1. HYPERTENSION
TREATMENT
OverallGoal of Treatment-
The overallgoal of treating hypertension is to reduce hypertension-associated morbidity and
mortality. This morbidity and mortality is related to hypertension-associated target-organ
damage (e.g., CV events, cerebrovascular events, heart failure, kidney disease).
GENERAL APPROACH TO TREATMENT:
After a diagnosis of hypertension is made, most patients should be placed on both lifestyle
modifications and drug therapy concurrently.
Lifestyle modification alone is appropriate therapy for most patients with prehypertension.
However, lifestyle modifications alone are not considered adequate for patients with
hypertensionand additional CV riskfactorsor hypertension-associatedtargetorgan damage.
2.
3. NONPHARMACOLOGIC THERAPY:
PHARMACOTHERAPY:
Primary Antihypertensive Agents
Class Subclass Drug
Usual Dose Range,
mg/day
Daily
Frequency
Diuretics
Thiazides***
Chlorthalidone 6.25–25 1
Hydrochlorothiazide 12.5–25 1
Indapamide 1.25–2.5 1
Metolazone 0.5 –1 1
Metolazone 2.5 –10 1
Loop
Bumetanide 0.5–4 2
Furosemide 20–80 2
Torsemide 5–10 1
Potassium sparing
Amiloride 5–10 1 or 2
Amiloride/
Hydrochlorothiazide
5–10/50–100 1
Triamterene 50–100 1 or 2
Triamterene/
Hydrochlorothiazide
37.5–75/25–50 1
Aldosterone
Antagonists
Eplerenone
50–100
1 or 2
Spironolactone 25–50 1 or 2
Spironolactone/
Hydrochlorothiazide 25–50/25–50
1
ACE
inhibitors
Benazepril 10–40 1 or 2
Captopril 12.5–150 2 or 3
Enalapril 5–40 1 or 2
Fosinopril 10–40 1
Lisinopril 10–40 1
Moexipril 7.5–30 1 or 2
Perindopril 4–16 1
Quinapril 10–80 1 or 2
Ramipril 2.5–10 1 or 2
Trandolapril 1–4 1
5. Alternative Antihypertensive Agents
α1-Blockers
Doxazosin 1–8 1
Prazosin 2–20 2 or 3
Terazosin 1–20 1 or 2
Directrenin
inhibitor
Aliskiren 150–300 1
Central α2-
agonists
Clonidine
0.1–0.8 2
Clonidinepatch
0.1–0.3
1
weekly
Methyldopa
250–
1000
2
Peripheral
adrenergic
antagonist
Reserpine
0.05–
0.25
-
Directarterial
vasodilators
Minoxidil 10–40 1 or 2
Hydralazine 20–100 2 to 4
A thiazide-type diuretic, ACE inhibitor, angiotensin II receptor blocker (ARB), or calcium
channel blocker (CCB) are considered primary antihypertensive agents that are acceptable
first-line options
β-blockers are effective antihypertensive agents that previously were considered primary
agents. They are now preferred either to treat a specific compelling indication, or in
combination with one or more of the aforementioned primary antihypertensive agents for
patients without a compelling indication.
Other antihypertensivedrugclassesareconsidered alternative drugclassesthatmay be used
in select patients after first-line agents
Left Ventricular Dysfunction (Systolic Heart Failure)
The primary physiologic abnormality in this compelling indication is decreased CO.
Standard pharmacotherapy, consists of three drugs: an ACE inhibitor plus diuretic therapy,
followed by the addition of an appropriate β-blocker.
Heart failure induces a compensatory high-renin condition, so ACEIs and starting ACE
inhibitors under these conditions can cause a pronounced first-dose effect and possible
orthostatic hypotension, so prefer low dose.
Diuretics are also a part of standard pharmacotherapy primarily to control symptoms. They
provide symptomatic relief of edema by inducing diuresis.
6. Bisoprolol, carvedilol, and sustained release metoprolol succinate are the only β-blockers
proven to be beneficial in left ventricular dysfunction. These are for to reduce sympathetic
effects on heart. But, it can cause acute exacerbation of heart failure. So, they must be
started in very low doses, doses much lower than that used to treat hypertension, and
titrated slowly to high doses based on tolerability.
