Cardiovascular System - Drugs for Hypertension

What is primary hypertension?

Hypertension with no known cause, most common type

What is secondary hypertension?

Hypertension with known cause, secondary to another condition (pheochromocytoma, adrenal cortical tumors, medications), less common than primary hypertension

What is the effect of hypertension on the cardiovascular system?

- Blood vessels thicken, resulting in reduced responsiveness

- Increased cardiac workload, thickening of left ventricle

-Damage to lining of blood vessels -> increase susceptibility of atherosclerosis

-Microvascular damage, can lead to losses in vision, kidney, and cerebral function

-These effects eventually lead to other conditions (cerebrovascular disease, CAD, CHF, etc.)

What are the three factors that control blood pressure?

1. Blood volume

2. Peripheral resistance/ Diameter of arterioles

3. Cardiac output

What factors impact blood volume?

Fluid excretion and retention (ADH and aldosterone)

What factors impact peripheral resistance?

SNS

Renin/Angiotensin II (Most impactful)

Increase in blood viscosity

What factors impact cardiac output?

Stroke volume + Heart rate

What is the body's compensatory mechanisms to increases in blood pressure?

Cardiovascular system

Vasodilation -> decrease TPR

Decrease stroke volume -> decrease cardiac output

Decrease HR -> decrease cardiac output

Renal System

Increased urine output -> decrease blood volume

Result is lowered bp

What is the diagnostic algorithm/criteria for hypertension?

1. Automated Office BP higher than >130/80mmHg on multiple readings (3-6)

(BP readings in clinical setting)

2. Out-of office BP higher than >130/80mmHg

(BP readings at home)

What is white coat hypertension?

Perceived hypertension due to measuring patient's bp in a clinical environment, which could be stressful to the patient and cause higher blood pressure readings

What are lifestyle recommendations for patients with hypertension?

1. Diet

-> Low in saturated fats and cholesterol

-> High in vegetables and fruit

-> Protein from plant sources

-> Low fat diary products

-> Whole grain food rich in fiber

-> Reduce sodium intake; products that are <5% of daily value of sodium

2. Healthy weight and waist circumference

->30-60 minutes of moderate-intensity physical exercise

->dynamic exercises 4-7 days per week

3. Stress management (can be difficult)

4. Abstain from alcohol <2 drinks per day

What are diet recommendations for patients with hypertension?

-> Low in saturated fats and cholesterol

-> High in vegetables and fruit

-> Protein from plant sources

-> Low fat diary products

-> Whole grain food rich in fiber

-> Reduce sodium intake; products that are <5% of daily value of sodium

What is the target blood pressure for pharmacotherapy management of hypertension?

Maintain bp lower than 130 mmHg systolic

What is the pharmacotherapy algorithm for patients with hypertension?

Overall recommendation -> combination therapy, use of multiple medications at once

If patient bp >140/90 or >130/90 with high cardiovasc risk, initiate pharmacotherapy

1. Angiotensin receptor blockers + Thiazide Diuretics

-If bp still not managed-

2. Angiotensin receptor blockers + Thiazide Diuretics + Calcium channel Blockers

-If bp still not managed-

3. Angiotensin receptor blockers + Thiazide Diuretics + Calcium channel Blockers + Potassium Sparing Diuretics

If patient bp 130-139 systolic bp, prioritize lifestyle interventions

Is combination therapy or monotherapy recommended for pharmacotherapy of hypertension?

Combination therapy preferred -> use of multiple drugs

What are thiazide and thiazide-like diuretics? (Use, Mechanism of Action, Adverse Effects, Drug-Drug interactions, Caution, Monitoring)

Use

Used as primary pharmacotherapy management of hypertension by reducing blood volume -> stroke volume

Mechanism of Action

Blocks sodium/chloride transporters in the distal tubules, preventing reabsorption and promoting excretion of electrolytes and -water-

Adverse Effects

GI upset (administer medication with food)

Orthostatic hypotension

Hyperglycemia

Fluid and electrolyte imbalance

->Hypokalemia (use of potassium sparing diuretic or consume potassium rich diet)

Drug-Drug interactions

Lithium (can result in accumulation, low TI)

NSAIDS (COX1 inhibition, renal effects)

Antidiabetic drugs (hyperglycemia, dose adjustments)

Caution

Severe renal disease (Diuretic increases workload of kidneys)

Gout (increased uric acid)

T2DM (increased blood glucose levels, associated with decreased potassium)

Monitoring

Sodium + Potassium levels

Kidney Function

Blood pressure within 4-6 weeks of initiating therapy (drug effect starts occuring)

I/O

Weight gain/loss -> rapid weight changes indicates fluid changes

Dizziness or light-headedness (Hypotension)

What is hypokalemia as an effect of thiazide/thiazide-like diuretics, and how is it treated?

