Flashcards in L52 – Anti-arrhythmic Drugs Deck (126):
Assign the following ECG landmark with the cardiac cycle: P wave
depolarization of atria in response to SA node triggering
Assign the following ECG landmark with the cardiac cycle: PR interval
delay of AV node (time lapse between atrial, ventricular contraction)
allow filling of ventricles
Assign the following ECG landmark with the cardiac cycle: QRS complex
depolarization of ventricles >> triggers main pumping contractions
Assign the following ECG landmark with the cardiac cycle: ST segment
beginning of ventricle repolarization
Assign the following ECG landmark with the cardiac cycle: T wave
Assign the following ECG landmark with the cardiac cycle:QT interval
duration of action potential in ventricle
Explain the action of sympathetic activation causing a change in pacemaker potential/ depolarization.
Sympathetic activation increases slope of pacemaker depolarization
(right) Sympathetic activation > hyperpolarization-activated L type funny channels OPEN EARLIER > Increase Na+ influx > steeper slope
Explain the action of parasympathetic activation causing a change in pacemaker potential/ depolarization.
Parasympathetic activation (vagus nerve) > increase K+ permeability in pacemaker phase (IKAch open) > DECREASE slope of phase 4 pacemaker potential
What are 3 ways to regulate pacemaker activity?
Change any of:
1) Threshold potential
2) Maximum diastolic potential
3) Slope of phase 4/ pacemaker depolarization
Compare the effects of parasympathetic and sympathetic activation on phase 4 depolarization?
Sympathetic = increase slope
Parasympathetic = decrease slope
Compare the speed of transmission between Non-nodal tissue and nodal tissu.
- Non-nodal tissue: usually Na+ current >> faster transmission
- Slow-response tissue (e.g. AV node): Ca2+
current >> slower transmission
What 2 factors are important in the regulation of impulse propagation?
Magnitude of depolarizing current
Geometry of cell-cell electrical connections
Explain how Geometry of cell-cell electrical connections can influence impulse propagation?
more gap junction proteins (governs direction of propagation) at ends than side of cardiac cells
impulse spread along cells 2-3 times faster than across cells
What 2 abnormalities can lead to arrhythmia?
Abnormalities in impulse conduction
Classification of arrhythmia?
1) Supraventricular: divided into atrial / nodal
Name some causes of arrhythmia?
Where are the sites of Abnormalities in impulse conduction?
atrial (A) / ventricular (V) / junctional (AV)
How does a decrease in rate of impulse conduction lead to uncoordinated cardiac contraction?
Decrease rate of conduction >> impulse conduction easy to be blocked >> atria and ventricles have different impulses >> no longer coordinated
What are the 2 types of impulse conduction block?
What is simple impulse conductance block due to? Where does the simple block usually occur?
Myocardial infarction>> dead muscle
Altered ionic balance
Most commonly in atrioventricular (AV) node
What is Transient impulse conductance block due to?
Hypoxia > Insufficient O2
What is the result of a transient block?
Weaker force of contraction
Initially same rhythm
How does a transient block of impulse lead to unidirectional block and fibrillation?
Transient block > impulses not synchronized > when tissue recovers conduction, impulse can be transmitted BACKWARDS causing unidirectional block
This triggers RE-ENTRY (circus movement) in different parts of the heart > Fibrillation
Abnormal automaticity is observed when the resting potential is...?
reduced resting membrane potential (decreased membrane K+ conductance
>> Vm more positive / less negative)
What 2 things can enhance abnormal automaticity?
Enhanced by sympathetic nerve activity >> tachycardia
Enhanced by hypokalemia >> activate less Na+ channel causing bradycardia
Extra heart beats are triggered by ___?
Why is long QT indicative of Early Afterdepolarization (EAD)?
prolonged repolarization phase >> Long QT
What are the 2 types of afterdepolarization?
EAD - early afterdepolarization
DAD - Delayed afterdepolarization
Compare the electrolyte abnormalities that cause EAD and DAD?