If a fourth agent needs to be added, many clinicians will select an aldosteroneantagonist, to
prevent pathological remodelling of heart by aldosterone.
Post-MI
β-Blocker [those without intrinsic sympathomimetic activity (ISA)] and ACEinhibitor therapy
are recommended
β-blockers decrease cardiac adrenergic stimulation. ACE inhibitors have been shown to
improve cardiac remodelling and cardiac function and to reduce CV events post-MI.
Coronary Artery Disease
Chronic stable angina and acute coronary syndrome (unstable angina and acute MI) are
forms of coronary artery disease (aka ischemic heart disease).
β-blockers are first-line therapy in chronic stable angina and have the ability to reduce BP
and improveischemic symptomsbydecreasingmyocardialoxygen consumptionanddemand
Long-acting CCBs are either alternatives (the nondihydropyridine CCBs diltiazem and
verapamil) or add-on therapy (dihydropyridineCCBs) to β-blockers in chronic stable angina
for patients with ischemic symptoms.
Once ischemic symptoms are controlled with β-blocker and/or CCB therapy, other
antihypertensivedrugs can be added to provide additional CV risk reduction and that would
be ACEIs
For acute coronary syndromes (ST-elevation MI and unstable angina/non-ST-segment MI),
first-line therapy should consist of a β-blocker and ACE inhibitor.
Diabetes Mellitus
All patients with diabetes and hypertension should be treated with an ACE inhibitor or an
ARB. Pharmacologically, both of these agents should provide nephro protection due to
vasodilatation in the efferent arteriole of the kidney.
A thiazide-type diuretic is recommended as the second agent to lower BP and provide
additional CV risk-reduction
7. CCBs are useful add-on agents for BP control for patients with diabetes. Nondihydropyridine
CCBs (diltiazem and verapamil) appear to have more renal protective effects than the
dihydropyridines.
β-blockers,similarto CCBs, areusefuladd-on agentsfor BP controlforpatients with diabetes.
β-blockers (especially non-selective agents) can possibly mask the signs and symptoms of
hypoglycemia in patients with tightly controlled diabetes because most of the symptoms of
hypoglycemia (i.e., tremor, tachycardia, and palpitations) are mediated through the
sympathetic nervous system.
Chronic Kidney Disease
In addition to lowering BP, ACE inhibitors and ARBs reduce intraglomerular pressure, which
can theoretically provide additional benefits by further reducing the decline in kidney
function
Patients may experience a rapid and profound drop in BP or acute kidney failure when given
an ACE inhibitor or ARB particularly who are having renal artery stenosis
Recurrent Stroke Prevention
An ACEinhibitor with a thiazide-type diuretic is an evidence based antihypertensiveregimen
for patients with a history of cerebrovascular disease. This recommendation does not apply
to patients with a history of hemorrhagic stroke (Only for Ischemic stroke and TIA)
Alternative Drug Treatments
It is necessary to use other agents such as a direct renin inhibitor, α-blockers, central α2-
agonists, adrenergic inhibitors, and arterial vasodilators in some patients.
They are generally reserved (becauseof their ADRs) for patients with resistant hypertension
or as add-on therapy with multiple other primary antihypertensive agents.
Special Populations
Geriatrics
Diuretics (Thiazide), CCBs (Long acting dihydropyridines), ACEIs, ARBs, Beta blockers can be
used.
Centrally acting agents and α-blockers should generally be avoided or used with caution in
the elderly becausethey are frequently associated with dizziness and orthostatic
hypotension.
Patients at Risk for Orthostatic Hypotension
Orthostatic hypotension is a significant drop in BP when standing and can be associated with
dizziness and/or fainting. It is defined as an SBP decrease of greater than 20 mm Hg or DBP
decrease of greater than 10 mm Hg when changing from supine to standing. Older patients
(especially those with isolated systolic hypotension) and patients with diabetes, severe
volume depletion, baroreflex dysfunction, autonomic insufficiency, and use of venodilators
(α-blockers,mixed α-/β-blockers,nitrates,and phosphodiesteraseinhibitors)all increaserisk
8. of orthostatic hypotension. For patients with these risks, antihypertensiveagents should be
started in low doses, especially diuretics, ACE inhibitors, and ARBs.
