CCBs

Question 1

What are the uses of CCBs?

Answer 1

• angina
• HTN
• supraventricular arrhythmias (a fib, a flutter, paroxysmal SVT)

Question 2

How does calcium initiate contraction in the heart? Smooth muscle?

Answer 2

Heart- binding to troponin C reduces the inhibition of actin-myosin cross-bridges

SM- binding to calmodulin activates MLCk, which phosphorylates myosin and triggers contraction

Question 3

Where do CCBs act specifically?

Answer 3

L-type voltage dependent, slowly inactivated Ca2+ channels. Other channels and regulators of calcium throughout the body (especially nerves (N and P type channels) are not affected by this process, this giving these drugs specificity)

Question 4

Describe the smooth muscle contraction in vasculature.

Answer 4

graded, Ca2+ dependent through L-type channels

slow and sustained

Question 5

Describe the smooth muscle contraction in the heart.

Answer 5

rely on L-type channels for contractile cells (atria, ventricles) AND slow response (SA, AV) cells

Question 6

What are the effects of CCBs?

Answer 6

increase the time L-type channels are closed reducing the magnitude of current (all) and slow the recovery of the channel (non-dihydropyridines)

relax ARTERIAL but not venous smooth muscle (reduce afterload not preload)

Question 7

What are the main effects of dihydropyridine CCBs?

Answer 7

arterial and coronary vasodilation (may increase reflex tachycardia and contractility)

Question 8

What are the main effects of non-dihydropyridine CCBs?

Answer 8

act on cardiac and smooth muscle- arterial and coronary vasodilation and reduce HR and contractility (SA and AV node reduced)

Question 9

What is the difference in the way NDHP and DHP CCBs act?

Answer 9

NDHPs bind to channels in a use-dependent way (channels that constantly open and close)

DHPs bind in a voltage-dependent way and prefer smooth muscle because their voltage changes very slowly

Question 10

Absorption and elimination of CCBs?

Answer 10

extensive first-pass and hepatic metabolism via CYP3A4 eliminates (also CYP3A4 inhibitors)

Question 11

Adverse effects of DHPs?

Answer 11

• excessive vasodilation
• GI pain
• peripheral edema
• paradoxical exacerbation of angina (coronary steal)- less with new slow-release reparations
• fetotoxic

Question 12

Adverse effects of NDHPs?

Answer 12

• bradycardia, asystole, AV block
• hypotension, peripheral edema
• constipation (verapamil only)
• CHF worsening (verapamil only)

-fetotoxic both

Never combine with a BB

Question 13

What is coronary steal?

Answer 13

when massive vasodilation occurs during an MI event, it can steal perfusion from the myocardium

Question 14

CYP3A4 inhibitors?

Answer 14

• grapefruit
• AZOLES
• cimetidine
• erythromycin
• NDHP CCBs

increase NDHP CCB effect

Question 15

CYP3A4 inducers?

Answer 15

-rifampin

decrease NDHP CCB effect

Question 16

Which CCBs have the most side effects?

Answer 16

DHP more than NDHPs (verapamil more than diltiazem in just about everything except hypotension and peripheral edema-same)