T3 - IE1 - Cardiology - Nauli - Intro Class (Hypertension I) + Thiazides

Blood Pressure =

Cardiac Output * Peripheral Resistance

Cardiac

- heart rate (chronotropic)

- heart contraction (inotropic)

Volume Control (renal)

renin-angiotensin

aldosterone

Cardiac Output is composed of __________ influences and ________ __________

- cardiac

- volume control (renal)

Peripheral resistance consists of ____________ ________ and ___________

- sympathetic control (flight or fight)

- humoral (hormones)

Sympathetic control

vasoconstrictor (α)

vasodilator (β)

Humoral

vasoconstrictor: angiotensin, catecholamines

vasodilator: prostaglandins

Cardiac Output is measured in...

L/min

Peripheral resistance is measured by...

(mm Hg * min)/L

What is an example of a decrease in cardiac output when there is an increase in heart contraction but the blood pressure remains the same?

Low blood volume due to trauma. Trauma increases causes greater contraction but loss of volume may cause no difference in blood pressure.

High sympathetic nerve activity can lead to...

high blood pressure and vice versa

__________ is the problem of using pharmacological therapy to treat hypertension

- Reflex

The body wants to return and go back to a certain blood pressure i.e., after exercise our heart rate may raise but our body does not maintain the new blood pressure but wants to return. Body wants to maintain blood pressure at a certain level.

Reflex of the body tries to _____________ the medication

- counteract

Humoral imbalance can cause hypertension by ________

a. decreasing cardiac chronotropic and vasoconstriction

b. increasing peripheral resistance and volume expansion

c. increasing cardiac chronotropic and volume expansion

d. increasing cardiac inotropic and vasoconstriction

Increasing peripheral resistance and volume expansion

Normal Blood Pressure at resting state

< 120 mmHg systolic AND < 80 mmHg diastolic

Hypertension, elevated at resting state

120-129 mmHg systolic AND < 80 mmHg diastolic

Hypertension, stage 1 at resting state

130-139 mmHg systolic or 80-89 mmHg diastolic

Hypertension, stage 2 at resting state

≥ 140 systolic or ≥ 90 mmHg diastolic

Hypertension crisis, at resting state

> 180 systolic and/or >120 mmHg diastolic

Ocular Hypertension

greater than normal intraocular pressure does not necessarily mean there is systemic hypertension

Portal Hypertension

the elevation of blood pressure within the portal venous system

Which of the following is defined as systemic hypertension?

a. increase resistance in ocular artery

b. decrease cardiac output

c. blood pressure of 140/100

d. blood pressure of 110/75

Blood pressure of 140/100

Non-pharmacological therapy for hypertension (elevated)

1. reduction of body weight

2. healthy diet (DASH)

3. sodium restriction ( > 40 y.o. patient)

4. high-K+ diet

5. exercise / relaxation

6. reduce alcohol / nicotine / caffeine intake

Non-pharmacological therapy for hypertension has NO...

adverse effects and is cost effective

In pharmacologic therapy, _____ of the population does not have a response in drugs

- 1/3

Due to reflex, genetics, and lifestyle choice

Non-pharmacological therapy for the patients that respond to the drug may ___________ effectiveness of the drug

- increase

Reduction of body weight decreases blood pressure due to..

a decrease in blood volume.

In obesity, patient produces excessive insulin. Insulin increases Na+ reabsorption and causes increase volume expansion.

Which causes increase in cardiac output and blood pressure.

In obesity, patient produces ________ insulin. Insulin increases ______ _______ and causes __________ volume expansion.

- excessive

- Na+ reabsorption

- increase

Which causes increase in cardiac output and blood pressure.

DASH

Dietary

Approach to...

STOP

Hypertension

Low fat diet, fruits, and vegetables.

More vitamins and minerals to increase enzyme (NOS - nitric oxide synthase, produces nitric oxide) activity.

Nitric oxide causes vasodilation.

Hypertension in younger patients may be due to...

defects in adrenal gland / hormonal control

Sodium restriction is more appropriate in patients...

older than 40.

