CCB/vasodilators/HTN

• Calcium channel blockers


  Drugs that prevent calcium ions from entering cells
• Calcium channel blockers


  • Greatest impact on heart and blood vessels
  • Used to treat hypertension, angina pectoris, and cardiac dysrhythmias
  • Controversy: Safety for patients with hypertension and diabetes
  • Also known as calcium antagonists and slow channel blockers
• Calcium channel blockers


  • Calcium channels: Physiologic functions and consequences of blockade
  • Calcium channel blockers: Classification and sites of action
  • Verapamil and diltiazem: Agents that act on vascular smooth muscle and the heart
  • Dihydropyridines: Agents that act mainly on vascular smooth muscle
• Verapamil: Hemodynamic effects


  • Blockade at peripheral arterioles - Reduces arterial pressure
  • Blockade at arteries and arterioles of heart - Increases coronary perfusion
  • Blockade at SA node - Reduces heart rate
  • Blockade at AV node (most important) - Decreases AV nodal conduction
  • Blockade in the myocardium -Decreases force of contraction
• Verapamil and Diltiazem: Hemodynamic effects 


  • Indirect (reflex) hemodynamic effects - Baroreceptor reflex
  • Net effects: Little or no net effect on cardiac performance
  • Vasodilation accompanied by reduced arterial pressure and increased coronary perfusion
• Therapeutic uses of verapamil

  • Angina pectoris - Vasospastic angina and angina of effort
  • Essential hypertension - second line agent
  • Cardiac dysrhythmias - Afib, Aflutter, paroxysmal SVT
• Adverse effects of verapamil

  • Constipation
  • Dizziness
  • Facial flushing
  • Headache
  • Edema of ankles and feet
  • Gingival hyperplasia
  • Heart block
• Diltiazem MOA


  • Blocks calcium channels in the heart and blood vessels (similar to verapamil)
  • Lowers blood pressure - Arteriolar dilation
  • Direct suppressant/reflex cardiac stimulation = Little net effect on the heart
• Dihydropyridines


  • Significant blockade of calcium channels in blood vessels
  • act mainly on vascular smooth muscle (nifedipine)
  • Minimal blockade of calcium channels in the heart
  • Similar to verapamil in some respects and quite different in others
• Nifedipine MOA


  • Vasodilation by blocking calcium channels
  • Blocks in vascular smooth muscle
  • Very little blockade of heart calcium (Ca) channels
  • Cannot be used to treat dysrhythmias
  • Less likely than verapamil to exacerbate preexisting cardiac disorders
• Direct effects of nifedipine

  • Limited to blockade of Ca channels in vascular smooth muscle (VSM)
  • No direct suppressant effects on: Automaticity, AV conduction, or contractile force
• Indirect effects of nifedipine

  • Lowered blood pressure (BP) activates baroreceptor reflex
  • Primarily with immediate release versus sustained release
• Net effect of nifedipine

  • Lowered blood pressure
  • Increased heart rate
  • Increased contractile force
• Therapeutic uses of nifedipine

  • Angina pectoris
  • Hypertension
• Adverse effects of nifedipine

  • Flushing
  • Dizziness
  • Headache
  • Peripheral edema
  • Gingival hyperplasia
  • Chronic eczematous rash in older patients
• Immediate release nifedipine (not sustained) has been associated with increased mortality in patients with MI and unstable angina
• National Heart, Lung, and Blood Institute (NHLBI) recommends that immediate release nifedipine be used with great caution
• Other dihydropyridines


  • Nicardipine
  • Amlodipine
  • Isradipine
  • Felodipine
  • Nimodipine
  • Nisoldipine
  • Clevidipine
• Vasodilators


  • Drugs that dilate resistance vessels (arterioles) cause a decrease in cardiac afterload
  • Drugs that dilate capacitance vessels (veins) reduce the force with which blood is returned to the heart, thus reducing preload
• Principal indications for vasodilators

  • Essential hypertension
  • Hypertensive crisis
  • Angina pectoris
  • Heart failure
  • Myocardial infarction
• Adverse effects related to vasodilation

  • Postural hypotension
• Hydralazine


  • Selective dilation of arterioles
  • Mechanism unknown
  • Postural hypotension minimal
• Therapeutic uses of hydralazine

  • Essential hypertension
  • Hypertensive crisis
  • Heart failure
• Adverse effects of hydralazine