Hypokalemia = low potassium levels due to excessive excretion caused by the diuretic

Can be treated by prescribing a potassium sparing diuretic, which the main function would be to prevent potassium excretion, or recommending the patient to consume a potassium rich diet

What is the use of thiazide and thiazide-like diuretics?

Used as primary pharmacotherapy management of hypertension by reducing blood volume -> stroke volume

What is the mechanism of action of thiazide and thiazide-like diuretics?

Blocks sodium/chloride transporters in the distal tubules, preventing reabsorption and promoting excretion of electrolytes (Na+, K+, Cl-, Ca2+) and -water-

What are adverse effects of thiazide and thiazide-like diuretics?

GI upset (administer medication with food)

Orthostatic hypotension

Hyperglycemia

Fluid and electrolyte imbalance

->Hypokalemia (use of potassium sparing diuretic or consume potassium rich diet)

What are drug-drug interactions of thiazide and thiazide-like diuretics?

Lithium (can result in accumulation, low TI)

NSAIDS (COX1 inhibition, renal effects)

Antidiabetic drugs (hyperglycemia, dose adjustments)

Which patient populations should be cautioned against the use of thiazide and thiazide like diuretics?

Severe renal disease (Diuretic increases workload of kidneys)

Gout (increased uric acid)

T2DM (increased blood glucose levels, associated with decreased potassium)

What monitoring should be done on patients who are prescribed with thiazide and thiazide like diuretics?

Sodium + Potassium levels

Kidney Function

Blood pressure within 4-6 weeks of initiating therapy (drug effect starts occuring)

I/O

Weight gain/loss -> rapid weight changes indicates fluid changes

Dizziness or light-headedness (Hypotension)

What is the role of renin in the RAA pathway?

Released by the kidneys in response to low blood pressure, converts angiotensinogen produced by the liver into angiotensin I

What is the role of angiotensin I in the RAA pathway?

Converted from angiotensinogen by renin. Converted into angiotensin II, a potent vasoconstrictor by Angiotensin converting enzyme.

What is the role of the angiotensin converting enzyme in the RAA pathway?

Converts angiotensin I into active angiotensin II

What is the role of angiotensin II in the RAA pathway?

Increases blood pressure by promoting vasoconstriction, increases peripheral resistance, and stimulating secretion of aldosterone and ADH

Aldosterone increases sodium and water retention

ADH increases water reabsorption in the kidneys

Overall result is increased blood pressure

Which medications are used to target the RAA pathway for hypertension management?

ACE inhibitors -> inhibits angiotensin converting enzyme, blocking production of angiotensin II and increasing production of vasodilatory kinins

Angiotensin Receptor Blockers -> inhibits binding of angiotensin II to receptor

What are ACE inhibitors? (Use, Mechanism of Action, Adverse Effects, Contraindications, Drug-Drug Interactions)

Use

Used as primary pharmacotherapy management of hypertension by lowering total peripheral resistance and blood volume

Mechanism of Action

Inhibits ACE, which converts angiotensin I into angiotensin II

Results in lower vasoconstriction, reduced aldosterone secretion -> increased sodium + water excretion, and increased production of vasodilatory kinins

Adverse Effects

-Persistent Dry cough-

Hyperkalemia

GI irritation and constipation

First dose phenomenon - first dose causes sudden drop in bp and compensatory tachycardia

Angioedema, allergic reaction mimicking anaphylaxis

Contraindications

Pregnancy

Drug-Drug Interactions

Caution with potassium-sparing diuretics and supplements

Decreased efficacy with NSAIDS

What is the use of ace inhibitors?

Used as primary pharmacotherapy management of hypertension by lowering total peripheral resistance and blood volume

What is the mechanism of action of ace inhibitors?

Inhibits ACE, which converts angiotensin I into angiotensin II

Results in lower vasoconstriction, reduced aldosterone secretion -> increased sodium + water excretion, and increased production of vasodilatory kinins

What are adverse effects of ace inhibitors?

-Persistent Dry cough- (Vasodilatory kinins)

Hyperkalemia

GI irritation and constipation

First dose phenomenon - first dose causes sudden drop in bp and compensatory tachycardia

Angioedema, allergic reaction mimicking anaphylaxis

Similar to ARBs w/ dry cough

What are drug-drug interactions of ace inhibitors?

Caution with potassium-sparing diuretics and supplements

Decreased efficacy with NSAIDS

Similar to ARBs

Which medications are contraindicated and recommended for treatment of hypertension during pregnancy?

Contraindicated

ACE Inhibitors

Angiotensin II Receptor Blockers

-> Can result in fetal development defects

Recommended

Primary treatment - Beta blockers

Secondary - Calcium channel blockers

What are angiotensin II blockers? (Use, Mechanism of Action, Adverse Effects, Contraindications, Drug-Drug Interactions)

Use

Used as primary pharmacotherapy management for hypertension by lowering total peripheral resistance and blood volume

Mechanism of Action

Blocks angiotensin II receptors from binding to angiotensin II in arteriolar SM and adrenal cortex, resulting in lowered vasoconstriction. Does not have an effect on vasodilatory kinins.

