Cardio Test 4 Gotlieb

Front 1

What are 7 things that cause an arrhythmia?

Back 1

Automaticity

After-Depolarizations

Re-entry

SNS stimulation
Ischemia
Myocardial Infarction
Heart Failure

Front 2

How does automaticity change? (4)

Back 2

1. B adrenergic stimulation (speeds HR)
2. Muscarinic stimulation (slows HR)
3.Ectopic pacemakers
Automatic behavior occurring in sites that ordinarily lack spontaneous pacemaker activity
4. Escape Rhythms
SA node malfunction leads to a different pacemaker

Front 3

What is a DELAYED after depolarization (DAD)?

Back 3

impulse that happens before its time is due.
After depolarization reaches threshold
Intracellular Ca++ overload, adrenergic stress, ischemia,
ex: Digoxin

Front 4

What is EARLY after depolarization (EAD)?

Back 4

Your heart is so slow you have bradycardia & HYPOkalema
You prolong that AP duration or refractory period
Now, you have an AP rolling on top of another
ex: Quinidine

Front 5

What is Re-entry?

Back 5

these patients have these accessory proteins that allows you to fire another AP w/out of pacemaker doing the initiation b/c you have this re-entry effect
accessory pathways allow the atrium to connect to the ventricle.
Genetic
Wolff-Parkinson-White
1) Anatomically circuit, 2) Heterogeneity in refractoriness, 3) Slow conduction
Functional
Alterations in cell-cell coupling following acute MI

Front 6

How can you conduct an impulse through dead cells?

Back 6

Conduction goes through the cells that are still alive
MI slows down the conduction of that impulse
After you have completely depolarize & repolarize, you have an early impulse forming that can continuously take away the synchronization of the heart.

Front 7

Arrhythmia Definition

Back 7

A variation in either the site or rate of cardiac impulse formation, and/or a variation in the sequence of cardiac impulse propagation

Front 8

What are the 4 different ion channels?

Back 8

1.Passive
Always open and provide free exchange of ion
Few numbers
Few molecules cross it because electro different charges

2.Ligand-Gated (ex: GABA binds to receptor and opens Cl- channel)
Usually closed & a ligand has to bind to the channel or receptor

3. Voltage-Gated (ex: Na+/Ca2+ channels)
Usually closed at RMP and open at depolarization

4. Mechanic (ex: Baroreceptors: sensitive to stretch and open or close channels and change SNS firing)
Gated and open in response to stress

Front 9

1. What is the difference b/t a SLOW and FAST action potential?

2. How is that modulated?

3. What channels are involved in a SLOW AP? What causes the upstroke?

4. In the FAST AP, what causes the upstroke?

Back 9

1. How fast you reach the threshold

2.Quality, not quantity

3. Ca2+ channels

4. Na+ channels
Can open up a lot faster so you get a fast AP & that steep upstroke

Front 10

What is Impulse Propagation?

What phases are affected?

What drugs affect those phases?

Back 10

1. Example of a SLOW action potential.
This is what is present on the SA node & AV node.

You can have a SNS or PSNS system modulating how fast you get to that threshold.

Once you reach the threshold, you can open voltage-gated channels & everything moves forward.

2. Phase 4 and 0

3.
Phase 4 – beta blockers delay the SA node to fire
Phase 0 – Ca2+ channel blockers decrease the slope to threshold

Front 11

What is the PR interval?

What drugs affect the PR interval?

Back 11

1. PR interval reflects your AV node conduction. There is a conduction delay b/t the atrium & ventricle by the AV node
PROLONGED/LONG PR interval means your HR is SLOW.
SHORT PR interval means your HR is FAST.
By slowing things down, you allow for a full filling of the ventricles to have the best EF at the end of the day.

2.
- Beta-blockers
- Atropine (muscarinic antagonist)
Not given to a lot of patients
- Digoxin
- Non-dihydropyridine Ca2+ channel blockers:
Verapamil & Diltiazem
- All of these can prolong the PR interval b/c it slows down the conduction even more through the AV node & slows down your ability to reach threshold on the SA node
So you have 2 effects: slows conduction on SA node AND AV node

Front 12

What does QRS wave represent?

