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Flashcards in Vasodilators and CCBs Deck (26):
1

Angina

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

2

Myocardial oxygen demand based on which 3 things

Wall stress, heart rate, contractility

3

Wall stress is based on

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

4

Drugs used for angina -- 3 main categories

Vasodilators, Cardiac depressants, other.

VD: Nitrates, calcium blockers

Cardiac Depressants: calcium blockers, beta blockers

Other: Metabolism modifiers, rate inhibitors

5

3 Nitrate drugs

Nitroglycerin
Isosorbide Dinitrate
Nitroprusside

6

Mechanism of Action of nitrates

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.

7

How do nitrates decrease angina?

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.

8

Secondary mechanism of nitrates

Increase coronary blood flow into ischemic areas by collateral vessels.

9

Side effect of nitrates?

Reduction in BP can cause reflex tachycardia.

Headache due to dilation of MMA

Orthostatic hypertension

10

What is nitroprusside used for?

Hypertensive emergencies because given IV.

11

Dont use nitrates with?

PDE5 inhibitors like sildenafil, can cause profound hypertension.

12

PK of nitroprusside

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

13

Nitrate tolerance

Tachyphylaxis. Mechanism misunderstood, but requires drug free intervals.

14

Two types of CCBs

Dihydropyridines (amlodipine and nifedipine)
Non-dihydropyridines (diltiazem and verapimil)

15

Dihydropyridines and mechanism of action

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

16

Non-dihydropyridines

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.

17

Mechanism of action for CCBs

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

18

Do CCBs interfere with neurotransmission/hormone release?

No. Different type of channels.

19

Side effects of Dihydropyridines

Nifedipine has reflex tachycardia, amlodipine less so.

20

What are CCBs used for?

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

21

Adverse effects of CCBs as a group

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

22

Side effects of non-dihydropyridines

Can exacerbate CHF

23

Other vasodilators not used for angina

Hydralazine and Minoxidil

24

Hydralazine

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

25

Minoxidil

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.

26

Minoxidil side effects

Hypotension
Reflex tachy
Edema
Hypertrichosis! Increased hair growth.