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ACE ACE InhibitorInhibitor
ATAT11AntagonistAntagonist
DiureticDiureticCaCa++++ Antagonist Antagonist
BetaBeta BlockerBlocker
Alpha BlockerAlpha Blocker
Drug of choiceDrug of choice
Dr. RxDr. RxRationaRationall
GanglionicGanglionic blockersblockers
- agonists- agonists
VasodilatorsVasodilators
Selection of Antihypertensive Drug
Level of blood pressureLevel of blood pressure
++ Presence of other risk factors for CVDPresence of other risk factors for CVD
& target organ damage& target organ damage
++Coexisting diseasesCoexisting diseases
Antihypertensive TherapyAntihypertensive Therapy
11
22
33
Selection of Antihypertensive Drug
Target organ damage/clinical CVDTarget organ damage/clinical CVD
• LVH - Heart failure - Angina - Prior MI LVH - Heart failure - Angina - Prior MI or revascularization or revascularization
• Stroke or TIAStroke or TIA
• NephropathyNephropathy
• Retinopathy Retinopathy
• Peripheral vascular diseasePeripheral vascular disease
Pharmacotherapy of Hypertension
Blood Pressure Classification
SBP DBPSBP DBP mm Hgmm Hg mmHg mmHg
• Normal
• Prehypertensive • Stage 1 Hypertension
• Stage 2 Hypertension
<120 and <80
120-139 or 80-89 140-159 or 90-99
> 160 or > 100
JNC 7JNC 7
Goal Blood Pressure
SBP DBPSBP DBP mm Hgmm Hg mmHg mmHg
• Most patients
• Diabetes • Chronic Renal Disease
< 140 < 90
< 130 < 80 < 130 < 80
JNC 7JNC 7
Lifestyle Modifications
Approximate SBP ReductionApproximate SBP Reduction mmHgmmHg
•Weight reduction
• DASH eating plan
• Reduced Sodium Intake • Physical activity
•Moderation of alcohol consumption
5 – 20
8 – 14
2 – 8
4 – 9
2 – 4
JNC 7JNC 7
Algorithm for Treatment of Hypertension
JNC 7JNC 7
LifestyleLifestyleModificationsModifications
Not at Goal Blood Pressure
Initial Drug Initial Drug ChoicesChoices
Algorithm for Treatment of Hypertension
JNC 7JNC 7
Initial Drug Initial Drug ChoicesChoices
““Excellent clinical trial outcome data prove that lowering BP with several classes of drug,
including ACE inhibitors, angiotensin receptors blockers (ARBs),”beta-blockers”, calcium channel
blockers (CCBs) and thiazide-type diureticswill reduce the complications of hypertension.” .”
Algorithm for Treatment of Hypertension
JNC 7JNC 7
Initial Drug Initial Drug ChoicesChoices
WithoutWithoutCompelling Compelling
Indication (s) Indication (s)
WithWithCompelling Compelling
Indication (s) Indication (s)
Algorithm for Treatment of Hypertension
JNC 7JNC 7
Initial Drug ChoicesInitial Drug Choices
Stage 1- Hypertension 140-159 / 90-99 mmHg Without Compelling Indication
Thiazide-like diuretics for most,Thiazide-like diuretics for most,ACEI, ARB, BB or CCB ACEI, ARB, BB or CCB
May consider combinationMay consider combination
Algorithm for Treatment of Hypertension
JNC 7JNC 7
Initial Drug ChoicesInitial Drug Choices
Stage 2 - Hypertension >160 / > 100 mmHg Without Compelling Indication
2-drug combination for most2-drug combination for mostUsually thiazide-like diuretic plus ACEI, Usually thiazide-like diuretic plus ACEI,
or ARB, or BB or CCBor ARB, or BB or CCB
Algorithm for Treatment of Hypertension
JNC 7JNC 7
Initial Drug ChoicesInitial Drug Choices
WithoutWithoutCompelling Indication (s)Compelling Indication (s)
WithWithCompelling Indication (s) Compelling Indication (s)
Not at Goal Blood PressureNot at Goal Blood Pressure
