and has been documented on at least two separate visits in the
office under proper conditions and out of the office with home BP monitoring or 24-hour
ABPM.
Causes:
An inadequate drug regimen and patient noncompliance account for 70% of total causes.
1. Patient noncompliance to therapy
2. Inadequate drug regimen :
 Drug doses too low
 Drug interactions- antihypertensive agents ( two central alpha-agonists, two ACE I or
beta-blockers and central alpha-agonist with beta blocker)
 Rapid metabolism and interfering agents
 Other drug interactions and interfering agents. : (a-o)
a. Corticosteroids and anabolic steroids
b. Aldosterone (florinef)
c. Sympathomimetics and phenylpropanolamine
d. NSAIDSs ( ACE, beta blockers, diuretics)
e. Antidepressants- tricyclics and central alpha agonist
f. Decongestants-pseudoephedrine, nasal sprays
g. Excess alcohol ingestion (over 30 ml/day)
h. Excess caffeine ingestion (variable)
i. Excess tobacco use (variable)
j. Oral contraceptives
k. Erythropoietin
l. Cyclosporine
m. MAO inhibitors and phenothiazines
n. Cocaine and amephetamines
o. Appetite suppressants
3. Volume overload states
 Inadequate diuretic therapy
 High sodium intake (10 to 15 g/day )
 Secondary to BP reduction with some agents (diuretic Vasodilators) and some betablockers pseudotolerance caused by reflex volume overload, tachycardia, or vaso-constriction)
 Nephrosclerosis and CRF
4. Obesity and rapid weight gain
Page 10 of 37
Hypertension
5. Secondary hypertension
 Renovascular hypertension (most common)
 Renal insufficiency and failure
 Phaeochromocytoma
 Primary aldosteronism
 Cushing’s syndrome
 Coarctation of aorta
 Sleep apnea
 Thyroid disease
 Hypercalcemia
 Licorice intoxication(in chewing tobacco)
6. Pseudo resistance
 Using regular cuff on obese arm
 White coat hypertension
 Pseudohypertension in elderly
7. Miscellaneous
 Chronic anxiety, panic attacks
 Chronic pain
 Diffuse vasoconstriction (arteries)
 Insulin resistance
 Inappropriate diuretic in patients with renal insufficiency and creatinine clearance
below 30cc/min (i.e. thiazide )
Page 11 of 37
Hypertension
The following procedures are followed when a patient is found to be
hypertensive:
Table 3
Hypertensive data base
1.
A.
B.
C.
D.
E.
F.
G.
H.
History
Family history of hypertension and its complicating
History of cardiovascular, cerebrovascular, or renal disease or diabetes
mellitus.
Known duration and levels of elevated BP
Results and side effects of previous treatment
Drugs or substances which may influence BP (e.g. contraceptive pills,
corticosteroids, licorice, non-steroidal anti-inflammatory agents,
decongestants, appetite suppressants, and exogenous thyroid.
Smoking habits
Sodium intake
Alcohol intake
II Physical Examination
A.
Two or more BP measurements in both arms with the patient seated and
standing
B.
Height and weight
C.
Funduscopic examination for arteriolar narrowing, hemorrhages,
exudates and papilledema
D.
Examination of the neck for carotid bruits, distended veins, or enlarged
thyroid
E.
Examination of the heart for rate, size, pericardial heave, murmurs,
arrhythmia’s and gallops
F.
Lung examination for rales or airway obstruction
G.
Examination of the abdomen for bruits, large kidneys, or dilation of the
aorta.
H.
Examination of the extremities for diminished or absent peripheral pulses
I.
Neuralgic examination
III.
Laboratory Tests
A.
omplete blood count
B.
rinalysis, including testing for protein, blood and glucose.
C.
erum potassium
D.
erum creatinine
E.
erum cholesterol
F.
lood sugar
G.
erum uric acid
Additional testing may include
H.
lectrocardiogram
I.
hest roentgenogram if warranted
J.
lasma rennin and or aldosterone levels
K.
lasma catecholamines
Page 12 of 37
C
U
S
S
S
B
S
E
C
P
P
Hypertension
L.
rine metanephrine or vanillylmandelic acid
M.
lasma cortisol
N.
ypertensive intravenous pyelogram or radioisotope renal scan
O.
igital subtraction angiography
Page 13 of 37
U
P
H
D
Hypertension
Treatment
The Joint National Committee on Detection, Evaluation and Treatment of Hypertension
recommends that the following information be communicated to hypertensive patients along
with methods to evaluate their understanding of the knowledge:
a.
The benefits and adverse effects of therapy
b.
Normal and abnormal blood pressure values and awareness of their individual blood
pressure measurement at the time of each reading.
c.
The asymptomatic characteristic of hypertension and the failure of symptoms to
reliability indicate high blood pressure levels.
d.
The serious consequences of uncontrolled high blood pressure.
e.
The need of extended follow-up and chronic therapy
f.
And that medications can control hypertension without curing the disease.
Goal
To gain the patient’s cooperation, motivate him/her to accept long term therapy, and to ensure
his/her understanding of illness and its treatment.
Reduction of elevated blood pressure, whatever the cause, unequivocally lowers the
morbidity and mortality from hypertension. The goal of therapy for G.P is ultimately to prevent
premature death and morbidity. This goal is achievable if elevated blood pressures are
lowered and maintained at controlled levels. Effective treatment of high blood pressure not
only can decrease hypertensive target organ damage, but also can reverse some of these
effects. The need, however, to maintain normal blood pressure must be balanced against
potential drug toxicity and unnecessary or intolerable adverse drug effects. The initial goal is
however is to attempt to achieve a diastolic blood pressure of less than 90 mm Hg. This initial
goal can be adjusted later, if necessary, based upon the clinical response of the patient.
Non-drug methods that are available to treat G.P ‘s high blood pressure are:
a.
Numerous diets
b.