  • Reflex tachycardia
  • Increased blood volume
  • Systemic lupus erythematosus–like syndrome
  • Headache, dizziness, weakness, and fatigue
• Drug interactions with hydralazine

  • Other antihypertensive agents
  • Avoid excessive hypotension
  • Combined with beta blocker to protect against reflex tachycardia and with diuretics to prevent sodium and water retention and expansion of blood volume
• Minoxidil


  • Selective dilation of arterioles
  • More intense dilation than hydralazine, but causes more severe adverse reactions
  • Used for severe hypertension unresponsive to safer drugs
• Adverse effects of minoxidil

  • Reflex tachycardia
  • Sodium and water retention
  • Hypertrichosis
  • Pericardial effusion
• ACC/AHA Classifications of blood pressure

  • Normal: <120 mm Hg AND <80 mm Hg
  • Elevated: 120-129 mm Hg AND <80 mm HG
  • Hypertension Stage 1: 130-139 mm HG OR 80-89 mm HG
  • Hypertension Stage 2: ≥140 mm HG OR ≥ 90 mm HG
• Types of hypertension


  • Primary (essential) hypertension: No identifiable cause, chronic, progressive disorder, older pops, african americans, postmenopausal women
  • Secondary hypertension: Identifiable primary cause, possible to treat the cause directly, some can be cured
• Lifestyle modifications for hypertension management

  • Sodium restriction
  • DASH eating plan
  • Alcohol restriction
  • Aerobic exercise
  • Smoking cessation
  • Maintenance of potassium and calcium intake
• Principal determinants of blood pressure

  • Arterial pressure = Cardiac output × Peripheral resistance
  • Cardiac output: Heart rate, Myocardial contractility, Blood volume, Venous return
• Systems that help regulate blood pressure

  • Sympathetic baroreceptor reflex
  • Renin-angiotensin-aldosterone system
  • Renal regulation of blood pressure
• Baroreceptor reflex


  1. Baroreceptors in the aortic arch and carotid sinus sense BP and relay information to the brain stem

  2. When BP is perceived as too low, the brain stem sends impulses along sympathetic nerves to stimulate the heart and blood vessels

  3. BP is then elevated by activation of beta 1 receptors in the heart resulting in increased cardiac out put and activation of vascular alpha 1 receptors resulting in vasoconstriction

  4. When BP has restored to an acceptable level sympathetic stimulation of the heart and vascular smooth muscle subsides
• Ways to cope with RAAS

  • Suppress renin release with β blockers
  • Prevent conversion of angiotensinogen to angiotensin I with a direct renin inhibitor (DRI)
  • Prevent the conversion of angiotensin I into angiotensin II with an ACE inhibitor (ACEI)
  • Block receptors for angiotensin II with an angiotensin II receptor blocker (ARB)
  • Block receptors for aldosterone with an aldosterone antagonist
• Kidneys


  • When BP falls, glomerular filtration rate (GFR) falls, resulting in retention of sodium, chloride, and water, which increases blood volume and arterial pressure
  • We can neutralize renal effects on BP with diuretics
• Antihypertensive mechanisms: Sites of drug action

  • Brainstem
  • Sympathetic ganglia
  • Terminals of adrenergic nerves
  • Beta1-adrenergic receptors on the heart
  • Alpha1-adrenergic receptors on blood vessels
  • Vascular smooth muscle
  • Renal tubules
  • Beta1 receptors on juxtaglomerular cells
  • Angiotensin-converting enzyme (ACE)
  • Angiotensin II receptors
  • Aldosterone receptors
• Classes of antihypertensive drugs

  • Diuretics - thiazide, loop, potassium-sparing
  • Sympatholytics (antiadrenergic drugs) - alpha/beta blockers (carvedilol, labetalol) centrally acting alpha 1 agonist, and adrenergic neuron blockers
  • Calcium channel blockers
  • Drugs that suppress RAAS - ACE, DRI, Aldosterone antagonist, Angio 2 blockers
• Fundamentals of hypertension drug therapy

  • Treatment algorithm
  • Initial drug selection
  • Adding drugs to the regimen
  • Rationale for drug selection
  • Benefits of multidrug therapy
  • Dosing
  • Step-down therapy
• Individualizing therapy


  • Patients with comorbid conditions: Renal disease, Diabetes
  • Patients in special populations: African Americans, Children and adolescents, Older adults
• Measures to minimize adverse effects and promote adherence

  • Educate the patient
  • Teach self-monitoring
  • Minimize side effects
  • Establish a collaborative relationship
  • Simplify the regimen