Adverse Effects

Hyperkalemia

GI irritation and constipation

First dose phenomenon - first dose causes sudden drop in bp and compensatory tachycardia

Angioedema, allergic reaction mimicking anaphylaxis

Contraindications

Pregnancy

Drug-Drug Interactions

Caution with potassium-sparing diuretics and supplements

Decreased efficacy with NSAIDS

What is the use of angiotensin II blockers?

Used as primary pharmacotherapy management for hypertension by lowering total peripheral resistance and blood volume

What is the mechanism of action of angiotensin II blockers?

Blocks angiotensin II receptors from binding to angiotensin II in arteriolar SM and adrenal cortex, resulting in lowered vasoconstriction. Does not have an effect on vasodilatory kinins, resulting in lack of persistent dry cough as an adverse effect

What are adverse effects of angiotensin II blockers?

Hyperkalemia

GI irritation and constipation

First dose phenomenon - first dose causes sudden drop in bp and compensatory tachycardia

Angioedema, allergic reaction mimicking anaphylaxis

Similar to ACE inhibitors w/o persistent dry cough

What are drug-drug interactions of angiotensin II blockers?

Caution with potassium-sparing diuretics and supplements

Decreased efficacy with NSAIDS

Similar to ACE inhibitors

What are calcium channel blockers in hypertension management? (Use, Mechanism of Action, Adverse Effects, Caution, Contraindications)

Use

Used as pharmacotherapy management for hypertension by lowering total peripheral resistance and cardiac output. Used after ARBs and thiazide diuretics have been prescribed

Mechanism of Action

Relaxes vascular smooth muscle, decreasing peripheral resistance.

Non selective calcium channel blockers also slow heart rate, reducing cardiac output and workload -> effective for patients with angina

Adverse Effects

Associated with hypotension, low TI

-> Dizziness

-> Light-headedness

-> Fatigue

-> Hypotension and compensatory/reflex tachycardia

-> Flushing

-> Nausea

Contraindications

Consuming grapejuice, affects metabolism due to impact on liver enzymes

What is the use of calcium channel blockers in hypertension management?

Used as pharmacotherapy management for hypertension by lowering total peripheral resistance and cardiac output. Used after ARBs and thiazide diuretics have been prescribed

What is the mechanism of action of calcium channel blockers in hypertension management?

Relaxes vascular smooth muscle, decreasing peripheral resistance.

Non selective calcium channel blockers also slow heart rate, reducing cardiac output and workload -> effective for patients with angina

What are adverse effects of calcium channel blockers in hypertension management?

Associated with hypotension, low TI

-> Dizziness

-> Light-headedness

-> Fatigue

-> Hypotension and compensatory/reflex tachycardia

-> Flushing

-> Nausea

What are beta blockers in hypertension management? (Use, Mechanism of Action, Adverse Effects, Caution)

Use

Used for management of concomitant cardiovascular conditions or as primary pharmacotherapy for hypertension management in pregnancy

Mechanism of Action

Binds to a1 receptors, blocking effect of norepi on arterioles, lowering vasoconstriction

Binds to B1 receptors on the heart, blocking effect of norepi and epi on the cardiac muscles, reducing cardiac output

Binds to kidneys to reduce renin secretion, inhibiting production of angiotensin I and decreasing peripheral resistance and blood volume

Non selective beta blockers will bind to B2 receptors as well, impacting the lungs and potentially causing bronchoconstriction

Adverse Effects

Fatigue and Activity Intolerance

Sleep Disturbances

Caution

Diabetes

Depression

Asthma (non cardioselective)

COPD (non cardioselective)

What is the use of beta blockers in hypertension management?

Used for management of concomitant cardiovascular conditions or as primary pharmacotherapy for hypertension management in pregnancy

What is the mechanism of action of beta blockers in hypertension management?

Binds to a1 receptors, blocking effect of norepi on arterioles, lowering vasoconstriction

Binds to B1 receptors on the heart, blocking effect of norepi and epi on the cardiac muscles, reducing cardiac output

Binds to kidneys to reduce renin secretion, inhibiting production of angiotensin I and decreasing peripheral resistance and blood volume

Non selective beta blockers will bind to B2 receptors as well, impacting the lungs and potentially causing bronchoconstriction

What are adverse effects of beta blockers in hypertension management?

Fatigue and activity intolerance

Sleep disturbances

Primary reason why beta blockers are not prescribed for normal management of hypertension - hard to encourage patients to increase physical activity as a lifestyle intervention when they are tired