Week 5: HTN and dyslipidemia

Question 1

What is the equation for cardiac output

Answer 1

CO= HR x SV

Question 2

What is HR controlled by?

Answer 2

Autonomic nervous system; rate increased by SNS acting through B1 receptors on SA node. Rate is decreased by PNS acting through muscarinic receptors in the SA node.

Question 3

What is stroke volume controlled by?

Answer 3

Myocardial contractility, afterload, preload

Question 4

What is the starling law of the heart?

Answer 4

Force of ventricular contraction is proportional to muscle fiber length up to a certain point). As fiber length (Vent diameter) increases, there is a corresponding increase in contractile force. The more blood that enters the heart, the more is pumped out.

Question 5

What is the formula for arterial pressure?

Answer 5

Arterial pressure= peripheral resistance x cardiac output

Question 6

What is arterial pressure controlled by?

Answer 6

the ANS, RAAS, the kidneys, and natriuretic peptides (natriuretic peptides only come into play under conditions of volume overload)

Question 7

Which of these systems controlling arterial pressure is fastest? Slowest?

Answer 7

ANS is fastest (responds in seconds or minutes to acute changes in BP); RAAS takes hours to days; kidneys take days to weeks

Question 8

Describe why we need to consider the baroreceptor reflex when giving drugs that lower arterial pressure

Answer 8

Lowered bp is sensed by baroreceptors, which activates the baroreceptor reflex, triggering SNS to increase HR, contractility. This causes reflex tachycardia. (concerning if we are worried about causing increased myocardial o2 demand; can temporarily negate efforts to lower AP with drugs).

Question 9

Can the baroreceptor reflex system be reset?

Answer 9

Yes- will reset to new pressure in 1-2 days.

Question 10

How do reductions in arterial pressure impact the kidneys?

Answer 10

Low AP > decreased renal blood flow > decreased renal filtration> more water retained, RAAS also activated bc of decreased renal perfusion. This results in increasing levels of Ang II and aldosterone, which causes vasoconstriction, retention of sodium and water to increase blood volume, which increases venous return/ preload, which increases CO and consequently arterial pressure.

Question 11

What drugs can result in postural hypotension? Why?

Answer 11

Drugs that interfere with venous constriction, as venous pooling is increased, reducing return of blood to heart > reduced preload> reduced CO

Question 12

When are natriuretic peptides released? What is their purpose

Answer 12

Released in response to stretching of atria (ANP), ventricles (BNP), and blood vessels (CNP) due to volume overload. Shift fluid from vascular system to extravascular compartment (by increasing vascular permeability) and act on kidney to cause diuresis and natriuresis (loss of sodium). Also cause dilation of arterioles and veins, in part suppressing SNS outflow. Help protect the heart in early stages of HF.

Question 13

What do CCBS do? Where are their greatest effects? What are they used to treat?

Answer 13

-prevent calcium ions from entering cells
-greatest effect in heart and blood vessels
-used in treatment of HTN, angina, and dysrhythmias

Question 14

What does calcium do in the vascular smooth muscle? What do CCBs do?

Answer 14

Calcium- regulates contraction of VSM (vasoconstriction)
CCB- act on peripheral arterioles (dilation, decreased arterial pressure), arteries and arterioles of heart (dilation, increased coronary perfusion)

Question 15

What does calcium do in the myocardium? What do CCBs do?

Answer 15

Calcium- positive inotropic effect.
CCB- if ca channels are blocked, heart contractile force decreased

Question 16

What does calcium do in the SA and AV node? CCBs?

Answer 16

Calcium influx regulates pacemaker activity in the SA node and impulse conduction in the AV node.
CCB- if calcium channels are blocked, heart rate and A>V conduction will be reduced.

Question 17

It seems like CCB have similar effects to beta blockers. Why?

Answer 17

Cardiac calcium channels are coupled to beta receptors in the heart. When beta receptors are activated, calcium influx with enhanced. When beta receptors are blocked, calcium influx is suppressed. So yes, CCB and beta blockers have identical effects on the heart- they both decrease force of contraction, slow HR, and suppress conduction through the AV node.

Question 18

What are the two types of CCBs? How do they differ?

Answer 18

Nondihydropyrimidines (verapamil) affect the blood vessels AND heart
Dihydropridines (nifedipine) affect mainly the blood vessels.

Question 19

Describe the hemodynamic effects of verapamil, a nondihydropyrimidine

Answer 19

Blocks calcium channels in the heart and the blood vessels (arterial dilation, increased coronary perfusion, reduced HR, reduced contractility). This results in lower blood pressure. However, the baroreceptor reflex kicks in to increased HR, AV conduction, and force of contraction. Net effect is little effect on cardiac performance (for most patients) and vasodilation with decreased arterial pressure and improved coronary perfusion

Question 20

Pharmacokinetics of verapamil

Answer 20

Oral of IV, first pass metabolism by liver, effects begin in 30 min and peak in 5 hours. Hepatic metabolism (reduce doses in pt with hepatic impairment)

Question 21

Uses of verapamil

Answer 21

angina, htn, dysrhythmias (aflutter, afib, paroxysmal svt)

Question 22

Adverse effects of verapamil/ food and drug interactions to be aware of

Answer 22

Can cause constipation. Can cause dizziness, facial flushing, HA, edema from vasodilation. Can compromised cardiac function- contraindicated in pts with hypotension, sick sinus, 2nd or 3rd degree AVB.
Caution with beta blockers (same effects on heart), grapefruit juice (can inhibit metabolism) and digoxin (increases risk for AVB)

Question 23

Briefly describe diltiazem- MOA, pharmacokinetics, and adverse effects

Answer 23

MOA- CCB affecting the heart and blood vessels; lowers BP through arterial dilation. Used for HTN, angina, dysrhythmias. Can be given orally. Complete hepatic metabolism, eliminated in urine and feces.
Adverse effects- less constipation than verapamil. Dizziness, flushing, HA, pedal edema from dilation. Can exaccerbate cardiac dysfunction in patients with bradycardia, sick sinus, AVB (2nd or 3rd degree). Interacts with digoxin, beta blockers.

Question 24

Nifedipine is a prototype drug for the dihydropyridines. What is its mechanism of action?

Answer 24

Blocks CCB in VSM, promoting vasodilation. Does not block calcium channels in heart (unlike verapamil and diltiazem), so cannot be used for dysrhythmias, does not cause cardiac suppression, and is less likely to exaccerbate cardiac disorders. More likely to cause reflex tachycardia.

Lowers arterial pressure, activating baroreceptor reflex, causing sympathetic stimulation of heart. Because it does not have cardio suppressant actions, this stimulation is unopposed. Net effects are lower BP, increased HR, increased contractile force.

Question 25

Does reflex tachycardia occur in both IR and SR formulations? Is one better than the other?

Answer 25

More likely to occur with IR. Increases myocardial O2 demand and can worsen angina :( therefore SR is preferred.

Question 26

Pharmacokinetics of nifedipine

Answer 26

Well absorbed after oral admin, undergoes first pass metabolism. Fully metabolized and excreted in urine.

Question 27

Therapeutic uses nifedipine

Answer 27

Angina WITH A BETA BLOCKER to prevent reflex stimulation of the heart
HTN (use SR)