This document discusses the management of two patients. For the first patient, a 47-year-old man with diabetes and hypertension, the goal blood pressure is less than 140/90 mmHg. ACE inhibitors are recommended due to their benefits for patients with diabetes. For the second patient, a 56-year-old woman with uncontrolled hypertension, the doctor's approach will focus on lifestyle modifications and optimizing her medication regimen given her multiple comorbidities.

1. Dr. Mostafa Rashed PGY2
Family Medicine Department
HMC
Dr. AbdulMutaleb al Qawasmeh

2.  Mr Zaki is a 47 years old man, coming to your
clinic to refill his medications. He has past
medical history of DMll for 12 years, smoker.
He works is an accountant for 20 years,
doesn’t play any sports. His current
medications are: sitagliptin 50/1000mg BID,
diamicron 120 mg OD, Crestor 10 mg.

3.  Vitals: BP: 147/96 bilaterally
pulse:86
temperature:37.1
RBS:180 mg/dl
BMI: 36
Physical examination:
General : looks well
Chest: clear
CVS: loud S2 over 2nd midclavicular line on Rt side.
Abdomen: soft, lax no organomegaly
Peripheral pulses: week bilateral dorsalis pedis
pulsations

4.  Labs:
 CBC: NORMAL
 Kft: Scr:104, Na:141, K: 4.2
 Albumin in urine 600 mg/day
 ECG:

6.  What is the goal BP ?
 What are the important advices you would tell
the patient ?
 What is your management ?

7.  Mrs Aziza is a 56 years old female coming to
your clinic today for FU, she is a k/c of HTN
,osteoarthritis, bronchial asthma, GERD.
Her BA is controlled, her heart burn is not
controlled all over the week, pt takes NSAIDs
frequently for her osteoarthritis, pt is not
following healthy diet where she eats most of her
food with extra salt. She is unemployed doesn’t
go out frequently. She has family history of HTN,
DM, CAD, Breast cancer. Her home medications
are lisinopril 20 mg, amlodipine 10 mg,
hyrochlorothiazide 25 mg, pantoprazole 20 mg,
diclophenac 100 mg.

8. Her home BP readings range between: systolic
150-180 mmhg, diastolic 90-110 mmhg
Vitals at your office:
BP 172/105, PULSE 78, TEMP 36.8
BMI 40
EXAMINATION: No significant findings
What is your approach to this patient ?

9. Based upon the average of two or more properly
measured readings at each of two or more
office visits after an initial screen
●Normal blood pressure: systolic <120 mmHg
and diastolic <80 mmHg
●Prehypertension: systolic 120 to 139 mmHg or
diastolic 80 to 89 mmHg (see
"Prehypertension")
●Hypertension:
•Stage 1: systolic 140 to 159 mmHg or diastolic
90 to 99 mmHg
•Stage 2: systolic ≥160 mmHg or diastolic ≥100
mmHg

10.  Isolated systolic hypertension is considered
to be present when the blood pressure
is ≥140/<90 mmHg, and isolated diastolic
hypertension is considered to be present
when the blood pressure
is <140/≥90 mmHg. Patients with blood
pressure ≥140/≥90are considered to have
mixed systolic/diastolic hypertension.

11.  Based upon ambulatory and home
readings Increasingly, the diagnosis of
hypertension is made using ambulatory blood
pressure monitoring (ABPM) or home blood
pressure monitoring. While there is some debate
about the most appropriate definition, the
following diagnostic criteria were suggested by
the 2013 ESH/ESC guidelines; meeting one or
more of these criteria qualifies as hypertension:
 ●A 24-hour average of 130/80 mmHg or above
 ●Daytime (awake) average of 135/85 mmHg or
above
 ●Nighttime (asleep) average of 120/70 mmHg or
above

12.  The 2007 United States Preventive Services
Task Force (USPSTF) guidelines on screening
for high blood pressure among adults
recommend screening every two years for
persons with systolic and diastolic pressures
below 120 mmHg and 80 mmHg, respectively
(normal blood pressure), and yearly for
persons with a systolic pressure of 120 to
139 mmHg or a diastolic pressure of 80 to 89
mmHg (prehypertension)