Behavioral modification (change of life style – dietary programme)
The subtitles of these above titles (a & b) are
 Moderate sodium restriction
 Weight reduction (The prevalence of hypertension is two times greater in
obese patients than non-obese patients)
 Exercise
 Stress reduction
 Alcohol Ingestion (to be eliminated or reduced)
 Cessation of Cigarettes/Injection of Caffeine (cigarette smoking is a major
risk factor for cardiovascular disease, nicotine raises blood pressure)
 Dietary electrolytes (potassium, calcium and magnesium)
 Dietary fats
Page 14 of 37
Hypertension
It seems reasonable that the first step in the treatment of hypertension would consist of a
carefully constructed aggressive promoted modification in lifestyle. A sensible dietary
programme should be desired for gradual weight reduction, if appropriate, and for reducing
the saturated fat and salt content of the diet. The rational or dietary treatment of
hypertension is based on the following observation and facts.
1. Hypertension is two to three times more prevalent in overweight as compared to lean
persons.
2. Sixty percent of hypertensive persons are overweight.
3. Weight loss even as little as 10 pounds decrease blood pressure in sixty to eighty
percent of hypertensive overweight individual.
4. Upper body obesity is associated with insulin resistance and hyperinsulinenia.
Hyperinsulinemia may be involved in the pathogenesis of hypertension as well as
hyper lipidenmia.
5. Diets low in total fact intake and high polyunsaturated/saturated ratio have been
shown to lower blood pressure in hypertensive individual. Moreover, reducing the
saturated fat and cholesterol content of the diet is indicated as the initial step in the
management of hyperlipidemia. Hyperlipidemia is a major independent risk factor in
coronary heart disease. This risk is compounded in hypertensive people.
6. Thirty to sixty per cent of hypertensive patients are salt sensitive. In this group blood
pressure will fall by an average of 10 mmHg if salt intake is reduced from 12gms to 6
grms daily.
In addition to these dietary measures, it is also important to reduce the intake of
alcohol, because excessive alcohol intake may either cause or worsen hypertension.
Since cigarette smoking is another major independent risk factor of coronary hear
disease, patients who smoke should undergo counseling and take advantage of any
available smoking cessation programs.
Categories on Antihypertensive drugs:
1.
2.
3.
4.
5.
6.
7.
DIURETICS
BETA-ADRENERIGC – BLOCKING DRUGS
ANGIOTENSIN – CONVERTING – ENZYME INHIBITORS (ACEIs)
CALCIUM – CHANNEL BLOCKING DRUGS
ALPHA II AGONISTS
VASODILATORS
PERIPHERAL ADRENERGIC NEURONAL BLOCKERS
Page 15 of 37
Hypertension
“Stepped
Care” & Individualized Sequential Therapy”
Approaches for the Management of G.P’s Hypertension
Table 4
Stepped care regimens for the treatment of hypertension
Joint National Committee recommendations
Step 1
Thiazide Diuretic
Or
Beta-Blocker
Alternative recommendations.
Step 1
ACE inhibitor
Or
Beta-blocker
Step 2
Add propranolol of alternate
Beta-blocker or thiazide
Diuretic, if initial therapy is a
beta-blocker
Or methyldopa
Or clonidine
Or guanfacine
Or guanabenz
Or prazosin
Or reserpine
Or terazosin
Step 3
Add hydralazine
Step 4
Add or substitute
Guanethidine
Minoxidil
ACE inhibitor
calcium entry blocker
Step 2
Diuretic1
Step 3
Beta-blocker or sympatholytic
Step 4
Add one or more sympatholytics
Diuretic1
ACE inhibitor or calcium entry
Blocker or vasodilator
Sympatholytic or calcium entry
Blocker
Add one or more sympatholytics
Thiazide Diuretic
ACE inhibitor or beta-blocker
Or
Calcium Entry blocker
Add agents with different actions
1 Substitute a calcium entry blocker or another sympatholytic for the ACE inhibitor or the beta-blocker.
Page 16 of 37
Add agents with different action
Hypertension
A standardized algorithm for the uniform treatment of hypertension (see table 4
above) has produced useful information on the effectiveness of long-term
antihypertensive therapy.
The principle of “stepped care” therapy of hypertension is:
Initiate therapy with a small dose of a diuretic, increase the dose if needed, and then
sequentially add one drug after another as needed. Each drug is administrated in gradually
increasing doses until the therapeutic objective is attained, intolerable adverse effects
develop, or the maximum recommended dose is reached.
Now clinicians prefer “individualized sequential therapy” or “ stepped care” therapy because
more choices are available for selecting the initial drug in the treatment of hypertension than
were available when “stepped-care” was first proposed.
ACE inhibitors and calcium-channel-blocking drugs are considered as possible first choice
drugs in the treatment of essential hypertension.
The newer antihypertensive drugs are unlike earlier drugs (e.g.: methyl-dopa and
guanethidine) which were associated with significant sodium and fluid retention and other
adverse effects, listed later.
Page 17 of 37
Hypertension
Classes of drugs used in the treatment
(in a broader idea).
(1) diuretics
There are four classes of diuretics: carbonic unhydrase inhibitors, thiazide and thiazide – like
agents, loop diuretics, and potassium – sparing diuretics.
In general, carbonicunhydrase inhibitors are weak antihypertensive agents and therefore are
not used in the treatment of hypertension. The potassium sparing diuretics are also weak
antihypertensive agents when used along, but provide an additive hypotensive effect when
used in combination with thiazide or loop diuretics. Moreover, they counteract the potassium
and magnesium – losing properties of other diuretics agents.
In a patients with adequate renal function (i.e. a geomerular filtration rate greater than 30
ml/min, thiazide diuretics appear to be more effective hypotensive agents than loop diuretics
such as furosenide. As renal function declines, however, sodium and fluid accumulate and
the use of a more potent diuretic necessary to counter the effects that volume and sodium
expansion have on arterial blood pressure.
All thiazide diuretics are equally effective in lowering blood pressure. The major differences
between the various thiazides are the serum half-life and the duration of diuretic effect.
