Medications for HTN and HF Flashcards
What are the main goals for treating HF?
Reduce the workload of the heart while still improving CO
Reduce remodeling
Increase contractility
Improve symptoms and quality of life
Diuretics MOA
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)
What are the different classes of diuretics? Where do they act on?
Loop
- Thick ascending limb of the LOH (furosemide)
Thiazides
- Early DCT (hydrochlorothiazide)
Potassium-sparing
- Late DCT (spironolactone)
How does the site of action affect the strength of the effect of diuretics?
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
Loop Diuretics MOA
Block Na+/K+/2Cl- symporter in the TAL of the LOH
Results in an increased excretion of NaCl –> increased diuresis
Thiazide Diuretics MOA
Block Na+/Cl- symporter in the early DCT
Results in increased NaCl excretion –> diuresis
Potassium-Sparing Diuretics MOA
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
What are the effects of angiotensin II?
Vasoconstriction –> increases SVR
Promotes reabsorption of Na+ and H2O
Increased NE release –> B1 receptor activation
Heart remodeling (hypertrophy)
Aldosterone release
Vasopressin thirst reflex
ACE Inhibitors MOA
Blocks the conversion of angiotensin I to angiotensin II
Decreases angiotensin II, increases bradykinin
Some vasodilation, ACEI cough, angioedema
Why are ACEIs and ARBs contraindicated in bilateral renal artery stenosis and other low renal blood flow conditions?
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
Alpha-1 Receptor location and response to its activation
Arterioles & veins
Constriction of both
Alpha-2 Receptor location and response to its activation
Presynaptic nerve terminals in the brain
Inhibition of norepinephrine release
Beta-1 Receptor location and response to its activation
Heart –> increased HR, contractility, AV conduction velocity
Kidneys –> Renin release
Beta-2 Receptor location and response to its activation
Arterioles in the heart, airways, skeletal muscle
Dilation
What is doing most of the work when alpha-adrenergic receptors are activated on vascular smooth muscle (VSM)?
Calcium
Leads to VSM contraction
How do alpha-2 agonists work?
Inhibit NE release
This leads to less activation of adrenergic receptors on blood vessels and the heart
Indirect-acting
Describe what B1 receptor activation results in:
Activation in the heart leads to increased cAMP in cardiac muscle –> increased Ca++ leading to:
Increased HR, speed of conduction, and force of contraction
You would expect an alpha-1 blocker to have what effect on vascular smooth muscle?
Relaxation
What effect would a beta-1 blocker have on HR, conduction velocity, and force of contraction?
Slow it down and reduce it
What would you expect a beta-blockade in the heart to do to the workload of the heart? To its oxygen demand?
Decrease workload
Decrease oxygen demand
What is the difference between nonselective and cardioselective beta blockers?
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
An increase in selectivity results in:
Why?
Less adverse effects
No interference with multiple receptors
Calcium Channel Blockers MOA
Vasodilate peripheral and coronary vessels
May slow HR and reduce cardiac conduction
Dihydropyridines vs. Non-dihydropyridines
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
