First-line medications used in the treatment of hypertension include diuretics, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), beta-blockers, and calcium channel blockers (CCBs). Some patients will require 2 or more antihypertensive medications to achieve their BP target. As per special consideration, modified treatment is given in the presentation.

1. HYPERTENSION PHARMACOTHERAPY
PART 2
Dr. Chavan P. R.
Pharm D

2. LEFT VENTRICULAR DYSFUNCTION (SYSTOLIC
HEART FAILURE)
 ACE inhibitor + diuretic therapy = first-line regimen
of choice ----reduced CV morbidity and mortality.
 Diuretics ---symptomatic relief of edema by
inducing diuresis.
 Loop diuretics ---patients with more advanced
disease.
 Because of the high renin status of patients with
heart failure, ACE inhibitors should be initiated at
low doses to avoid orthostatic hypotension.

3.  β-Blocker therapy ---modify disease in LV
dysfunction and is a component of this first-line
regimen (standard therapy) for these patients.
 Titration of low to high dose as per tolerability due
to the risk of exacerbating heart failure
 Bisoprolol, carvedilol, and metoprolol succinate are
the only β-blockers proven to be beneficial in LV
dysfunction

4. POSTMYOCARDIAL INFARCTION
 β-Blocker (without ISA) and ACE inhibitor therapy is
recommended.
 βBlockers decrease cardiac adrenergic stimulation
and reduce the risk of a subsequent MI or sudden
cardiac death.
 ACE inhibitors improve cardiac function and reduce
CV events after MI.
 ARBs are alternatives to ACE inhibitors in
postmyocardial patients with LV dysfunction.

5.  The aldosterone antagonist eplerenone reduces CV
morbidity and mortality in patients soon after an
acute MI (within 3 to 14 days) in patients with
Hypertension symptoms of acute LV dysfunction.
 Its use should be limited to selected patients, and
then with diligent monitoring of serum potassium.

6. CORONARY ARTERY DISEASE
 β-Blockers (without ISA) --- first-line therapy in chronic
stable angina ---reduce BP, improve myocardial
consumption, and decrease demand.
 Long-acting CCBs are either alternatives (the
nondihydropyridines verapamil and diltiazem) or add-on
therapy (dihydropyridines) to β-blockers in chronic
stable angina.
 Once ischemic symptoms are controlled with β-blocker
and/or CCB therapy, other antihypertensive drugs (e.g.,
ACE inhibitor, ARB) can be added to provide additional
CV risk reduction.

7.  Thiazide diuretics may be added thereafter to
provide additional BP lowering and further reduce
CV risk.
 For acute coronary syndromes, first-line therapy
should consist of a βblocker and ACE inhibitor; the
combination lowers BP, controls acute ischemia,
and reduces CV risk.

8. DIABETES MELLITUS
 The BP goal <130/80 mm Hg.
 diabetes and hypertension treatment ---either an
ACE inhibitor or an ARB---nephroprotection and
reduced CV risk.
 A thiazide-type diuretic ---second agent to lower BP
and provide additional CV risk reduction.

9.  CCBs ---add-on agents for BP control in
hypertensive patients with diabetes.
 β-Blockers ---reduce CV risk in patients with
diabetes ---add-on therapy with other standard
agents or to treat another compelling indication
(e.g., postmyocardial infarction).

10.  masking the symptoms of hypoglycemia (tremor,
tachycardia, and palpitations but not sweating) in
tightly controlled patients, delay recovery from
hypoglycemia, and produce elevations in BP due to
vasoconstriction caused by unopposed α-receptor
stimulation during the hypoglycemic recovery
phase.
 Despite these potential problems, β-blockers can
be used safely in patients with diabetes.

11. CHRONIC KIDNEY DISEASE
 ACE inhibitor or ARB --- first-line therapy to control
BP and preserve kidney function in chronic kidney
disease.
 Because these patients usually require multiple-
drug therapy, diuretics and a third antihypertensive
drug class (e.g., β-blocker, CCB) are often needed.

