L13

Question 1

What are 2 direct vasodilator drugs

Answer 1

Hydralazine

Minoxidil

Question 2

When do you use hydralizine

Answer 2

HFail

Acute, severe HTN

Question 3

What drugs must you combine these direct vasodilators with?

Answer 3

Diuretic = combat ↑renin

BB (sympatholytic) = stop reflex tachycardia

Question 4

SE of hydralazine

Answer 4

Lupus-like syndrome

Esp for pts with liver disease aka “slow acetylators” since hydralazine inactivated in liver

Question 5

Where is minoxidil activated?

Answer 5

Liver via sulfonation

Question 6

How do direct vasodilators vasodilate?

Answer 6

Hydralazine = ↑cGMP
Minoxidil = open Katp channels

Question 7

Net effect of vasodilators

Answer 7

↓afterload

Question 8

What is pseudo-tolerance in relation to direct vasodilators?

Answer 8

Get temp ↓BP

BP rebounds due to sympa reflex response: ↑HR + ↑renin

Question 9

What 3 tissues should you remember contain Katp channels? What determines the channel’s tissue specificity?

Answer 9

Heart
Vasc smooth muscle
Pancreatic B cells
Isoform = tissue specificity

Question 10

Normal fxn Katp channels

Answer 10

Couples metabolic state of cell to its electrical activity

Question 11

3 drugs that open Katp channels

Answer 11

Minoxidil
Diazoxide
Adenosine

Question 12

Minoxidil is tissue specific for… + drug use

Answer 12

Vasc smooth muscle - vasodilator to ↓BP

Anti-HTN

Question 13

Diazoxide is tissue specific for… + drug use

Answer 13

Pancreas - ↓insulin release

Hypoglycemia or hyperinsulinemia

Question 14

Adenosine is tissue specific for + drug use

Answer 14

Cardiac = A1 receptor = anti-arrhymthic

Vasc smooth muscle = A2 receptor = dilator

Question 15

Explain Katp channels in heart under ↓ATP

Answer 15

Hypoxia/E depletion = ↓ATP = ↑ADP
Avail adenosine binds A1 receptors
Katp channels open –> hyperpol membrane
NET = shorter AP, ↓contractility

Question 16

Explain Katp channel in vasc smooth muscle under ↓ATP

Answer 16

Baseline vasc smooth muscle = tonically contracted
↓ATP –> open Katp
↑K+ in, ↓Ca2+ in via voltage Ca2+ channels
Hyperpol –> relaxation = vasodilation

Question 17

How does adenosine act as vasc smooth muscle?

Answer 17

↓ATP = ↑ADP = ↑adenosine + A2 receptor - helps open Katp channels

Question 18

What are 2 parts of the Katp channel in pancreatic B cells

Answer 18

SUR1 & Kir 6.2

Question 19

Explain ↓blood glucose result on Katp channels in pancreas

Answer 19

↓BG –> ↓ATP –> Katp opens –> hyperpol –> ↓insulin release

Question 20

Where does diazoxide binds the Katp channel in pancreas

Answer 20

SUR1 to open channel

Question 21

Where does sulfonylurea bind the Katp channel in pancreas - does it open or close the receptor?

Answer 21

SUR1 to close channel

Question 22

What is the action of ATP and MgADP on the Katp channel in the pancreas? Where does each bind?

Answer 22

ATP closes via Kir 6.2

MgADP opens via SUR 1

Question 23

How does a gain of function Katp mutation present? Treat

Answer 23

Neonatal diabetes (↓insulin)
\+ Sulfonylurea

Question 24

How does a loss of fxn Katp mutation present? Treat

Answer 24

Neonatal hyperinsulinemia

Diazoxide

Question 25

What is the cardioprotective mechanism of adenosine & diazoxide

Answer 25

Open cardiac MITOCHONDRIAL Katp channels

Question 26

What is ischemic pre-conditioning

Answer 26

Post short-term coronary artery occlusion
Change myocyte fxn of tissue affected by occlusion + abnormal wall motion of normal myocardium
After reperfusion during “stunned” period, protected from long duration occlusions that are v damaging

Question 27

What is the acute phase of ischemic preconditioning

Answer 27

Katp open - including mitochondrial Katp channels

Important to maintain mito fxn

Question 28

What is the delayed phase of ischemic preconditioning

Answer 28

RISKinases turn on genes for protective proteins –> ↑transcription of these

Question 29

Which during do you give during ischemic preconditiong, why?

Answer 29

ADENOSINE
Binds A1 receptor to help open Katp channels
- Mitochondial fxn
- ↓HR & contractility 
Binds A2 - vasodilation

Question 30

What is ischemic post-conditioning

Answer 30

Short periods of ischemia during reperfusion can be beneficial b/c limit extent of damage

Question 31

What is remote pre/post conditioning

Answer 31

Transient ischemia of some pt of body (arm)
Liberates an unknown effector
Induces remote cell adaptation to an ischemia that isn’t happening to it - get protection w/o damage

Question 32

Which drug do you give during stress tests

Answer 32

Adenosine