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)
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