L13 Flashcards

1
Q

What are 2 direct vasodilator drugs

A

Hydralazine

Minoxidil

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2
Q

When do you use hydralizine

A

HFail

Acute, severe HTN

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3
Q

What drugs must you combine these direct vasodilators with?

A

Diuretic = combat ↑renin

BB (sympatholytic) = stop reflex tachycardia

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4
Q

SE of hydralazine

A

Lupus-like syndrome

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

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5
Q

Where is minoxidil activated?

A

Liver via sulfonation

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6
Q

How do direct vasodilators vasodilate?

A
Hydralazine = ↑cGMP
Minoxidil = open Katp channels
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7
Q

Net effect of vasodilators

A

↓afterload

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8
Q

What is pseudo-tolerance in relation to direct vasodilators?

A

Get temp ↓BP

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

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9
Q

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

A

Heart
Vasc smooth muscle
Pancreatic B cells
Isoform = tissue specificity

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10
Q

Normal fxn Katp channels

A

Couples metabolic state of cell to its electrical activity

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11
Q

3 drugs that open Katp channels

A

Minoxidil
Diazoxide
Adenosine

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12
Q

Minoxidil is tissue specific for… + drug use

A

Vasc smooth muscle - vasodilator to ↓BP

Anti-HTN

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13
Q

Diazoxide is tissue specific for… + drug use

A

Pancreas - ↓insulin release

Hypoglycemia or hyperinsulinemia

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14
Q

Adenosine is tissue specific for + drug use

A

Cardiac = A1 receptor = anti-arrhymthic

Vasc smooth muscle = A2 receptor = dilator

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15
Q

Explain Katp channels in heart under ↓ATP

A

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

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16
Q

Explain Katp channel in vasc smooth muscle under ↓ATP

A

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

17
Q

How does adenosine act as vasc smooth muscle?

A

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

18
Q

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

A

SUR1 & Kir 6.2

19
Q

Explain ↓blood glucose result on Katp channels in pancreas

A

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

20
Q

Where does diazoxide binds the Katp channel in pancreas

A

SUR1 to open channel

21
Q

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

A

SUR1 to close channel

22
Q

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

A

ATP closes via Kir 6.2

MgADP opens via SUR 1

23
Q

How does a gain of function Katp mutation present? Treat

A
Neonatal diabetes (↓insulin)
\+ Sulfonylurea
24
Q

How does a loss of fxn Katp mutation present? Treat

A

Neonatal hyperinsulinemia

Diazoxide

25
What is the cardioprotective mechanism of adenosine & diazoxide
Open cardiac MITOCHONDRIAL Katp channels
26
What is ischemic pre-conditioning
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
27
What is the acute phase of ischemic preconditioning
Katp open - including mitochondrial Katp channels | Important to maintain mito fxn
28
What is the delayed phase of ischemic preconditioning
RISKinases turn on genes for protective proteins --> ↑transcription of these
29
Which during do you give during ischemic preconditiong, why?
``` ADENOSINE Binds A1 receptor to help open Katp channels - Mitochondial fxn - ↓HR & contractility Binds A2 - vasodilation ```
30
What is ischemic post-conditioning
Short periods of ischemia during reperfusion can be beneficial b/c limit extent of damage
31
What is remote pre/post conditioning
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
32
Which drug do you give during stress tests
Adenosine