EAD = Reduction of repolarizing K+ currents
DAD = increased intracellular Ca2+ level
What is early afterdepolarization?
Another depolarization occurs BEFORE repolarization is complete
What is DAD?
another depolarization occurs AFTER repolarization but
sooner than normal
Compare the abnormal automaticity in EAD and DAD?
EAD = depolarize BEFORE complete repolarization
DAD = depolarize AFTER complete repolarization but sooner than normal
In which phases of non-nodal cardiac cycle does EAD occur?
phase 2 (plateau)
phase 3 (rapid repolarization)
What is polymorphic ventricular tachycardia/ Torsades de Pointes?
uncoordinated impulses generated in all parts of heart
What causes polymorphic ventricular tachycardia?
Caused by EAD
triggers functional re-entry and circus movement
because of the heterogeneity of AP durations across the ventricular wall **many AP each with different timing**
2 Therapeutic goals of Anti-arrhythmic drugs?
Terminate ongoing arrhythmia
What are some acute therapies for arrhythmia?
What is the Vaughan-Williams Classification for Antiarrhythmic drugs?
Natalie Borrows Kelvins Car
Class I - Sodium channel blockers
Class II- B-adrenergic receptor blockers
Class III - Potassium channel blockers
Class IV - Calcium channel blockers
Describe the m (outer) and h (inner) gates of sodium channel during resting potential?
m gates closed, h gates
Describe the m (outer) and h (inner) gates of sodium channel during threshold to activation?
m gates open, h gates
Describe the m (outer) and h (inner) gates of sodium channel during Inactivation?
m gates remain open, h gates close
>> then recover to resting
Na+ channel blockers preferentially bind to during which phases?
Bind preferentially to pore area when channel is:
1) activated (open)
(i.e. when m gates are open)
What is the effect of Class I antiarrhythmic drug on tachycardia?
Block Na channel during activated or inactivated state > Decrease Na+ conduction velocity > Decrease slope of depolarization > Block Tachycardia
What is the relationship between the frequency of Na channel activation and the degree of channel block by Class I drug?
more frequently the channels are activated, the greater is the degree
What are the 3 subtypes of Class I drugs?
Class Ib: rapid kinetics
Class Ic: Slow kinetics
Name some Class Ia sodium channel blockers?
Name some Class Ib sodium channel blockers?
Name some Class Ic sodium channel blockers?
Compare the rate of dissociation from Na channels between Class I a,b,c drugs?
Ia = intermediate rate
Ib = rapid
Ic = slow
What period of cardiac cycle does Class Ia drug increase?
effective refractory period
Explain the action of Class Ia drug given it is non-selective?
Also block K+ channels > decrease rate of repolarization > increase duration of AP to prevent extra beat
What is the adverse effect of Class Ia drug? (think K+)
Risk of EAD due to Reduction of repolarizing K+ currents
= risk of inducing
torsades de pointes arrhythmia/polymorphic ventricular tachycardia
What is the gross effect of Class Ia drug?
-Inhibit increase in automaticity
-Moderate decrease in conduction
-Decrease rate of repolarization = increase duration of AP/ ERP
Adverse effect from long term use of procainamide?
lupus-related symptoms, e.g. arthralgia, arthritis
Adverse effect of procainamid and quinidine (less with disopyramide)?
Gastrointestinal disturbances, e.g. diarrhea / constipation, nausea, vomiting
Rank each of the class Ia drugs on their effects on lowering force of contraction?
disopyramide > quinidine >
What does Class Ib drugs block?
preferentially block premature beats
What is the action of Class Ib on sodium channels? (which state, when...)
Selective for inactivated (refractory) Na+ channels > suppress depolarized cells
Dissociate RAPIDLY within the time frame of normal heartbeat
(before next impulse from SA node)
Explain why Class Ib drugs can cause CNS disturbances?
Affect faster-acting Na+ channels in central nervous system for impulse conduction
What are some adverse effect symptoms of Class Ib drug?
What is the gross effect of class Ic drugs?
