Hypertension Cardiovascular Therapies (Exam #3)

Arterial Blood Pressure

Arterial BP - Pressure in arterial wall measured in millimeters of mercury (mmHg)

Two Arterial BP Values

• Systolic Blood Pressure (SBP)

• Diastolic Blood Pressure (DBP)

SBP represents

the heart contracting

DBP represents

the heart chambers filling

Under normal physiologic conditions arterial blood pressure fluctuates throughout the day

• Lowest?

• Highest?

• Increased by?

• BP is lowest during sleep and sharply rises a few hours prior to awakening

• BP is highest in the mid-morning

• BP is increased by physical activity or emotional stress

BP values increase with

age

HTN common in elderly

• Lifetime risk of developing HTN > 55 years is 90%

Essential Hypertension

Also known as primary hypertension

• > 90% of individuals with high BP

Unknown pathophysiological etiology

• Multiple factors contribute to development of essential hypertension

• Genetic factors may have an important role

Essential Hypertension Effects on BP

• Increase in cardiac output (CO)

• Increase in total peripheral resistance (TPR)

• OR A combination of both

Which HTN can be cured?

Secondary HTN may be cured if cause is identified

Essential Hypertension cannot be cured, but can be controlled

Secondary Hypertension

Comorbid disease or product (like a drug) induced

• < 10% of patients have secondary hypertension

Disease(s) that may cause Secondary Hypertension

• Chronic Kidney Disease

• Renovascular Disease

• Cushing Syndrome

• Obstructive Sleep Apnea

• Thyroid Disease

• Parathyroid Disease

Drug(s) that may cause Secondary Hypertension :

• Alcohol

• Amphetamines

• Antidepressants (MAOIs, SNRIs, TCAs)

• Atypical Antipsychotics

• Caffeine

• Corticosteroids

• Decongestants (Phenylephrine & Pseudophedrine)

• Herbals (St Johns Wart, Ephedra, Yohimbine)

• Cyclosporine

• Estrogen-containing Oral Contraceptives

• NSAIDS

• Venlafaxine

• Cocaine

• Bupropion

• Angiogenesis Inhibitors

• Tyrosine Kinase Inhibitors

Diagnosis of HTN is based on

the average of 2 or more properly measured BP values from 2 or more clinical encounters

• Measuring blood pressure should occur at every healthcare encounter

Tools to measure blood pressure:

• Sphygmomanometer

• Cuff

• Stethoscope

Factors Resulting in Inaccurate BP Measurements:

• Suboptimal technique taking a blood pressure

• Environmental factors (not extensive list)

• Time of day

• Posture

• Nicotine

• Emotions

• White coat hypertension (15-20% of patients)

• Pseudohypertension

• Auscultatory gap

Self Blood Pressure Monitoring

• Can document BP frequently throughout the day

• Typically lower than clinic-measured BP

• Helpful in patients with white coat hypertension or episodic hypertension

Self Blood Pressure Monitoring Limitations

• Complexity of use

• Cost

• Lack of data describing normal ranges

• Omitted or fabricated readings

Normal BP Range for SBP & DBP

SBP < 120

AND

DBP < 80

Elevated BP Range for SBP & DBP

SBP: 120 - 129

AND

DBP < 80

Stage 1 HTN BP Range for SBP & DBP

SBP: 130 - 139

OR

DBP: 80 - 89

Stage 2 HTN BP Range for SBP & DBP

SBP >/Equal to 140

OR

DBP >/Equal to 90

HTN Signs & Symptoms:

• Patients usually asymptomatic

• Physical exams often are normal

• Elevated BP is commonly the only sign of hypertension

A _______________________ should be done after diagnosis of HTN

Complete medical exam

• Identify secondary causes

• Identify other CV risk factors or comorbid conditions

• Assess for the presence or absence of HTN-associated target-organ damage

Additional cardiovascular risk factors aside from elevated BP:

• Age (> 55 in men, > 65 in women)

