Comprehensive Overview of Antihypertensive Drugs and Hypertension Management

Comprehensive Overview of Antihypertensive Drugs and Hypertension Management

• 1.
  Antihypertensive Drugs Mr. SATENDRAPRADHAN Assistant Professor Department of Pharmacology COP, SVITS, Bilaspur Ms. MANISHA SAHU Assistant Professor Department of Pharmacology SCCP, Rajnandgaon
• 2.
  O V ER V IE W What Is Hypertension? Hypertension (HTN) is a chronic medical condition characterized by persistently elevated arterial blood pressure, defined as systolic BP ≥ 130 mmHg or diastolic BP ≥ 80 mmHg on repeated measurement (ACC/AHA). It is often called the “silent killer” because it usually produces no symptoms while steadily damaging blood vessels, heart, brain, and kidneys. BP Classification (ACC/AHA 2017) Category Systolic Diastolic Normal < 120 < 80 Elevated 120–129 < 80 Stage 1 HTN 130–139 80–89 Stage 2 HTN ≥ 140 ≥ 90 Hypertensive Crisis > 180 > 120
• 3.
  B A CKG R O U N D Epidemiology & Risk Factors Roughly 1 in 3 adults worldwide live with hypertension, making it the leading modifiable risk factor for cardiovascular death. Non-Modifiable Risk Factors • Age (risk rises after 45–65 y) • Family history / genetics • Male sex (before menopause) • Ethnicity Modifiable Risk Factors • High salt intake • Obesity & sedentary lifestyle • Smoking & alcohol use • Chronic stress, poor sleep
• 4.
  P A TH O P H Y S I O L O G Y What Determines Blood Pressure? Blood pressure (BP) is the product of Cardiac Output (CO) and Total Peripheral Resistance (TPR). Antihypertensive drugs work by reducing one or both variables. BP Blood Pressure = CO Cardiac Output (HR × Stroke Volume) × TPR Total Peripheral Resistance (vessel tone) Regulatory Systems Controlling CO & TPR Sympathetic Nervous System Renin-Angiotensin- Aldosterone System (RAAS) Renal Fluid Volume Regulation Vascular Smooth Muscle Tone
• 5.
  CO N SE Q U E N CE S Untreated Hypertension: Target-Organ Damage Brain • Stroke • Transient Ischemic Attack • Vascular Dementia Heart • Left ventricular hypertrophy • Heart failure • CoronaryArtery Disease • Myocardial Infraction Kidneys • Nephrosclerosis • Chronic Kidney Disease • Renal Failure Eyes • Hypertensive Retinopathy • Vision Loss Arteries • Atherosclerosis • Aortic Aneurysm/Dissection • Peripheral Artery Disease Sexual/Other • Erectile Dysfunction • Cognitive Decline
• 6.
  P H AR M A CO L O G Y Classification of Antihypertensive Drugs
• 7.
  P H AR M A CO L O G Y Classification of Antihypertensive Drugs 1 Diuretics Thiazide, Loop, K+-sparing 2 Sympatholytics Beta-blockers, Alpha-blockers, Central agonists 3 RAAS Inhibitors ACE Inhibitors, ARBs, Direct Renin Inhibitors 4 Calcium Channel Blockers Dihydropyridine & Non-dihydropyridine 5 Direct Vasodilators Hydralazine, Minoxidil, Sodium Nitroprusside
• 8.
  M E CHA N I S M Where Each Drug Class Acts BLOOD PRESSURE = CO × TPR ↓ Cardiac Output ↓ Peripheral Resistance Beta-Blockers ↓ HR & contractility Diuretics ↓ Blood volume/preload ACE Inhibitors / ARBs ↓ Angiotensin II action Calcium Channel Blockers Vascular smooth muscle relax. Direct Vasodilators / Alpha-Blockers Direct/receptor-mediated relax. 7
• 9.
