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P&T Block 1 > L27 > Flashcards

L27 Flashcards

1
Q

What is the effect of venous dilation?

A

↓preload

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2
Q

What diseases should you try to ↓preload for?

A

Pulmonary congestion

MI

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3
Q

What is the effect of arterial dilation?

A

↓afterload

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4
Q

What is the reflex response to arterial dilation?

A
  1. ↓BP - baroreceptor decreased firing - ↑sympa - ↑HR

2. ↑renin

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5
Q

What diseases do you want to ↓afterload for?

A

Weak pump

Poor organ perfusion - HTN

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6
Q

What is an endothelium specific product that mediates arterial smooth muscle relaxation?

A

Endothelial derived relaxing factor = EDRF

Aka not just ACh as previously thought

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7
Q

Describe the steps to NO production in endothelial cells

A

+ ACh, shear stress, other stimuli
↑Ca2+ –> calmodulin –> eNOS on
Arginine + O2 (eNOS) –> NO

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8
Q

Describe how NO made in endothelium affects vasc smooth muscle

A

Diffuses into v.s.m
Binds heme subunit of sGC = activate
GTP –> cGMP
↑cGMP = smooth muscle relaxation

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9
Q

What are the 2 parts of NOS enzymes

A

Oxidase domain
Reductase domain
Ca-calmodulin couples these into a catalytically active enzyme

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10
Q

Where do you find eNOS - constitutively or transiently expressed?

A

On endothelium

Always there - varying levels of intracell Ca tell on/off

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11
Q

Where do you find nNOS - constitutively or transiently expressed?

A

Neuronal

Always there

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12
Q

Where do you find iNOS - constitutively or transiently expressed?

A

Inducible
Need TF to activate expression - transiently expressed
When there, enough baseline Ca-calmodulin to activate enzyme immediately
Caution of cytotoxic NO levels

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13
Q

What does oxidation to do BH4 cofactor

A

BH4 -> BH2

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14
Q

How does BH2 change eNOS activity

A

Makes superoxide
Interacts with existing NO –> bad molecules
Oxidized heme subunit of sGC = unresponsive to NO
NO VASODILATION

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15
Q

What are NOS inhibitors? What are they predictors of?

A

ADMA - vasocontrictors
No eNOS - no dilation
Predictive CV morbidity

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16
Q

Normal situations that you’d activate iNOS

A

Bacterial infection

Get toxic levels NO locally to kill infection

17
Q

What 2 things can NO become in circulation

A 
NO3 = nitrate - stored in salivary glands
NO2 = nitrite - reservoir in blood for hypoxia and acidosis
18
Q

Nitroprusside or organic nitrates: relaxes veins, coronary arteries AND resistance vessels?

A

Prusside

- Organic nitrates have little effect on resistance vessels

19
Q

Nitroprusside or organic nitrates: release NO enzymatically and selectively in target cells

A

Organic nitrates

- Prusside releases NO non-enzymatically in circulation (stays intravascular)

20
Q

What limits duration of nitroprusside

A

Accumulation of toxic thiocyanate

21
Q

What limits duration of organic nitrates

A

Tolerance

22
Q

Disease to use organic nitrates

A

Angina - symptomatic relief

Acute HF - relieve pulmon congestion

23
Q

What drug are organic nitrates combined with to reduce HR M&M

A

Hydralazine

24
Q

SEs of organic nitrates

A

Headache - transient

Postural hypotension

25
Q

3 types of organic nitrates

A

Nitroglycerin
Isosorbate dinitrate
Isosorbate mononitrate

26
Q

Do nitroglycerin or iso have longer t1/2

A

Iso

27
Q

What are the forms of organic nitrates that you can form tolerance to?

A

PO isos
Patch nitroglycerin
The long acting forms

28
Q

What must you encorporate into organic nitrate use to avoid tolerance

A

8-12 hr free period every 24 hrs

29
Q

What is the mechanism of organic nitrate tolerance? How do you resolve this?

A

Inactivate ALDH2 enzyme via oxidative stress

+ antioxidants - why + hydralazine

30
Q

What is the fxn of ALDH2 enzyme

A

Takes organic nitrate –> NO

31
Q

What happens with LOF mutations to ALDH2

A

Less responsive to organic nitrates - more at risk for tolerance + coronary spasm
LOF associate with alochol flushing syndrome (aldehyde build up)

32
Q

1ary effect of organic nitrates

A 
Venous > arterial dilation 
↓preload = 
↓LV DP
↓O2 demand 
↑O2 supply via subendo perfusion = good for MI
33
Q

Why is it good that organic nitrates do no dilate coronary resistance vessels?

A

Avoid coronary steal
Vessels to damaged area are already dilated to allow BF there
Dilating elsewhere will remove that compensation

34
Q

Use of PDE5 I for CV diseases

A

Pulm HTN

35
Q

What drugs can’t you prescribe viagra with?

A

PDE 5 I potentiate nitrovasodilators and should not be combined

36
Q

What are sGC activators

A

Mimic NO at heme-free sGC

Use when tissue already suffered oxidative stress (can’t use nitrates)

37
Q

What are sGC stimulators

A

Amplify response of reduced sGC to low level NO

= Riociguat

38
Q

Does nitroprusside ↓preload or afterload?

A

Dilates resistance vessels = arterial dilation
↓afterload = FAST ↓BP
Ex: use if hear mitral regurg

P&T Block 1 (43 decks)

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