12. RECURRENT STROKE PREVENTION
 The combination of an ACE inhibitor and thiazide
diuretic --- reduces the incidence of recurrent stroke
in patients with a history of ischemic stroke or
transient ischemic attacks.
 Reductions in risk of recurrent ischemic stroke have
also been seen with ARB-based therapy.

13. SPECIAL POPULATIONS
OLDER PEOPLE
 Elderly patients may present with either isolated
systolic hypertension or an elevation in both SBP
and DBP.
 Diuretics and ACE inhibitors provide significant
benefits and can be used safely in the elderly, but
with dosage titrations
 Centrally acting agents and β-blockers should
generally be avoided or used with caution because
of dizziness and postural hypotension.

14. CHILDREN AND ADOLESCENTS
 Secondary hypertension --much more common---
Kidney disease (e.g., pyelonephritis,
glomerulonephritis) is the most common cause
 Coarctation of the aorta can also produce
secondary hypertension. Medical or surgical
management of the underlying disorder usually
restores normal BP.
 Nonpharmacologic treatment (particularly weight
loss in obese children) is the cornerstone of therapy
of primary hypertension.

15.  ACE inhibitors, ARBs, β-blockers, CCBs, and
thiazide-type diuretics are all acceptable drug
therapy choices.
 ACE inhibitors, ARBs, and direct renin inhibitors are
contraindicated in sexually active girls because of
potential teratogenic effect or with bilateral renal
artery stenosis or unilateral stenosis in a solitary
kidney.

16. PREGNANT WOMEN
 Preeclampsia, defined as BP ≥140/90 mm Hg that
appears after 20 weeks’ gestation accompanied by
new-onset proteinuria (≥300 mg/24 hours)
 Definitive treatment of preeclampsia ---delivery, and
this is indicated if pending or frank eclampsia
(preeclampsia and convulsions) is present.
 Otherwise, management consists of restricting
activity, bedrest, and close monitoring.

17.  Chronic hypertension is defined as elevated BP that
was noted before pregnancy began.
 Methyldopa ---drug of choice
 β-Blockers, labetalol, and CCBs ---reasonable
alternatives.
 ACE inhibitors and ARBs are known teratogens and
are absolutely contraindicated.
 The direct renin inhibitor aliskiren also should not
be used in pregnancy.

18. AFRICAN AMERICANS
 Hypertension is more common and more severe in
African Americans than in those of other races.
 Differences in electrolyte homeostasis, glomerular
filtration rate, sodium excretion and transport
mechanisms, plasma renin activity, and BP
response to plasma volume expansion have been
noted.
 Lifestyle modifications are recommended to
augment drug therapy.

19.  Thiazide diuretics ---first-line drug therapy for most
patients, but recent guidelines aggressively promote
combination therapy.
 Two drugs are recommended in patients with SBP
values ≥15 mm Hg from goal.
 Thiazides and CCBs are particularly effective in
African Americans.
 Antihypertensive response is significantly increased
when either class is combined with a β-blocker, ACE
inhibitor, or A

20. PULMONARY DISEASE AND PERIPHERAL
ARTERIAL DISEASE
 Although β-blockers (especially nonselective
agents) avoided in hypertensive patients with
asthma and chronic obstructive pulmonary disease
----cardioselective β-blockers can be used safely.
 Consequently, cardioselective agents should be
used to treat a compelling indication (i.e.,
postmyocardial infarction, coronary disease, or
heart failure) in patients with reactive airway
disease.

21.  PAD is a coronary artery disease risk equivalent,
and a BP goal of <130/80mmhg is recommonded.
 ACE inhibitors may be ideal in patients with
symptomatic lower-extremity PAD; CCBs may also
be beneficial.
 B-Blockers ---decreased peripheral blood flow
secondary to unopposed stimulation of α-receptors -
---vasoconstriction.
 However, β-blockers are not contraindicated in PAD
and have not been shown to adversely affect
walking capability.

