Which ion mediates phase 0 of the purkinje cells?

Phase 1

Phase 2

Phase 3

Phase 4

[image]

Phase 0: Na+ in

Phase 1: K+ out

Phase 2: Ca++ in

Phase 3: K+ out (Ca in)

Phase 4: Na and Ca in, K goes out

Blocks Fast Na+ channels

Local anesthetic effects

Binds open or inactive state

Decreases Vmax of depolarization

Decrease the slope of phase 0 of PK AP

PK cells: Decreases slope of phase 3 (blocking K channels too). This prolongs repolarization

PM cells: Decreases slope phase 4, so threshold for depolarization also increases

[image]

Quinidine

Procainamide

Disopyramide

(Pretty Darn Quick)

or

(Quit procrastinating in climing the pyramid)

Quinidine can cause this

blurred vision, tinnitus, HA, disorientation and psychosis (antimuscarinic activity)

All these Sx occur after getting wasted at a loud concert (except psychosis maybe..)

Diarrhea

Worry is that by having so much diarrhea, you are crapping out all your K and can have hypokalemia and this may induce Torsades de Pointes.

With renal failure, NAPA can accumulate and increase risk of Torsades de Pointes.

Give lower dose of Procainamide then

Depression

Hallucination

Psychoses 

Arrhythmias

(PHAD- Procainamide was a "phad" until ppl realized that the crazy SE)

Anti-muscarinic activity:

Constipation

Urinary retention

Blurred vision

dry mouth

(Poop, pee, see, salivate)

Glaucoma

It narrows the __?__ angle and increases the pressure.

(I don't know name..)

Anti-muscarinic activity (poop, pee, see, salivate)

Heart failure

Glaucoma

Diabetes (hypoglycemia)

open and inactivated, but prefer inactivated.

Recover rapidly

PK cells: increases slope phase 3, thereby decreasing AP time and decreasing repolarization time

PM cells: Same as Class 1a

Decreases phase 4 slope and increases threshold

Ventricular arrhtymias

Also has local anesthetic effect

Atrial APs are too short and channels aren't open long enough for lidocaine to penetrate

Atrial arrhythmias are usually not in ischemic tissues, which would be partly depolarized (more time spent in inactivated state)- ischemic tissue is ventricles and non-ischemic tissue is atrial

Slow IV because of extensive 1st pass metabolism.

Fast IV causes arrhythmias or seizure**

nystagmus

tremors

slurred speech

dysarthria

altered consciousness

What is mexiletine used for?

How is it administered?

Ventricular arrhythmias

Orally.

ventricular and digoxin-induced arrhythmias

seizures

Gingival hyperplasia

Enzyme induction- drug interactions

Hirsutism- give eflornithine (inhibits ornithine decarboxylase involved in hair growth)

Open channels

Recover is very slow

What are some effects of class 1c having slow recovery?

What is this drug generally used for?

Makes these Rx more dangerous. Class 1c are associated with excessive mortality or non-fatal cardiac arrest. 

Used for life threatening situations

PK cells: decreases slope of phase 0, increasing time for depolarization

PM cells: Same as for Class 1a/1b: decr slope phase 4 and incr threshold

Flecainide

Propafenone

(Probably Free ;p)

Lidocaine

Mexiletine

Phenytoin 

(Please Lick Me!)

What is flecainide used for?

How administered?

Paroxysmal A-fib

Paroxysmal SVT

AV reentrant tachy

other SVTs

Oral

Na+ channels

Ryanodine Ca channels in SR and prevents arrhthmogenic Ca rel from SR.

Useful if genetic defect in Ryanodine Ca channels whcih causes CA polymorphic ventr tachy

Na channels

Produces significant Beta block (Class II activity)

A-fib

A-flutter

paroxysmal SVT

other ventricular arrhythmias

Oral

CYP2D6

This is absent in 7% pts, so can exaggerate effects and toxicity (mostly GI) if pt doesn't have this

1) incr cAMP->activate PKA->phosph a1 subunit of Ca channels->incr Ca++ influx->incr myocardial contractility

2)Phosph Troponin-> incr sensitivity of contractile prots to Ca

3)Facilitates Ca capture by ryanodine-R on SR-> incr Ca available for release

4)Incr Ca entry increases automaticity-> delayed after-depolarizations. Via the Na/Ca exchanger, one Ca moves out for every 3 Na moving in->net influx of 1 charge per exhange.

*Beta blockers inhibit all this*

B1- receptor that's on the heart 

B2- on vasculature and bronchioles and no effect arrhythmias

PK cells: NO EFFECT

PM cells: Phase 4 slope is decreased, so it takes longer to reach threshold (but threshold doesn't change)

Phase 3 slope is decreased, prolonging repolarization

-AP is wider

[image]

What are the non-selective beta blockers?

Which are the B1 selective beta blockers?

Acebutalol

Propranolol (non selective) 

Esmolol

(APE- ooh ooh ahh ahh)

It blocks b1 and b2.

