NUR 3031-002 Basic Concepts in Pharmacology: Hypertension and ACE-I and ARBS

Types of Hypertension: Primary (Essential) Hypertension

Hypertension that presents and persists with no Identifiable cause

Types of Hypertension: Secondary Hypertension

Hypertension that presents due to identifiable causes, such as:

• Renal disease

• Oral contraceptive Use

• Renovascular Disease

• Cushings Syndrome

• Pheochromocytoma

Consequences of Hypertension

Asymptomatic until long after injury has developed.

• Degree of injruy related to degree of elevation/higher pressure, higher risk

  • Heart Failure

  • Kidney Disease

  • Stroke

  • Angina

  • MI

Goals of Hypertension

• NO CURE

• Goals related to improve outcomes

• ↓ CV and renal morbidity and mortality without ↓ quality

  of life

Assessment of Hypertension

Start with Identifiable causes to rule out secondary hypertension

• Cushings

• Pheochromocytoma

• Oral contraceptives

• Etc.

Assessment of Hypertension: Factors that increase CV Risk

• Target organ damage

• Major CV risk factors

  • Cigarettes

  • Obesity

  • Diabetes

  • Sedentary

Classes of Antihypertensive Drugs:

• Diuretics

• Sympatholytics (Adrenergic Antagonists)

• Drugs that influence RAAS System

  • ACE Inhibitors

  • Angiotensin Receptor Blockers

• Calcium Channel blockers

• Direct Acting Vasodilators

Angiotensin Convertng Enzyme (ACE) Inhibitors

Block converions of Angiotensin I into Angiotensin II resulting in:

• Vasodilation and decreased peripheral resistance

• Reduction in blood volume

• Prevention or reversal of pathologic changes in the heart and blood vessels mediated by angiotensin II and aldosterone

Angiotensin Convertng Enzyme (ACE) Inhibitors Pharmacokinetics

• Absorption: Give PO, (enalaprilat given IV)

• Metabolism: Most are prodrugs, converted into active form in small intestines an the liver

• Excretion: Renal; reduce dose in renal impairment

Indicications for Angiotensin Convertng Enzyme (ACE) Inhibitors

• HTN

• Heart Failure

• MI

• Diabetic and non-diabetic nephropathy

  • Slows progression but does not prevent

• Prevention of MI, stroke, and death in patients with high CV Risk

• Diabetic Retinopathy

Adverse effects: Angiotensin Convertng Enzyme (ACE) Inhibitors

• Renal Failure

  • Particulary in renal artery stenosis

• Angioedema

  • Results from accumulation of bradykinin

  • Treat with epinephrine

Side Effects: Angiotensin Convertng Enzyme (ACE) Inhibitors

• First dose Hypotension

• Cough:

  • Results from accumulation of bradykinin

  • More common in elderly, female, or Asian ancestry patients.

• Hyperkalemia:

  • Rare: unless taking potassium supplements or salt substitutes, or potassium-sparing diuretics

Drug Interactions: Angiotensin Convertng Enzyme (ACE) Inhibitors

• Diuretics and other Antihypertensive agents

  • Increase risk of hypotension

• Drugs that raise potassium levels

  • Increase risk of hyperkalemia

• Lithium

  • Increase risk of lithium toxicity

• NSAIDs

  • Reduce the antihypertensive effects of ACE inhibitors

ACE INHIBITORS: End in “Pril”

• Benazepril (Lotensin)

• Captopril (Capoten)

• Lisinopril (Prinvil) (Zestril)

• Quinapril (Accupril)

• Ramipril (Altace)

• Enalapril (Vasotec)

• Enalaprilat (Vasotec) IV form

  • Enalaprilat is the only ACE available in solution (IV form)

Angiotensin Receptor Blockers (ARB’s):

Blocks action of Angiotensin II at receptor sitesthe

• Vasodilation = decreased peripheral; resistance

• Decreased release of aldosterone by adrenals = increased sodium and water excretion

• Reduces pathologic changes to the heart

• Same effects as ACE inhibitors without accumulation of bradykinin

  • Lower risk of cough and angioedema

Indications: Angiotensin Receptor Blockers (ARB’s):

• HTN

• Heart failure

• Post myocardial infarction (MI)

• Diabetic Nephropathy

• Prevention of stroke, MI, and death in high risk patients

Adverse Effects: Angiotensin Receptor Blockers (ARB’s):