22. DYSLIPIDEMIA
 Dyslipidemia is a major CV risk factor, and it should
be controlled in hypertensive patients.
 Thiazide diuretics and β-blockers without ISA may
affect serum lipids adversely, but these effects
generally are transient and of no clinical
consequence.

23.  The α-blockers have favorable effects (decreased
low-density lipoprotein cholesterol and increased
high-density lipoprotein cholesterol levels).
 However, because they do not reduce CV risk as
effectively as thiazide diuretics, this benefit is not
clinically applicable.
 ACE inhibitors and CCBs have no effect on serum
cholesterol.

24. HYPERTENSIVE URGENCIES AND
EMERGENCIES
 Hypertensive urgencies are ideally managed by
adjusting maintenance therapy by adding a new
antihypertensive and/or increasing the dose of a
present medication.
 ✓ Acute administration of a short-acting oral drug
(captopril, clonidine, or labetalol) followed by careful
observation for several hours to ensure a gradual
BP reduction is an option.
 ✓ Oral captopril doses of 25 to 50 mg may be given
at 1- to 2-hour intervals. The onset of action is 15 to
30 minutes.

25.  ✓ For treatment of hypertensive rebound after
withdrawal of clonidine, 0.2 mg is given initially,
followed by 0.2 mg hourly until the DBP falls below
110 mm Hg or a total of 0.7 mg has been
administered; a single dose may be sufficient.
 ✓ Labetalol can be given in a dose of 200 to 400
mg, followed by additional doses every 2 to 3
hours.

26.  Hypertensive emergencies require immediate BP
reduction to limit new or progressing target-organ
damage.
 The goal is not to lower BP to normal; instead, the
initial target is a reduction in mean arterial pressure
of up to 25% within minutes to hours.
 If BP is then stable, it can be reduced toward
160/100– 110 mm Hg within the next 2 to 6 hours.
Precipitous drops in BP may cause end-organ
ischemia or infarction.
 If BP reduction is well tolerated, additional gradual
decrease toward the goal BP can be attempted
after 24 to 48 hours

27.  Nitroprusside is the agent of choice for minute-to-
minute control in most cases.
 It is usually given as a continuous IV infusion at a
rate of 0.25 to 10 mcg/kg/min.
 Its onset of hypotensive action is immediate and
disappears within 1 to 2 minutes of discontinuation.

28.  When the infusion must be continued longer than
72 hours, serum thiocyanate levels should be
measured, and the infusion should be discontinued
if the level exceeds 12 mg/dL.
 The risk of thiocyanate toxicity is increased in
patients with impaired kidney function.
 Other adverse effects include nausea, vomiting,
muscle twitching, and sweating.

29. EVALUATION OF THERAPEUTIC
OUTCOMES
 Clinic-based BP monitoring
 BP response evaluation 2 to 4 weeks after initiating
or making changes in therapy.
 BP monitoring can be done every 3 to 6 months,
More frequent evaluations in patients with a history
of poor control, nonadherence, progressive target-
organ damage, or symptoms of adverse drug
effects.
 Self-measurements of BP or automatic ambulatory
BP monitoring

30.  Patients should be monitored for signs and
symptoms of progressive target-organ disease.
 history for chest pain (or pressure), palpitations,
dizziness, dyspnea, orthopnea, headache, sudden
change in vision, one-sided weakness, slurred
speech, and loss of balance to assess for the
presence of complications.
 funduscopic changes on eye examination, LV
hypertrophy on ECG, proteinuria, and changes in
kidney function.

31.  Monitoring for adverse drug effects should typically
occur 2 to 4 weeks after starting a new agent or
dose increases, and then every 6 to 12 months in
stable patients.
 Additional monitoring may be needed for other
concomitant diseases.
 Patients taking aldosterone antagonists should have
potassium concentration and kidney function
assessed within 3 days and again at 1 week after
initiation to detect potential hyperkalemia.
 Patient adherence, general health perception,
energy level, physical functioning, and overall
satisfaction with treatment.

32. THANK YOU