Session 7 Cardiac Arrhythmia Drugs Flashcards
What are arrhythmias?
Heart condition where disturbances in:
- pacemaker impulse formation
- contraction impulse conduction
- combination of the two
What do arrhythmias results in? (Refer to rate etc)
Results in rate and/or timing of contraction of heart muscle that may be insufficient to maintain normal cardiac output
What is meant by resting potential and what is it caused by?
= a transmembrane electrical gradient (potential) is maintained, with the interior of the cell negative with respect to outside the cell
Caused by unequal distribution of ions inside vs outside ell
- Na+ higher outside than inside cell
- Ca+ much higher outside than inside cell
- K+ higher inside cell than outside
Maintenance by ion selective channels, active pumps and exchangers
What are the effects of class 1 drugs?
What do they block?
Block Na+ channels
= marked slowing conduction in tissue (phase 0 - the steep upward stroke)
Plus minor effects on action potential duration
What are the effects of class 2 beta-blockers?
They diminish phase 4 depolarisation and automaticity
Effect of class 3 drugs?
what do they block?
Block K+ channels
= increase action potential duration
What are the effects of class 4 drugs?
What do they block?
Calcium blockers
= calcium channel blockers DECREASE INWARD Ca2+ currents .. this results in a DECREASE of phase 4 spontaneous depolarisation
= they affect plateau phase of action potential
What drugs affect automaticity?
Beta agonists - increase the slope at phase 4 (i.e. make it steeper)
Muscarinic agonists, adenosine - decrease slope at phase 4
(Check this)
What are the two classes of rhythms associated with abnormal impulse generation?
NB: think about flow chart in slides
- Automatic rhythms
2. Triggered rhythms
What can automatic rhythms be broken down into (class wise)?
Enhanced normal automaticity —> increased AP from SA node
OR
Ectopic Focus —> AP arises from sites other than SA node
What can ‘triggered rhythms’ be broken down into?
delayed afterdepolarisation
OR
Early afterdepolarization
When referring to abnormal conduction, what two classes of problems come under this?
Conduction block (1st, 2nd or 3rd degree) =when the impulse is not conducted from the aria to the ventricles
Reentry (circus movement or reflection)
What is wolf-Parkinson-white syndrome?
An example of abnormal anatomic conduction that is present only in small populations
It leads to preexcitation
What are the actions of drugs either;
A) if there is abnormal generation
B) if there is abnormal conduction
Abnormal generation
- decrease of phase 4 slope (in pacemaker cells)
- raises the threshold
Abnormal conduction
- decrease conduction velocity
- increase EPR (so the cell wont be reexcited again)
Why do arrhythmias occur? 2
Automatic or triggered activity
Re-entry due to scar, anatomy of AV node slow and fast pathway/WPW
What is the goal for anti-arrhythmic drugs?
To restore normal sinus rhythm and conduction and to prevent more serious and possible lethal arrhythmias from occurring
These drugs are used to
A) decrease conduction velocity
B) change the duration of ERP
C) suppress abnormal automaticity
Class 1A drugs:
Action
Drug example
Action = moderate phase 0
Drugs = Quinidine, procainamide
Class 1B drugs
Action
Drug name
Action = no change in phase 0
drug name = lidocaine
Class IC drugs
Action
Drug name
Action = marked phase 0
Drugs = flecainide, propafenone
Class II drugs
Action
Drugs
Action = beta-adrenergic blockers
Drugs = bisoprolol, metoprolol, propranolol (esmolol)
Class III drugs
Action =
Drugs =
Action = prolong repolarisation
Drugs = amiodarone, sotalol
Class IV drugs
Action
Drugs
Action = calcium channel blockers
Drugs = verapamil, diltiazem
Class 1A agents
Absorption and elimination?
Oral or IV
Class 1A agents
Effects on cardiac activity?
Decrease conduction (decrease phase 0 of the action potential (Na) )
Increase refractory period (increase APD (K+) and increase Na inactivation)
Decrease automaticity (decrease slope of phase 4, fast potentials)
Increase threshold (Na+)
Class 1A agents
Effects on ECG?
Increase QRS
+/- PR
Increase QT
Uses of class 1A drugs?
Wide spectrum
Quinidine = maintain sinus rhythms in atrial fibrillation and flutter and to prevent recurrence, Brugada syndrome
Procainamide = acute IV treatment of supraventricular and ventricular arrhythmias
Side effects of class 1A drugs?
Hypotension
Reduced CO
Proarrhythmia (generation of a new arrhythmia)
E.g. Torsades de Points (increased QT interval)
Dizziness, confusion, insomnia, seizure (at high doses)
GI effects (common)
Lupus-like syndrome (particularly with procainamide)
Class 1B agents
Absorption and elimination?
Lidocaine = IV only
Mexiletine = oral phase
Class 1B agents.