Optimize dosage or add additional Optimize dosage or add additional drug until goal BP is achieved. Considerdrug until goal BP is achieved. Consider
consultation with HNT specialistconsultation with HNT specialist
Compelling Compelling Indication*Indication* Diuretic BB ACEI ARB CCB ALD & ANT
Heart failure ● ● ● ● ●
Postmyocardial infarction ● ● ●
High coronary disease risk ● ● ● ●
Diabetes ● ● ● ● ●
Chronic kidney disease ● ●
Recurrent stroke prevention
● ●
Clinical trial and guideline basis for compelling indications for individual drug classes
Class Drug (Trade Name) Usual Dose
Range in
mg/Day
Usual Daily
mg/Day
Frequency*
Thiazide diuretics
chlorothiazide
chlorthalidone
hydrochlorothiazide
polythiazide
indapamide
metolazone
metolazone
125–500
12.5–25
12.5–50
2–4
1.25–2.5
0.5–1.0
2.5–5
1–2
1
1
1
1
1
1
Loop
diuretics
bumetanide
furosemide
torsemide
0.5–2
20–80
2.5–10
2
2
1
Potassium-sparing diuretics
amiloride
triamterene
5–10
50–100
1–2
1–2
Aldosterone receptor blockers
eplerenone
Spironolactone
50–100
25–50
1
1
Class Drug (Trade Name) Usual Dose
Range in
mg/Day
Usual Daily
mg/Day
Frequency*
BBs Atenolol
Propranolol
propranolol long-acting
25–100
40-160
60-180
1
2
1
Combined
alpha- and
BBs
Carvedilol
labetalol
12.5–50
200–800
2
2
ACEIs enalapril
ramipril
5-40
2.5-20
1-2
1
Angiotensin II antagonists
losartan 25-100 1-2
CCBs—nondihydropyridines
diltiazem extended release
diltiazem extended release
verapamil immediate release
verapamil long acting
Verapamil
180-420
120-540
80-320
120-480
120-360
1
1
2
1-2
1
Class Drug (Trade Name) Usual Dose
Range in
mg/Day
Usual Daily
mg/Day
Frequency*
CCBs-dihydropyridines
amlodipine
nifedipine long-acting
2.5-10
30-60
1
1
Alpha-1
blockers
doxazosin
prazosin
terazosin
1-16
2-20
1-20
1
2-3
1-2
Central alpha-2 agonists and other
centrally acting drugs
clonidine
clonidine patch
methyldopa
reserpine
guanfacine
0.1-0.8
0.1-0.3
250-1000
0.1-0.25
0.5-2
2
1 wkly
2
1
1
Direct vasodilators
hydralazine
minoxidil
25-100
2.5-80
2
1-2
Hypertension in Elderly
Pharmacological treatment: - Lower initial doses (1/2 dose than in younger patients)
- The reduction in BP should be gradual - Greater caution in patients with co-existing diseases or
orthostatic hypotension.
Choice of therapy: - Thiazide diuretic (hydrochlorothiazide, HCTZ 12.5 mg) - STOP-Hypertension trial: ACE inhibitors, long-acting calcium antagonist and beta- blockers may provide
the same protection as diuretics.
Choice of therapy: special considerations
A diuretic should be used for heart failure or edema
A beta-blocker should be used for patient with coronary
heart disease, tachyarrhitmias or migraine
An ACE inhibitors in patients with heart failure
Calcium antagonist should be used in patients with
angina pectoris,and peripheral vascular disease
Alpha-blocker in patient with benign prostatic hyperplasia
Hypertension in Elderly
Treatment:Treatment:• Early treatmentEarly treatment to prevent cardiovascular disease to prevent cardiovascular disease
and minimize progression of renal and retinal disease. and minimize progression of renal and retinal disease.
• The benefits ofThe benefits of tight blood pressure controltight blood pressure control in in diabetics may be as great or greater than benefits of diabetics may be as great or greater than benefits of strict glycemic control.strict glycemic control.
• Initial therapy should includeInitial therapy should include non-pharmacological non-pharmacological methodsmethods. .
