Pharmacotherapy of Hypertension tre.pptx

Pharmacotherapy of
Hypertension
Prof. Dr. Ghada Suddek
Clinical Pharmacy Program
(2023-2024)
Pharmacotherapy of
cardiovascular diseases Course

Steps of Drug Therapy for
Hypertension
1st Step → Monotherapy
Diuretics
Ca Channel Blockers
ARBs
ACEI

Treatment of Hypertension – combination
therapy
• In clinical practice a large number of patients require combination
therapy – the combination should be rational and from different patterns
of haemodynamic effects
• 1st Step→ Monotherapy
• 2nd Step → Two Drugs
• If failed → 3 drugs
• If failed → Resistant hypertension:
• (failure to achieve BP goal on full doses of 3 drug
regimen including a diuretic)
(give 4 or 5 drugs including vasodilators)

Treatment of Hypertension –
 6 compelling Indications:
 Heart failure
 Postmyocardial Infarction
 Coronary artery disease
 Diabetes Mellitus
 Chronic Kidney Disease
 Recurrent Stroke Prevention

SPECIAL POPULATIONS
Older People
 • Elderly patients may present with either isolated systolic hypertension or
elevation in both SBP and DBP. CV morbidity and mortality are more
closely related to SBP than to DBP in patients 50 years of age and older.
 • Diuretics, Calcium channel blockers, ACE inhibitors, and ARBs provide
significant benefits and can be used safely in the elderly,
 Smaller-than-usual initial doses must be used for initial therapy.

SPECIAL POPULATIONS
Children and Adolescents
 • Secondary hypertension is more common in children and adolescents than in adults.
 Medical or surgical management of the underlying disorder usually normalizes BP.
 • Nonpharmacologic treatment (particularly weight loss in obese children, exercise) is the
cornerstone of therapy of primary hypertension.
 • ACE inhibitors, ARBs, β-blockers, CCBs, and thiazide diuretics are all acceptable drug
therapy choices.
 • ACE inhibitors, ARBs, and direct renin inhibitors are contraindicated in sexually active girls
because of potential teratogenic effects.

SPECIAL POPULATIONS
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.
•African Americans have an increased need for combination therapy to achieve and
maintain BP goals. Start therapy with two drugs in patients with SBP values greater than or
equal to 15 mm Hg above goal.
• Thiazides and CCBs are most effective in African Americans.
• Antihypertensive response is significantly increased when either class is combined with a β-
blocker, ACE inhibitor, or ARB.

SPECIAL POPULATIONS
Pulmonary Disease and Peripheral Arterial Disease
•Although β-blockers (especially nonselective agents) have generally been avoided
in hypertensive patients with asthma and COPD because of fear of inducing bronchospasm,
data suggest that cardioselective β-blockers can be used safely. Consequently,
cardioselective agents should be used to treat a compelling indication (ie, post-MI, coronary
disease, or HF) in patients with reactive airway disease.
•PAD is considered a coronary artery disease risk equivalent. β-Blockers can theoretically
be problematic because of possible decreased peripheral blood flow secondary to
unopposed stimulation of α-receptors that results in vasoconstriction. This can be mitigated
by using a β- blocker with α-blocking properties (eg, carvedilol). However, β-
blockers are not contraindicated in PAD and have not been shown to adversely affect walking
capacity.

Hypertension in Pregnancy
Pre-existing chronic hypertension
Give only methyl dopa, Nifedipine OR Labetalol
Pre-eclampsia
>140/90 mmHg after 20 weeks’ gestation with proteinuria, Hypertension,
edema & hyperuricemia
Fetal death or growth retardation
 restricted activity, bed rest, close monitoring beneficial
 definitive treatment: delivery
In severe case, give iv bolus injection of hydralzine
Then methyl dopa, Nifedipine OR labetalol
Important to differentiate preeclampsia from chronic gestational hypertension

Hypertensive crisis
 Systolic blood pressure (SBP) > 180 mmHg OR diastolic blood
pressure (DBP) > 110 mmHg
 2 Categories:
 Hypertensive urgency: severely elevated blood pressure (BP)

NO evidence of organ damage
 Typically managed with oral antihypertensives
 Hypertensive emergency: severely elevated blood pressure (BP) with
acute/life-threatening end organ damage

Example of organ damage: acute coronary syndrome (ACS), unstable
angina, encephalopathy, intracerebral hemorrhage, dissecting aortic
aneurysm, renal failure, etc.

