- If heart rate is too fast, less diastole, less filling, lower CO.

- Fibrillation: heart beating in syncronous way, have different part of heart contracting at different times, heart cannot pump blood. 

- Asyncronous beats can make CO go very low

1.  Impulse-generation cells (pacemakers)

2.  Rapid-Conduction cells

3.  Essentially contractile cells

- Determine heart rate

- Small group of cells that has pacemaker activities, continuous depolarization

- Always in phase 4 depolarization?

- Characterized by calcium influx and potassium efflux to control charge of cytosol.

SA Node - 75 times/min

AV Node - 50 times/min

Bundle of His - 30 times/min

Note: Majority of heart is NOT a pacemaker

Bundle of His Conduction Velocity - 4 m/s

Rest of heart's Conduction Velocity - 0.5 m/s

- Lots of gap junctions

- Most rapid conduction cells are Bundle of His

- Problems in these conduction systems could cause asynchronous beats

- These cells do not depolarize spontaneously like pacemaker cells

- Major cell of the heart

- No phase IV depolarization

- When threshold is reached VGC of Na+ open, and there is an AP

- Next a VGC of Ca+ opens and causes a second phase

- Ca+ that enters during plateau phase is what is used during contraction

- If impulse travels towards left arm, this is positive, and there will be a spike

- If impulse travels toward your right arm, this is nevative, and there will be a depression on the EKG

- If impulse travels straight down to the ground, nothing will show up on EKG

P wave - contraction of the atrium

QRS - Contraction of the ventricles

T- relaxation of ventricles, beginning of diastole

- Abnormally low heart rate

- Often due to structural defect of the heart

- Theray often involves implantation of a mechanical pacemaker

- abnormally high heart rate

- Common clinical problem

- Causes could be drugs, ischemia/infarction, cardiomyopathy, etc. 

- Treated with antiarrhythmic drugs

- Can be synchronous or nonsynchronous

- Bradyarrhythmias are for surgeons, not pharmacists

Disturbances in impulse formation: increase in automaticity at SA or ectopic focus, or afterdepolarizations

Disturances in impulse conduction: Unilateral blocks (re-entry)

- Reducing threshold potential increases automaticity because you reach depolarization easer, may have 3 AP instead of 2. 

- Increasing slope of phase IV may also increase automaticity

- Also known as Sinus Tachycardia

- Heart rhythm is normal because same pacemaker is used

- Heart RATE is faster

- Synchronous

- Occurs somewhere else other than SA, acts as a pacemaker, COMPETES with the SA Node

- Refractory period MAY change

- Increased automaticity by an irregular pacemaker

- P wave happens early on, premature heart beat, not spaced evenly, ASYNCHRONOUS in general.

- 2 types, early and late

- Early depolarization finds a cell that is not refractory, causes an AP in another cell. 

- Delayed afterdepolarization is when the cell repolarizes, but when it should be refractory, you get a delayed depolarization, and if that reaches threshold you get another AP.

- When cells in the ventricles suffer an afterdepolarization

- Generates rhythm within the ventricle

- Lots of QRS, contract without specific rhythm. 

- Ventricles keep contracting in synchronous, regardless of what the pacemaker is doing.

- Atrial Flutter and Ventricular Fibrillation are examples of this

- Atrial Flutter is when reentry is in the atrium, atrium is always depolarizing, if ventricle isn't refractory it contracts. 

- You'll see a bunch of P waves for this. 

- Ventricullar Fibrillation is worse, when ventricles are fibrillated, blood isn't ejected.  If you stay like this, you'll die.

- No discrete P waves, EKG looks chaotic

- Procainamide

- Absorbed in GI

- Given orally or parentally

- T 1/2 is 3-4 hours

- Indication is atrial and ventricular arrhythmias

- Bind when the VGC are in the open and inactive state, keeping sodium from entering the cell and causing AP's

- In order of affinity for depolarized, refractory cells, it goes PLF.  Otherwise, they're the same

- Decrease automaticity by decreasing phase 4 depolarization and increasing TP.

- Decrease late afterpolarizations

- Solves re-entry, the two ways to solve re-entry are to increase conduction velocity or decrease conduction velocity, these do the latter

A - Decreases K+ current, slows repolarization, increases AP duration

B - No effect, Na+ blockade accelerates repolarization, decreases AP duration

C - Decreases K+ current, slows repolarization a bit, Na+ blockade accelerates repolarization, no net effect on AP duration.

- Increasing AP duration may prevent EARLY afterdepolarizations

- Increasing AP duration may prevent re-entry by prolonging refractory period.

1A - Precipitation of certain types of arrhythmias (same effect with other drugs), prolonging AP may cause EARLY afterdepolarizations

1B - Paresthesia (peripheral or CNS effect), Tremor (CNS), Nausea of central origin (CNS), Convulsions (CNS), lidocaine is LEAST cardiotoxic

1C - Precipitation of certain types of arrhythmias.  Extension of therapeutic effects where decreased conduction leads to heart block, this may also cause re-entry circuits that were previously silent b/c re-entry tried to occur before when it was in refractory.

- Absorbed in the GI tract

- T 1/2 3.5-6 hours

- Beta 1 receptor antagonist, blocks these receptors in the heart

- Decreases SA node activity

- Decreases Automaticity

- Effects not well understood, not as effective as other classes

- Causes asystole and cardiac arrest, possibly because of exacerbation of effects in patients with AV node dysfunction or taking other agents (CCB's)

- May exacerbate asthma complications

-

- Example is amiodarone

- T3/T4 analog

- Absorbed in GI or parentally

- T 1/2 3.5-6 hours

- Indication is serious ventricular tachyarrhythmias

- Shares actions with other antiarrhythmics

- Blocks K+ channels without touching Na+ channels, this prolongs AP, this will also prevent EARLY afterdepolarizations, may also prevent re-entry by prolonging refractory period

Adverse Effects:  Bradycardia and heart block, Torsades de Pointes, hypotension, Pulmonary fibrosis, Liver dysfunction, Hyper/Hypothyroidism

- Example is Verapamil

- Absorbed in the GI tract

- T 1/2 is 4-6 hours

- Drug of choice in supraventricular tachyarrhythmias (atrial flutter, anything originating in atrium)

- Block L-type Ca+ channels

- Block open and inactive state VGC

- In SA, block Ca+ channel, raises TP

- In contractile cell, during plateau, blocks Ca+ channel, decreases AP duration and conduction

- Slow firing rate, so decreases automaticity

- Doesn't affect Phase IV b/c that has to do with Na+ channels

- Prevents late afterdepolarizations

- Causes bradycardia, hypotension, constipation

- T 1/2 10 seconds

- Bolus IV administration

- Indication: termination of supraventricular tachyarrhythmias

- Binds to A1, activating Gi and Gq, decreasing cAMP, which decreases Ca+.  Increases IP3-DAG, which increases K+ current out of cell

- Efflux of K+ causes cell to repolarize to more negative vale, harder to reach TP

- Decreased Ca+ reduces automaticity and late afterdepolarization

- Reduce conduction velocity, may prevent re-entry

- Net effects SHORTENS AP (not primary therapeutic effect)

- No serious adverse effects