Mechanism:
The exact hypotensive mode of action of diuretics is not known. Of course, actually diuretics
lower blood pressure by causing a dieresis. The reduction in plasma volume and stroke
volume associated with a dieresis decreases cardiac out put and consequently, blood
pressure. The initial drop in cardiac out put produced by the dieresis causes a compensatory
increase in peripheral vascular resistance. With continuing diuretic therapy, the extra cellular
fluid volume and plasma volume return almost to pretreatment levels, and peripheral vascular
resistance falls below its pretreatment baseline. It is the reduction in peripheral vascular
resistance that accompanies chronic use of diuretics that is responsible for their long terms
hypotensive effectiveness. Still another possible antihypertensive mode of action of the
thiazide diuretics is direct relaxation of vascular smooth muscle. The theory is based on the
known mechanism of action of dioxide, a chemical closely related to the thiazide diuretics.
Diazoxide is a direct vasodilator, and it is possible that the thiazide diuretics exert a similar
action.
Side effects:
Include hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyper glycemia,
hyper lipidemia, and sexual dysfunction, loop diuretics may cause the same side effects. The
hypokalemia and hypomagnesemia caused by diuretics may lead to cardiac arrhythnias in
susceptible patients. Patients at greatest risk are those receiving dyitalis therapy, those with
left ventricular hypertrophy and those with ischemic heart disease.
Diuretics – induced hyperuricemia may produce gouty arthritis or uric acid stones, especially
in individuals who are predisposed to gout.
Chronic use of thiazide diuretic therapy may alter glucose metabolism in at least two ways.
First, a diuretic – inducted deficiency of potassium and magnesium may lead to a reduction in
postprandial insulin secretion. Second, long term diuretic therapy may result in the
development of insulin resistance. Either of these mechanisms may contribute to the
production of diabetes in prediabetic individuals and worsening of metabolic control in
diabetic patients, therefore use diuretic therapy with caution.
Potassium – sparing diuretics have the potential for causing hyperkalemia, especially inpatients with renal insufficiency or diabetic, and in-patients receiving concurrent treatment
with on ACE inhibitor, NSAIP, or potassium supplements. The potassium sparing drug
spironolactone may cause gynecomastia.
Page 18 of 37
Hypertension
(2) Beta- Adrenergic- Blocking Drugs:
Beta blockers reduce cardiac output through their negative chronotropic and inotropic effects
on the heart. It is reasonable to postulate that drugs that lower cardiac output lower blood
pressure is the product of cardiac output and peripheral vascular resistance, however even
though cardiac output is reduced output after both intravenous and oral administration of
propanolol therapy, both pressure falls only when propanolol is given orally.
Another possible explanation of the hypotensive action of B-blockers is related to a central
action. Blocking B-adrenergic receptors in the brain might cause a reduction in sympathetic
outflow from the vasomotor centre. All B-blockers traverse the blood brain barrier, but the
extent to which they enter the brain depends or their degree of lipophilicity.
It has been suggested that a peripheral mechanism common to all B-blockers may be
responsible for the long term reduction in blood pressure. The proposed peripheral
mechanism involves the possible presence of B-adrenoceptor on the surface of sympathetic
B receptors could lead to a reduction in the release of norepinephrine into the synaptic cleft.
This intriguing hypothesis is based on the theory that norepinephrine release from neuronal
endings is regulated to some extent by presynaptic adreneric feed back loops. Stimulation of
presynaptic B-receptors would engender a positive feed back increase in norepinephrine
release. If presynaptic B-receiptors to indeed exist, blocking them would interrupt the positive
– feedback loop and this reduce the release of norepinephrine from the neuronal ending. This
hence lowers blood pressure.
Most of the side effects of B-lockers represent physiologic consequences of antagonizing B
and renoceptors in various organs and tissues. For example B-blockade in the myocardium
can be associated with bradycardia, atrioventricular conduction abnormalities and the
development of congestive hear failure. In the lungs acute exacerbation’s of bronclospasm in
patients with asthma or COPD.
Beta blockers may induce glucose intolerance by inhibiting insulin secretion and by
generating insulin resistance.
Page 19 of 37
Hypertension
(3) Angiotensin – Converting Enzyme Inhibitors (ACE I)
They are suitable for salt restricted patients (eg: tid captopril). Most of them are excreted in
the urine and therefore an adjustment in dosage may be necessary in patients with renal
dysfunction.
ACE inhibitor block the conversion of angistensin I to angiotensin II. This latter substance is a
potent vasoconstrictor and stimulator of aldosterone. ACE also block the degradation of
bradikinin and stimulate the synthesis of other vasodilating substances.
The worst effects of ACE I are neutropenia and agranulocytosis, proteinuria, glomery
lonephritis, and angio edema (they are rare though). Patients with pre-existing renal or
connective tissue diseases appear to be most vulnerable to the renal and hematoglogic side
effects, Patient with bilateral renal artery stenosis or unilateral stenosis of a solitary
functioning kidney and patients dependent on the vasoconstrictive effect of angiotensin II on
the efferent arteriole are particularly susceptible to develop acute renal failure on ACEI.
Hyperkalemia is observed in patient on ACE I. 10-20% of patients will develop a persistent
cough while on ACEI. Some may even develop acute bronchospasm.
ACE I are absolutely contraindicated in pregnant females because of serious neonated
problems, including renal failure and death
(4) Calcium Channel Antagonists
These causes relaxation of cardiac and smooth muscle by blocking voltage sensitive calcium
channels thereby reducing the entry of extra cellular calcium into the cells. Vascular smooth
muscle relaxation leads to vasodilatation and a corresponding reduction in blood pressure.
Currently there are seven calcium channel antagonists in use; they are all similar in their
antihypertensive effectiveness, but they differ somewhat in other pharmacologic effects. The
reason that pharmacologic differences exist among the three major classes of calcium
channel antagonists – verapamil, diltiazein, and the dihydropyridines – is that they all act at
specific receptors. The density and distribution of the receptors varies from tissue to tissue.
