Antihypertensive Pharmacology

Antihypertensive Pharmacology

David Ray Velez, MD

Table of Contents

Inpatient Hypertension Management
IV PRN (As Needed) Agents
IV gtt (Continuous Drip) Agents
PO (Oral) Agents

Inpatient Hypertension Management

Inpatient Blood Pressure Goal

  • General Inpatient Goals:
    • SBP < 160 mmHg
    • DBP < 100 mmHg
  • Inpatient Goals are Poorly Defined with Minimal Evidence to Support Treating Isolated, Episodic Asymptomatic Hypertension
  • Some Patients May Require Stricter Blood Pressure Goals – Blunt Aortic Injury, Carotid Endarterectomy (CEA), etc.
  • Outpatient Goals are Generally Lower

Initial Managements

  • Aggressively Manage for Any Signs of Hypertensive Emergency – Symptomatic or Signs of End-Organ Damage
  • Treat Any Possible Secondary Causes – Pain, etc.
  • Restart Any Previously Held Home Antihypertensive Medications

General Approach

  • Generally Start with PRN IV Medications (Hydralazine/Labetalol)
  • May Require Antihypertensive Drip (gtt) for Urgent and Precise Control
  • Consider Adding a Long-Acting Oral Medication if Continuing to Require Frequent IV Dosing

IV PRN (As Needed) Agents

Agents

  • Hydralazine
  • Labetalol
  • Enalaprilat

Hydralazine

  • Mechanism of Action: Direct Vasodilator
  • Dosing: 10-20 mg Every 4-6 Hours as Needed
  • Timing:
    • Onset: 5-30 Minutes
    • Duration: 2-6 Hours
  • Contraindications:
    • Hypersensitivity
    • Coronary Artery Disease (CAD)
    • Mitral Valve Rheumatic Heart Disease

Labetalol

  • Mechanism of Action: Beta Blocker
  • Dosing: 5-20 mg Every 10 Minutes as Needed
  • Timing:
    • Onset: 5-10 Minutes
    • Duration: 4-6 Hours
  • Contraindications:
    • Severe Bradycardia
    • 2nd/3rd Degree Heart Block
    • Cardiogenic Shock
    • Decompensated Heart Failure
    • Bronchial Asthma or History of Obstructive Airway Disease
    • Hypersensitivity

Enalaprilat

  • Mechanism of Action: Angiotensin Converting Enzyme (ACE) Inhibitor
  • Response is Unpredictable Due to Variable Plasma Volume and Plasma Renin Activity
  • Dosing: 1.25 mg Every 6 Hours
    • Can Use Up to 5 mg per Dose if Needed
  • Timing:
    • Onset: 15 Minutes
    • Duration: 6 Hours
  • Contraindications:
    • Pregnancy
    • Severe Renal Artery Stenosis
    • Severe Hyperkalemia
    • Hypersensitivity
  • Generally Avoid ACE Inhibitors in Surgery Patients – Increased Difficulty Managing Blood Pressure Intraoperatively

IV gtt (Continuous Drip) Agents

Agents

  • Esmolol
  • Fenoldopam
  • Nicardipine (Cardene)
  • Clevidipine (Cleviprex)
  • Nitroglycerin
  • Sodium Nitroprusside
  • Phentolamine

Esmolol

  • Mechanism of Action: Beta Blocker
  • Dosing:
    • Bolus: 500-1,000 mcg/kg
    • Infusion: 50-300 mcg/kg/min (Start at 50-150 mcg/kg/min)
  • Timing:
    • Onset: 1-2 Minutes
    • Duration: 10-30 Minutes
    • *Rapid Onset with Short Duration Allows for Rapid Titration
  • Contraindications:
    • Severe Bradycardia
    • 2nd/3rd Degree Heart Block
    • Cardiogenic Shock
    • Decompensated Heart Failure
    • Sick Sinus Syndrome
    • Pulmonary Hypertension
    • Hypersensitivity

Fenoldopam

  • Mechanism of Action: Dopamine-1 Agonist
  • Dosing: 0.1-1.6 mcg/kg/min (Start at 0.1-0.3 mcg/kg/min)
  • Timing:
    • Onset: 5-10 Minutes
    • Duration: 30-60 Minutes
  • Intended Only for Short-Term (< 48 Hour) Management
  • Supports Renal Perfusion – Beneficial Over Others in AKI
  • Contraindications: None
    • Caution in Patients with Glaucoma

Nicardipine (Cardene)