Paediatrics
ACE inhibitors, ARBs, β-blockers, CCBs, and thiazide-type diuretics are all acceptable choices
in children.
ACE inhibitors and ARBs are contraindicated in sexually active girls due to potential
teratogenic effect
Pregnancy
Hypertension during pregnancy is categorized as preeclampsia, eclampsia, gestational,
chronic, and superimposition of preeclampsia on chronic hypertension.
Preeclampsia, defined as an elevated BP greater than 140/90 that appears after 20 weeks’
gestation accompanied by new-onset proteinuria (greater than or equal to 300 mg/24
hours), can lead to life-threatening complications for both mother and fetus.
Eclampsia, the onset of convulsions in preeclampsia, is a medical emergency.
Gestational hypertension is defined as new onset hypertension arising after mid-pregnancy
in the absence of proteinuria
Chronic hypertension is elevated BP that is noted before the pregnancy began
Definitive treatment of preeclampsia is delivery. Delivery is indicated if pending or frank
eclampsia is present.
Otherwise, management consists of restricting activity, bed rest, and close monitoring. Salt
restriction, or any other measures that contract blood volume, should not be employed.
Intravenous hydralazineis most commonly used, and intravenous labetalol is also effective.
9. Other Concomitant Conditions
Pulmonary Disease andPeripheral Arterial Disease
cardioselective β-blockers should be used to treat a compelling indication (i.e., post-MI,
coronary disease, or heart failure) for patients with reactive airway disease.
ACE inhibitors may be ideal for patients with symptomatic lower extremity PAD who also
have hypertension
β-blockers can theoretically be problematic for patients with PAD due to possibledecreased
peripheral blood flow secondary to unopposed stimulation of α-receptors that results in
vasoconstriction. If problematic, this can be mitigated by using a β-blocker that also has
α-blocking properties (e.g., carvedilol)
Metabolic Syndrome
Itdefined as the presence of 3 of the following 5 criteria:
Abdominal obesity (based on waist circumferencemeasurements),
Elevated triglycerides,
low HDL cholesterol,
Elevated BP (≥130/≥85 mmHg or receiving drug treatment for high BP), and
Elevated fasting blood glucose.
Using an ACE inhibitor or ARB is associated with the lowest rate of developing new onset
diabetes in patients with hypertension.
Thiazide-typediuretics can be used firstline for patients with metabolic syndrome, similar to
ACE inhibitors, ARBs, or CCBs, but treated patients will have a higher risk of developing
elevated fasting glucose.
Erectile Dysfunction
β-blockers havetraditionally been labeled as agents that significantly cause sexual
dysfunction, and many practitioners have avoided prescribing them as a result.
Centrally acting agents are associated with higher rates of sexual dysfunction and should be
avoided in men with erectile dysfunction, probably dueto vasodilation and pooling of blood
in veins.
COMBINATIONTHERAPY
Initial therapy with a combination of two drugs is highly recommended for patients with
Stage 2 hypertension and is an option for treating patients with Stage 1 hypertension where
goal achievement may be difficult (e.g., those with BP goals of less than 130/80 mm Hg,
African-Americans).
Under no circumstanceshould two drugs from the sameexact class of medications (e.g.,
two β-blockers, two ACEinhibitors) be used to treat hypertension.
10. RESISTANTHYPERTENSION
Resistant hypertension is defined as patients who are uncontrolled (failure to achieve goal
BP of <140/90 mm Hg, or lower when indicated) with the use of three or more drugs.
Difficult-to-control hypertension is persistently elevated BP despite treatment with two or
three drugs that does not meet the criteria for resistanthypertension (e.g., maximum doses
that include a diuretic).
However, there are treatment philosophies that are germane to the management of
resistanthypertension:
(1) assuring adequatediuretic therapy,
(2) appropriateuse of combination therapies, and
(3) using alternative antihypertensive agents when needed
Appropriatediuretic therapy means, use Thiazide (main stay of therapy), if not effective
consider Chlorthalidone, Aldosteroneantagonist, Loop diuretics.