Nifedipine rarely may cause an increase in the frequency, intensity, and duration of angina in
association with acute hypotension. This effect may be obviated by the administration of
nifedipine with meals or by using sustained – released formulations of nifidepine. Other side
effects include dizziness, flushing, headache, mood changes and various gastrointestinal
complaints.
Diltiazem and verapamil rarely cause cardiac conduction abnormalities such as bradicardia,
atrioventricualr block, and congestive hear failure. Both cause anorexia, nausea, peripheral
oedena, and hypotension. Verapamil causes constipation in about 7% of patients.
Page 20 of 37
Hypertension
(5) Alpha II Agonistic
They lower blood pressure primarily by stimulating X2 – adrenergic receptors in the brain.
Such actions leads to a reduction in sympathetic outflow from the vasomotor centre in the
brain and an associated increase in vegal tone. As a consequence of reduced sympathetic
activity together with some enhancement of parasympathetic activity, hear rate is decreased,
cardiac output decreases slightly, total peripheral resistance is lowered, plasma rennin
activity is reduced, and baroreceptor reflexes are blunted.
Chronic use of the centrally acting X agonists results in sodium and fluid retention, which
appears to be most prominent with methyldopa. Low doses of either clonicline, guanfacine, or
guanabenz can be used to treat mild hypertension without the addition of a diuretic, however,
methyldopa, even at low does, usually leads to enough sodium and fluid accumulation that
tolerance to its hyptotensive effect soon develops in the absence of concurrent diuretic
therapy.
These drugs can cause sedation, dry mouth and also depression. A good advantage is that
rebound hypertension may rarely occur when a central and receptor agonist is stopped.
(6) Vasodilators
Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation through
mechanisms that increase the intracellular concentration of cydic GMP. They exert little, if
any, on the venous side of the circulation. By decreasing the amount of systemic pressure in
the arterial system, they reduce impedance to myocardial contractility (therefore the latter two
drugs are used in the management of congestive heart failure also).
Direct vasodilator use can precipitate angina in patients with underlying coronary artery
disease unless the baroreceptor reflex is completely blocked (use B-blocking agents). One
side effect that is unique to hydralazike is a lupus like syndrome (more common in women) it
is reversible upon discontinuation of the drug. Other side effects of hydraline include
dermatis, drug fever, hepatitis, vascular headache. A very troublesome side effect of
minoxidil is hypertrichosis. Increased hair growth occurs on the face, arms, back and chest,
(hirsutism); this ceases with discontinuation of drug.
Page 21 of 37
Hypertension
(7) Peripheral Adrenergic Neuron Blockers
(also called Post ganglionic sympathetic inhibitors)
Guanethedine and guanadrel depelete norepinephrine from postganglionic sympathetic nerve
terminals and they inhibit the release of norepinephrine in response to sympathetic nerve
stimulation.
The fall in blood pressure produced by post ganglionic inhibitors is associated with a
reduction in cardiac output and peripheral vascular resistance, because reflex mediated
vasoconstriction is blocked by these drugs, a much great hyptotensive effect occurs in the
upright posture, and postural hypertension is common. The use of postganglionic
sympathetic inhibitors is associated with many other unwarranted side effects including
impotence, diarrhea, and weight gain. The gastro intestinal side effects occur as a result of
unopposed parasympathetic activity.
Long term norepinephrine depletion leads to postsympatic receptors “upersensitivity”.
Therefore, the administration of drugs that compete with post garglionic inhibitors for uptake
into the nerve terminals (such as TCAs) may occasionally provoke acute severe hypertensive
episodes.
Because of the previous side effect, this class of drugs is restricted to use in patients with
refractory hypertension.
Reserpine lowers blood pressure through several different mechanisms. It depletes
norepinephrine from sympathetic nerve endings and it blocks transport of norepinephrine into
its storage granules. Reserpine also depletes catecholamines from the brain and
myocardium. Consequently, the use of reserpine may lead to sedation and depression and
decreased cardiac output.
Reserpine is a very long acting drug and it may take 2-6 weeks before the maximal effect of
the drug is realized. Its use is associated with significant sodium and fluid retention and
therefore it should be administered in combination with a diuretic.
The most important side effect is mental depression, which is a consequence of CNS
depletion of catecholamines and serotonix.
Page 22 of 37
Hypertension
Recently, new anti-hypertensive drug classes were discovered:1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Renin inhibitors
Vasopressin antagonists
Angiotension II receptor blocks (losartan)
Serotonin receptor antagonists (ketanserin)
Dopamine receptor antagonists (fenoldopam)
Prostaglandin analogs (PGI2 – iloprost)
Lipoxygenase inhibitors (phenidone)
Cicletanine
Potassium channel activators (BRL – 34915)
Sodium channel blockers (6 – iodoamiloride)
Conclusions:
1.
The treatment of mild hypertension (DBP<110 mmHg) with certain antihypertensive
agents may induce metabolic or structural changes and adversely affect other risk factors
that partially or completely negate the beneficial effects of lowering BP because of
increases in CHD risk or risk factors for other end-organ damage.
2.
Diuretic agents (except spironolactone and indapamide), beta-blockers without ISA,
reserpine, and methyl-dopa have adverse effects on the hypertensive – atherosclerotic
syndrome and other risk factors for end organ damage. These agents also have
significant clinical side effects with a corresponding poor quality of life.
3.
The only antihypertensive agents available to date that do not adversely effect serum
liquids are calcium channel blockers, alpha-1 blockers, central alpha agonists (except
methyl-dopa), ACE inhibitors, indapamide, and Ang-II receptor blockers.
All of these agents are effective as initial monotherapy in about 50% to 60% of patients
with mild hypertension. All are well tolerated (in >90% of patients) if dosed appropriately
(start low, go slow), and have a low side effect profile – combination therapy in 90% to
95% effective.
4.
Diuretic agents in high doses (50 to 100 mg of HCTZ daily or an equivalent diuretic)
may induce hypokalaemia, hypomagnesemia, or other electrolyte and acid base
abnormalities that increase the incidence of sudden death in predisposed patients
secondary to cardiac arrhythmias. Predisposing factors include exercise, the presence of
LVH – abnormal ECGs, silent or clinical ischemia, acute stress, or digitalis treatment.