• Diabetes Mellitus

• Dyslipidemia

• Microalbuminuria

• Family history of premature CV disease

• Obesity (BMI > 30 kg/m2)

• Physical Inactivity

• Tobacco Use

All patients with HTN should have the following laboratory tests prior to initiating therapy:

• BUN & Serum Creatinine

• Fasting Blood Glucose

• Fasting Lipid Panel

• Serum Electrolytes (sodium, potassium)

• Urinalysis

There is a STRONG correlation between BP and CV morbidity & mortality which includes the risk of

• Stroke

• Myocardial Infarction (MI)

• Angina

• Heart Failure

• Kidney Failure

• Early Death from a CV cause are directly correlated with BP

Starting at a BP of _______________ risk of CV disease doubles with every _________________ increase

115/75 mmHg

20/10 mmHg

• Patients with prehypertension also have an increased risk of CV disease

Antihypertensive therapy is associated with ________________

reduced risk of CV events

_____________ is a stronger predictor of CV disease than ______________ in adults > 50 years old

SBP

DBP

Isolated systolic hypertension

• Can occur with aging

• Increases risk of CV morbidity and mortality

Primary causes of CV morbidity and mortality

Target organ damage

Probability of CV events is directly correlated with

severity of BP elevation

Pathophysiology of HTN and target organ damage:

• Accelerates atherosclerosis

• Stimulates left ventricular dysfunction

• Promotes vascular dysfunction

Target Organ Damage to the Brain may result in

• Stroke

• Transient Ischemic Attack

• Dementia

Target Organ Damage to the Eyes may result in

• Retinopathy

Target Organ Damage to the Heart may result in

• Left Ventricular Hypertrophy

• Angina

• Myocardial Infarction

• Heart Failure

Target Organ Damage to the Kidney may result in

• Chronic Kidney Disease

Target Organ Damage to the Arteries may result in

Peripheral Arterial Disease

Goals of Hypertension Therapy

• Reduce morbidity and mortality associated with HTN

• Reduce HTN associated target organ damage

• Reduce cardiovascular events

• Minimize or control other risk factors for CV disease

• We use blood pressure goals as surrogate targets

** Focus is on overall patient health

Blood Pressure Goals for patients with HTN

< 130/80

BP threshold for secondary stroke prevention

BP threshold for no clinical CKD & a 10 year ASCVD risk of < 10%

Non-Pharmacologic Therapy for HTN:

+ Weight Loss

• Maintain normal body weight

• BMI 18.5 - 24.9 kg/m2

• SBP reduced 1 mmHg for every 1 kg weight loss

+ DASH Diet (Dietary Approaches to Stop Hypertension)

• Fruits, vegetables, low fat dairy products

• Reduced saturated and total fat

• SBP reduction ~ 11 mmHg

+ Reduced Salt Intake

• 1.5 g daily of sodium

• SBP reduction of 2 - 8 mmHg

+ Potassium Supplementation

• Preferably through dietary changes (foods heart healthy)

• Higher impact in patients consuming high sodium

• Controversy: only in patients with low K intake

+ Physical Activity

• 30 minutes/day most days of the week

• SBP reduction of 4 - 8 mmHg

+ Moderation of Alcohol Intake

• < 2 drinks/day for men, < 1 drink/day for women

• SBP reduction of 2 - 4 mmHg

+ Tobacco Cessation

DASH Diet

Dietary Approaches to Stop Hypertension

• Fruits, vegetables, low fat dairy products

• Reduced saturated and total fat

• SBP reduction ~ 11 mmHg

Sodium limit for patients with HTN

1.5 g daily of sodium

First Line Agents For Hypertension

+ ACE Inhibitors

• Benazepril

• Lisinopril

• Enalapril

+ ARBs

• Losartan

• Olmesartan

• Valsartan

+ Thiazide-like diuretics

• Chlorthalidone

• Hydrochlorothiazide

+ CCBs

Dihydropyridine CCBs

• Amlodipine

• Nifedipine

+ Isolated systolic hypertension

+ Raynaud's syndrome

Non-Dihydropyridine CCBs

• Diltiazem

• Verapamil

+ Used to treat supraventricular tachyarrhythmias (e.g. atrial fibrillation)