Sodium restriction reduces hypertension because...

Reduces body volume and decreases cardiac output and lowers blood pressure

Increase in K+ diet reduces hypertension because...

excretion of body Na+

Increased K+ diet should NOT be used in patents on...

ACE-Inhibitors or ARB

Exercise reduces hypertension because...

it increases ANP (atrial natriuretic peptide)

ANP mechanism of action

decrease catecholamines (e.g., epinephrine / dopamine), which causes a decrease in blood volume and peripheral resistance

Alcohol / nicotine / caffeine intake will only cause a ___________ in blood pressure

- spike

But it will normalize and thus, it will not have very much of an effect. Studies are still being done.

Obesity can induce hypertension through __________

a. insulin-induced expansion of extracellular volume

b. insulin-induced sympathetic nerve inhibition

c. enhancement of renal tubular Na+ secretion

d. inhibitor of renal tubular K+ secretion

Insulin induced expansion of extracellular volume

Diuresis

increased formation and secretion of urine volume (H2O excretion)

Natriuresis

increased renal sodium excretion

Diuretics are used to ___________ body volume

- decrease

In order to reduce blood pressure, this will also decrease sodium in the body.

5 Classes of Diuretics

Used to treat hypertension and other diseases:

- thiazide diuretics (most commonly used due to safety and efficacy)

- loop diuretics

- K+ - sparing diuretic

Not used to treat hypertension:

- carbonic anhydrase inhibitors

- osmotic diuretics

In general, preferred initial therapy for treatment of uncomplicated HTN is...

diuretics (usually thiazide diuretics) and CCB (calcium channel blocker)

In hypertensive crisis, we do not use...

diuretics because we need to immediately reduce the hypertension immediately.

Diuretics still need excretion to function.

The effectiveness of diuretics in hypertensive patient is reduced in _________.

a. pheochromocytoma

b. pulmonary edema

c. renal failure

d. stage 2 hypertension

Renal failure

Thiazides are not usually used in renal failure.

Hydrochlorothiazide Primary Site

Kidney (Na/Cl Symporter)

Thiazides block Na+ from entering the body during reabsorption and more Na+ leaves in the urine.

Hydrochlorothiazide Secondary Site

Vascular smooth muscle cells (blood vessels)

Hydrochlorothiazide activates Ca2+ -activated K+ channels

The mechanism of action of thiazide diuretics is to block.

a. Na/K/2Cl symporter

b. Na/Cl symporter

C. Na channel

D. mineralocorticoid receptor

Na/Cl symporter

Thiazide has ____________ side effects

- minimal (or none)

Especially in regard to reflexes, however decrease Na+ in body, INCREASES aldosterone in the body.

However, this is not a reflex but a long-term effect

Hypertensive Reflex

Short-term compensation in the body to adjust to changes in cardiac output or peripheral resistance to maintain blood pressure

Loop Diuretics are the ___________ __________ diuretics

- most potent

Loop diuretics are the highest capacity diuretics, especially if renal is abnormal

"High-ceiling"

For loop diuretics, there is a increase output of _______ and _____ in the urine

- Na+

- K+

Loop diuretics may cause electrolyte imbalance. Hypokalemia, hyponatremia, hypercholemia

Loop Diuretics Site of Action

Kidney: inhibits the activity of the Na/K/2Cl symporter

Potassium imbalance can cause...

arrhythmia (i.e., Loop diuretics can cause arrhythmia)

ACE-Inhibitors can ______________ body potassium

- increase

Loop diuretics and ACE-inhibitors are well known combinations in congestive heart failure because it neutralizes the potassium imbalance.

The mechanism of action of loop diuretics is __________

a. activate Na/Cl symporter

b. inhibit Na/K/2Cl symporter

c. activate Na channel

d. inhibit mineralocorticoid receptor

Inhibit Na/K/2Cl symporter

What are the potential side effects of Loop Diuretics due to electrolyte imbalance?

- Hypotension (due to hyponatremia)

- Heart Arrhythmia (due to hypokalemia)

- Metabolic Alkalosis (due to the loss of chloride which causes the reabsorption of bicarbonate)

What are the types of potassium sparing diuretics?

