HYPERTENSION

PHARMACOTHERAPY
 Definition
• A sustained elevation in blood pressure above the normal
value (120/80 mmHg) is called hypertension.
• As per ACC/AHA guideline - 2017

. As per JNC7/8 Guideline –

 Aiming for BP target in therapy of HTN
Hypertensive JNC 7 JNC 8 ACC/ AHA
Patients Target BP to be Target BP to be Target BP to be
achieved achieved achieved
( SBP/DBP mm hg) ( SBP/DBP mm hg) ( SBP/DBP mm hg)

Elderly < 140/90 <150/90 < 130

(Age (Age ≥ 60 yrs) *
≥ 60 yrs) (Age ≥ 65 yrs)

Adults < 140/90 < 140/90 130/80

(Age < 60 yrs) (Age < 60 yrs) (with/without
clinical CVD

Coronary heart <130/80 < 140/90 <130/80

disease /Diabetes
/CKD
 Therapy of Hypertension
Sr.No Class of Drugs Examples
1 Diuretics Thiazide – Hydrochlorthiazide , Chlorthalidone , Indapamide
2 Loop Diuretics – Furosemide , Ethacrynic acid .
3 K sparing – Spirinolactone, Amiloride
4 ACE inhibitors Captopril , Enalapril , Lisinopril , Ramipril , Fosinopril
5 Angiotensin ( AT1) Losartan , Telmisartan
Blockers
6 Beta Blockers Propranolol , Atenolol , Metoprolol
7 Ca++ Channel Diltiazem , Verapamil , Nifedipine , Amlodipine , Lacidipine
Blockers
 Diuretics
Name of Drug Mode of Action Pharmacology Side effects/ other
remarks
Hydrochlorthiazide Acts on DCT & prevent Increase excretion Recommended first
( Thiazide) reabsorption of Na , K of K line drug
by inhibiting Na+ Cl- Increase excretion D/A : 6 -12 hrs
symport of uric acid but Effective at the dose of
Reduce T.P.R. decrease on 25mg/day
Increase excretion of Na chronic use Long duration of action
and K. It may cause Mg. than Loop diuretics
Reduce plasma volume Deficiency
Restore cardiac output

Chlorthalidone Acts on DCT & prevent Increase Longer acting that

( Thiazide like reabsorption of Na , K reabsorption of HCTZ
diurtetic) by inhibiting Na+ Cl- Ca++ , reduce I.C Better efficacy than
symport Ph and cell volume HCTZ but more risk of
Block carbonic hypokalaemia
unhydrase High volume of
distribution & taken by
RBCs
Dose: 12.5 to 25 mg
 ANGIOTENSION II RECEPTOR BLOCKER
• Blood Pressure- Renal control
• Renin Angiotensin Aldosteron System (RAAS)
 ARB : Mechanism of action
Renin-Angiotensin System
Angiotensinogen
Non-Renin
Renin Renin inhibitors •Tonin
•Cathepsin
BKR Bradykinin Angiotensin I
ACE/ Non-ACE
ACE inhibitors
BPF •Chymase
NO
Angiotensin II
• Vasodilation
•  Ischemia
•  Platelet agg Inactive
•  inotrope Peptides AT I AT II
• Vasoconstriction • Vasodilation
• Cell growth • Anti proliferation
• Na+/H2O retention •  Kinins
• SNS activation •  NO
RAAS MODULATORS:
Enzymatic activity Spironolactone
Enzymatic blockade Eplerenone
Product/receptor stimulation Beta blockers
 ARB
1986- Losartan- become first successful ARB
1990- Valsartan , candesartan , Irbesartan
1991- Telmisartan – Longest acting ARB
1992- Olmesartan
2011- Azlisartan – Newest ARB in Market
• Telmisartan :
• M/A: blocks AT1 receptor mediated actions of angiotensin II like
– Vasoconstriction
– Release of Aldosterone
– Na & Water reabsorption
– Release of Norepinephrine
It is also found to be effective as agonist of PPAR-gamma (peroxisome
proliferator-activated receptor –gamma) receptor.
c
 ACE Inhibitors
• Enalapril , Captopril , Ramipril
• Enalapril : It inhibits the conversion of
angiotensin I to angiotensin II and there by
reduces the action of angiotensin II. so supress
RAAS & reduce BP. Also increases bradykinin level
and cause vasodilation.
 It also decrease B.V. , P.R. and cardiac load.
 It inhibit the release of aldosterone
 Calcium Channel Blockers
CCBs: Major classes:
1. Phenylalkylamines- Verapamil
2. Benzothiazepine- Diltiazem
3. Dihydrpyridines Nifedipine, Amlodipine, Nicardapine
• M/A : Block voltage sensitive (L-type, slow) calcium
channels
• Inhibits transmembrane influx of calcium ions into
vascular muscle & cardiac muscle
• Increase the time that Ca channels are closed
• Significant reduction in after load.
 Beta blockers
Non Selective β- Blocker; Propranolol,
β1 Blocker : Atenolol , Metoprolol , Acebutolol
Mixed α1/β-adrenergic antagonists; carviedilol