13.  The following tests should be performed in all
patients with newly diagnosed hypertension
●Electrolytes and serum creatinine (to calculate the
estimated glomerular filtration rate)
●Fasting glucose
●Urinalysis
●Lipid profile (total and HDL-
cholesterol,triglycerides)
●Electrocardiogram (ECG)
Additional tests — Additional tests may be
indicated in certain settings:

14. ●The evidence supporting benefit from the
treatment of hypertension
●The choice of antihypertensive drugs
●The goal blood pressure

15.  BENEFIT OF TREATMENT : Early treatment of
hypertension is particularly important in
diabetic patients both to prevent
cardiovascular disease and to minimize
progression of renal disease and diabetic
retinopathy

16.  Interventions to prevent hypertension include
nonpharmacologic methods, such as weight
reduction, increased consumption of fresh fruits,
vegetables, and low-fat dairy products, exercise,
salt restriction, and avoidance of smoking and
excess alcohol ingestion. This is consistent with
the American Diabetes Association 2015
guidelines, which state that, among patients with
a systolic blood pressure of 120 to 139 mmHg,
or a diastolic pressure of 80 to 89 mmHg, such
nonpharmacologic methods should be used to
reduce blood pressure. Pharmacological agents
should be initiated in patients who develop
hypertension (blood pressure ≥140/≥90 mmHg)

17.  Major guidelines suggest that the goal blood pressure in
patients with diabetes mellitus is less than 140/90 mmHg,
although prior guidelines had suggested more intensive lowering
to less than 130/80 mmHg . Two small trials (Normotensive
ABCD and SANDS) and the large ACCORD BP trial addressed the
value of lower goal blood pressures in patients with diabetes,
with mean attained systolic pressures below 120 mmHg in the
aggressive therapy groups in SANDS and ACCORD BP. A meta-
analysis of the ACCORD BP, ABCD, and HOT trial (suggested that
intensive blood pressure lowering in patients with diabetes
significantly lowers the incidence of stroke (2 versus 3.1 percent)
but does not significantly lower the risk of mortality (5.5 versus
6.3 percent) or myocardial infarction (7.9 versus 8.5 percent).
 This is consistent with major guidelines published by members
of the eighth Joint National Committee (JNC 8) and the European
Societies of Hypertension and Cardiology (ESH/ESC)

18.  A goal blood pressure of less
than 130/80 mmHg in patients with diabetic
nephropathy and proteinuria (500mg/day or
more). Patients with moderately increased
albuminuria are treated similarly to diabetic
patients without proteinuria.

19. CHOICE OF ANTIHYPERTENSIVE DRUGS
Overall approach to selecting a therapy — The
choice of antihypertensive agents in diabetic
patients is based upon their ability to do the
following:
●Prevent mortality
●Prevent adverse cardiovascular events, such
as myocardial infarction, stroke, and heart
failure
●Prevent the progression of renal disease, if
present

20.  ●In patients with severely increased albuminuria (formerly called
"macroalbuminuria"), we treat with an ACE inhibitor or an ARB.
We also use these drugs in patients with moderately increased
albuminuria (formerly called "microalbuminuria
 ●In patients without increased albuminuria, initial monotherapy
can consist of an ACE inhibitor, ARB, thiazide diuretic, or calcium
channel blocker. However, because angiotensin inhibitors can
prevent albuminuria, and because thiazide diuretics have the
disadvantage of an adverse effect on glucose metabolism, many
experts will choose an ACE inhibitor or ARB even in patients
without albuminuria.
 ●In patients who require more than one drug to control their
blood pressure, we treat with a combination of an ACE inhibitor
(or ARB if unable to take an ACE inhibitor) and a dihydropyridine
calcium channel blocker (eg, amlodipine).

