Antiarrhythmic Agents Flashcards
1
Q
What are the phases of the action potential and what electrolytes are moving in each phase?
When is the refractory period?
A
-
Phase 0: rapid depolarization
- fast Na channels open- inward flow of Na
- closing of K channels
-
Phase 1: begin repolarization
- Na channels close
- K channels open
-
Phase 2: plateau
- Slow Ca channels open- slow inward flow of Ca
-
Phase 3: repolarization
- Ca channels close
- K channels open- slow outward K
-
Phase 4: pacemaker potential
- return to resting membrane potentials
- Refractory period is phases 1-3
2
Q
How is sinus rhythm maintained?
What is the flow of the depolarization?
A
- Sinoatrial node is cardiac pacemaker
- normal sinus rhythm is 60-100 bpm
- depolarization triggers depolarization of atrial myocardium
- conducts more slowly through AV node
- Conducts rapidly through bundle of His and Purkinje fibers
3
Q
What controls the SA node rate?
How is this done?
A
- Sympathetic nervous system stimulation- B1 receptors are activated
- increases catecholamines
- increased HR
- increased automaticity
- Facilitation of conduction of AV node
- Parasympathetic system predominates- M2 muscarinic receptors
- decreases HR
- inhibits AV conduction
- reduced automacity
4
Q
What is an arrhythmia?
How are they classified?
A
- An arrhythmia is a disturbance in the elecrical activity of the heart
- Classified according to side or origin of abnormalitiy
- atrial
- junctional- rhythm coming from AV node
- ventricular
5
Q
What are the different mechanisms of arrhythmia production?
A
-
Altered automaticity- latent pacemaker cells take over the SA node’s role
- escape beats
-
Delayed after-depolarization- normal action potential of cardiac cell triggers a train of abnormal depolarizations that start earlier in phase 4 than it should
- keeps firing again and again
- usually due to elevated cytosolic Ca levels or digoxin toxicity
-
Re-entry- Signal hits AV node and then one signal goes down to ventricle and one goes back up to atria. The signal that went back up to the atria immediately comes back to AV node for another depolarization.
- must be a unidirectional block (see pic)
- Conduction block- impulse fail to propagate in non-conducting tissue
6
Q
What underlying factors can lead to arrhythmias?
A
- arterial hypoxemia
- electrolyte imbalance
- acid/base abnormalities
- myocardial ischemia
- altered sympathetic nervous system activity
- bradycardia
- administration of certain drugs
- enlargement of a failing ventricle
7
Q
When do cardiac arrhythmias require treatment?
A
- When they cannot be corrected by removing the precipitating cause
- hemodynamic function is compromised
- the disturbance predisposes to more serious cardiac arrhythmias or co-morbidities
8
Q
What are some non-pharmacologic ways of treating arrhythmias?
A
- Acute
- vagal maneuvers
- cardioversion
- Prophylaxis
- radiofrequency catheter ablation
- implantable defibrillator
- Pacing
- external, temporary, permanent
9
Q
What are the different Vaughan Williams classes of antiarrhythmic drugs?
What should you keep in mind with these classes?
A
- Class 1: Na channel blockers
- Class II: Beta adrenergic blockers
- Class III: K channel blockers
- Class IV: Ca channel blockers
- Class V: Unclassified drugs
- **remember that some of these drugs will have an affect on other channels besides the channel that designates what class it is in
10
Q
How do Class I agents work? Rate of dissociation?
What is the effect?
A
- Block Na channels (intermediate dissociation)
- blocks inward Na ion flow during depolarization which will slow conduction rate and result in suppression of the maximum upstroke velocity of the cardiac action potential
- Slows conduction velocity
- depresses Phase 0- decreases depolarization rate
- increases refractory period
- increases action potential duration
- decreased automaticity
11
Q
What are the Class IA agents?
A
- Quinidine- prototype, but no longer used
- procainamide
- disopyramide
12
Q
Procainamide:
Class?
What is it used for?
Side effects?
A
- Class IA
- Used to treat ventricular tachyarrhythmias
- less effective with atrial tachyarrhythmias
- Side effects:
- myocardial depression leading to hypotension
- syndrome that resembles lupus erythematosus
13
Q
Disopyramide:
Class?
use?
side effects?
A
- Class IA
- used to treat atrial and ventricular tachyarrhythmias
- Side effects:
- significant myocardial depressant effects leading to hypotension
- anticholinergic effects, which result in blurred vision, dry mouth, constipation, and urinary retention
14
Q
How do Class IB agents work and what are the effects?
Rate of dissociation?
A
- Fast Na channel blocker
- Fast dissociation
- Decreases AP duration
- decreases effective refractory period
- produces little effect on maximum velocity depolarization rate
- d/t rapid association/disassociation
- decreases automaticity
15
Q
What are the class IB agents?
A
- Lidocaine - prototype
- Mexiletine
- Tocainide- not used, don’t care
- phenytoin
16
Q
Lidocaine:
Use
metabolism
SE
A
- Use: Ventricular arrhythmias
- used in acute Ventricular dysrhythmias immediately after MI
- no longer recommended for prophylaxis after MI
- particularly effective in suppression reentry rhythms (vtach, fibrillation, PVCs)
- Metabolism: Hepatic
- active metabolite with antiarrhythmic activity
- SE
- hypotension, bradycardia, sz, CNS depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, arrest, HB
17
Q
What might impair the metabolism of lidocaine?
A
- Impaired by:
- drugs:
- cimetidine
- propanolol
- physiologic altering conditions:
- CHF
- MI
- liver dysfunction
- GA
- drugs:
- Induced by:
- drugs
- barbs
- phenytoin
- rifampin
- drugs
18
Q
Mexiletine:
administration/structure
use
A
- Orally effective amine analogue of lidocaine
- Use:
- treat chronic ventricular tachyarrhythmias
- chronic pain
19
Q
Phenytoin:
Use
A
- Used to treat ventricular arrhythmias associated with digitalis toxicity
- maybe torsades de pointes and ventricular tachycardias with prolonged QTc interval
20
Q
Phenytoin:
administration
therapeutic levels
SE
A
- Mix with NS, can precipitate in D5W
- may cause pain or thrombosis when given in small peripheral IV
- Therapeutic blood levels 10-18 mcg/ml
- SE
- CNS disturbances
- inhibits insulin secretion–high blood glucose
- bone marrow depression
- nausea
21
Q
How do the Class IC agents work and what are the effects?
A
- Slow Na channel blocker
- slow dissociation
- Potent decrease of depolarization rate (phase 0)
- potent slowing conduction velocity
- no effect on AP length
- No effect on refractory period
- decreased automaticity
25
Q
How do Class II agents work?
A
- Beta-adrenergic antagonists
- Decrease rate of spontaneous phase 4 depolarization resulting in decreased SA node discharge and decreased autonomic nervous system activity
- decreased conduction velocity
- decreased automaticity
31
Q
How do Class III Agents work?
A
- Block potassium ion channels (phase 3)
- Results in prolongation of cardiac repolarization by increasing the duration of the cardiac action potential and the effective refractory period, which results in prolongation of the QTc interval on ECG