M/A: Competitive antagonism of catecholamines

at peripheral (especially cardiac) adrenergic
neuron sites, leading to decreased cardiac output;

A central effect leading to reduced sympathetic

outflow to the periphery
Suppression of renin activity.
JNC -8 Guideline treatment
Comparison of Guidelines
 Combination therapy
• Important combination :
• CCB and β-blocker : Amlodipine + Metoprolol/Atenolol
• CCB and ACE-inhibitor: Amlodipine + Enalapril
• ACE-inhibitor and Diuretic
• β-blocker and Diuretic : Atenolol + Chlorthalidone
• ARB and diuretics : Telmisartan /Olmesartan +
HCTZ/Chlorthalidone
• ARB and CCB : Telmisartan/Olmesartan +
Clinidipine/Amlodipine
 Combination therapy
1) Telmisartan + HCTZ Best choice for resistant patients of monotherapy
It neutralize hypokalaemia effect
Both shows complimentary Antihypertensive effect
Suitable for Type 2 Diabetic Nephropathy & other conditions
Renal & cardio vascular protection beyond powerful B.P.
Control in Type 2 Diabetic patients
2) Telmisartan + CTD – reduce the risk of stroke and total cardiovascular
Chlorthalidone mortality and morbidity
Telmisartan is more effective then Ramipril in reducing B.P. last 6
hours ( high risk of CV attack)- PRISMA
Telmisartan – greater renoprotection in TYPE2DM
,microalbuminuria – INNOVATION
Telmisartan – long term Reno protection like ramipril
Greater reduction in proteinuria
3) Telmisartan + Provide 24 hrs effective control on B.P.
Amlodipine Suitable for diabetic patients and reduce the risk of diabetes &
CVD
Prevent artherosclerosis , reduce oxidative stress
 Combination therapy
4) Amlodipine + As per ADHT trial , Adding to second drug in ARB or ACEi ( mono)
Enalapril double the control rate in hypertension patients
Causes natriuresis and improve renal blood flow
Lesser incidence of tachycardia and peripheral edema along with
lesser risk of hyperkalemia
Combination is safe and well tolerated
5) Amlodipine + Beneficial combination in MI , Reduce infarct size
Metoprolol Synergistic Anti hypertensive and Antianginal effects
Reduce renin secretion
Effectively manage morning surge in blood pressure
Decrease the heart rate and
6) Amlodipine + Effective and recommended in IHD and tachycardia
Atenolol Risk of constipation due to amlodipine is reduced with atenolol
Atenolo reduce renin secretion and oxygen demand
Ideal for stage 2 hypertensive patients
Amlodipine having excellent potency with slow/sustained action
7) Metoprolol + As per AHA/ACC – Effective in first line therapy HTN with coronary artery
Ramipril disease , heart failure and diabetes
Upregulation of renin is prevented by Ramipril – Reversible slow and
tight binding inhibitor
Greater protection against – CV risks and target organ damage U
8) Telmisaratan + Metoprolol 2015 AHA/ACC/ASH guidelines recommend…
Combination of β Blocker & ARB in
treatment of hypertension in patients with
CAD (
2016 AACE/ACE guidelines recommend….
Combination of β Blocker & ARB in
treatment of hypertension in T2DM to
achieve targeted BP goal
2012 KDIGO guidelines recommend…..
Use of Metoprolol & ARB in CKD patients