What channels affect this?

Back 12

1. impulse spread in the ventricle. Conduction time in the ventricle
The WIDER the QRS, the SLOWER the conduction of the ventricles.
The NARROWER the QRS, the FASTER the conduction of the ventricles.


2. Na+ channels are fast so you have a fast upstroke.

Front 13

What does the QT interval represent?

What channels affect the QT interval?

What does the T wave represent?

Back 13

1. How long it takes for your ventricles to completely depolarize
So, your AP duration to depolarize & repolarize

APD = action potential duration can be measured by the QT interval

2. K+ channels
- K+ channel blocker
Prolong/widen QT interval
- HYPERkalemia
Shorten QT interval(tachycardia)


3. repolarization

Front 14

Na+ channels.
What are the 3 different states on an AP and what phases (0-4) apply to each.

Back 14

1. Resting State= Phase 4 (most Na)(no Na+ will go through)

2. Active State= phase 0 (allows Na+ to go through)

3. Inactive State= btw phase 1, 2, 3
(no Na+ will go through)
Now, you can have those DADs or EADs b/c you have enough Na+ channels to start a new AP
So, if there is any high SNS or some kind of infarction that is causing high levels of Ca2+ or K+, you can have an early or delayed after depolarization  now you have an arrhythmia.

Front 15

What is a refractory period?

What can change a refractory period?

Back 15

1. There are 2 types: Absolute & Relative
Point in time on the AP curve where you cannot fire another AP, it’s just not going to happen.

-Inactive state is where you will not get an AP, known as absolute refractory period(??)

-But as you move from phase 2 to 3, your Na+ is going from the inactive to the resting state.
Now you can have a relative refractory period.
If you have an AP high enough, you can trigger another AP  leading to a DAD or EAD

2. Depending on what state your Na+ are, that’s going to change your refractory period.
(ex: active, inactive, resting)

Front 16

What channels are affected by each phase 0-4?

Back 16

Phase 4= Resting

Phase 0=
Threshold
Active

Phase 1 & 2=
K+ efflux
Ca++ influx

Phase 3=
Ca++ close
K+ efflux

Phase 4=
Na/K ATPase

Front 17

Where does the FAST cardiac AP happen

Back 17

1. Atrium
2. Ventricle
3. Purkinje

Front 18

What phase/stage do you have Absolute Refractory period?

Back 18

Phase 4 (INACTIVE STATE)
- period in which another AP cannot be elicited

-Lack of Na+ channels in the resting conformation

Front 19

Which phase/stage can you have Relative refractory period?

Back 19

Phase 3 up to phase 4
-A large AP can elicit a response but it is smaller in magnitude
-Depend on how many channels have recovered from inactivation

Front 20

what is the major determining factor in having another AP forming on the SA node or AV node (SLOW AP)?

Back 20

Time

Front 21

what is the major determining factor in having another AP forming in the Atrial, Ventricular, or Purkinje cells (FAST AP)?

Back 21

AP is determined by how many Na+ channels available in the resting state  Na+ CHANNEL-DEPENDENT, Na+ channels have to be in the resting conformation

Front 22

What happens to these when you block Na+ channels?
1. Threshold
2. Slope
3. QRS wave

Back 22

1. increase threshold
so it’ll take a higher AP to go through & reach that threshold before it can open up all the Na+ channels
2. decrease steepness of upstroke
so take longer for the impulse to propagate through the ventricles
3. QRS is wider (due to decreaesed conductance velocity)
*Na+ channels are located on the FAST action potential
**passive channels are not affected by our drugs

Front 23

What happens when you Block K+ channels?
1. duration of AP
2. QT interval

Back 23

1. increase duration of AP
2. takes longer to repolarize
3. QT interval is prolonged

Front 24

What happens when you Block Ca2+ channels?
1. AV node conduction
2. SNS

Back 24

1. decreases AV node conduction
2. SA node & AV node but more effects on the AV node
3. If HR decrease so much, body will increase SNS to try to increase HR.