21. Why
ACE INHIBITORS
?????

22. ●They lower the blood pressure, although no drug is likely to be sufficient
as monotherapy.
●They have no specific toxicity, except for cough and raising the plasma
potassium concentration in patients with underlying hyperkalemia or
renal insufficiency.
●They have no adverse effects on lipid metabolism.
●They may lower the plasma glucose concentration by increasing
responsiveness to insulin. In one study, for example, 130 patients with
type 2 diabetes were stabilized for three months; the subsequent
administration of captopril for four months led to a reduction in
hemoglobin A1C values from 8.6 to 6.5 percent with no change in
insulin dose, dietary intake, or body weight . A possible effect of ACE
inhibitors in reducing the incidence of new onset type 2 diabetes is
discussed elsewhere.
●They protect against the progression of moderately increased
albuminuria and severely increased albuminuria due to types 1 and 2
diabetes and have been evaluated for primary prevention of diabetic
nephropathy.
●They may slow the progression of retinopathy.

23.  If a beta blocker is given, carvedilol may be
the drug of choice because of potential
benefits on glycemic control and lower rate of
development of moderately increased
albuminuria compared with metoprolol. A
loop diuretic is likely to be necessary in
patients with renal disease or heart failure.

24.  The presence of severe and symptomatic
paroxysmal hypertension should always
generate suspicion of a catecholamine-
secreting pheochromocytoma. However, the
reality is that this tumor is rarely found
among such patients. In one report, the
diagnosis was established in only 1 of 300
patients evaluated for pheochromocytoma.
Up to 40 percent of patients in this series
fulfilled the criteria for panic disorder.

25. Pseudopheochromocytoma most likely involves
activation of the sympathetic system; this has
been shown from the following observations :
 Paroxysmal nature
 Association with tachycardia in some patients
 Increase in plasma catecholamines
documented during attacks
 Increase in baseline plasma epinephrine and
metanephrines
 Response to alpha/beta blockade

26. In patients in whom the diagnosis of a pheochromocytoma has
been excluded, who are considered to have
pseudopheochromocytoma, hypertensive episodes are generally
characterized by the following three features:
 An abrupt elevation of blood pressure (which can be greater
than 200/110 mmHg in some patients) that is documented by a
clinician or home blood pressure monitor
 Equally abrupt onset of distressful physical symptoms, such as
headache, chest pain, dizziness, nausea, palpitations, flushing,
and diaphoresis
 Attacks are not triggered by fear or panic, although fear does
occur as a consequence of the frightening physical symptoms
 The duration of episodes can range from 10 minutes to many
hours, with frequency ranging from several per day to once every
few months. Between episodes, the blood pressure is normal or
may be mildly elevated

27.  Anxiety.
 Hyperthyroidism
 Cluster or migraine headaches
 Hypertensive encephalopathy
 Coronary insufficiency.
 Renovascular hypertension
 Central nervous system lesions, such as stroke, tumor,
hemorrhage, compression of lateral medulla, and trauma
 Seizure disorder.
 Carcinoid
 Drugs – cocaine, lysergic acid diethylamide, amphetamine,
and clozapine.
 Tyrosine ingestion combined with monoamine oxidase
inhibitors.

28.  Successful treatment of
pseudopheochromocytoma is usually possible, it
involves the use of the following three
modalities, either alone or in combination:
●Antihypertensive agents
●Psychopharmacologic agents
●Psychological intervention
Antihypertensive agents :Severe or very
symptomatic paroxysms often require acute
intervention, either with an oral or IV agent, as
well as chronic preventative therapy.

29.  Acute management of paroxysms :
Intravenous labetalol (beginning with a bolus of
20 mg initially, followed by 40 to 80 mg every 10
minutes to a maximum dose of 200 to 300 mg)
is usually very effective. If the blood pressure
elevation is not extreme, oral agents, such as
clonidine, can be employed acutely. Response to
oral labetalol is less predictable due to
considerable inter-individual differences in
bioavailability. An anxiolytic agent such as
alprazolam, used alone or in combination with an
antihypertensive agent, can also effect rapid
improvement in both symptoms and blood
pressure

30.  Chronic preventive management: Since
pseudopheochromocytoma involves activation of the sympathetic
system, treatment with adrenergic blockade is more likely to be
effective than management with agents such as angiotensin-
converting enzyme (ACE) inhibitors and diuretics, which are
directed at mechanisms other than the sympathetic nervous
system. The combination of any beta blocker (eg, atenolol at a
dose of 12.5 to 50 mg per day or bisoprolol 2.5 to 10 mg daily)
and an alpha blocker (eg, doxazosin at a dose of 0.5 to 2 mg per
day) is frequently effective as preventive therapy in reducing the
magnitude of blood pressure elevation. Labetalol and carvedilol
can also be effective but provide a less reliable degree of alpha
and beta blockade. In addition, central alpha agonists (eg,
clonidine) may be effective, but fatigue and somnolence usually
hamper chronic administration. In patients who are normotensive
between paroxysms, the risk of hypotension is often a limiting
factor in prescribing an antihypertensive regimen.