  • Mechanism of Action: Calcium Channel Blocker (CCB)
  • Dosing: 5-15 mg/hr (Start at 5 mg/hr)
  • Timing:
    • Onset: 1-2 Minutes
    • Duration: Less Than 8 Hours (50% Within the First 30-45 Minutes)
  • Contraindications:
    • Severe Aortic Stenosis
    • Hypersensitivity

Clevidipine (Cleviprex)

  • Mechanism of Action: Calcium Channel Blocker (CCB)
  • Dosing: 1-21 mg/hr (Start at 1-2 mg/hr)
  • Timing:
    • Onset: 2-4 Minutes
    • Duration: 5-15 Minutes
  • Contraindications:
    • Severe Aortic Stenosis
    • Allergy to Soy or Eggs
    • Defect in Lipid Metabolism
    • Hypersensitivity

Nitroglycerin

  • Mechanism of Action: Nitrate Vasodilator by Generation of Free Radical Nitric Oxide
  • Dosing: 5-200 mcg/min (Start at 5-10 mcg/min)
  • Timing:
    • Onset: Immediate
    • Duration: 3-5 Minutes
  • Should Not Be Used Longer than 24-48 Hours – Develop Tachyphylaxis
  • Contraindications:
    • Concurrent Use of PDE-5 Inhibitors
    • Increased Intracranial Pressure
    • Hypersensitivity

Sodium Nitroprusside

  • Mechanism of Action: Nitrate Vasodilator by Generation of Free Radical Nitric Oxide
  • Dosing: 0.1-10 mcg/kg/min (Start at 0.3-0.5 mcg/kg/min)
  • Timing:
    • Onset: Immediate
    • Duration: 1-10 Minutes
  • Contraindications:
    • Pregnancy
    • Concurrent Use of PDE-5 Inhibitors
    • Acute Heart Failure with Reduced Systemic Vascular Resistance
    • Hypersensitivity
  • Limit Use in Renal Impairment – Toxicity Due to Thiocyanate Accumulation

Phentolamine

  • Mechanism of Action: Alpha Blocker
  • Most Often Used in the Setting of Catecholamine Excess (Pheochromocytoma)
  • Dosing:
    • Bolus: 1-5 mg
    • Infusion: 1-40 mg/hr
  • Timing:
    • Onset: 1-2 Minutes
    • Duration: 10-30 Minutes
  • Contraindications:
    • Coronary Artery Disease (CAD)
    • Myocardial Infarction (MI)
    • Hypersensitivity

PO (Oral) Agents

Classes of Agents

  • Beta Blockers
  • Calcium Channel Blockers (CCB)
  • Angiotensin Converting Enzyme (ACE) Inhibitors
  • Angiotensin II Receptor Blocker (ARB)
  • Thiazide Diuretic
  • Alpha Blockers

Beta Blockers

  • Beta Blockade:
    • Beta-1: Decrease Heart Rate and Contractility
    • Beta-2: Decrease Blood Pressure and Bronchodilation
  • Nonselective Agents – Both Beta-1 and Beta-2 Activity
    • Propranolol (Inderal)
    • Carvedilol (Coreg)
    • Labetalol (Trandate)
    • Nadolol (Corgard)
    • Nebivolol (Bystolic)
    • Pindolol (Visken)
    • Sotalol (Betapace)
    • Timolol (Blocadren)
  • Cardio-Selective Agents – Only Beta-1 Activity
    • Metoprolol (Lopressor, Toprol-XL)
    • Esmolol (Brevibloc)
    • Acebutolol (Sectral)
    • Atenolol (Tenormin)

Calcium Channel Blocker (CCB)

  • Dihydropyridine Agents – Decrease Systemic Vascular Resistance
    • Amlodipine (Norvasc)
    • Nicardipine (Cardene)
    • Nifedipine
  • Phenylalkylamine Agents – Cardio-Selective and Decrease Myocardial Oxygen Demand
    • Verapamil
    • Gallopamil
    • Fendiline
  • Benzothiazepine – Both Cardiac and Systemic Vascular Activity
    • Diltiazem (Cardizem)

Angiotensin Converting Enzyme (ACE) Inhibitor

  • Lisinopril
  • Enalapril
  • Captopril
  • Benazepril
  • Imidapril
  • Alacepril
  • Zofenopril

Angiotensin II Receptor Blocker (ARB)

  • Losartan
  • Valsartan
  • Irbesartan
  • Candesartan

Thiazide Diuretic

  • Hydrochlorothiazide (HCTZ)
  • Chlorthalidone

Alpha Blockers

  • Prazosin
  • Doxazosin
  • Terazosin