Medications for HTN and HF

Question 1

What are the main goals for treating HF?

Answer 1

Reduce the workload of the heart while still improving CO

Reduce remodeling

Increase contractility

Improve symptoms and quality of life

Question 2

Diuretics MOA

Answer 2

Mobilize fluids

Block sodium and chloride reabsorption in the kidney –> prevention of passive reabsorption of water –> excretion of sodium, chloride, and water

DIURESIS (bc water follows sodium)

Question 3

What are the different classes of diuretics? Where do they act on?

Answer 3

Loop
- Thick ascending limb of the LOH (furosemide)

Thiazides
- Early DCT (hydrochlorothiazide)

Potassium-sparing
- Late DCT (spironolactone)

Question 4

How does the site of action affect the strength of the effect of diuretics?

Answer 4

The greater % of sodium reabsorption at the site = greater effect

EXAMPLE: Loop diuretics (furosemide) act on the ascending limb of the LOH which has 20% sodium reabsorption compared to 10% for thiazide in the early DCT

Question 5

Loop Diuretics MOA

Answer 5

Block Na+/K+/2Cl- symporter in the TAL of the LOH

Results in an increased excretion of NaCl –> increased diuresis

Question 6

Thiazide Diuretics MOA

Answer 6

Block Na+/Cl- symporter in the early DCT

Results in increased NaCl excretion –> diuresis

Question 7

Potassium-Sparing Diuretics MOA

Answer 7

Block the actions of aldosterone (which normally acts to retain sodium and water) in the late DCT and collecting duct

Promotes the excretion of sodium and retention of potassium –> increased diuresis

Question 8

What are the effects of angiotensin II?

Answer 8

Vasoconstriction –> increases SVR

Promotes reabsorption of Na+ and H2O

Increased NE release –> B1 receptor activation

Heart remodeling (hypertrophy)

Aldosterone release

Vasopressin thirst reflex

Question 9

ACE Inhibitors MOA

Answer 9

Blocks the conversion of angiotensin I to angiotensin II

Decreases angiotensin II, increases bradykinin

Some vasodilation, ACEI cough, angioedema

Question 10

Why are ACEIs and ARBs contraindicated in bilateral renal artery stenosis and other low renal blood flow conditions?

Answer 10

Blocking angiotensin II in pt. with these conditions can cause acute renal failure

They already have low GFR, blocking angiotensin II will not allow the EA to vasoconstrict, resulting in a continued low GFR

Question 11

Alpha-1 Receptor location and response to its activation

Answer 11

Arterioles & veins

Constriction of both

Question 12

Alpha-2 Receptor location and response to its activation

Answer 12

Presynaptic nerve terminals in the brain

Inhibition of norepinephrine release

Question 13

Beta-1 Receptor location and response to its activation

Answer 13

Heart –> increased HR, contractility, AV conduction velocity

Kidneys –> Renin release

Question 14

Beta-2 Receptor location and response to its activation

Answer 14

Arterioles in the heart, airways, skeletal muscle

Dilation

Question 15

What is doing most of the work when alpha-adrenergic receptors are activated on vascular smooth muscle (VSM)?

Answer 15

Calcium

Leads to VSM contraction

Question 16

How do alpha-2 agonists work?

Answer 16

Inhibit NE release

This leads to less activation of adrenergic receptors on blood vessels and the heart

Indirect-acting

Question 17

Describe what B1 receptor activation results in:

Answer 17

Activation in the heart leads to increased cAMP in cardiac muscle –> increased Ca++ leading to:

Increased HR, speed of conduction, and force of contraction

Question 18

You would expect an alpha-1 blocker to have what effect on vascular smooth muscle?

Answer 18

Relaxation

Question 19

What effect would a beta-1 blocker have on HR, conduction velocity, and force of contraction?

Answer 19

Slow it down and reduce it

Question 20

What would you expect a beta-blockade in the heart to do to the workload of the heart? To its oxygen demand?

Answer 20

Decrease workload

Decrease oxygen demand

Question 21

What is the difference between nonselective and cardioselective beta blockers?

Answer 21

Nonselective block both beta-1 and beta-2 receptors; they may interfere with beta-2 agonists used in asthma and COPD

Cardioselective: selective for beta-1 receptors

Question 22

An increase in selectivity results in:
Why?

Answer 22

Less adverse effects

No interference with multiple receptors

Question 23

Calcium Channel Blockers MOA

Answer 23

Vasodilate peripheral and coronary vessels

May slow HR and reduce cardiac conduction

Question 24

Dihydropyridines vs. Non-dihydropyridines

Answer 24

Dihydropyridines
- Act primarily on VSM
- Potent vasodilation with reflex tachycardia (baroreceptor)
- Produce no change in cardiac conduction when given at therapeutic doses

Non-Dihydropyridines
- Act on VSM and the heart
- Vasodilator
- Decrease AV node and SA node conduction, inotropy (force of contraction), chronotropy (rate)
- NOT used in HF bc can lower the heart’s function too much

Question 25

What do organic nitrates act on?

Answer 25

Organic nitrates act on veins not arterioles

Question 26

Why do we care about HYPOtension? What problems accompany hypotension?

Answer 26

Worried about organ perfusion

Affects organ function