Thiazide-Type Diuretics are the preferred diuretic class for most patients with HTN, only when GFR

> 30 mL/min

Thiazide-Type Diuretics

• MOA

• Adverse Effects

• Counseling Points

MOA: Thiazide-type diuretics mobilize sodium and water from arteriolar walls

• Reduces peripheral vascular resistance

• Low salt intake can enhance this effect

+ Adverse Effects:

• Hypokalemia

• Hypercalcemia

• Hyperuricemia --> Gout

• Hyperglycemia

• Dyslipidemia

• Sexual Dysfunction

+ Counseling Points:

• Take early in the day to prevent nocturnal diuresis (before 4 pm)

• May increase blood glucose in diabetic patients

• May precipitate gout flares

• Increased sun sensitivity - use sunscreen

Thiazide-Type Diuretics Drugs

• Chlorthalidone

• Hydrochlorothiazide

Chlorthalidone

Thiazide-Type Diuretics

Hydrochlorothiazide

Thiazide-Type Diuretics

Loop Diuretics + Drugs

+ The most potent diuresis agents

• Furosemide

• Bumetanide

• Torsemide

Furosemide Drug Class

Loop Diuretics

Bumetanide Drug Class

Loop Diuretics

Torsemide Drug Class

Loop Diuretics

Loop Diuretics

• Uses

• Adverse Effects

• Counseling Points

+ Uses:

• Not ideal antihypertensive agents unless edema relief is also needed

• Preferred over thiazide-type diuretics when GFR < 30 mL/min in patients with chronic kidney disease

+ Adverse Effects:

• Less impact on glucose and lipids compared to thiazides

• Hypocalcemia or hypokalemia may occur

• Ototoxicity may occur in high doses

+ Counseling Points:

• Dose in the morning and early afternoon

Potassium Sparing Diuretics Hypertensive Effect + Drugs

+ Very weak antihypertensive agents

• Amiloride

• Triamterene

Amiloride Drug Class

Potassium Sparing Diuretics

Triamterene Drug Class

Potassium Sparing Diuretics

Potassium Sparing Diuretics

• Uses

• Adverse Effects

+ Uses:

• Provides small additive effect combined with a thiazide or loop diuretic

• May counteract potassium wasting properties of other diuretics

• May be used in resistant HTN

+ Adverse Effects:

• May cause hyperkalemia

- Patients with CKD and diabetes

- Patient being treated with ACE inhibitor, ARB, direct renin inhibitor, or potassium supplements

Aldosterone Antagonists Drugs

+ Potassium Sparing Agents

• Spironolactone

• Eplerenone

Spironolactone Drug Class

Aldosterone Antagonists

Eplerenone Drug Class

Aldosterone Antagonists

Aldosterone Antagonists

• Uses

• Adverse Effects

+ Uses:

• More potent antihypertensive agents than potassium sparing diuretics

• May be used for resistant HTN

+ Adverse Effects:

• May cause hyperkalemia

• Especially in combination with an ACE inhibitor or ARB

• Spironolactone causes gynecomastia in 10% of patients

Angiotensin Converting Enzyme (ACE) Inhibitors Drugs

+ First line antihypertensive agents

• Benazepril

• Lisinopril

• Enalapril

Angiotensin Converting Enzyme (ACE) Inhibitors Dosing

• Most ACE inhibitors are dosed once to twice daily

• Captopril is dosed two to three times daily

Angiotensin Converting Enzyme (ACE) Inhibitors

+ Adverse Effects

+ Contraindications

+ Counseling

+ Adverse Effects:

• Block the degradation of bradykinin which may cause a dry cough (20%)