  CLASS 1 OF5 Diuretics Mechanism of Action Diuretics lower BP primarily by reducing plasma & extracellular fluid volume, which decreases venous return, cardiac output, and (with chronic use) peripheral resistance. Thiazide (e.g. Hydrochlorothiazide) Inhibits Na⁺/Cl⁻ co-transporter in the distal convoluted tubule Loop (e.g. Furosemide) Inhibits Na⁺/K⁺/2Cl⁻ co-transporter in the thick ascending loop of Henle K⁺-Sparing (e.g. Spironolactone) Blocks aldosterone receptor / ENaC channels in the collecting duct Diuretic Action Flowchart Block Na⁺ / fluid reabsorption in renal tubule ↑ Na⁺ & water excretion in urine ↓ Extracellular & plasma volume ↓ Venous return → ↓ Cardiac output ↓ Blood Pressure
• 10.
  CLASS 1 OF5 Diuretics Clinical Uses • First-line therapy for essential hypertension (esp. thiazides) • Heart failure & pulmonary/peripheral edema (loop diuretics) • Reducing risk of stroke & CV events • Adjunct in resistant hypertension (K+-sparing add-on) Adverse Effects • Hypokalemia (thiazide, loop) • Hyperkalemia (K+-sparing agents) • Hyponatremia & metabolic alkalosis • Hyperuricemia – may precipitate gout • Hyperglycemia & dyslipidemia (thiazides) • Ototoxicity at high doses (loop diuretics)
• 11.
  CLASS 2 OF5 Beta-Blockers Mechanism of Action Beta-blockers competitively antagonize β1-adrenergic receptors in the heart and juxtaglomerular apparatus, blunting sympathetic drive. Cardioselective (β1) Atenolol, Metoprolol, Bisoprolol Non-selective (β1 & β2) Propranolol, Nadolol Combined α/β blockers Carvedilol, Labetalol Beta-Blockade Flowchart Block β1 receptors in heart & kidney ↓ Heart rate & contractility ↓ Renin release from JG cells ↓ Cardiac Output & ↓ RAAS activity ↓ Blood Pressure
• 12.
  CLASS 2 OF5 Beta-Blockers Clinical Uses • Hypertension with comorbid coronary artery disease • Post-myocardial infarction (secondary prevention) • Heart failure with reduced ejection fraction (select agents) • Tachyarrhythmias & atrial fibrillation rate control • Migraine prophylaxis, essential tremor, performance anxiety Adverse Effects • Bradycardia & AV conduction block • Bronchospasm – avoid non-selective agents in asthma/COPD • Fatigue, cold extremities, sexual dysfunction • Masking of hypoglycemia symptoms in diabetics • Rebound hypertension/tachycardia if stopped abruptly
• 13.
  CLASS 3 OF5 ACE Inhibitors Mechanism of Action ACE inhibitors block Angiotensin-Converting Enzyme, preventing conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II, and reducing bradykinin breakdown. Examples: Enalapril, Lisinopril, Ramipril, Captopril Note: ↑ Bradykinin contributes to the characteristic dry cough and angioedema risk unique to this class. RAAS Blockade Flowchart Renin converts Angiotensinogen → Angiotensin I ACE Inhibitors block conversion to Angiotensin II ↓ Vasoconstriction & ↓ Aldosterone secretion ↓ Peripheral resistance & ↓ Na⁺/water retention ↓ Blood Pressure
• 14.
  CLASS 3 OF5 ACE Inhibitors Clinical Uses • First-line in hypertension with diabetes (renoprotective) • Heart failure with reduced ejection fraction • Post-MI left ventricular dysfunction • Diabetic & non-diabetic chronic kidney disease (↓ proteinuria) Adverse Effects • Dry, persistent cough (bradykinin-mediated) • Angioedema – rare but potentially life- threatening • Hyperkalemia • Acute kidney injury in bilateral renal artery stenosis • Contraindicated in pregnancy (fetotoxic)
• 15.
  CLASS 3 OF5 Angiotensin Receptor Blockers (ARBs) Mechanism of Action ARBs directly block the AT₁ receptor, preventing Angiotensin II from binding – regardless of how it was formed. Bradykinin metabolism is unaffected, so cough is far less common than with ACE inhibitors. Examples: Losartan, Valsartan, Telmisartan, Candesartan ARB Mechanism Flowchart Angiotensin II is formed (via ACE or alternate pathways) ARBs block AT₁ receptors on vascular smooth muscle Angiotensin II cannot exert vasoconstrictor effect ↓ Vasoconstriction & ↓ Aldosterone release ↓ Blood Pressure
• 16.