5.
The use of lower doses of diuretics (HCTZ 12.5 to 25mg / day) is effective for the
treatment of hypertension and may have fewer adverse effects. A dose of 25mg / day
achieves 95% of the antihypertensive effect and 12.5 mg achieves 80% of the
artihypertensive effect. Indapanide is a preferred diuretic.
6.
The selection of non-pharmacological therapy or antihypertensive drugs that have a
neutral or favorable effect on serum liquids, glucose electrolytes and other risk factors
and improve endothelial function may reduce the risk of CHD and other end-organ
damage in patients with hypertension. Optimal treatment aims to reduce all risk factors,
thereby reducing all end-organ damage.
7.
Selection of drug therapy should be individualized and based on the subsets of
hypertension approach (see below):
Page 23 of 37
Hypertension
Subset selection of Antihypertensive therapy:
1.
2.
3.
4.
5.
6.
7.
8.
Pathophysiology
Hemodynamics
End-organ damage and risk factor reduction
Concomitant medical diseases or problems
Demographic selection
Adverse effects and quality of life with therapy
Compliance
Total health care cost
Guidelines for selecting drug treatment of hypertension:
Class of drug
Compelling indications
Possible indications
Compelling contra indications
Possible contra indication
Diuretics
Heart failure
Elderly patients
Systolic hypertension
Angina
After myocardial infarct
Tachyarhythmias
Diabetics
Gout
Dyslipidaemia
Sexually active males
Heart failure
Pregnancy
Diabetes
Asthma and COPD
Heart blocka
Dyslipidaemia
Atheletes and physically active
-Blockers
Peripheral vascular disease
ACE inhibitors
Calcium antagonists
Heart failure
Left ventricular dysfunction
After myocardial infarct
Dabeticnephropathy
Angina
Elderly patients
Systolic hypertension
-Blockers
Prostatic hypertrophy
Angiotensin II
antagonists
ACE inhibitor cough
Pregnancy
Hyperkalaemia
Bilateral renal artery stenosis
Peripheral vascular disease
Glucose intolerance
Dyslipidaemia
Heart failure
Heart blockb
Congestive heart failurec
Orthostatic hypotension
Pregnancy
Bilateral renal artery stenosis
Hyperkalaemia
(a) Grade 2 or 3 atrioventricular block; (b) grade 2 or 3-atriioventricular block with verapamil or diltiasem, (c) verapamil or diltiazem, ACE, angiotension converting enzyme.
Page 24 of 37
Hypertension
Demographics And Anti-hypertensive Drugs
Demographic
Profile
Drug(s) of choice
Alternatives
Young Patient
Ang-II blocker
ACE inhibitor
Alpha blocker
calcium Channel
blocker
Central alpha agonist
Beta-blocker with
ISA
Direct vasodilator
Alpha and beta
blocker
Elderly patient
Alpha blocker
calcium Channel
blocker
Central alpha agonist
Ang-II blocker
ACE blocker
Beta-blocker without
ISA
Beta-blocker with ISA
Diuretic Alpha and
beta blocker
Direct vasodilator
Neuronal inhibitor
Reserpine
African
American
patients
Alpha blocker
calcium Channel
blocker
Central alpha agonist
Ang-II blocker
ACE blocker
Direct vasodilator
Beta-blocker with ISA
Beta-blocker without ISA
Alpha and beta blocker
Neuronal inhibitor
Reserpine
White patient
Ang-II blocker
ACE inhibitor
Alpha blocker
calcium Channel
blocker
Central alpha agonist
Direct vasodilator
Alpha and beta
blocker
Diuretic
Beta-blocker with ISA
Beta-blocker without ISA
Neuronal inhibitor
Reserpine
Page 25 of 37
Relative or Absolute
Contra-indication
Beta blocker without ISA
Hypertension
A study carried out:
Hypertensive Diabetics: Mortality and CHD and Antihypertensive Therapy 94
Mortality per 1000 person-years in diabetic patients without proteinuria and with
proteinuria according to hypertension status and type of antihypertensive treatment
Without Proteinuria
225
200
Mortality/1000 Person - Years
175
150
125
Other Mortality
Cardiovascular mortality
100
75
50
25
Bo
th
x
R
Di
ur
et
ic
s
U
R
x
R
x
O
th
er
Ag
en
ts
yp
er
te
ns
io
n
H
nt
re
at
ed
N
or
m
ot
en
si
on
0
With Proteinuria
225
200
Mortality/1000 Person - Years
175
150
125
Other Mortality
Cardiovascular mortality
100
75
50
25
Bo
th
x
R
Di
ur
et
ic
s
x
R
x
R
O
th
er
Ag
en
ts
yp
er
te
ns
io
n
H
U
nt
re
at
ed
N
or
m
ot
en
si
on
0
(Rx) during each year of follow-up. Diuretics increased cardivascular mortality and total
mortality compared to other anihypertensive drugs or no treatment.
P <0.025;
P<0.025 vs treatment with diuretics alone. (From Warram JH, Laffel LMB, Valsnia P et
al. Excess mortality associated with diuretics therapy in diabetics mellitus. Arch Intern
Med 1991; 151:1350-1356, with permission)
Characteristics of the ideal antihypertensive drug:
1.
Efficacious as monotherapy in more than 50% of all patients
Page 26 of 37
Hypertension
2.
BP control during all activities for 24 hours
3.
Once-a-day dosing
4.
Hemodynamically logical and effective: Reduces SVR, improves arterial compliance,
preserves CO, and maintains perfusion to all vital organs.
5.
Lack of tolerance or pseudotolerance: No reflex volume retention or stimulation of
neurohumoral mechanisms
6.
Favorable biochemical effects, metabolic effects, and risk factor profile
7.
Reverse structural, vascular smooth muscle, and cardiac hypertrophy; improves
systolic and diastolic compliance and left ventricular contractility and function; reduces
ventricular ectopy, if present.