**Slow channels**

Front 25

What does HR reflect on heart?

Back 25

SA NODE automaticity

Front 26

What does PR interval reflect?

Back 26

AV NODE conduction time

Front 27

What does QRS duration reflect?

Back 27

conduction time in the VENTRICLES

Front 28

What does QT reflect?

Back 28

a measure of VENTRICULAR APD action potential duration

Front 29

What drugs are Class I?
What drugs are in IA, IB, IC?

Back 29

Na+ Channel Blockers
1A: Intermediate Dissociation
Quinidine, procainamide, disopyramide
1B: Rapid Dissociation
Lidocaine, mexiletine
1C: Slow Dissociation
Flecainide, propafenone, moricizine

Front 30

What are Class II drugs?

Back 30

β-Blockers
Propranolol, esmolol, sotalol

Front 31

What are Class III drugs?

Back 31

AP Prolongation (K+ Channel Blockers)
Amiodarone, Sotolol, Dofetalide, Ibutilide

Front 32

What are Class IV drugs?

Back 32

Class IV: Ca2+ Channel Blockers
Verapamil, Diltiazem

Front 33

What effects does Na+ channel blockers have on the ECG? ***Test Quest***

Back 33

1. Widen QRS (decrease phase 0)
2. Prolong QT interval (Increases Duration of Action Potential)
3. Prolong PR interval (AV node conduction cuz non-selective (slow channels))
4. Prolong the Refractory Period (b/c Na+ being blocked)
5. Increase Threshold (will take higher AP to reach threshold before all the Na+ channels open)

Front 34

What is TONIC Na+ channel blockers?

Back 34

Slow onset & offset
doesn’t matter what phase you are in
you can be at rest or exercising, you won’t be able to increase your HR

***Class 1C: Slow***
Flecainide, propafenone, and moricizine

Front 35

What is Phasic Na+ channel blockers?

Back 35

Fast onset & offset
depend on the phase that you are in: rest or have high HR
will only affect you if you have a high HR

**Class 1B: Fast***
Lidocaine (IV)
Mexiletine (Oral)

Front 36

Quinidine (1A)
1. MOA
2. CV effects

Back 36

1. Blockade of Na+, K+, Ca++ & α-adrenergic and muscarinic (M2)

2. By blocking the Na+ channels, you can increase the QRS
-By blocking the K+ channels, you are going to prolong the QT (could lead to Torsades)
-By blocking the alpha-adrenergic receptors you are going to get orthostatic hypotension, reflex tachycardia
-Block Ca2+ channels at a high dose = INCREASE PR interval
-Block muscarinic receptors= DECREASE PR interval

Front 37

Quinidine
1. ADRs
2. DDIs

Back 37

1. Diarrhea (Unknown MOA)
2. Hypotension
3. Immunological reactions
4. Headache and tinnitus
5. Marked QT prolongation and TdP

2. Potent inhibitor of CYP2D6
Codeine
Propafenone
Inhibits P-glycoprotein-mediated transport of digoxin
Quinidine metabolism is induced by phenobarbital and phenytoin

Front 38

Procainamide (1A)
1. MOA
2. CV effects

Back 38

1. Blockade of Na+ & K+ (Procainamide)
K+ (N-acetyl procainamide)

2. Blocks Na+ channels =
- Widen QRS interva (Decrease steepness of the slope)
-↓ Automaticity
-↓ Conduction through the ventricles
-Threshold will go up

Block K+ channels
-Prolongs QT interval
-Prolongs effective refractory period (ERP)- due to Na+ blockage on phase 0.
-Increases APD (action potential duration QT)




Na channel blocker, class 1A
which means it has intermediate or medium onset and offset; it binds fast but it takes a little bit longer to leave.
What kind of confirmation does it bind to?
The ACTIVE and the INACTIVE
In phase 2 and 3, what confirmations are your sodium channels at?
majority are in the INACTIVE state, but some are going into the resting state
so b/c it takes a little bit longer for the drug to come off the channels, you are going to prolong the ability to go from the inactive to the resting state; thus the refractory period is going to be prolonged