Supraventricular arrhythmias

 ventricular arrhythmias indcued by CAs

digoxin-induced arrhtymias

Decreases HR and contractility

This decreases CO and leads to reflex vasoconstriction to maintain BP

Acebutalol- limits its use

(think Acebutalol is kinda like ASSbutalol and it has ISA which if say fast sounds like an english person saying ASS)

Metoprolol

Atenolol

Pindolol

(MAP)

Inhibit K outward current and this prolongs the plateau and the AP.

This increases the refractory time and decreases risk of reentry, but increases risk of Torsades

PK cells: decreases slope phase 3, prolongs repolarization (similar to class 1a)

PM cells: NO EFFECT

Bretylium

Amiodarone

Dronedarone

Dofetilide

Sotalol

Ibutilide

(BAD DIS- K)

Has properties of all 4 classes:

Class I: decr rate firing of pacemaker

Class II: antagonism of beta receptors

Class IV: AV block and bradycardia

Amiodarone

It has I and is related to thyroid hormone.

Can cause hyper-hypothyroidism

T1/2=50 days

It's lipophilic and accumulates and is slowly eliminated

Increases risk of toxicity

Fatal acute pulmonary toxicity

-cough

-dyspnea

-bronchospasms

-infiltrates

-hemoptysis

-alveolar hemorrhage

-resp failure

hypo/hyperthyroidism

Corneal deposits

Hepatotoxicity

peripheral neuropathies

photodermatitis (blus skin and ears-smurffs)

Cyp3A4

Cyp2C9 

P-glycoprotein

Used for Afib/Aflutter

Analog of amiodarone but without the I.

CAUTION- increases risk of CV events including 2x incr risk of death in pts w/ Afib

SE: N,V,D, abdl pain, asthenia (weakness).

Rare, but severe liver injury could require liver transplant

Cyp3A4 (same as amiodarone)

Cyp2D6

P-glycoprotein (same as amiodarone)

Prolongs AP thru ion channel effects

Displaces NE: initially increases NE release and contractility with a transient incr BP and potential ventr arrhythmias. This is followed by decr in BP as NE is depleted

LOW: Class II- beta block

HIGH: effects on AP 

Ikr blocker

Actiavtes slow inward Na channels

Prolongs QT interval

monitor carefully

Pure Ikr blocker (no extracardiac effects)

Used to convert Afib/flutter

Thiazide Diuretic

it will increase dofetilide's level and cause significant prolongation of QT interval

Ca channel blockers

open channels

Thus, are more effective against reentrant SVT

PK cells: NO EFFECT

PM cells: Decreases phase 4, 0 and 3 slope

Prolongs depolarization and repolarization and elongates the AP.

[image]

Verapamil

Diltiazem

The L racemate is more potent than the D, but L undergoes more 1st pass metabolism.

A certain amt given IV prolongs the PR interval more than the same amt given orally so be careful. (bc oral causes 1st pass and metabolism)

CONSTIPATION

more notable with verapamil than other Ca channel blockers bc it has high affinity for GI sm.

*Treat this bc if strain to poop (valsalva), can increase o2 consumption of heart and since there is an increase in intrathoracic pressure the volume going back to heart decreases, so could cause an MI

Where does verapamil work?

What about diltiazem?

More selective for heart

Acts on heart and vascular sm

Decreased BP from vasodilitation

Decrease in contractility

Digoxin

Atropine

Aenosine

Magnesium

(DAAM- imagine a goat saying Dam..)

Afib

Aflutter

Also used for CHF (Rx increases contractility)

its vagomimetic (mimics parasympathetics)

a) inhibits stmpathetics

b)vagal stimulation->

incr ACh release->

incr K efflux->

hyperpolarized SAN->

closes Ca++ channels->

Decr Ca influx->

decreased slope 0 in AVN->

and this slows ventricular contraction 

What is Digoxin better at?

Ventricular arrhythmias or Atrial arrhythmias?

Atrial Arrhthmias=

There isn't much parasympathetic activity in ventricles. 

BUT by controlling conduction thru the AV node, Digoxin controls the ventricular response to Afib and Aflutter

What can cause increased risk of Digoxin toxicity?

What can this toxicity lead to potentially?

Hypokalemia (low K)

Can lead to Torsades de Pointes

In cardiac cells, digoxin binds to phosphorylated form of NA/K ATPase.

The problem is that K promotes dephosphorylation of this pump. If there is low K, then dephosphorylation doesn't happen and you get phosphorylaton of the channel.

Phosphorylated channel promotes digoxin binding and toxicity.

What should you not mix Digoxin with and why?

Diuretic

CAuses K+ loss and if low K, will have phosphorylated Na/K pumps and lead to toxicity of digoxin..

Digoxin immune Fab (digibind)- an antibody to digoxin that forms a 1:1 complex w/ digoxin and is then rapidly excreted. 