  CLASS 3 OF5 Angiotensin Receptor Blockers (ARBs) Clinical Uses • Hypertension – preferred when ACE inhibitors cause cough • Diabetic nephropathy (renoprotective) • Heart failure (ACE-I intolerant patients) • Stroke risk reduction in high-risk patients Adverse Effects • Hyperkalemia • Hypotension, dizziness • Acute kidney injury in renal artery stenosis • Contraindicated in pregnancy (fetotoxic) • Angioedema – rare (much less than ACE inhibitors)
• 17.
  CLASS 4 OF5 Calcium Channel Blockers Mechanism of Action CCBs block L-type voltage-gated calcium channels, reducing calcium influx into vascular smooth muscle and/or cardiac cells. Dihydropyridines Amlodipine, Nifedipine – mainly vascular smooth muscle (vasodilation) Non-Dihydropyridines Verapamil, Diltiazem – also act on cardiac nodal tissue (↓ HR, ↓ contractility) CCB Mechanism Flowchart Block L-type Ca²⁺ channels ↓ Ca²⁺ entry into vascular smooth muscle / myocardium Vascular smooth muscle relaxation (↓ TPR) ± ↓ Heart rate & contractility (non-DHP agents) ↓ Blood Pressure
• 18.
  CLASS 4 OF5 Calcium Channel Blockers Clinical Uses • Hypertension – especially in older adults & Black patients • Angina pectoris (stable & vasospastic/Prinzmetal) • Supraventricular tachyarrhythmias (non-DHP agents) • Raynaud phenomenon Adverse Effects • Peripheral edema (dihydropyridines) • Flushing, headache, reflex tachycardia (DHPs) • Bradycardia, AV block, constipation (non-DHPs) • Gingival hyperplasia (rare) • Avoid non-DHP + beta-blocker combo (heart block risk)
• 19.
  A D DIT IO N A L A G E N T S Other Antihypertensive Drug Classes Alpha-1 Blockers Prazosin, Doxazosin MECHANISM Block α1 receptors → arteriolar & venous vasodilation KEY USE • Hypertension with BPH SIDE EFFECTS • Orthostatic hypotension • First-dose syncope Central Sympatholytics Methyldopa, Clonidine MECHANISM Stimulate central α2 receptors → ↓ sympathetic outflow KEY USE • Hypertension in pregnancy (methyldopa) SIDE EFFECTS • Sedation • Dry mouth • Rebound HTN on withdrawal Direct Vasodilators Hydralazine, Minoxidil MECHANISM Direct relaxation of arteriolar smooth muscle KEY USE • Resistant hypertension • Hypertensive emergency SIDE EFFECTS • Reflex tachycardia • Fluid retention • Lupus-like syndrome (hydralazine)
• 20.
  C L INIC A L D E C IS IO N - M A K IN G Choosing an Antihypertensive: Compelling Indications Comorbidity Preferred Class Diabetes mellitus / CKD with proteinuria ACE Inhibitor or ARB Heart failure (reduced EF) ACE-I/ARB + Beta-blocker + Diuretic Post-myocardial infarction Beta-blocker + ACE Inhibitor Older age / isolated systolic HTN Calcium Channel Blocker or Thiazide Pregnancy Methyldopa, Labetalol, Nifedipine Angina pectoris Beta-blocker or Calcium Channel Blocker Benign prostatic hyperplasia Alpha-1 Blocker
• 21.
  SUM M ARY KeyTakeaways Hypertension is defined & staged by BP thresholds (≥130/80 mmHg), and is a major driver of stroke, MI, heart failure, and CKD. Five major drug classes – Diuretics, Beta-blockers, ACE-I/ARBs, CCBs, and Vasodilators – lower BP by reducing cardiac output and/or peripheral resistance. RAAS inhibitors (ACE-I, ARBs) are preferred in diabetes & CKD; CCBs/thiazides favored in older adults; beta- blockers favored post-MI or with CAD. Each class carries characteristic adverse effects – know them to anticipate, monitor, and manage therapy safely. Most patients ultimately require combination therapy to achieve BP control.