Front 39

Procainamide (1A)
ADRs

Back 39

Hypotension & Slow of Conduction (IV)
Dose related nausea (oral)
Torsades de Points
Potential fatal bone marrow aplasia
Lupus syndrome (chronic)

Front 40

Disopyramide (Norpace) (1A)
1. MOA
2. CV effects
3. ADRs

Back 40

1. Higher anti-muscarinic Blockade and also blockage of Na+, K+, Ca++ (similar to Quinidine)

2.
- Wider QRS
- Prolong QT (APduration)

3.
-Anti-SLUDE
-Depression of contractility, which can precipitate heart failure

Front 41

Lidocaine (1B)
1.MOA
2. CV effects
3. ADRs

Back 41

1. Blocks both open and inactivated cardiac Na+ channels
Greater effects in depolarized (ischemic/MI) and/or rapidly driven tissues

2. Only in fast beating or ischemic tissue (normal tissue lidocaine has no effect)
- Increase threshold
-so it takes longer for you to fire an AP
-Decrease steepness of the slope (slower)
-wider QRS (decrease in phase 0)
- Decreases automaticity
- NO EFFECT on PR, or QT

3. Least cardiotoxic with rare proarrhythimic effects
-Neurologic effects (slurred speech, nausea,tremor)

Front 42

Mexiletine (1B)
1. MOA
2. CV effects

Back 42

1. Analog of Lidocaine with reduced 1st pass effect
- blocks Na+ channels
-only works on ischemic tissue

2. - Increase threshold
-so it takes longer for you to fire an AP
-Decrease steepness of the slope (slower)
-wider QRS (decrease in phase 0)
- Decreases automaticity
- NO EFFECT on PR, or QT

Front 43

Flecainide (1C)
1. MOA
2. CV
3. ADRs

Back 43

1. Potent Na+ blockers
In vitro studies have shown it to block K+ (Ikr) and Ca++

2. Very slow binding offset kinetics (>10 s)
-TONIC (works on both normal and fast HR) 
-Substantially decrease phase 0 (Na+)
-Decrease automaticity ( threshold)
-Increase APD (K+) and
-Increases refractory period, especially in rapidly depolarizing atrial tissue
**Increases PR (Ca2+), QRS, and QT intervals**

3.
-Dose-related blurred vision
-It can exacerbate CHF in pts with depressed LV function
-It can cause or exacerbate lethal arrhythmias

Front 44

Propafenone (1C)
1. MOA
2. CV
3. ADRs

Back 44

1. Potent Na+ blockers, K+, Ca2+ (same as flecainide) AND B-BLOCKER (s-isomer)

2. Increase PR (ca2+)
-Prolong QRS interval

3. It can cause or exacerbate lethal arrhythmias
-Sinus bradycardia (b-blocker)
- bronchospasm (b-blocker)

Front 45

How do B-blockers (class II) work?
How are they similar and different from Ca2+ channel blockers?

Back 45

1. -Reduce HR
-Decrease intracellular Ca2+ overload
-Inhibit afterdepolarization-mediated automaticity (DAD, EAD)

ECG:
= increase PR interval
= increase refractive period
= decrease HR
= decrease mortality

2. Ca chan blockers and beta blockers both work on slow AP, they do diff things

Beta blockers reduce the ability of pacemaker to get to threshold; it delays the TIME it takes you to create a pace or rhythm

Ca channel blockers slow the slope of phase 0, and, by dec this slope, you’ll change the refractory period

Front 46

Propanolol (b1/b2) and Esmolol (b1 given IV) (class II)

MOA
ADRs

Back 46

MOA
-Have shown to decrease mortality in the 1st week following MI
-Increase AV nodal conduction time (Increase PR interval)
-Prolong AV node refractoriness

ADRs:
Fatigue (Propanolol)
Bronchospasm (Propanolol)
Hypotension (both)
Depression (Propanolol)
Aggravation of HF ( both)

Masking the symptoms of hypoglycemia in diabetics (Propanolol)