• ACE Inhibitors, ARBs, C++ Channel Blockers,ACE Inhibitors, ARBs, C++ Channel Blockers,
Hypertension and DiabetesHypertension and Diabetes
Hypertension and DiabetesHypertension and Diabetes
Pathogenesis:Pathogenesis:
• Kidneys in diabetic patients are more sensitive Kidneys in diabetic patients are more sensitive to any increase in blood pressureto any increase in blood pressure
• Proteinuria is not only the marker of renal Proteinuria is not only the marker of renal damage, damage, but also risk factor for progression of renal but also risk factor for progression of renal diseasedisease
Asthma COPD and Hypertension
• Beta-blockersBeta-blockers (i) increase bronchial obstruction, (i) increase bronchial obstruction, (ii) increase in airways reactivity, and (iii) inhibit the (ii) increase in airways reactivity, and (iii) inhibit the bronchodilatatory effects of beta agonist bronchodilatatory effects of beta agonist
• Cardioselective, beta-blockers none should be considered Cardioselective, beta-blockers none should be considered safe.Even topical administration for the treatment of safe.Even topical administration for the treatment of glaucoma may led to asthmatic exacerbations.glaucoma may led to asthmatic exacerbations.
• ACE inhibitorsACE inhibitors are not contraindicated and may be used; are not contraindicated and may be used; very rarely worsen airflow obstruction; produce persistent very rarely worsen airflow obstruction; produce persistent dry cough and are not first line drug for hypertensive dry cough and are not first line drug for hypertensive patients with asthma or COPD. patients with asthma or COPD.
• Diuretics: Diuretics: can be effectively used but there is an can be effectively used but there is an increased risk of increased risk of hypokalemiahypokalemia (inhaled (inhaled -2 agonist drive -2 agonist drive potassium into cell and orally administered potassium into cell and orally administered corticosteroids mildly increase urinary potassium corticosteroids mildly increase urinary potassium excretion). excretion).
• Only low dose (12.5-25 mg) of thiaizides to be used. Only low dose (12.5-25 mg) of thiaizides to be used.
• In patients with COPD and chronic hypercapnia, In patients with COPD and chronic hypercapnia, diuretics-induced metabolic alkalosis may suppress the diuretics-induced metabolic alkalosis may suppress the ventilatory drive and exacerbates the hypoxia. ventilatory drive and exacerbates the hypoxia.
Asthma COPD and Hypertension
Asthma, COPD and Hypertension
Calcium channel blockersCalcium channel blockers (CCB) are (CCB) are preferred for preferred for treatmenttreatment of hypertension in astma & COPD. May of hypertension in astma & COPD. May be combined with diureticsbe combined with diuretics
Short-acting CCB (niphedipine) should not be used Short-acting CCB (niphedipine) should not be used because they increase CV risk. because they increase CV risk.
Only long-acting CCB or slow-release niphedipine Only long-acting CCB or slow-release niphedipine formulation should be used.formulation should be used.
Ischemic Heart Disease and Hypertension
• IHD is the most common form of target-organ damage associated with hypertension.
• Beta blockers and long acting Ca++ channel blockers are the first choice in HTN patient with stable angina pectoris.
• HTN patients with unstable angina or MI should be treated with beta blocker or ACE inhibitor.
• In patients with post-myocardial infarction, ACE inhibitors, beta blockers and aldosterone antagonists; all reduce progression of left ventricular dysfunction and mortality.
– ACE inhibitors and beta blockers are recommended for HTN patients with asymptomatic ventricular dysfunction
– In HTN patients with symptomatic ventricular dysfunction (NYHA III and IV) in addition to ACE inhibitors and beta blockers, treatment with diuretics, Ang II receptor antagonists and aldosterone antagonists.
– In hypertensive HF patient, if volume depleted, ACE inhibitors may induce hypotension and acute renal failure. Beta blockers may induce initial/transient worsening of HF.
Hart Failure and Hypertension
-Pregnancy : Methyl Dopa, HydralazinePregnancy : Methyl Dopa, Hydralazine
- Gout & Dyslipidemia: Avoid diureticsGout & Dyslipidemia: Avoid diuretics
- Benign prostatic hypertrophy: Alfa-1 adrenergicBenign prostatic hypertrophy: Alfa-1 adrenergic blockers blockers
Pharmacotherapy of Hypertension
ACE ACE InhibitorInhibitor
ATAT11AntagonistAntagonist
DiureticDiureticCaCa++++ Antagonist Antagonist
BetaBeta BlockerBlocker
Alpha BlockerAlpha Blocker
Drug of Drug of choicechoice
Dr. RxDr. RxRationaRationall
GanglionicGanglionic blockersblockers
- agonists- agonists
VasodilatorsVasodilators
Pharmacotherapy of Hypertension