• Initiation of an ACE inhibitor may cause acute hypotension

• Doses should start small and titrate up

• Hyperkalemia

• Especially in patients with diabetes or CKD

• Acute kidney failure (< 1%)

• Patients with preexisting renal disease or renal artery

stenosis

• Angioedema (< 1%)

• Swelling of lips and throat

• More likely in African Americans or smokers

+ Contraindications:

• Absolutely contraindicated in pregnancy

• Teratogenic effects in all states of pregnancy

+ Counseling:

• May cause skin rash or impaired taste perception

• Do not use potassium supplements or salt substitutes

• If a persistent cough develops notify your physician

• Contact a physician if you notice sore throat, fever, swelling of lips/tongue, difficulty breathing

Angiotensin II Receptor Blockers (ARBs) Drugs + Efficacy

• Losartan

• Olmesartan

• Valsartan

Efficacy:

• CV event lowering benefits of ARBs similar to ACE inhibitors

• No shown benefit to using ACE inhibitors and ARBs together

Angiotensin II Receptor Blockers (ARBs) Dosing

Once to twice a day dosing

Angiotensin II Receptor Blockers (ARBs)

+ Adverse Effects

+ Contraindications

+ Adverse Effects:

• Reduced risk of angioedema compared to ACE inhibitors

• May cause kidney insufficiency

• Hyperkalemia

• Hypotension

+ Contraindications:

• Absolutely contraindicated in pregnancy

Medications in the _______________ should not be used together

RAS pathway

+ ACEIs, ARBs, Direct Renin Inhibitors

• Possible Harm

Calcium Channel Blockers (CCBs) Drugs + Mechanism

Effective antihypertensive agents

+ MOA: Inhibit the influx of calcium across the cell membrane

• CCBs do not interfere with diabetes, lipids, or uric acid

Dihydropyridine CCBs

+ Action through vasodilation

• Amlodipine

• Nifedipine

Non-Dihydropyridine CCBs

+ Action through decreased heart rate and slowing of AV nodal conduction

• Diltiazem

• Verapamil

Dihydropyridine CCBs

+ Uses

+ Adverse Effects

+ Uses:

• Effective in older patients with isolated systolic hypertension

• Additional benefits in Raynaud's syndrome

** Not effective agents for tachyarrhythmias

+ Effects:

• May cause reflex tachycardia due to potent peripheral vasodilating effects

• Do not alter conduction through the AV node

+ Adverse Effects

• Dizziness

• Flushing

• Headache

• Peripheral Edema

• GI Complaints

Non-Dihydropyridine CCBs

+ Uses

+ Adverse Effects

+ Risks

+ Uses:

• May also be used to treat supraventricular tachyarrhythmias (e.g. atrial fibrillation)

+ Adverse Effects:

• Anorexia

• Nausea

• Peripheral Edema

• Hypotension

• Constipation

+ Risks:

• Risk of heart block, especially in combination with BBs

• May precipitate or cause systolic heart failure

• Verapamil highest risk

Sympathetic Activity on the Heart

Accelerates heart rate, constricts blood vessels, raises blood pressure

Effects of renin on the blood vessels

Increases blood pressure to return perfusion to kidneys

Preferred agents in patients post-MI and coronary artery disease

Beta Blockers

Beta Blockers Type

+ NOT A FIRST LINE AGENT

+ Four types

• Cardioselective

• Nonselective

• Intrinsic sympathomimetic activity (ISA)

• Mixed alpha & beta blockers

Beta Blockers BBW

Abrupt discontinuation can cause unstable angina, MI, rebound hypertension, and death

+ Taper Dose

Beta Blockers Pharmacokinetics:

All beta blockers cross the blood brain barrier

• Lipophilic agents more than hydrophilic agents

• Propranolol (lipophilic) > metoprolol > atenolol (hydrophilic)

Beta Blockers Uses

• Bradycardia

• AV conduction abnormalities (heart block)