- Sodium channel inhibitors

- Mineralocorticoid receptor inhibitors

What drugs are considered sodium channel inhibitors?

- Triamterene (Midamor)

- Amiloride (Dyrenium)

What drugs are considered mineralocorticoid receptor inhibitors?

- Spironolactone (Aldactone)

- Eplerenone (Inspra)

What drugs are considered potassium sparing diuretics?

- Triamterene (Midamor)

- Amiloride (Dyrenium)

- Spironolactone (Aldactone)

- Eplerenone (Inspra)

What is the mechanism of action for Potassium Sparing Diuretics?

Inhibit the sodium channel and/or inhibit the mineralocorticoid receptor

What effects on potassium do Thiazides, Loops, and Potassium sparing drugs have on the body?

Thiazides decrease potassium in the body

Loop diuretics decrease (more potent than thiazide) potassium in the body

Potassium sparing increase potassium in the body

What effects on potassium do Diuretics and ACE inhibitors (or ARB) have on the body?

Diuretics decrease potassium in the body

ACE inhibitors (or ARB) increase potassium in the body

What combination of Thiazide drugs can be used together?

- Thiazide and ACE inhibitors (or ARB)

- Loop Diuretics and ACE inhibitors (or ARB)

Thiazide Diuretics Onset

4-6 weeks

Which one is not a side effect of Furosemide?

a. acidosis

b. hypochloremia

c. hypokalemia

d. hypotension

Acidosis

Furosemide can cause alkalosis

Which diuretic can magnify the risk of hyperkalemia when taken with an ACE inhibitor?

a. Bumetanide (BUMEX)

b. chlorthalidone (HYGROTON)

c. furosemide (LASIX)

d. triamterene (MIDAMOR)

Triamterene (Midamor)

Triamterene is the only potassium sparing diuretic out of the bunch.

Which of the following hypertensive therapy would most result in reflex vasoconstriction?

a. physical exercise

b. vasodilators

c. thiazides

d. beta-blockers

Beta-blockers

Physical exercise does not cause reflex due to the lack of side effects.

Vasodilators are part of peripheral resistance similar to vasoconstriction so reflex does not work that way for compensation.

Thiazides reflex would involve humoral control.

Thiazide Diuretics Drugs

Bendroflumethiazide (Naturetin)

Chlorthiazide (Diuril)

Hydrochlorothiazide (Hydrodiuril)

Hydroflumethiazide (Saluron)

Methylclothiazide (Enduron)

Polythiazide (RENESE)

Trichlormethiazide (NAQUA)

Chlorthalidone (Hygroton)

Indapamide (Lozol)

Metolazone (Mykrox, Zaroxolyn)

Quinemethazone (Hydromox)

Bendroflumethiazide

Naturetin

Chlorothiazide

Diuril

Hydrochlorothiazide

Hydrodiuril

Hydroflumethiazide

Saluron

Methyclothiazide

Enduron

Polythiazide

Renese

Trichlormethiazide

Naqua

Chlorthalidone

Hygroton

Indapamide

Lozol

Metolazone

Mykrox, Zaroxolyn

Quinethazone

Hydromox

Loop Diuretic Drugs

Furosemide (Lasix)

Bumetanide (Bumex)

Ethacrynic Acid (Edecrin)

Torsemide (Demadex)

Furosemide

Lasix

Bumetanide

Bumex

Ethacrynic acid

Edecrin

Torsemide

Demadex

Two Main Types of Potassium-Sparing Diuretics

1) Na Channel Inhibitors

2) Mineralocorticoid Receptor Inhibitors

Potassium Sparing Diuretics Drugs

Na Channel Inhibitors:

Triamterene (Midamor)

Amiloride (Dyrenium)

Mineralocorticoid Receptor Inhibitors:

Spironolactone (Aldactone)

Eplerenone (Inspra)

Triamterene

Midamor

Amiloride

Dyrenium

Spironolactone

Aldactone

Eplerenone

Inspra