31.  Psychopharmacologic agents : Adding an antidepressant is
usually dramatically effective in eliminating paroxysms
and restoring a normal quality of life in patients in whom
severe or very symptomatic paroxysms recur despite alpha
and beta blockade, particularly when the disorder is
substantially affecting quality of life. Even when the
patient rejects the possibility of an emotional basis, an
antidepressant drug, such as a selective serotonin
reuptake inhibitor (eg, paroxetine or citalopram at a
starting dose of 10 to 20 mg per day), or a tricyclic
antidepressant, such as desipramine (starting dose 10 to
25 mg per day), perhaps initially combined with an
anxiolytic agent, such as clonazepam (0.5 to 1 mg twice
daily), can eliminate attacks. There are inadequate data to
indicate whether one antidepressant agent or class is more
effective than any other.

32.  A cure is sometimes possible in patients who are
willing to consider the possibility that the
disorder is linked to emotional factors. However,
many patients, particularly those whose
psychological well-being depends upon
continued repression of deep-seated, potentially
overwhelming, emotions, cannot and will not
consider such a possibility. Their refusal to
pursue psychotherapy should be honored. It is
never appropriate to coerce a patient into
psychotherapy, which would be fruitless and
potentially harmful

33.  Isolated systolic hypertension (ISH) has
generally been defined as a systolic blood
pressure above 160 mmHg, with a diastolic
blood pressure below 90 mmHg.
 However, as used in the eighth Joint National
Committee report and supported by other
experts, a systolic blood pressure of 140
mmHg is the upper limit of normal at all ages

34.  although adverse outcomes that can be ascribed
only to excessive blood pressure lowering with
antihypertensive drugs are probably not common
in patients with isolated systolic hypertension,
cardiovascular events can occur if the diastolic
pressure is reduced below the level needed to
maintain perfusion to vital organs, particularly
the heart. Recommended a minimum
posttreatment diastolic pressure of 60 mmHg
overall or 65 mmHg in patients with known
coronary artery disease unless symptoms that
could be attributable to hypoperfusion occur at
higher pressures

35. A number of issues need to be considered before initiating
antihypertensive drug therapy in the elderly :
●Lower initial doses (approximately one-half that in younger
patients) should be used to minimize the risk of side effects.
●Elderly patients may have sluggish baroreceptor and
sympathetic neural responses, as well as impaired cerebral
autoregulation. Thus, in the absence of a hypertensive
emergency or urgency, blood pressure should be lowered
gradually over a period of weeks to months rather than hours to
days in order to minimize the risk of ischemic symptoms,
particularly in patients with orthostatic hypotension. This
approach is consistent with recommendations made by the
ESH/ESC. Even more caution is advised in the very old, although
the benefits from careful therapy probably outweigh the risks in
these patients.
●The trials showing benefit from the treatment of hypertension
in the elderly were performed in relatively fit patients. Greater
caution should be applied to frail patients, and treatment may be
withheld if orthostatic hypotension is limiting.

