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
22
Q
Class IC agents
A
- Flecainide- prototype
- Propafenone
23
Q
Flecainide:
class
use
SE
duration
contraindications
A
- Class IC
- Used to treat recurrent tachyarrhythmias associated with abnormal conducting pathways
- Ex. Wolff-Parkinson-White syndrome (re-entry rhythm)
- treats atrial tachyarrhythmias also
- SE: LOTS
- Long acting
- should not be used post- MI (sudden death)
24
Q
Propafenone:
Class
Use
administration
A
- Class 1C
- Used to treat ventricular and atrial tachyarrhythmias
- Has weak beta-blocking and Ca channel blocking properties
- Oral
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
26
Q
What are Class II agents used for?
A
- Used to treat SVT, atrial and ventricular arrhythmias
- Used to treat ventricular dysrhythmias during MI and reperfusion
- prevents catecholamine binding to beta receptors
- slows HR
- decreases myocardial O2 requirements
- don’t trigger new arrhythmias- unlike lidocaine
27
Q
What are the Class II agents?
A
- Propanolol- prototype
- Metoprolol
- Esmolol
- Labetolol (off-label use)
28
Q
Propranolol:
Class?
use?
Cardiac effects?
SE?
Caution with?
A
- Class II antiarrhythmic drug- prototype
- Beta-adrenergic antagonist
- non-selective
- Used to prevent reoccurence of tachyarrhythmias (supraventricular and ventricular) precipitated by sympathetic stimulation
- Cardiac effects: bradycardia, myocardial depression
- SE:
- hypotension, fatigue, bronchospasm, rash, nausea, worsening raynauds
- Caution with RAD, hypovolemia, CHF, AV block
29
Q
Metoprolol:
Class?
Dose?
Onset?
Half life?
metabolization?
A
- Class II antiarrhythmic drug
- Beta-adrenergic antagonist
- selective B1
- Dose: 5 mg IV over 5 min; max 15 mg over 20 min
- Onset: 2.5 min
- Duration: 3-4 hours
- Mebabolized in liver
- Can be used in mild CHF
30
Q
Esmolol:
Class?
Dose?
Duration?
effects?
metab?
A
- Class II antiarrhythmic drug
- Beta-adrenergic antagonist
- selective BI
- Dose: 0.5 mg/kg IV bolus over I min, then 50-300 mcg/kg/min
- Duration <15 min
- Effects HR without decreasing BP significantly in small doses
- Rapidly metabolized by plasma esterases
- different ones from succ metabolization
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
32
Q
What are Class III agents used for?
A
- Suppressing supraventricular and ventricular arrhythmias
- Prophylaxis in cardiac surgery patients d/t high incidence of Afib
- preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD
- Control rhythm in Afib
33
Q
What are the Class III agents?
A
- Amiodarone- prototype
- Dronedarone- has black box warnings
- Sotalol
- Ibutilide
- Dofetilide
34
Q
Amiodarone:
Class?
Use?
Dose?
A
- Class III; also has Class I, II, and IV properties
- K, Na, & Ca channel blocker, alpha and beta adrenergic antagonist
- Use: prophylaxis or acute treatment of atrial and ventricular arrhythmias
- refractory SVT, VT/VF, AF
- 2nd line drug for VT/VF when resistant to defib
- after epi
- Dose: bolus 150-300 mg IV over 2-5 min
- up to 5 mg/kg, then 1 mg/minx6 hours, then 0.5 mg/min x 18 hours
35
Q
Amiodarone:
E1/2t
metabolization
therapeutic plasma level
PB
VD
A
- E1/2t: 10-100 days
- hepatic metabolism, active metabolite
- biliary/intestinal excretion
- Therapeutic plasma level 1.0-3.5 mcg/ml
- Extensive PB
- large VD
36
Q
What are the adverse effects of amiodarone?
A
- pulmonary toxicity/fibrosis
- pulmonary edema
- ARDS
- photosensitive rashes
- Grey/blue discoloration of skin
- pro-arrhythmic effects (torsades de pointes)
- HB
- hypotension
- inhibits CYP450
37
Q
Sotalol:
Class
Use?
SE?
Caution?
A
- Class II and III
- Beta-adrenergic antagonist (nonselective) and K channel blocker
- Used to treat severe sustained ventricular tachycardia and ventricular fibrillation
- to prevent reoccurrence of tachyarrhythmias, esp after Aflutter or Afib
- SE: prolonged QT interval, bradycardia, myocardial depression, fatigue, dyspnea, AV block
- Caution in patients with asthma
38
Q
Ibutilide
Class?
Use?
SE?