Decrease conduction even at normal HR
What is the interaction between Class Ic drug and Na channels?
dissociate slowly from Na+ channels (still blocked when next impulse comes)
What are some adverse effects of Class Ic drugs (flecainide, propafenone)
Worsen Heart failure
How does class Ic drug cause pro-arrhythmia as adverse rxn?
Decrease in HR = decrease cardiac output
Increase incidence of
sudden death especially in presence of severe heart failure
What is the adverse reaction caused by propafenone (class Ic)? (think heart failure and chemical structure)
structurally similar to propranolol
can act as weak B -adrenergic receptor blocker > -ve inotropic effect > worsens
What are the gross effects of Class II drugs?
B blockers oppose B-adrenergic stimulation
SA : lower heart rate
AV: Increase nodal conduction time (slow down)
Ventricle: lower intracellular Ca2+ overload
Can Class II drugs prevent DAD?
2 types of B-blockers?
Selective B1-adrenergic receptor blockers, e.g.:
Non-selective β-adrenergic receptor blockers, e.g. propranolol
Why does esmolol have a short half life?
Rapidly metabolized by erythrocyte esterases
When are selective B1-adrenergic receptor blockers used?
primarily used for intraoperative, acute arrhythmias
>> need IV admin.
When are Non-selective B-adrenergic receptor blockers used?
arrhythmia induced by
**associated with severe stress e.g. acute MI, resuscitation from cardiac arrest
What is the action of Non-selective B-adrenergic receptor blockers?
Antagonize both B1- and B2-adrenergic receptors
Which groups of patients cannot use Class II drugs?
Asthma or COPD
Why cant class II drugs be used in patients with HF?
B blocker decreases both force and rate of contraction
Why cant class II drugs be used in patients with asthma or COPD?
B blocker can cause bronchospasm
Why cant class II drugs be used in patients with diabetes?
B blocker can cause hypoglycaemia by inhibiting glycogenolysis in liver
What are the gross effects of Class III drugs?
Decrease rate of repolarisation
Decrease normal automticity and disable re-entry
> increase AP duration/ ERP
What does Dodetilide block?
Potent, “pure” blocker for the rapid delayed
rectifier potassium channel
Adverse effect of Dodetilide?
Reduced rate of repolarization > risk of EAD and torsades de pointes
Dodetilide is avoided in which patients?
advanced renal failure
Taking inhibitors of renal cation transport
What are the gross effects of Amiodarone?
- K+ channel blockade
- Block inactivated Na+ channel
- Weak adrenergic block
- weak calcium channel block
What is the commonly used drug for most kinds of arrythmia?
What are some adverse effects of Amiodarone on the heart?
Low incidence of torsades de pointes
May cause bradycardia and heart block >> chance of arrhythmia
What are some adverse effects of Amiodarone on organs other than the heart? Why ?
Due to Iodine:
Skin >> photosensitivity
Eye - corneal deposits >> visual problems
Thyroid >> hypo- / hyper-thyroidism
Lung >> pulmonary fibrosis
Liver >> hypersensitivity hepatitis
What are the symptoms of photosensitivity?
skin rashes, grey-blue skin discoloration following sun exposure
What are some drug interactions of Amiodarone?
Metabolized by cytochrome P450 (CYP3A4):
Plasma level of amiodarone can be increased or decreased by drugs interacting with CYP3A4
What is the interaction between Amiodarone and cimetidine?
Cimetidine inhibits CYP3A4 >> increase Amiodarone plasma level
What is the interaction between Amiodarone and Rifampin?
Rifampin induces CYP3A4 >> Decrease amiodarone plasma
What is the interaction between Amiodarone and drugs that depend on CYP 3A4 for metabolism?
Amiodarone increases the plasma levels of drugs that depends on CYP3A4 for metabolism (e.g. statins, warfarin, digoxin)
What influence does Amiodarone have on cardiac devices?
Need to increase pacing and defibrillation threshold
What is the action of Dronedarone?
Same mechanisms of actions as amiodarone > broad spectrum
Why is Dronedarone taken after eating?
