Vasodilators and CCBs

Question 1

Angina

Answer 1

Retrosternal pain caused by cardiac ischemia. Treat by reducing myocardial oxygen requirement or increasing myocardial oxygen demand.

Question 2

Myocardial oxygen demand based on which 3 things

Answer 2

Wall stress, heart rate, contractility

Question 3

Wall stress is based on

Answer 3

Pressure (afterload and preload), volume (preload), ventriclar wall thickness

Question 4

Drugs used for angina – 3 main categories

Answer 4

Vasodilators, Cardiac depressants, other.

VD: Nitrates, calcium blockers

Cardiac Depressants: calcium blockers, beta blockers

Other: Metabolism modifiers, rate inhibitors

Question 5

3 Nitrate drugs

Answer 5

Nitroglycerin
Isosorbide Dinitrate
Nitroprusside

Question 6

Mechanism of Action of nitrates

Answer 6

Endothelial cells release nitric oxide which stimulates cGMP in vascular smooth muscle cells. cGMP increases GC, which dephosphorylates myosin light chains causing relaxation. Nitrates stimulate NO.

Question 7

How do nitrates decrease angina?

Answer 7

By decreasing myocardial O2 demand by dilating veins >arteries>arterioles. Venodilation decreases preload, which reduces wall stress. Artery dilation increases blood flow through partially occluded epicardial coronary vessels and decreases afterload.

Question 8

Secondary mechanism of nitrates

Answer 8

Increase coronary blood flow into ischemic areas by collateral vessels.

Question 9

Side effect of nitrates?

Answer 9

Reduction in BP can cause reflex tachycardia.

Headache due to dilation of MMA

Orthostatic hypertension

Question 10

What is nitroprusside used for?

Answer 10

Hypertensive emergencies because given IV.

Question 11

Dont use nitrates with?

Answer 11

PDE5 inhibitors like sildenafil, can cause profound hypertension.

Question 12

PK of nitroprusside

Answer 12

Metabolism in RBCs creates cyanide. Long term use can cause cyanide poisoning, especially w/ renal failure.

Question 13

Nitrate tolerance

Answer 13

Tachyphylaxis. Mechanism misunderstood, but requires drug free intervals.

Question 14

Two types of CCBs

Answer 14

Dihydropyridines (amlodipine and nifedipine)

Non-dihydropyridines (diltiazem and verapimil)

Question 15

Dihydropyridines and mechanism of action

Answer 15

Amlodipine and nifedipine. Relax smooth muscle more in BVs more than cardiac. Mostly vasodilation of arterioles and arteries. So afterload reduction, not preload.

Question 16

Non-dihydropyridines

Answer 16

Diltiazem and verapimil. More potent on cardiac L-types Ca channels. Decrease cardiac contractility, decrease heart rate by decreasing AV node conduction and SA node conduction.

Question 17

Mechanism of action for CCBs

Answer 17

Block VG L-type calcium channels, which are most important channels in cardiac/smooth muscle. For vascular smooth muscle: calcium enters, binds to calmodulin.

Question 18

Do CCBs interfere with neurotransmission/hormone release?

Answer 18

No. Different type of channels.

Question 19

Side effects of Dihydropyridines

Answer 19

Nifedipine has reflex tachycardia, amlodipine less so.

Question 20

What are CCBs used for?

Answer 20

Angina, Hypertension, SVT and afib (for diltiazem and verapemil)

Question 21

Adverse effects of CCBs as a group

Answer 21

Hypotension, edema (stimulates RAAS, aldosterone causes water and salt retension), constipation.

Question 22

Side effects of non-dihydropyridines

Answer 22

Can exacerbate CHF

Question 23

Other vasodilators not used for angina

Answer 23

Hydralazine and Minoxidil

Question 24

Hydralazine

Answer 24

Vasodilator that dilates arterioles but not veins. Decreases afterload. Used in hypertension and CHF. Can cause reflex tachycardia and lupus-like syndrome.

Question 25

Minoxidil

Answer 25

Opens ATP-dependent K channels in arterioles. Used for HTN.

Dilates arterioles, not veins.

This works because K exiting smooth muscle in arterioles hyperpolarizes the cell. VG ca channels then become inactive, so less calcium in, less Ca Calmodulin phosphorylation of MLCK, less P of MLC, less contraction.

Question 26

Minoxidil side effects

Answer 26

Hypotension
Reflex tachy
Edema
Hypertrichosis! Increased hair growth.