Give IV over 15-30 minutes

IV K- this would work bc K causes dephosphorylation of the channel that digoxin binds to. Without this channel, Digoxin has not effects.

Makes it worse

The more Ca you have, the more Na that is brought out of the cell...

Actually I don't Know :/

What is the effect of Mg?

What if have low Mg?

It competes with Ca and decreases risk of arrhythmia because basically blocking Ca channels so depolarization doesn't happen like normal.

Low Mg causes increased risk for arrhthmia because there will be no competition w/ Ca and so depolarization happens.

What is Atropine used for?

How is it administered?

Why?

Bradyarrhythmias

IV

Atropine is a competitive antagonist of the muscarinic ACh-R, meaning that it blocks the effects of parasympathetics. It makes sense that if it's blocking Parasympathetics, which normally decr HR, it'd lead to an increased HR.

What is the T1/2 of Adenosine?

Why is it good?

T1/2= 15 seconds!!!!!

Easy to control and so decreases risk of significant SE. Yeay!

Stimulates P1 purine-R->

activates Ach-sensitive K channels->

K efflux in atria and SA/AV node->

Hyperpolarization->

decreases automaticity and causes a transient AV block

What other channel does Adenosine block?

What is the result?

Transient asystole (lasts less than 5 sec) Scares the shit out of new doctors who have to administer it

Facial flushing, chest pain, dyspnea, N, vfib, vtach or bradycardia. Short lived SE bc T1/2 is so short

Methylxanthine is an antagonizer of adenosine

a purine base found in most human body tissues and fluids and in other organisms

Methylxanthines affect not only the airways but stimulate heart rate, force of contraction, cardiac arrhythmias at high concentrations. 

Sotalol

Adenosine

Disopyramide

Propranolol

Amiodarone (for refractory)

Procainamide

Quinidine

Flecainide

(SAD PAP- Quit Fucking)

Quinidine

Procainamide

Diopyramide

Lidocaine

Mexilitine

Phenytoin (digoxin induced)

Propafenone

Propranolol (Ca and digoxin induced)

Amiodarone

Bretylium

Sotalol

(All the drugs that Tx SVT are here except for Flecainide and Adenosine (Ademir flees). The extra ones are bolded and make

Lick My Butt Pretty Please!

Flecainide (fib)

Ibutilide

Bretylium (fib-life threatening)

Propafenone

Dronedarone

Dofetilide (converts them)

Digoxin

(FIB P-DDD)

Sounds like P-diddy and he "FIB"-ed us with all his name changes)- also Fib for A-fib.. DUH!

Flecainide (AV)

Adenosine

(Ademir Flees.. and then reenters)

Atropine

Makes sense because Atropine is a blocks ACh-R basically blocking parasympathetics, causing incr in HR.

Class Ia

Class III

(Na and K blockers)

Class 1b

(Na blocker- rapid recovery)

Class II

Class IV

(Beta blocker and Ca blockers- affect nodes)

Which antiarrhythmetics increase the threshold for firing in Pacemaker cells?

Which ones don't affect threshold?

Which one has NO EFFECT on Pacemaker cells?

Class Ia

Class Ib

Class Ic

Class II and Class IV

Class III 

Class IV

Decr slope of 4, 0, 3

Class II

Class IV

Quinidine (in high doses)

Sotalol

Procainamide (if increased NAPA like in renal failure or if pt is a fast acetylator)

Digoxin

Class III- K blockers

Quinidine

Procainamide

Quinidine

Disopyramide

Digoxin

Phenytoin

(Penny is a hairy little girl)

Acebutalol

amiodarone

(ASS-ISA)

Disopyramide

Class IV- Ca channel blockers- ESP verapamil

(climbing pyramides makes you veray constipated)

Dronedarone

Digoxin (NV, HA)

Adenosine (N)

Quinidine (HA)

(Dronedarone sounds like Dramamine which you take for sea sickness... so just think about those Sx)

(Ademir makes me nauseous sometimes)

Disopyramide (heart failure)

Class 1c (cardiac arrest)

Dronedarone (CV events)

Adenosine (asystole, vfib, vtach, bradycardia)

Amiodarone (highly lipophilic and accumulates)

Digoxin (if low K because of phosphorylation of the Na/K pump.. remember?)

Amiodarone (hepatotoxicity)

Dronedarone (liver damage)

Procainamide (if rapid IV- ganglionic block)

Digoxin

Disopyramide

Beta blockers- right? Blocks the B2 mediated stimulation of glycogenolysis and decrease blood sugar.

Amiodarone

Adenosine

Amiodarone:

 Possible fatal acute pulmonary toxicity: cough, dyspnea, bronchospasms, infiltrates, hemoptysis, alveolar hemorrhage, respiratory failure

Which antiarrhythmetic can cause thyroid problems?

What can you give instead?

Amiodarone

Contains Iodine and can cause hyper-hypothyroidism (potentially fatal thyrotoxicosis)

Can give dronedarone because it's an analog of amiodarone but without the Iodine