8.
Reduces all end-organ damage; cardiac, cerebrovascular, renal, retinal, and large
artery.
9.
Maintains normal hemodynamic response to aerobic and anaerobic exercise.
10.
Low incidence of side effects, good quality of life.
11.
Good compliance with regimen
12.
Good profile for concomitant diseases or problems
13.
Reasonable cost.
Page 27 of 37
Hypertension
Differential Antihypertensive Therapy In Specific Clinical Situation
Advantageous
CHFa
Angina
Elderly
Black
Young
Diabetes
Asthma, COPD
Pregnancy
Renal insufficiency
Tachycardia
Hyperlipidemia
Gout/hyperuricemia
ACE inhibitor, diuretic, hydrazine
B Blocker, Ca channel antagonist
Diuretic, a agonist, Ca channel antagonist
Diuretic, Ca channel antagonist
B Blocker, a agonist, ACE inhibitor
a Agonist, ACE inhibitor, Ca channel antagonist
Ca channel antagonist
Methyldopa, hydralazine, labetolol
a Agonist, Ca channel antagonist, minoxidil,
Hydralazine, loop diuretic.
B Blocker, a agonist, reserpine, verapamil, diltiazem
a Blocker, ACE inhibitor, Ca channel antagonist
a Agonist, a blocker, Ca channel antagonist, ACE inhibitorb
Disadvantageous
B Blocker, reserpine, Ca channel antagonist
Hydralazine, Minoxidil
B blocker as initial therapy
Diuretic
B Blocker, diuretic
B Blocker, ACE inhibitor
Diuretic, B blocker
Thiazide diuretic.
Nifedipine, hydralazine, minoxidil
Diuretic, B blocker
Diuretic, B blocker, ACE inhibitor
(a) CHF, congestive hear failure; ACE, angiotensin-convertin enzyme; COPD, chronic obstructive pulmonary disease.
(b) ACE inhibitors may increase urinary clearance of uric acid thereby reducing hyperuricemia but increasing the risk of uric acid deposition in the urine or kidneys.
Page 28 of 37
Hypertension
Combination Antihypertensive Therapy : Selected Drugs
1. Calcium channel blocker plus:
a. Alpha-blocker or
b. ACE inhibitor, ANG-II receptor blocker or
c. Central alpha-agonist
2. Alpha blocker plus:
a. Calcium channel blocker or
b. ACE inhibitor ANG-II receptor blocker
c. Do not generally use with central alpha-agonist (reduced response rate)
3. Central alpha-agonist plus:
a. Calcium channel blocker or
b. ACE inhibitor, ANG-II receptor blocker
c. Do not generally use with alpha-blocker (reduced response rate )
4. ACE inhibitor plus :
a. Calcium channel blocker or
b. Alpha-blocker
c. Central alpha-agonist
d. Diuretic
5. Diuretic plus:
a. Any other antihypertensive class
b. Possible exception: calcium channel blocker (does not usually
Enhance effects)
6. Beta-blocker plus:
a. Calcium channel blocker – use caution in the presence of systolic
Dysfunction or conducting problems, particularly with verapamil
Or diltiazem or mibefradil
b. ACE inhibitor, ANG-II receptor blocker
c. Diuretic
d. Alpha-blocker
e. Do not use with central alpha-agonist because of possible central antagonism
and potential for severe withdrawal syndrome
7.
ANG-II receptor blocker plus :
a. Calcium channel blocker
b. Central alpha-agonist
c. Alpha-blocker
d. Diuretic
Page 29 of 37
Hypertension
Antihypertensive Therapy
Efficacy of Monotherapy
Drug Class
White (%)
African-American (%)
Diuretic
Beta-blocker
Calcium channel
Blocker
ACE inhibitor
Alpha-blocker
Central alpha
Agonist
Ang-II blocker
50
50
75
60
30-40
75-80
50
20-30
75-80
60
60
60
60
60
60
60
60
60
60
60
60
Page 30 of 37
Elderly (%)
Hypertension
The antihypertensive agents
Drug
Diuretics
Thiazides and related sulfonamide
Diuretics
Bendroflumethiazide
Benzthiazide
Chlorothiazide sodium
Chlorthalidone
Cyclothiazide
Hydrochlorothiazide
Hydroflumethiazide
Indapamide
Methyclothiazide
Metolazone
Polythiazide
Quinethazone
Trichlorimethiazide
Loop diuretics
Bumetanide
Ethacrynic acid
Furosemide
Potassium-sparing agents
Amilorids hydrochloride
Spironolactone
Triamterene
Adrenergic inhibitors
B-Adrenergic blockers
Acebutolol
Atenolol
Betaxolol
Bisoprolel
Careolol
Metoprolel tartrate
Nadolol
Oxprenolol hydrochloride
Penbutolol
Pindolol
Propranolol hydrochloride
Propranolol long-acting (LA)
Timolol maleate
Dose Range (mg/d)
Initial
Maximum
2.5
25
250
25
1
25
25
2.5
2.5
2.5
2
50
2
5
50
500
50
2
50
50
5
5
5
4
100
4
0.5
50
80
10
200
480
5
50
50
10
100
100
400
25
10
5
2.5
50
20
160
20
20
40
80
20
1200
100
40
20
10
300
120
480
80
60
480
480
60
Page 31 of 37
Drug
Adrenergic Inhibitors (contd..)
