Ch 14: Anti- Arrhythmic's Flashcards
Anti-Arrhythmics
- atria and ventricles MUST work in a coordinated fashion to EFFECTIVELY pump blood to body cells
- any arrhythmic event could potentially be damaging, OR DEADLY
** NORMAL CYCLE: SA node depolarization, spreads over atria, atrial contraction, slow conduction through AV node, to bundle of His, bundle branches, Purkinje fibers, then ventricle depolarization
AP in slow response tissue
- SA node and AV nodal tissue
- have a net positive charge influx at 4 phase due to Na+ entry
Effective refractory period
Na+ channels become unable to open again until they reach -60 mv
Relative refractory period
between -60 and -90, may be able to activate some Na+ channels if intense AP occur
SA nodal action potential
” Funny Channels” (HCN)
- SLOW Na+ = Na+ influx & “pacemaker potential” –> 4 phase
To depolarize:
T-type Ca++ channels (transient) & L-type Ca+ channels (long lasting) –> 0 phase
Repolarization through K+ efflux –> 3 phase
How do we impact HR speed?
Your heart rate is lower when you are at rest. When you exercise, you heart speeds up and pumps more blood, which allows oxygen-rich blood to flow easily and reach your muscles.
Fast Response Tissue Action Potential
- Including atria, ventricles, bundle of His, Purkinje fibers
a) 0 phase: from resting (-90) to -60 opens Na+ (fast inward) channels >> +20mv
b) 1 phase:
Na+ channels inactivate, K+ efflux (slow transient K+ ch) brings back 0mv
c) 2 phase:
slow L-type Ca++ channels open to allow plateau
d) 3 phase:
Ca++ inactivates, delayed rectifier K+ opens to efflux
e) 4 phase:
stable potential at baseline (K+ ch open)
If channels don’t work?
1) Loss of function
result in the gene product having less or no function (being partially or wholly inactivated).
2) Gain of function
A mutation that confers new or enhanced activity on a protein.
Arrhythmias are caused by:
- Disease state, scarring
- Acidosis or Alkalosis
- Electrolyte imbalance
- Drug toxicity
- too many catecholamines
- Ischemia/hypoxia
Mechanisms of Arrhythmia
1) disturbances of impulse formation
2) disturbances of impulse conduction
3) Both above
Disturbances in impulse formation
- Abnormal action potentials “triggered” by a preceding AP
- Early afterdepolarization (EAD; phase 3)
- from an abnormally long QT interval. Could be from genetic defect or drugs that prolong QT (potassium-ch blockers)
- Delayed afterdepolarizations (DAD; phase 4)
- often w/ high intracellular Ca++
Afterdepolarizations
abnormal depolarizations of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the cardiac action potential in the electrical conduction system of the heart. Afterdepolarizations may lead to cardiac arrhythmias.
Early (EAD): interrupt phase 3 of the myocardial action potential
Delayed (DAD): Interrupt phase 4 of AP
Early Afterdeopolarizations
Lead to Tachyarrhythmias
treat w/ drugs that reduce action potential duration
Types of Arrhythmias
1) Enhanced automaticity
2) Triggered beats
3) Reentry
Enhanced automaticity
Increased phase 4 slope increases rate of AP’s (DAD)
- Can lead to flutter or fibrillation if in multiple sites
- Due to increased B stimulation, hypokalemia, hypercalcemia
Triggered beats
Linked to prior AP if slow phase 3 (EAD).. (membrane stays above -30 to -50, another AP can begin
- due to high catechizes, hypoxia/ischemia, CO2
- EAD (triggered beats) or DAD(enhanced automaticity) are issues w/ impulse propagation
Reentry
Due to pathology (Ischemia, etc), conduction velocity in an area is impaired
- due to a block, by time the depolarization can emerge the tissue is no longer refractory and sets off a new AP
- due to impulse conduction
Drugs to Treat Arrhythmia
Class I anti- arrhythmics
- Are Na+ channel blockers
- Reduce conduction velocity and reduce triggered beats
I-A Drugs: slow phase 0 and AP propagation
- Quinidine, Procainamide
I-B Drugs: slow rate of rise of 0 phase only in impaired tissue
(lidocaine, mexilitine)
I-C Drugs: slow 0 phase and propagation (propafenone, flecainide)
side effect: arrhythmias, dizziness, nausea
Class I anti- arrhythmic’s
- reduce Na+ influx, and thus conduction velocity
- tendency to reduce abnormal pacemakers
- since arrhythmic tissue spends more time in “open state” (Na+ channels), will tend to block faster than non- arrhythmic tissue
Class II anti- arrhythmic’s
- Beta Blockers (esmolol, propanolol)
- block B-1 receptors
- decrease phase 4 slope and prolong effective refractory period
Side effects: reduced CO, arrhythmia (rare)
Class III anti- arrhythmic’s
- Repolarization prolongers (amiodarone, sotalol, dofetilide)
- block K+ channels (Increase QT interval)
- Lengthen AP duration/ effective refractory period
- side effects for amiodarone:
pulmonary toxicity, liver damage, etc
Sotalol: main side effect
- Torsade de pointes arrhythmias
- Polymorphous ventricular tachycardia
- can be disastrous to use a Class Ia
Class IV anti- arrhythmic’s
- Ca++ channel blockers
- Reduce slow calcium current in SA and AV nodes (phase 4), slows rise of 0 phase
- Increased PR interval
- Diltiazem, verapamil (most effective)
Side effects:
slow HR, peripheral vasodilation
leads to dizziness, headache
All anti-arrhythmic’s can cause
dizziness
arrhythmia
hypotension
OTHER DRUGS
- Adenosine at High Concentrations
(hyperpolarizes tissue) - Digitalis Glycosides
(block Na-K-ATPase)
can increase parasympathetic activity - K+ can either improve or worsen, but perhaps can help
- Mg++ can have an effect similar to K+
- Ablation
(radio waves through intracardiac catheter) - Defibrillators, pacemakers