Treatment with rapid onset, short-acting intravenous (IV) antihypertensives

Treatment goals
 Patients experiencing hypertensive urgency or emergency should
present to the emergency department for evaluation
 Hypertensive urgency:
 BP may be lowered gradually over several hours

Avoid rapid reduction in blood pressure
 Observe patient, monitor for signs of organ damage
 Discharge with oral medications
 Hypertensive emergency:
 Immediate reduction in BP indicated
 Reduce mean arterial pressure (MAP) by 10 - 20% over 60 minutes, then 5
– 15% over next 23 hours
 Reduce DBP by 10 – 15% or < 110 mmHg over 30 – 60 minutes

Hypertensive Urgency: Treatment
 GRADUALLY reduce BP
 Adjust maintenance therapy
 Add new antihypertensive +/-
 Increase dose of current antihypertensive
 Follow-up appointment within 1 week
 Ideally, within 24 – 72 hours
 Short-acting antihypertensives:
 Captopril 25 – 50 mg PO q 1 – 2 hours

If BP does not decrease within 30 – 60 minutes, unlikely to successfully
treat
 Clonidine 0.2 mg PO q1hr
 Continue therapy until DBP < 110 mmHg or total of 0.7 mg has been given
 Labetalol 200 – 400 mg PO q 2 – 3 hours

Hypertensive Emergency
 Parenteral therapy indicated
 Choice of medication can be guided based on clinical presentation
 Reduce mean arterial pressure (MAP) by 10 - 20% over 60 minutes, then 5
– 15% over next 23 hours
 Reduce DBP by 10 – 15% or < 110 mmHg over 30 – 60 minutes
 Continue to reduce BP over next 24 – 48 hours as tolerated
 Once BP stable with IV agents and organ damage resolving, initiate
oral therapy and titrate IV meds down

1
6
Hypertensive Crisis
Drug Clevidipine Enalaprilat Esmolol Fenoldopam
Class DHP CCB ACEI Cardioselective beta blocker Dopamine1 receptor agonist
Indication Most HC but avoid in AHF HC HC HC
Regimen 1 – 2 mg/hr IV gtt; double dose at 90
second intervals to reach BP
goal Max: 32 mg/hr.
1.25 mg IV q 6 hours.
No more than 5 mg per dose.
If patient receiving diuretic, start
with 0.625 mg.
CrCl < 30 ml/min → renally adjust
250–500 mcg/kg IV bolus, then 50–
100 mcg/kg/min IV infusion.
0.1–0.3 mcg/kg/min IV infusion
Maximum 1.6 mcg/kg/min IV
infusion Short term therapy.
AE rebound HTN (Monitor x 8 hours
after discontinuation), tachycardia,
atrial fibrillation.
Angioedema, hyperkalemia,
hypotension, increased SCr.
Hypotension, nausea, bradycardia,
first- degree heart block, heart
failure
Tachycardia, headache, nausea, flushing
No rebound effect
CI Soy or egg allergy, defective lipid
metabolism, hypertriglyceridemia (>
500), severe aortic stenosis.
history of angioedema, diabetes
mellitus AND aliskiren,
pregnancy.
bradycardia, decompensated heart
failure, recent IV non-DHP CCB
Monitor: Serum potassium, BP,
heart rate (HR).
Notes Rapid onset, rapid offset Rapid onset, rapid offset Caution: glaucoma, angina,
sulfite sensitivity.
Drug Hydralazine Labetalol Nicardipine Nitroglycerin Sodium nitroprusside
Class Direct vasodilator Nonselective beta blocker DHP CCB Vasodilator Vasodilator
Indication HC HC HC HC HC
Regimen 10–20 mg IV q 4 – 6
hours Useful if
bradycardic
20 – 80 mg IV bolus q 10
minutes Max cumulative dose
of 300 mg OR
0.5 – 2 mg/min IV infusion
Max cumulative dose of 300
mg
5 – 15 mg/hr IV infusion
Titrate by 2.5 mg/hr q 5
min
5–100 mcg/min IV infusion
Must use nitroglycerin
(NTG) specific tubing
AE Tachycardia, exacerbation of
angina, nasal congestion,
drug- induced lupus-like
syndrome.
orthostatic hypotension,
bronchoconstriction, heart
block
tachycardia, headache, flushing,
injection site reaction
headache, flushing,
vomiting, xerostomia,
tolerance with prolonged use
muscle twitching, sweating,
thiocyanate/cyanide toxicity
CI (CAD), mitral valve
rheumatic heart
disease.
bradycardia, asthma,
decompensated heart failure,
recent IV non-DHP CCB
severe aortic stenosis concurrent (PDE-5),
hypersensitivity to corn or
corn products
Black Box: cyanide toxicity
Metabolized to cyanide,
then thiocyanate
Increased risk of cyanide
toxicity in renal
impairment
Notes Caution: may increase (ICP) Rapid onset, rapid
offset Protect from
light

