Calcium Channel Blockers

Question 1

What are the first line agents for hypertension treatment?

Answer 1

Diuretics, ACE inhibitors, ARBs, Calcium channel blockers

Question 2

Which calcium channel blockers are Non dihydropyridines?

Answer 2

Verapamil, diltiazem, bepridill, and diphenylpiperazines

Question 3

What is the suffix for dihydropyridines?

Answer 3

Pine

Question 4

Whats the significance of the dihydropyridine stuff?

Answer 4

Some have a dihydropyridine ring, which makes them more selective for vascular tissue. The nondihydropyradines are not selective for vascular tissue, therefore they work on cardiac muscle as well

Question 5

What is calcium channel blockers MOA?

Answer 5

Reduction of calcium influx into the vascular smooth muscle by blocking L-type calcium channels, reducing activation of MLCK. This causes a negative inotropic effect

It also has similar blocking at pacemaker cells, causing slowing of conduction, making it have a negative chronotropic effect as well

Question 6

What are the dihydropyridines selective for?

Answer 6

Vascular smooth muscle

Question 7

What makes cardiac muscle contraction different from vascular smooth muscle?

Answer 7

Cardiac has calcium induced calcium release.

Most of the effects on cardiac contraction comes from within the SR INSIDE the cell

Question 8

So what are the two main CCB that effect cardiac muscle?

Answer 8

Verapamil and diltiazem

Question 9

Do dihydropyridines and non dihydropyridines bind to the same site?

Answer 9

NNOOO

Question 10

Why doesn’t non dihydropyridines affect smooth muscle as well as cardiac?

Answer 10

Psych. It does. At therapeutic doses, verapamil and diltiazem will affect both smooth and cardiac muscle

Question 11

What do all CCB do to vascular smooth muscle? Causing what?

Answer 11

Relax ARTERIAL smooth muscle, causing vasodilation and a reduction in TPR and afterload

Note- It does not effect venous system, so no effects on preload

Question 12

What are all the CCB effects on coronary vascular resistance?

Answer 12

Increase coronary blood flow

Question 13

Are dihydropyradines or non dihydropyradines more potent arterial vasodilators?

Answer 13

Dihydropyradines

Question 14

What is the cardiac response to dihydropyradines?

Answer 14

Increased HR due to increased sympathetic outflow

Question 15

How well are CCB absobed?

Answer 15

Pretty good, but significant first pass effect

Question 16

What are all CCB substrates of? In other words, what metabolized it?

Answer 16

CYP450 and CYP3A4

make sure to adjust doses for liver patients

Question 17

What are the ADEs for CCB?

Answer 17

Hypotension
Bradycardia (only verapamil and diltiazem)
GI-constipation and GERD (r/t L type channels being in there)

Question 18

If a drug is a substrate for P450 is also a substrate for _____

Answer 18

P-glycoprotein mediated interactions

Question 19

Why does it matter that CCB are P-glycoprotein mediated substrates?

Answer 19

PGP are multidrug resistant. They pump out drugs that get into the cell as a protective mechanism. Verapamil can inhibit this pump. By doing this, drugs stay inside the cell and get absorbed. So they can potentially increase drug concentrations by inhibiting PGP

Question 20

How does CCB affect hypertension?

Answer 20

Reduces peripheral resistance and blood pressure

Question 21

What is other uses for CCB?

Answer 21

Variant angina (prinzmetals angina)- Spasms
Stable angina- It reduces myocardial oxygen usage, making the hearts work easier
Unstable angina
MI
Arrhythmias
SAH
Migraines-vasospasms

Question 22

Can dihydropyradines treat angina by itself? Why or why not?

Answer 22

They lead to an increase in sympathetic outflow that can aggravate angina. Need to use nondyhdropyradines

Question 23

What are the two things to know about clevidipine?

Answer 23

Its a dihydropyridine and has a half life of 15 minutes