36.  Problem of orthostatic hypotension:
A potential limiting factor to the use of
antihypertensive drugs is that orthostatic
(postural)and/or postprandial hypotension are
found in as many as 20 percent of elderly
patients with isolated systolic hypertension.
Hypertensive older adults with orthostatic
hypotension are significantly more likely to fall
than those without orthostatic hypotension. In
addition, antihypertensive treatment in elderly
patients is associated with an increased risk of
hip fracture during the first one to two months
following initiation of therapy

37.  In older adults with isolated systolic hypertension, we
recommend lowering the systolic pressure to less than
150 mmHg compared with higher values. This evidence-
based recommendation is consistent with guidelines
produced by the (ESH/ESC), (JNC-8), (AHA), the American
Society of Hypertension/InternationalSociety of
Hypertension (ASH/ISH), and the Canadian Hypertension
Education Program (CHEP) .There is general agreement
supporting a blood pressure goal of less
than 150/90 mmHg among adults 80 years and older. In
patients aged 60 to 79 years, we also suggest lowering the
systolic pressure to less than 140 mmHg if it can be
achieved without producing significant side effects. This
opinion-based suggestion is broadly consistent with
the ESH/ESC, AHA, ASH/ISH, and CHEP guidelines.

38.  In general, three classes of drugs are
considered first-line therapy for the
treatment of hypertension in elderly patients:
low-dose thiazide diuretics (eg, 12.5 to
25 mg/day of chlorthalidone), long-acting
calcium channel blockers (most often
dihydropyridines), and ACE inhibitors or
ARBs. A long-acting dihydropyridine or a
thiazide diuretic is generally preferred in
elderly patients because of increased efficacy
in blood pressure lowering

39. Preferred initial therapy with a long-acting
dihydropyridine calcium channel blocker. If additional
therapy is required, a long-acting
ACE inhibitor/ARB can be added to achieve the
desired combination regimen. This suggestion differs
slightly from the ESH/ESC and the (JNC-8) guidelines
in the following way: ESH/ESC suggests that
monotherapy should consist of either a long-acting
calcium channel blocker or a thiazide diuretic and
combination therapy can consist of any two drugs
from the three previously mentioned drug classes,
JNC-8 suggests that, of the three major drug classes,
there is no preference for either monotherapy or
combination therapy

40. DEFINITION
 Resistant hypertension — Resistant hypertension
is defined in the 2008 American Heart
Association scientific statement and the 2013
guidelines from the European Societies of
Hypertension and Cardiology (ESH/ESC) as blood
pressure that remains above goal in spite of
concurrent use of three antihypertensive agents
of different classess. Thus, patients whose blood
pressure is controlled with four or more
medications should be considered to have
resistant hypertension

41.  RISK FACTORS: Patient characteristics that predict difficult to control
hypertension include higher baseline blood pressure (particularly systolic),
presence of left ventricular hypertrophy, older age, obesity, African-
American race, chronic kidney disease, and diabetes.
 Suboptimal therapy — Suboptimal therapy is a common cause of resistant
hypertension It is most often due to the lack of administration of more
effective drugs and failure to prevent volume expansion with adequate
diuretic therapy
 Lifestyle and diet — Obesity, a high-salt diet, physical inactivity, and heavy
alcohol intake all contribute to hypertension, although not all have been
examined specifically among patients with resistant hypertension.
 The contribution of dietary salt to resistant hypertension was examined in a
randomized trial in which twelve patients with resistant hypertension were
assigned to low (50 meq/day)- or high (250 meq/day)-sodium diet for one
week [23]. After a two-week washout, the patients received the other diet.
Switching from the high- to low-salt diet was associated with an average
reduction in office blood pressure of 23/9 mmHg, and a reduction in the 24-
hour ambulatory blood pressure of 20/10 mmHg.
 Medications — A variety of medications can raise the BP and, in some cases,
reduce the response to antihypertensive drugs. The most commonly
implicated agents are over-the-counter and prescribed medications
including nonsteroidal anti-inflammatory drugs (NSAIDs), including some but
not all (eg, celecoxib) of the selective cyclooxygenase-2 (COX-2) inhibitors.
 The NSAIDs that raise blood pressure can interfere with the antihypertensive
effect of virtually any agent, except calcium channel blockers. A presumed
mechanism by which the blood pressure rises is a reduction in sodium
excretion, thereby increasing the intravascular volume.
 Other agents that may contribute to hypertension include sympathomimetics
(diet pills, decongestants, amphetamine-like stimulants), glucocorticoids,
herbal preparations, estrogen-containing contraceptives, and
antidepressants.

