How are propagation blocks created?
Decreased resting membrane potential/depolarization
How does ischemia lead to depolarization?
Ischemia leads to increased extracellular [K] which depolarizes the cell because 1) Phosphate and lactate that normally accumulate in the cell leave and K follows, and 2) ATP depletion activates I-kATP which is protective short term but depletes intracellular K long term
Change in Ek is primary determinant of Vm
How does depolarization lead to propagation block?
Na channel inactivation and so slowing the rate of rise and the amplitude of Na current --> Total amount of Na current reduced and get slowed propagation [*significant in reentry]
When AP propagates slowly, more likely to get block
How do the PKJ prevent backward propagation?
Longer duration of distal PKJ inmpulse than with ventricular fiber impulse and so the PKJ are refractory for longer
What are the 3 conditions necessary for reentrant propagation?
1) 2 parallel conduction pathways that are anatomically or physiologically distinct
2) unidirectional block
3) slowed or delayed conduction - required for refractoriness to disappear and enable effective reentry
Antidromic vs orthodromic
Antidromic - V to A
Orthodromic - A to V
Where are the extra beats coming from?
Atrial premature beats
What are the general categories of anti-arrhythmic drugs that I need to know?
Na channel blockers = Quinidine, Procainamide, Lidocaine, Flecainde, Propafenone
Beta-Blockers = Metoprolol, Atenolol, Esmolol
K-Channel Blockers = Amiodarone, Sotalol, Ibutilide or Dofetilide
Ca-Channel Blockers = Verapamil and Diltiazem
What are the general actions and characteristics of Class 1 Anti-arrhythmics?
Fast Na channel blockers - decrease Na current and rate of rise of Phase 0 in AP
Reduce excitability of non-nodal tissues where inward Na current in important - working fibers of the heart
What are the Class 1a drugs? What is their mechanism/effect? How are they used?
Class 1a drugs = Quinidine and Procainamide
Lower Na current and rate of AP
INCREASE AP DURATION - block K channels and prlong ventricular effective refractory period
Not really used except Procainamide is used acutely
1A = Broaden AP
What are the Class 1b drugs? What is their mechanism/effect? How are they used?
Class 1b = Lidocaine
lower Na current and rate of rise of AP modestly
DECREASE AP DURATION!!! no effect on conduction velocity
Administered IV for acute treatment ofventricular arrhythmias
1B = narrows AP
What are the Class 1c drugs? What is their mechanism/effect? How are they used?
Class Ic drugs = Flecainide and Propafenone
Lower na current and the rate of rise of AP strongly
NO CHANGE TO AP DURATION
1C = no change in AP
What are the Class 2 drugs? What is their mechanism/effect? How are they used?
Class 2= Beta Blockers
Propanolol = non-specific beta blocker avoided now for use
Beta-1 Antagonists = Metoprolol, Esmolol, ATenolol
Non-selective Beta and A1 blocker = Carvedilol
Non-selective Beta and A blocker = Labetalol
Reduce excitability and decrease conduction velocity in the AV node
TARGET THE AV NODE
What are the Class 3 drugs? What is their mechanism/effect? How are they used?
Class 3 = K+ Channel Blockers
Amiodarone, Dronedarone, Sotalol*
Ibutilide* (IV) and Dofetilide* (oral) - *tend to produce Long QT and Torsade
Prolong duration of AP without altering rate of rise of AP or resting membrane potential - Increase refractory period
What are the Class 4 drugs? What is their mechanism/effect? How are they used?
Class 4 Drugs = Ca Channel Blockers
Verapamil and Diltiazem
Block L type Ca channels and so block slow, non-inactivating Ca crrent
SLOW AP INITIATION, conduction and increase refractoriness in SA and AV node
Multiple targets of Quinidine
Blocks Na channels
Moderately blocks K channels
Low block on M2 and A/B adrenergic
Multiple targets of Amiodarone
Moderate block K channel
Low Na channel block
Low Ca channel block
Moderate A/B adrenergic block
*rarely causes Torsade
What is a prolbem with Potassium channel blockers?