A
- “Pure” Class III
- Used to convert Afib or Aflutter to NSR
- Used to control rate in Afib or Aflutter
- Prolongs AP duration and increases refractory period
- Minimal effects on BP and HR
- High incidence of ventricular arrhythmias, need to continuously monitor for at least 4-6 hours post administration
39
Q
Dofetilide
Class?
Use
A
- Class III
- Used for maintenance of NSR after Afib or conversion of Afib to sinus
- Seems to be ok in post MI pts
40
Q
How do Class IV agents work? What is the effect?
A
- Block slow Ca channels
- primary site is AV node
- blocks slow Ca channels, which decreases conduction through AV node and shortens phase 2 of the AP in ventricular myocytes
- contractility of the heart decreases
41
Q
What are Class IV agents used for?
A
- SVT and ventricular rate control in Afib and Aflutter
- prevent recurrence of SVT
- NOT used in ventricular arrhythmias
42
Q
What are the Class IV agents?
A
verapamil
diltiazem
43
Q
Verapamil:
class?
dose?
E1/2t?
PB?
metab?
contraindications?
A
- Class IV- Ca channel blocker
- Dose: 2.5-10 mg IV over 1-3 minutes (max dose 20 mg)
- continuous infusion 5 mcg/kg/min
- E1/2t 6-8 hours
- Highly PB
- Hepatic metabolism with active metabolite
- contraindicated with Beta blockers
44
Q
What are the SE of Verapamil?
Caution?
A
- myocardial depression
- constipation
- bradycardia
- nausea
- prolongs effects of neuromuscular blockers
- Caution:
- myocardial depression and vasodilation with inhalational agnets
- can potentiate NMB
- can increase risk of LA toxicity
- hyperkalemia with Dantrolene
- dcreased clearance of digoxin
- contraindicated with WPW syndrome
- contraindicated with BB
45
Q
Diltiazam:
Class?
dose?
E1/2t
PB
metab
SE
A
- Class IV- Ca channel blocker
- Dose: 5-20 mg IV (0.25-0.35 mg/kg) over 2 min
- continuous infusion 10 mg/hr
- Ei/2t 4-6 hours
- Highly PB
- hepatic metabolism
- SE
- myocardial depression
- hypotension
- constipation
- bradycardia
- nausea
- prolongs NMB
46
Q
What are the Class V agents?
A
Adenosine
Digoxin
Atropine
47
Q
Adenosine
Class?
MOA?
Use
A
- Not in Vaughan Williams class
- Binds to A1 purine nucleotide receptors
- activates adenosine receptors to open K channels and increase K currents
- slows AV nodal conduction
- used for acute treatement only
- used to terminate SVT/diagnosis of VT
48
Q
Adenosine:
dose
duration
elimination
SE
A
- Dose 6 mg IV, rapid bolus
- Repeated if necessary after 3 minutes, 6-12 mg IV
- Duration 20-30 seconds
- eliminated by vascular endothelial cell enzymes
- SE:
- excessive AV or SA nodal inhibition
- facial flushing
- HA
- dizzinsess
- SOB
- chest discomfort/pain
- nausea
- bronchospasm (contraindicated in asthma or HB)
49
Q
Digoxin
Class?
MOA
A
- Not in Vaughan Williams class
- Cardiac glycoside
- Increases vagal activity, thus decreasing activity of SA node and prolonging conduction of impulses through the AV node
- slows AV node by increasing AV node refractory period
- Decreases HR, preload and afterload
- positive inotrope, used to treat CHF
50
Q
Digoxin
use
dose
onset
E1/2t
A
- Used for the managment of atrial fibrillation or flutter (controls ventricular rate), especially with impaired heart function
- dose: 0.5 mg in divided doses over 12-24 hours
- Onset 30-60 min
- E1/2t 36 hours
*
51
Q
Digoxin:
therapeutic index
PB
excretion
A
- Therapeutic index 0.5-1.2 ng/ml
- weak PB
90% excreed by kidneys- reduce dose in elderly/renal impaired
52
Q
Digoxin:
SE
A
- Arrhythmias
- HB
- anorexia
- nausea/diarrhea
- confusion
- agitation
- potentiated by hypokalemia and hypomg
53
Q
How is digoxin toxicity treated?
A
- phenytoin for Ventricular arrhythmias
- pacing
- atropine
- antidote: digoxin immune Fab (1st line)
54
Q
Atropine:
class
use
dose
onset
metab
A
- muscarinic receptor antagonist
- used to treat unstable bradyarrhythmias
- 0.4 to 1.0 mg IV, repeat as necessary
- peds 0.02 mg/kg
- Onset less than 1 min, duration 30-60 min
- metabolized by liver