Central-acting adrenergic inhibitors
Clonidine hydrochloride
Guanabenz acetate
Guanfacine
Methyldopa
Peripheral-acting adrenergic antagonists
Guanadrel sulfate
Guanethidine monosulfate
Rauwolfia alkaloids
Rauwolfia inhale root
Reserpine
Adrenergic blocker
Doxazosin
Prazosin hydrochloride
Terazosin
Combined a-and B-adrenergic blockers
Labetolol
Vasodilators
Hydrazine hydrochloride
Minoxidil
Angiotensin-converting enzyme inhibitors
Benazepril
Captopril
Enatapril maleate
Fosinopril
Lisinopril
Ouinapril
Ramipril
Calcium channel antagenists
Amtodipins
Diltiazem hydrochloride
Isradipine
Nicardipine
Nifedipine
Nitrendipine
Verapamil hydrochloride
Dose Range (mg/d)
Initial
Maximum
0.2
8
1
500
1.2
32
3.0
2000
10
10
150
300
50
100
0.05 0.25
1
2
1
16
20
5.0
200
1200
50
5
300
100
10
25
10
10
10
10
1.25
20
150
40
80
80
80
20
5
120
5
60
30
10
240
10
240
20
120
180
40
480
Hypertension
Case studies
Case 1 : Evaluation/Study case:
G.P. is a 50-year-old black male who is referred to the primary care clinic for
evaluation of high blood pressure noted on routine screening. His only compliant is
the presence of a pounding, occipital, morning head ache.
Hypertension was detected four years ago and was treated with a weight reduction
diet and sodium restriction. He takes no medication. A gradual fifteen pound weight
gain is noted over the previous 12 to 18 months. He also had a peptic ulcer 10
years ago. His father had hypertension and died of a heart attack at age 59. His
mother died of a stroke at age 62 and was an insulin dependent diabetic. He has a
history of smoking cigarettes for the past 20 years. He believes his elevated blood
pressure is caused by tension over his recent loss of employment. He has lost four
weeks of work “due to his blood pressure” in the last eight weeks.
Physical examination reveals a well developed, over weight black male who looks
his age and is in no acute distress. His height is 175 cm and his weight is 107 kg.
Blood pressure are as follows: 160/115 mm mg (right arm) and 166/116 mm Hg (left
arm) while sitting; 158/113 mm Hg (right arm) and 162/114 mm Hg (left arm) while
standing. His pulse is 76 beats per minute and regular. Funduscopic examination
reveals mild arterial narrowing, sharp discs, and no exudates or hemorrhages. The
remainder of the physical examination is within normal limits.
Laboratory examination reveals the following:
Serum electrolytes within normal limits, BUN 30 mg/dl (8-25), serum creatinine 2.0
mg/dl (0.6 – 1.5), serum glucose 90 mg/dl (70-110), serum uric acid 12 mg/dl (3-7),
hematocrit 42% (45-52), and mildly elevated fasting cholesterol and triglycerides.
Urinalysis reveals ± 1 proteinurea. An electrocardiogram and a chest X-ray reveal
mild left ventricular hypertrophy.
G.P. does have some evidence in his hypertensive data base that is suggestive of
end organ damage from long standing hypertension. His electrocardiogram and
chest X-ray demonstrate mild left ventricular hypertrophy. G.Ps retinophaty and the
mild funduscopic changes is not enhancing because of his age and duration of
hypertension. Successful control of G.P.s blood pressure may reverse his left
ventricular hypertrophy and improve his other cardiovascular symptoms. The
proteinuria noted in G.P.s urinalysis is important because the kidney is damaged in
long standing or malignant hypertension, and renovascular disease may be a cause
of secondary hypertension. Therefore, his 1 + proteinuria requires further
evaluations, especially since his creatinine serum concentration also is increased.
G.P. has
a number of risk factors that would increase the likelihood of
cardiovascular morbidity, he should be aware of the serious consequences of
uncontrolled high blood pressure and that he should follow a stable healthy diet
(restricting sodium in take) and also take his treatment regularly (tell him the
benefits and adverse effects of his therapy). He should measure his blood pressure
regularly too, and should have extended follow-up and chronic therapy.
Page 32 of 37
Hypertension
G.P. should stop smoking and alcohol intake, he should exercise regularly and
reduce stress; eat healthy food (decrease dietary fats).
In his drug therapy, the “stepped-care” regimens are followed (recommended by
“Joint National Committee”).
He was treated with a diuretic, a thiazide diuretic (G.P. responded favorably to it
because, he is black (blacks have a low rennin form of hypertension that usually is
more responsive to either diuretics or calcium – channel blockers), has moderate
hypertension. He also has financial problems and the cost of therapy can be a
significant factor in his compliance. The best choice was hydrochlorothiazide (dose
= 50 mg/day).
Two weeks later:
G.P. had no compliance; in fact, his head-ache had resolved. His blood pressure
was 150/105 mg Hg without orthostasis. His weight was 105.5 kg. His serum
potassium concentration was normal, his serum glucose concentration was
unchanged.
Page 33 of 37
Hypertension
Case 2 :
A 60 year old lady presented to a doctor complaining of shortness of breath on
exertion. She is known hypertensive and diabetic. She is a known hypertensive and
diabetic. She is currently on moduretic OD and Nifedipine 10 mg P.O. TID . He
blood pressure is 170/80 (left arm). CSs : JVP (N) ; HS (heart sound) 1+2+S4; she
has peripheral ankle oedema. Her chest is clear, but she is suffering from left
ventricular hypertrophy. Her Cxr: increased CT ratio. Urinalysis reveals +1 sugar
and +1 protein. Electrolytes: Na : - 135; K : +3.0; Cr: 1-6; Urea : 50; HCO3 : 25.
Expectedly, her systolic hypertension should be treated we should target the B.P. to
reach the value of (130/85) mmg Hg) . According to her symptoms & signs, she
should be treated with more than one day. Nifedipine should be discontinued
because of her ankle oedema (this is not a sign that the heart is not pumping
properly and fluids are accumulating in her body. Niphedipine is a calcium channel
blocker – it weakens the heart, which lead to shortness of breath.
The best combination therapy for her case is ACE inhibitor – eg Renitec – with a
diuretic (moduretic), small doses of diuretic is given because she is diabetic –
optional dose is 12.5 mg.
Obviously the diuretic is given to relieve from the oedma that she is suffering form
the ACE inhibitors are ideal to save the endothelial system in diabetic patients.
Page 34 of 37
Hypertension
Case 3 :
Mr. CT, a 71 year old man, was admitted to hospital after a fall due to blackout while
shopping. He had been unable to get up as his right arm and leg were numb, so a
passer by had called an ambulance and he was admitted to the hospital.