Reverse Use Dependence:
K channel blockers, like Sotalol, bing in a resting, closed state and can promote long QT and Torsade with slow HR
Risk with use during bradycardia
Multiple targets of Sotalol
Blocks K channels and blocks Beta-adrenergic
Multiple targets of Digoxin
Na-K Exchange pump inhibitor
Muscarininc M2 agonist to activate vagal input
Metabolism and side efects of 1a drugs
Liver metabolism to NAPA metabolite which is also a K channel blocker
High incidence of Torsade with thse drugs
Also can cause Nausea and Diarrhea
Metabolism and Side Effects of Amiodarone
High Iodine content
Long half life as it partitions into liver and fat so delayed onset
NO RENAL EXCRETION!
Can cause Pulmonary Fibrosis, Hypo or Hyperthyroidism bc Iodine, Liver toxicity, neuropathy, skin discoloration to blue, photo-sensitivity, corneal deposits and optic neuritis
MEtabolism and Side effects of Dronedarone
Amiodarone derivatie that is NOT iodinated
Acts more quickly (within hours) and shorter half life
Hepatic metabolism and elminated in feces
Less side effects but also not as effective
Used for Atrial Fibrillation
Metabolism and side effects of Digoxin
Small therapeutic index so plasma lvels must be monitored
Kidney ecretion - Toxic levels can cause kidney damage!!!
Long half life
Acts to shorten refractory periods BUT can enhance excitability in some fibers so DO NOT GIVE TO SOMEONE WITH ACCESSORY PATHWAY!
What are the anti-arrhythmics that cross the BBB and what are their CNS side effects?
Lisa's Poop causes Mental Death = L, P, M, D
Lidocaine - congition changes and seizures
Propaniolol - nightmares and sedation
Metorprolol - anti-anxiety
Digoxin - cognitive and vision effects
Atrial Flutter - Mechansm, Clinical Presentation
Atrial Flutter = rates of 250-350 bom
Mechanism = can be triggered by atrial Premature beats; Reentry loop within the RA, high rates of firing blocked at AV node bc refractory so ventricles beat regularly for every 204 atrial beats
Clinical = Can be transient or persistent, asymptomatic or like palpitations
(Can deteriorate into AFIB)
Risk of thrombi from pooling in Atrial appendages and can lead to stroke - anti-coagulate
Atrial Flutter - Treatment and drugs
Anti-coagulate!! for >3 weeks bc greatest risk is thrombi formation!!
First - Ventricular Rate Control with Beta blockers or Ca channel blockers to reduce AV node excitability
Second - Convert back to Sinus rhythm with Class 3 drugs (like IV ibultilde, Amiodarone etc) or electrical cardioversion
- Class 3 for effective for atrial flutter bc block K current and increase AP duraion and refractory period to help maintain sinus rhythm
- Class 1c drugs like Flecainide or Propafenone lower Na current and increase Relative Refractory Period may slow propagation and improve AV following 1:1
Atrial Fibrillation - Mechanism, Clinical Presentation
AFib = 350-600 discharges/min (ventricular 100-120)
***Irregularly Irregular*** ventricular beating where high frequency atrial impilses encounter refractory AV node and irregular pattern of propagation
one or more ectopic pacemaker sites initiating erratic pattern usually from pulmonary veins region and SA node no longer initiating impulse
RISK of blood stasis (esp in LA appendage!) leading to Stroke or PE
Rapid ventricular rate reduces CO for Hypotension and pulmonary congetsion (mre severe in people with LV hypertrophy)
Atrial Fibrillation - treatment
Control Ventricular rate - with Beta blockers or Ca channel blockers to reduce AV node propagation
If no heart disease but still symptomatic after ventricular rate control - Class Ic = flecainide [or can try class 3 Amiodarone but less reliable due to multiple reentr loops]
*IF asymptomatic, pts do not need long term treatment so long as ventricular rate is controled!!
AVNRT - mechanism and what's happening
AV node has 2 functionally distinct conduction pathways and 1 is slower than the other
Atrial Premature Beta goes down slow while the fast is refractory from normal beat and then by the time it reaches bottom of the loop can go up fast which has recovered