Absorption increases 2- to 3-fold when taken with food
What are some adverse effects of Dronedarone?
Pro-arrhythmia (bradycardia and heart block)
Low incidence of iodine adverse effects
Low incidence of torsades de pointes
What is the action of Sotalol?
class III antiarrhythmic drug with class II
What is he mixture in Sotalol?
Racemic mixture of:
l-sotalol (contains B -adrenergic receptor blocking activity)
What patient group is Sotalol used for?
Treat supraventricular and ventricular
arrhythmias in the pediatric age group
Adverse Effect of Sotalol?
1 ) Pro-arrhythmia (risk of torsades de pointes)
2) Block β >> depress left ventricular function
caution in patients with heart failure
Effect of Sotalol on cardiac devices?
decrease threshold for cardiac defibrillation
Gross action of Class IV drugs? (CCB)
Decrease in :
AV nodal conduction velocity
Calcium overload (thus effective against DAD)
How could Class IV/ CCBs cause heart failure?
Decrease force of heart contraction
>> all can lead to HF
Does CCBs cause peripheral edema?
Class IV drugs are avoided in which patient groups?
Explain how CCBs can cause centricular tachycardia?
Cause Hypotension >. reflex tachycardia >> cardiac arrest
Which anti-arrhythmic drugs are rate control?
Class Ic, II
Which anti-arrhythmic drugs are Rhythm control?
Class Ia/b, III, IV
Explain how adenosine can decrease normal automaticity?
Activate presynaptic purinergic receptors on sympathetic nerve terminals > decrease release of noradrenaline
Explain how adenosine can decrease calcium overload?
Activate A1 receptors on SA and AV nodes > inhibit adenylyl cyclase > decrease intracellular cAMP production > decrease calcium overload
Explain how adenosine can decrease conduction velocity?
Activate K channels in SA and AV nodes > increase maximal diastolic potential (more hyperpolarized) > prolong phase 4/ pacemaker depolarization > decrease conduction velocity
Adenosine is potentiated and inhibited by what?
Potentiate ( drug A boosts the effects of drug B ) by dipyridamole
Inhibited by Caffeine
Why do adverse effects of Adenosine rapidly resolve?
Rapid uptake into cells for metabolism > short half life in blood
Why does Adenosine cause flushing, hypotension + chest pain and shortness of breathe?
activate A2 receptors in vascular smooth muscle >> decrease calcium release >> VASODILATION
> Hypotension >> reflex hyperventilation
Gross effect of Cardiac
glycosides: e.g. digoxin?
Decrease in both
- heart rate
- conduction velocity (especially at AV node)
Which two electrolytes can be taken to treat arrhythmia?
How could cardiac glycosides cause DAD?
Inhibit Na+-K+ ATPase activity > increase ntracellular Na+
level >> less Ca2+ expulsion by Na+/Ca2+ exchanger >> increase
> DAD/ ectopic beats
Adverse effects of cardiac glycosides?
GI disturbances, e.g. diarrhea, nausea, vomiting
CNS disturbances, e.g. drowsiness, disorientation
Risk of DAD is increased by which electrolyte imbalances?
Name one muscarinic receptor antagonist>
How does Atropine manage bradycardia?
Block muscarinic receptor = decrease vagal influence
Increase HR and conduction veolcity (esp. at AV node)
Name some side effects of Atropine after OD or repeated dosing?
Dilation of pupils
List some non-pharmacological therapy of cardiac arrhythmia?
Heart surgery (Maze procedure)
Route of administration of drug for emergency arrhythmia?
Why is combo therapy given for arrhythmia?
prevent adverse effects
What are 3 signature symptoms of Arrhythmia?
If patient has arrhythmia and syncope, which antiarrhythmic drug should you NOT use?
hypotension: do not give IV (CCB)
If patient has arrhythmia and cardiac arrest, which antiarrhythmic drug should you NOT use?
Ic (Na channel blocker, slow response)
III (Potassium channel blocker)