42.  Secondary causes of hypertension — Patients
with resistant hypertension are much more
likely to have an identifiable cause of
hypertension (ie, secondary hypertension).
The most common are primary aldosteronism
and renal artery stenosis, chronic kidney
disease, and obstructive sleep apnea (table
2). Less common causes include
pheochromocytoma, Cushing's syndrome,
and aortic coarctation

43.  Primary aldosteronism — Primary aldosteronism has been reported
in approximately 10 to 20 percent of patients with resistant
hypertension. Otherwise unexplained hypokalemia is the major clue
to the presence of primary hyperaldosteronism. However, more than
50 percent of patients with proven primary hyperaldosteronism are
normokalemic at presentation. Thus, the absence of hypokalemia
does not exclude this disorder.
 Renal artery stenosis — Renal artery stenosis is a common cause of
resistant hypertension and can be due to either atherosclerotic
disease or, in younger patients, fibromuscular dysplasia.
 Chronic kidney disease — As renal function declines in patients with
chronic kidney disease, there is an increasing need for additional
antihypertensive medications. Diuretics play a central role. Diuretics
should be pushed until the blood pressure goal.
 Obstructive sleep apnea — Obstructive sleep apnea is common
among patients with resistant hypertension who are referred for
sleep studies.

44.  Hypertensive emergency in adults (often
defined as systolic blood pressure ≥180
mmHg and/or diastolic blood pressure ≥120
mmHg) can be associated with a variety of
acute, life-threatening complications, These
include hypertensive encephalopathy, retinal
hemorrhages, papilledema, or acute and
subacute kidney injury.

45.  Hypertensive urgency is the relatively
asymptomatic patient with a blood pressure in
the "severe" range (ie, ≥180/≥120 mmHg), often
a mild headache, but no signs or symptoms of
acute end-organ damage, as with hypertensive
emergencies, occurs more frequently among
patients who have been nonadherent with either
their chronic antihypertensive drug regimen or
their low-sodium diet. Severe hypertension can
also develop in medication-adherent patients
following ingestion of large quantities of salt and
can be controlled by resuming a low-salt diet.

46. How quickly should
the blood pressure
be reduced?

47.  The blood pressure should be reduced over a period of hours to days,
although slower reductions may be needed in older adult patients at high
risk for cerebral or myocardial ischemia resulting from excessively rapid
reduction of blood pressure.
 What is the blood pressure target during this period of time? − The blood
pressure should usually be lowered to <160/<100mmHg. However, the
mean arterial pressure should not be lowered by more than 25 to 30 percent
over this relatively short period of time. Thus, the short-term blood pressure
target may need to be above 160/100 mmHg in patients who present with
very high pressures. This approach has not been well studied and is based
mostly upon experience. In the long-term, the blood pressure should usually
be reduced further (eg, <140/<90 mmHg).
 If the blood pressure needs to be lowered over a period of hours, we use oral
furosemide, oral clonidine, or oral captopril.
 Rapidity of blood pressure lowering — The rapidity with which blood
pressure should be brought to safe levels is controversial and not based
upon high-quality medical evidence. In the absence of symptoms, a gradual
reduction in pressure is suggested over a period of several hours to several
days

48. To achieve relatively rapid initial blood
pressure reduction, we use one of the
following agents:
●Oral furosemide (if the patient is volume
overloaded) at a dose of 20 mg (or higher if
the renal function is not normal)
●Oral clonidine (but not intended as long-term
therapy) at a dose of 0.2 mg
●Oral captopril (if the patient is not volume
depleted) at a dose of 6.25 or 12.5 mg

49.  However, sublingual nifedipine is contraindicated in
this setting and should not be used, cerebral or
myocardial ischemia or infarction can be induced by
aggressive antihypertensive therapy if the blood
pressure falls below the range at which tissue
perfusion can be maintained by autoregulation. This
has been most often described with sublingual
nifedipine, which may produce an unpredictable and
uncontrolled blood pressure reduction as well as
severe ischemic complications. This was a major
reason why the use of nifedipine capsules for
hypertension is not approved by the United States
Food and Drug Administration (US FDA), and why
most hospitals' intensive care units and emergency
departments restrict the use of this medication.