Later in the hospital, the numbness improved, but a x-ray taken showed a hairline
fracture of the pelvis. So his admission was for observation and pain relief. He was
taking no medication and has never experienced a blackout before. Mr. CT is
slightly over weight (80 Kg) and smoked 10 cigarettes per day. His blood pressure is
170/110 mm Hg. Pulse rate is 75 beats/min. Further observations of his BP
confirmed that Mr. CT was hypertensive.
His serum biochemistry and hematology results were:
1. Sodium
138 mmol/L
(135-145)
2. Potassium
4.1 mmol/L
(3.5-4.5)
3. Creatinine
95 micromol/L
(60-120)
4. Urea
6.7 mmol/L
(2.5-7.5)
5. Hemoglobin
15.2 g/dL
(12-18)
The doctor suspected a transient ischaemic attack (due to the blackout that
occurred). The doctor gave him paracetamol with high doses of codeine for a short
time to relieve his pain. Bendrofluazide 2.5mg (diuretic) was given in the morning.
Requested for twice daily monitoring of B.P. and also to stop smoking and reduce
fat intake, proper diet for weight reduction. Atenold 50mg was given along with the
Bendrofluazide (in the morning)
Enhancement of Mr. CT occurred after this medication as well as his pain was
relieved. Mr. CT has no problem with Atenold (B blocker) since his heart is fine with
an ACE inhibitor. Upon this treatment we should note down to monitor his potassium
levels (give supplements if necessary if level is below 3.5 mmol/L)). Diuretics cause
hypo kalaemia. The heart rate should be monitored for signs of more significant
bradycardia.
After a couple of weeks, Mr. CT complained of cold hands and feet (extremities) as
well as fatigue. Blood pressure was found to be 140/95 and a pulse rate of 48 beats
per minute. He lost some weight (75 Kg). Investigation for signs of urinary tract
infection proved negative. So the GP discontinued the atenolol permanently and the
Bendrofluazide temporarily for two days and commenced Mr. CT on captopril 6.25
mg twice daily (ACE inhibitor). The side effects were 'Beta blocker side effects'.
Therefore another line of treatment should be followed. Low doses of ACE inhibitors
are commenced. Renal function tests (urea & Creatinine) should be monitored as
the latter drug may cause renal dysfunction. Patient should be advised and aware of
the side effects of captopril (e.g. Take the first dose at bed time, aware of the
possibility of cough, and not to take the diuretic for the first two days to avoid
hypotension.
Page 35 of 37
Hypertension
Case 4 : Lupus nephritis case
A fifty three year old woman presented with mild headache and was found to have a
BP of 160/100 mm Hg which did not settle on repeated measurement. Serum
Creatinine was in normal range. She was treated with alcohol 50mg daily with good
effect. She presented again two months later with Lethargy, nausea and pruritis.
Blood pressure on this occasion was 190/130 mm Hg. She had fundul hemorrhages
and urine analysis was positive for protein and blood. Repeat serum Creatinine level
was 450 micro mol/L. She was admitted to hospital and after hypertension had been
controlled again. Renal biopsy reveled clear evidence of rapidly progressive lupus
nephritis.
This case indicates the importance of urine analysis in assessing hypertensive
patients. Most cases of renal hypertension can be detected by an elevation of serum
Creatinine or positive urine testing for protein or blood and can then be investigated
and managed appropriately. (Lupus nephritis caused her case of elevated blood
pressure), it should be treated first cortisones then she will notice a regulation to her
blood pressure.
Page 36 of 37
Hypertension
Case 5 : (Syndrome X)
Mr. HM, a 32-year-old male factory worker, was referred to the hospital with severe
hypertension and a sensation of retrosternal pressure during strenuous exercise. He
is a heavy smoker and alcohol consumer and liked pork and other fatty foods. He is
over weight; “apple shaped obesity” (BMI=27), with mainly upper body fat
distribution. Blood pressure measurement=180/110 mm Hg. His heat was enlarged,
and there was a systolic murmer. The ECG showed mild strain at the level of the left
ventricle.
The liver was enlarged by 4cm, with a smooth surface. We performed an oral sugarloading test with 75g saccharose. At the same time we also checked the endogenous
insulin levels. It revealed an impaired glucose tolerance (IGT), which is an abnormal
metabolic state between normal and diabetic metabolism. The insulin levels show
extreme hyperinsulinism. Based on these results we carried out a simplified clamp
study, in order to measure steady state plasma glucose. This test clearly
demonstrated a significant peripheral insulin resistance. Blood lipid levels were also
abnormal; serum cholesterol: 6.2 mmol/L (<5.2 mmmol/L), triglycerides 4.6 mmol/L
(<1.9 mmol/L), HDL: cholesterol 0.96 mmol/L C>1.45 mmol/L).
So after diagnosing this clinical entity, we prescribed a low calorie diet (1200-1400
calories/day). Consume vegetable oils, fish, eat more fibre and reduce animal fat,
meat…). We recommended mild regular exercise. To treat the hypertension we
prescribed ACE inhibitors (captopril). it will save the endothelial system because he
is diabetic. it also improves the function of the kidney by strengthening the structure
of endothelial system (reduce protein urea). A diuretic is given (MODURETIC) to
reduce the oedema (the heart is enlarged , fluid accumulated, cardiac output is
decreased). Potassium levels as well as electrolyte levels should be monitored.
Doctor prescribed coronary vasodilators (Isordil).
The patient is advised urgently to stop smoking and alcohol intake and maintain the
diet previously prescribed. For his diabetes, the doctor prescribed glucophage
(reason: obese patient).
After 3 months, the patients general well being had improved, and he had lost more
than 6 Kg. His blood pressure is 165/90 mm Hg. Lipid levels improved. ECG returned
to normal. Chest pain disappeared. The patient was relieved (happy). The doctor
diagnosed his case as Metabolic Syndrome (Syndrome X).
Page 37 of 37