• Bronchospasm

• Raynaud's phenomenon

• Sexual dysfunction

• Increased triglycerides

• Decreased HDL

• Depression

Cardioselective Beta Blockers Drugs

+ Uses

+ MOA

+ Patient Indications

+ Preferred agents in hypertension

• Atenolol

• Bisoprolol

• Metoprolol

+ Affinity for beta-1 receptors over beta-2 receptors

• Beta-1 - increases heart rate, contractility

• Beta-2 - bronchodilation, vasodilation, insulin secretion

• Dose dependent selectivity for beta-1 receptors

• Block beta-2 receptors at high doses

** Safer in patients with asthma, COPD, or diabetes

Nonselective Beta Blockers Drugs

+ MOA

+ Contraindications

+ Extra Benefits

+ Blocks both beta-1 and beta-2 receptors at all doses

• Propranolol

• Nadolol

• Timolol

+ Beta-2 Blockade

• Inhibits bronchodilation in the lungs

• Inhibits insulin production in the pancreas

+ Contraindications:

• Not safe for use in patients with Diabetes, COPD, or Asthma

+ Extra Benefits:

• May have benefits in patients with essential tremor or migraine headaches

Intrinsic Sympathomimetic Activity (ISA) Beta Blockers Drugs

+ MOA

+ Risks/Warnings

+ Have Intrinsic Sympathomimetic Activity (ISA)

• Acebutolol

• Pindolol

+ Partial Beta Receptor Agonists

• Reduces effects of catecholamines

+ Does not reduce cardiac output, resting heart rate, or peripheral blood flow

• No evidence of reduced CV events

• May increase risk post-MI or in coronary artery disease

Mixed Alpha & Beta Blockers Drugs

+ MOA

+ Risks

+ Blocks alpha and beta receptors

• Carvedilol

• Labetalol

+ Additional alpha blockade produces vasodilation

Risks:

• Greater risk of orthostatic hypotension

Beta Blocker Counseling

• Never stop taking without contacting physician

+ Notify physician if you notice:

• Extremely slow heart rate

• Blurred vision

• Depression

• Skin rash

Direct Renin Inhibitor

+ Drugs

+ MOA

+ Uses

+ Adverse Effects

+ Monitoring Parameters

+ Contraindications

Aliskiren (Tekturna ®)

MOA:

• Blocks RAS at its point of activation

• Prevents formation of angiotensin I and II

• Results in reduced plasma renin activity and BP lowering

+ RAS Cascade

• Renin cleaves angiotensin, converting it to angiotensin I

• Angiotensin I is converted to angiotensin II by the angiotensin converting enzyme

• Angiotensin II is a vasoconstrictor

+ Uses:

• Approved for treatment of HTN alone or in combination

• Role in therapy unclear

+ Adverse Effects:

• Reports of angioedema

• Hyperkalemia

+ Monitoring Parameters:

• Serum Creatinine

• BUN

• Hyperkalemia

+ Contraindications:

• Avoid in pregnancy due to risk of teratogenic effects of other RAS agents

Alpha-1 Blockers

+ Drugs

+ MOA

+ Uses

+ Effects

+ Counseling

• Terazosin

• Doxazosin

• Prazosin

+ MOA:

• Inhibit the uptake of catecholamines in smooth muscle cells (Vasodilation and BP lowering)

+ Uses:

• Provide symptom improvement in men with benign prostatic hypertrophy (BPH)

+ Effects

• First-dose phenomenon - dizziness, faintness, palpitations, and syncope within 1-3 hours of first dose or dose increase

• Orthostatic hypotension and dizziness may occur with chronic administration

• Caution in elderly patients

• Crosses blood brain barrier

• Vivid dreams and depression

+ Counseling:

• May cause dizziness

• Avoid rapid posture changes

• May cause drowsiness

• Take at bedtime

Central Alpha-2 Agonists

+ Drugs

+ Uses

+ Adverse Effects

+ BBW

• Clonidine

• Guanfacine

• Methyldopa

+ MOA:

• Stimulates alpha-2 adrenergic receptors in the brain

+ Uses:

• Clonidine frequently used in resistant HTN

• Methyldopa is first line in pregnancy

+ Adverse Effects:

• Methyldopa can cause hepatitis or anemia (rare)

• Chronic use can result in sodium and water retention

• Sedation and dry mouth common

• High rates of orthostatic hypotension & dizziness

+ Abrupt cessation of alpha-2 agonist may result in rebound HTN

• Do NOT discontinue abruptly • Taper Dose

Direct Arterial Vasodilators

+ Drugs

+ MOA

+ Uses

+ Long Term Use

+ Adverse Effects

• Hydralazine

• Minoxidil

+ MOA: Directly relaxes arteriolar smooth muscle

+ Vasodilation and BP lowering

• Used in resistant HTN

+ All patients utilizing long term should receive a Beta Blocked and Diuretic first

• Reduces risk of angina and sodium/water retention

+ Adverse Effects:

• May result in drug induced lupus

• Troublesome minoxidil side effect is hypertrichosis

Peripheral Adrenergic Antagonist

+ Drugs

+ MOA

+ Adverse Effects

• Reserpine

+ MOA:

• Depletes norepinephrine from sympathetic nerve endings

• Blocks transport of norepinephrine into storage granules

• Reduces sympathetic tone, peripheral vascular resistance, and BP

+ Takes 2-6 weeks for full antihypertensive effects

+ Adverse Effects (Limit Use):

• Sedation

• Depression

• Nasal Stuffiness

• Diarrhea

• Bradycardia

• Significant sodium & water retention

• Depression is dose dependent

Combination Therapy Commonly Utilized

Consider Initially If:

• Stage 2 HTN

• Average BP > 20/10 mmHg above target

BP response should be evaluated _____________ after starting therapy, if stage 2 HTN, or stage 1 HTN w/ASCVD 10-y risk > 10%

4 weeks

Stage 1 HTN with ASCVD 10-y risk < 10% BP Monitoring

3 to 6 months

BP in range monitoring

annually

Signs/symptoms of target organ damage

• Chest Pain

• Palpitations

• Dizziness

• Dyspnea

• Headache

• Sudden Vision Changes

• One-sided Weakness

• Slurred Speech

• Loss of Balance

Escalating Therapy

• Increase Existing Dose

OR

• Add another 1st line agent

Improving Patient Adherence

+ ~50% of patients with newly diagnosed HTN continue treatment at 1 year

• Be aware of signs of non-adherence

• Work with patient to reduce blood pressure with minimal or no adverse effects

• Educate patient about disease and involve family in treatment

• Maintain contact with patients

• Keep care simple and inexpensive

• Encourage lifestyle modifications

• Utilize once daily regimen if possible

• Be willing to modify therapy

• Anticipate AEs, and adjust therapy to prevent/minimize

• Ask patients periodically about their general health perception, and satisfaction with treatment

Hypertensive Urgency

+ Treatment

+ Goals

• High BP (> 180/120) NOT associated with acute or immediately progressing targetorgan injury

+ Ideally Adjust maintenance therapy by adding new agent or increasing dose of present medication

• May administer short acting oral agent (captopril, clonidine, or labetalol) followed by careful observation

+ Goal is to gradually reduce BP

• Never administer immediate release nifedipine due to risk of MI and stroke

• Most common error is overly aggressive antihypertensive therapy

• Re-evaluate patient in 7 days

Hypertensive Emergency

+ Treatment

• High BP (> 180/120) associated with acute or immediately progressing target-organ injury

• Rare situation

+ Requires immediate BP reduction to limit organ damage

• Typically parenteral (IV) therapy is required

HTN in Older Adults

+ Risks

+ Treatments

+ Avoid

• High risk for target organ damage

• Sensitive to volume depletion

• Increased risk of orthostatic hypotension

+ Diuretics, ACE inhibitors, and ARBs have shown benefit

• Must be started at low doses and titrated up slowly

+ Avoid the use of centrally acting agents and α-blockers