Drug Dose
Onset
(minutes)
Duration (minutes) Special Indications
Clevidipine 1–2 mg/h (32 mg/h
maximum) IV infusion
2–4 5–15 Most hypertensive emergencies except acute heart failure;
contraindicated in soy or egg allergy, defective lipid metabolism, and
severe aortic stenosis
Enalaprilat 1.25–5 mg IV q6 hours 15–30 360–720 Acute left ventricular failure; avoid in acute myocardial infarction,
eclampsia
Esmolol hydrochloride 250–500 mcg/kg IV bolus,
then 50–100 mcg/kg/min
IV infusion
1–2 10–20 Aortic dissection; perioperative; avoid in patients already on β-blocker,
bradycardic, or decompensated heart failure
Fenoldopam mesylate 0.1–0.3 mcg/kg/min IV
infusion
<5 30 Most hypertensive emergencies; caution with glaucoma
Hydralazine
hydrochloride
10–20 mg IV q 4 – 6 hours 10–20 60–240 Eclampsia; useful if patient bradycardic
Labetalol hydrochloride 20–80 mg IV bolus q 10
minutes; 0.5–2 mg/min IV
infusion
5–10 180–360 Most hypertensive emergencies except acute heart failure or heart
block
Nicardipine
hydrochloride
5–15 mg/hr IV infusion 5–10 15–30, may exceed
240
Most hypertensive emergencies except acute heart failure
Nitroglycerin 5–100 mcg/min IV infusion 2–5 5–10 Coronary ischemia
Sodium nitroprusside 0.25–10 mcg/kg/min IV
infusion
Immediate 1–2 Most hypertensive emergencies; caution with chronic kidney disease
Adapted from Table 3-11 Parenteral Antihypertensive Agents for Hypertensive Emergency. Saseen JJ, MacLaughlin EJ. Chapter 3. Hypertension. In: DiPiro JT,
Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014

Follow-up and Monitoring
 Patients should return for follow-up and adjustment of medications until the BP goal is
reached.
 The frequency of follow-up visits for patients with hypertension varies but is influenced by
the severity of hypertension, comorbidities, and choice of agent selected.
 At a minimum, assessment of response to medications should be done at 1-month
intervals.
 More frequent visits for stage 2 HTN or with complicating comorbid conditions. shorter
time frame of less than or equal to 2 weeks is more appropriate.
 After BP at goal and stable, follow-up visits at 3- to 6-month intervals.
 Serum potassium and creatinine monitored 1–2 times per year.

Resistant hypertension
 It is defined as a blood pressure that remains above goal
despite concurrent use of three antihypertensive agents of
different classes taken at maximally tolerated doses, one of
which should be a diuretic
 they require more aggressive medication treatment
 An essential management of resistant hypertension is identification
and subsequent treatment of potentially reversible causes of
secondary hypertension

Management of resistant
hypertension
 1. Lifestyle modification (eg, weight loss, exercise, eating a healthy
diet) has multiple health benefits and can also lower blood
pressure and reduce the need for further medications in
patients with resistant hypertension.
 2. Nonadherence to antihypertensive therapy is a major contributor
to inadequate blood pressure control and should be addressed.
 3. Regimens should be simplified, and long-acting combination
agents should as possible in order to reduce the number of
prescribed pills and to permit once-daily dosing.

hypertension
 4. The following stepwise approach to pharmacologic therapy applies
to patients with confirmed resistant hypertension who do not
have a reversible secondary cause of hypertension
 Pharmacologic therapy in non secondary cause of HTN
 A. In patients who are taking a thiazide-type diuretic
(eg,
hydrochlorothiazide), and who have an estimated glomerular
filtration rate (eGFR) ≥30 mL/min/1.73 m2, we suggest switching to
a thiazide- like diuretic (either chlorthalidone or indapamide.
 B. In patients with an eGFR ≥30 mL/min/1.73 m2 who are
already treated with a thiazide-like diuretic, and who have
persistent signs of hypervolemia (ie, edema), we suggest adding a
loop diuretic to the thiazide-like diuretic.

hypertension
 C. In patients with an eGFR <30 mL/min/1.73 m2, we
suggest switching to a loop diuretic; if such patients are already
taking a loop diuretic, then we intensify the loop diuretic dose,
unless the patient develops signs of hypovolemia.
 D. In patients with resistant hypertension and uncontrolled
blood pressure despite potent diuretic therapy, we suggest
adding a mineralocorticoid receptor antagonist (spironolactone or
eplerenone). Apotassium-sparing diuretic (eg, amiloride, triamterene)
is an alternative if a mineralocorticoid receptor antagonist cannot be
used

hypertension
 E. Some patients remain hypertensive despite taking a four-
drug regimen that ideally includes a thiazide-like diuretic,
such as chlorthalidone, and a mineralocorticoid receptor
antagonist, such as spironolactone. Patient factors (eg, preferences,
side effects) and other characteristics can help guide choices.
 F
. As an example, those with faster heart rates (eg, >70 beats
per minute) may benefit from next adding a beta blocker. Centrally
acting agents that lower sympathetic activity may also be
effective, but adverse effects are more common.

hypertension
 G. Other options include alpha-1 antagonists such as doxazosin
or direct vasodilators (hydralazine or minoxidil).
 H. The direct vasodilators hydralazine and minoxidil are
generally reserved for patients who remain hypertensive despite
trying the other approaches previously listed.

Class Parameters
Diuretic
s
blood pressure
BUN/serum
creatinine
serum electrolytes (K+, Mg2+,
Na+) uric acid (for thiazides)
β-
Blockers
blood
pressure
heart rate
Aldosterone
antagonists ACE
inhibitors
Angiotensin II
receptor blockers
Direct Renin
inhibitors
blood pressure
BUN/serum
creatinine serum
potassium
Calcium channel
blockers
blood
pressure
heart rate 2
5

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