Volume overload is a common cause, thus highlighting the importance of diuretic therapy
in the management of hypertension. Patients should be closely evaluated to see if any of
these causes can be reversed.
11. HYPERTENSIVE URGENCIES AND EMERGENCIES
Hypertensive urgencies and emergencies both are characterized by the presence of very
elevated BP, typically greater than 180/120 mm Hg.
Urgencies are not associated with acute or immediately progressing target-organ injury,
while emergencies are.
Examples of acute target-organ injury include encephalopathy, intracranial hemorrhage,
acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, unstable
angina, and eclampsia or severe hypertension during pregnancy.
Hypertensive Urgency
Hypertensive urgencies are ideally managed by adjusting maintenance therapy, by adding
a new antihypertensive, and/or by increasing the dose of a present medication. This is the
preferred approach to these patients as it provides a more gradual reduction in BP.
Veryrapid reductionsin BP to goalvalues shouldbediscourageddueto potential risks include
cerebrovascular accidents, MI, and acute kidney failure.
Acute administration of a short-acting oral antihypertensive (e.g., captopril, clonidine, or
labetalol) followed by careful observation for several hours to assurea gradual reduction in
BP is an option for hypertensive urgency
Oralcaptopril is one of the agents of choice and can be used in doses of 25 to 50 mg at 1- to
2-hour intervals. The onset of action of oral captopril is 15 to 30 minutes, and a marked fall
in BP is unlikely to occur if no hypotensive response is observed within 30 to 60 minutes.
Labetalol can be given in a dose of 200 to 400 mg, followed by additional doses every 2 to 3
hours.
12. For patients with hypertensive rebound following withdrawalof clonidine, 0.2 mg can be
given initially, followed by 0.2 mg hourly until the DBP falls below 110 mm Hg or a total of
0.7 mg clonidine has been administered.
Hypertensive Emergency
Hypertensiveemergencies arethose rare situations that require immediate BP reduction to
limit new or progressing target-organ damage
Hypertensiveemergencies requireparenteral therapy, at least initially, with one of the
agents listed in Table 19–11.
The goal in hypertensiveemergencies is not to lower BP to less than 140/90 mm Hg; rather,
the initial target is a reduction in MAP of up to 25% within minutes to hours.
If the patient is then stable, BP can be reduced toward 160/100 mm Hg to 160/110 mmHg
within the next 2 to 6 hours.
Precipitous drops in BP may lead to end-organ ischemia or infarction.
If patients tolerate this reduction well, additional gradualreductions toward goal BP values
can be attempted after 24 to 48 hours.
The exception to this guideline is for patients with an acute ischemic strokewhere
maintaining an elevated BP is needed for a much longer period of time.
Nitroprussideis widely considered the agent of choice for most cases, butit can be
problematic for patients with chronic kidney disease.
Itis a direct-acting vasodilator that decreases peripheral vascular resistancebut does not
increase CO unless left ventricular failure is present.
Nitroprussidecan be given to treat most hypertensiveemergencies, but in aortic dissection,
propranololshould be given firstto preventreflex sympathetic activation.
Nitroprussideis metabolized to cyanide and then to thiocyanate, which is eliminated by the
kidneys. Therefore, serum thiocyanate levels should be monitored when infusions are
continued longer than 72 hours.
Nitroprussideshould be discontinued if the concentration exceeds 12 mg/dL. The risk of
thiocyanate accumulation and toxicity is increased for patients with impaired kidney
function.
Intravenous nitroglycerin dilates both arterioles and venous capacitance vessels, thereby
reducing both cardiac afterload and cardiac preload, which can decrease myocardialoxygen
demand.
13. It also dilates collateral coronary blood vessels and improves perfusion to ischemic
myocardium. These properties make intravenous nitroglycerin ideal for the management of
hypertensive emergency in the presence of myocardial ischemia.
Fenoldopam, nicardipine, and clevidipine are newer and more expensive agents.
Fenoldopam is a dopamine-1 agonist. Itcan improve renal blood flow and may be especially
useful for patients with kidney insufficiency.
Nicardipine and clevidipine are dihydropyridine CCBs that provides arterial vasodilatation
and can treat cardiac ischemia similar to nitroglycerin, but they may provide more
predictable reductions in BP.
