Acute vs. Chronic:

Clinical manifestations depend on what two factors?

1. rate at which the syndrome develops

2. duration of the disease

anatomical abnormality develops gradually or develops following survial of acuteHF

- adaptive mechanisms

pulmonary edema is frequent in these types of HF

rare in this type:

acute and decompensated

rare: chronic

peripheral edema is rare in this type of HF:

frequent in these types:

acute (rare)

decompensated and chronic (frequent)

1. convenient pk

2. alternative routes of administration

3. widespread availability of serum drug level measurements

inhibits the Na/K ATpase pump

reversibly binds to a subunit of the Na/K ATPase on the extracellular surface of cardiac cells

increased the availability of intracellular calcium

calcium enters through voltage depenent calcium channels (l-type) on cell membrane

Once inside, calcium triggers release ofmore Calcium from SR stores 

During repolarizationi and relaxation, what removes the majority of intracellular calcium?

what is the minor contributor?

majority = Ca-ATPase SERCA removes calcium from cytosol to SR

less calcium is removed from cytosol through the Na/Ca exchanger on the cell membrane

What is the Na/Ca exchanger dependent on?

what is is indirectly depenendent on?

relies intracellular sodium concentration to drive exchange

indirectly dependent on the Na/K ATP ase 

• reduces concentration gradient for Na/Ca exhanger
• in the re-polarized state (calcium out, sodium in), less calcium is extruded from the cell
• high intracellular Na may activate the na/Ca exhanger

What two sites get the effects of cAMP?

How does camp activate that causes increased activatioin?

L- type CA channel

Ca ATP ase pump on SR

cAMP activates PKA which phosphorylates the Ca channel or SERCA, for increasing activation

increased cystolic calcium during systole, which:

- increases the velocity and extent of sarcomere shortening

- increases systolic function

The baroreflex afferent signaling utilizes Na/K ATPase 

Under non heart failure conditions: 

inhibitory (non-stim) inputs from arterial and cariopulmonary baroreceptor afferent nerves dominate

During HF: the inhibitory input decreases 

See diagrams...

In breif, doses in the therapeutic range:

____ SNS activity

______ PNS activity

decrease SNS activity

increases PNS activity

regulations of baroreceptor sensitivity

(this is an important benefit of these drugs)

directly stimulates vagal nuclei in the brain, hence increased parasympathetic outflow

decreases conduction velocity in the heart and prolongs the refractory period of pacemaker cells 

toxicity occurs from altering peripheral NS

- SNS activity: increases dramatically (opposite therapeutic dose)

- PNS activity: markedly increases

sinus bradycardia, and possible heart block 

High intracellular calcium in a conducting cell, increases ___A________ of pacemaker cells

This may produce ventricular _____B______ or ______C________ from toxicty at pacemaker and conducting cells of heart

A: automaticity

B: tachycardia

C: fibrillation

What is a low dose of dopamine?

What two receptors does it stimulate and causes dilation of renal vessels?

0.5 - 3 mcg/kgLBW/min

D1 and D2

- the stimulation of the renal vessles causes an increase in GFR, natriuresis, diuresis which is useful in patients refractory to diuretics

How do you get the positive inotropic effect of dopamine?

What receptor is responsible for this effect?

1. dose of 3-10 mcg/kg/LBW/min 

2. beta 1 in the heart

Name this drug:

I am a direct-acting sympathomimetic, administered CI IV infusion. 

I stimulate beta1, b2, and alpha adernergic receptors. 

vasodilation produced by beta 2 activation

Therefore, modest decrease in systemic vascular resistance

Summary of receptor selectivity of adernergic agents.

I'll give the summary and you name that drug...woohoo.

 Α1=B1>>B2,DA

(no beta 2 or DA)

 A1=B1>B2>>DA

(no DA)

 DA = B1>A1>B

 Β1=B2>>A1,D

no alpha 1 or dopamine

 B1>B2>A1>>DA

zero DA, very little alpha 1

inhibit PDE type 3. 

PDE is responsible for the breakdown of cAMP.  If you block the breakdown in the heart, then the increased cAMP level causes increased intracellular calcium

This increase in storage of calcium, means more can be released during systole which increases contractile protein interactions

first of a novel class of iontropes:

sensitizes torponinC in myofibrils to intracellular calcium ions

does not increase calcium concentrations

increases the force of cardiac muscle contractions