Similar to ACE: Hypotension, Renal Failure, Fetal Harm,

• Lower risk of hyperkalemia; Lower risk of cough and angioedema (No bradykinin accumulation)

Angiotensin Receptor Blockers (ARB’s): NTK

End in “Sartan”

• Losartan (Cozaar)

• Valsartan (Diovan)

• Olmesartan (Benicar)

• Irbesartan (Avapro)

• Telmisartan (Micardis)

Calcium Channel Blockers

Regulates the contraction of smooth muscle

• Regulates the conduction of electrical signals through the SA and AV nodes

  • As an action potential travels across the surface of a smooth muscle cell, calcium channels allow influx of calcium, which initiates the contractile process

Calcium Channel Blocker Therapeutic Effects:

• Vascular smooth muscle relaxation and vasodilation of both peripheral and cardiac arteries and arterioles:

  • Decreased peripheral resistance

  • Decreased BP

  • Decreased Force of cardiac contraction

  • Decreased Heart rate

  • Decreased Conduction of electrical signals through the heart

• Some have greater actions on the heart, others more on the arteriolar smooth muscle

• Useful for treatment of hypertension, angina, and cardiac dysrhythmias

Calcium Antagonists: Non-dihydropyridine CCBS NTK

• Verapamil (Calan)

• Diltiazem (Cardizem)

Block Ca channels in blood vessels and in the heart

Calcium Antagonists: Nonhydropyridine CCBS Therapeutic Indications

• Essential HTN

• Angina

• Cardiac Dysrythmias

Calcium Antagonists: Non-dihydropyridine CCBS Direct Effects

Non-dihydropyridine CCBs Direct effects:

• Decreased arterial pressure

• Decreased HR

• Decreased AV nodal conduction

• Decreased force of contraction

• Decreased coronary perfusion

Calcium Antagonists: Nonhydropyridine CCBS Adverse Effects

• Constipation – from calcium channel blockade in smooth muscle of intestine

  • Worse among older adults

  • Increase dietary fluids and fiber

• HA, dizziness, lightheadedness, flushing, peripheral edema

  • Secondary to vasodilation

• Gingival hyperplasia

  • 10-20% of patients

  • Good oral hygiene

Calcium Antagonists: Non-dihydropyridine CCBs Contraindications

• Certain dysrhythmias

• Bradycardia

• Sick Sinus Syndrome

• Second or Third Degree AV Block

• Use with caution in Heart Failure

Calcium Antagonists: Non-dihydropyridine CCBS Toxicity

• Treat toxicity with IV calcium gluconate

Calcium Antagonists: Nonhydropyridine CCBS Drug Interactions

• Digoxin:

  • Increases available digoxin, increasing the risk of toxicity

• Beta Blockers:

  • Excessive cardiac supression

  • Hypotension, Bradycardia

Calcium Antagonists: Dihydropyridines CCBS

End in “Dipine”

• Nifedipine (ProcardiaXL, Adalat)

• Amlodipine (Norvasc)

Inhibits calcium ion influx

Calcium Antagonists: Dihydropyridines CCBS Therapeutic Effects

• Vasodilating effects on coronary and peripheral arterioles

• Does not slow AV node conduction

Used for angina and HTN

Calcium Antagonists: Dihydropyridines CCBS Toxicity

May cause cardio suppression in toxic doses

Calcium Antagonists: Dihydropyridines CCBS Adverse Effects

• Flushing

• Dizziness

• Reflex tachycardia with immediate release formulation

Vasodilators Indications:

• Essential HTN

• Hypertensive crisis

• Heart failure

Direct Acting Vasodilators: Hydralazine (Apresoline)

Hydralazine (Apresoline)

• Selective dilation of arterioles = ↓Peripheral resistance

Direct Acting Vasodilators: Adverse Effects

• Lupus-like syndrome

• Reflex tachycardia

  • Combine with a beta-blocker to prevent reflex tachycardia

• Fluid retention

  • Combine with a diuretic to offset fluid retention

Direct Acting Vasodilators: Nitroprusside (Nitropress, Nipride)

Drug of choice for hypertensive crisis (DBP>120)

• Relaxes vascular smooth muscle by releasing nitric oxide

• Dilates veins and arteries = ↓ preload and afterload

• Decreased BP dramatically and quickly, effect reverses quickly after discontinuation

Direct Acting Vasodilators: Nitroprusside (Nitropress, Nipride) Pharmacokinetics

• IV use only

• MUST use a pump

• Protect from light