Effects on cardiac activity
Fast binding offset kinetics
No change in phase 0 in normal tissue (no tonic block)
APD slightly decreased (normal tissue)
Increase threshold - Na+
Decrease phase 0 conduction in fast beating or ischaemic tissue
Class 1B agents
Effects on ECG?
None in normal
In fast beating or ischaemic
Increase QRS
Class 1B agents
Uses
Acute: ventricular tachycardia (esp during ischaemia)
NB: Not used in atrial arrhythmias or AV junctional arrhythmias
Class 1B agents
Side effects?
They’re less pro-arrhythmic than class 1A (less QT effect)
CNS effects: dizziness and drowsiness
Abdominal upset
Class 1C agents
Absorption and elimination?
Oral or IV
Class 1C agents
Effects on cardiac activity
Very slow binding offset kinetics (>10 s)
Substantially decrease phase 0 (Na+) in normal
Decrease automaticity so increase threshold
Increase APD (K+) and increase refractory period
Class 1C agents
Effects on ECG?
Increase PR
Increase QRS
Increase QT
Class 1C agents
Uses?
Wide spectrum
Supraventricular arrhythmias (fibrillation and flutter)
Premature ventricular contractions
WPW syndrome does
Class 1C drugs
Side effects
Pro arrhythmias and sudden death especially in chronic disease
structural heart disease - there is Increased ventricular response to supraventricular arrhythmias (flutter)
Class 2 agents
Absorption and elimination =
Cardiac effects =
Effects on ECG =
Uses =
Side effect =
Absorption and elimination
- propranolol = oral or IV
- metoprolol 5mg IV (oral too)
- bisoprolol = oral
- esmolol = IV ONLY (very short acting - half life is 9 mins)
Cardiac effects
- increase APD and refraction period in AC node to slow AV conduction velocity
- decrease phase 4 depolarisation (catecholamine dependent)
Effects on ECG
- increase PR
- decrease HR
Uses
- treating sinus and catecholamine dependent tachycardia
- converting reentrant arrhythmias at AV node
- protecting the ventricles from high atria rates (slow AV conduction) in atrial flutter or atrial fibrillation
Side effect
- bronchospasm
- hypotension
Class III agents - AMIODARONE
Absorption and elimination =
Cardiac effects =
Effects on ECG =
Uses =
Side effect =
Absorption and elimination = oral or IV (half life is about 3 months)
Cardiac effects
- increase refractory period and increase APD
- decrease phase 0 and conduction
- increase threshold
- decrease phase 4 (beta blocker and calcium block)
- decrease speed of AV conduction
Effects on ECG
- increase PR
- increase QRS
- increase QT
- decrease HR
Uses
* very wide spectrum! Effective for most arrhythmias
Side effect
- serious ones that increase with time!
- pulmonary fibrosis
- hepatic injury
- increase LDL cholesterol
- thyroid disease
- photosensitivity
- optic neuritis (transient blindness)
Class III = SOTALOL
Absorption
Cardiac effects
ECG effects
Uses
Side effects
Absorption = oral
Cardiac effects
- increase APD and refractory period in atrial and ventricular tissue
- slow phase 4 (beta blocker)
- slows AV conduction
ECG effects
- increases QT interval
- decreases HR
Uses
- wide spectrum!
- supraventicular and ventricular tachycardia
Side effects
- proarrhythmia
- fatigue
- insomnia
Class IV agents : verapamil and diltiazem
Absorption
Cardiac effects
ECG effects
Uses
Side effects
Absorption / administration
- verapamil = oral or IV
- diltiazem = oral
Cardiac effects
- slow conduction through AV (calcium)
- increase refractory period in AV node
- increases slope of phase 4 in SA to slow HR
ECG effects
- increases PR interval
- can increase OR decrease HR depending on BP response and baroreflex
Uses
- control ventricles during supraventricular tachycardia
- convert supraventricular tachycardia (re-entry around AV)
Side effects
- caution when partial AV block is present as can get asystole if beta blocker being used
- caution when hypotensive, decrease CO or sick sinus
- some GI problems e.g. constipation
Adenosine
Administration
Mechanism
Cardiac Effects
Uses
Administration
* rapid IV bolus (very short half life - seconds!)
Mechanism
- natural nucleoside that Indus A1 receptors an activates K+ currents in AV and SA node
- decrease APD and hyperpolarisation can lead to decreased HR
Cardiac Effects
* slows AV conduction
Uses
- convert re-entrant supraventricular arrhythmias
- diagnosis of coronary artery disease (scans)
Vernakalant
Admin
Mechanism
Cardiac effects
Side effects
Uses
Vernakalant
Admin = IV bolus over 10 minutes
Mechanism = blocs atrial specific K+ channels
Cardiac effects = slows atrial conduction
* increased potency with higher heart rates
Side effects
- hypotension
- AV block
- sneezing and taste disturbances
Uses
* convert recent onset atrial fibrillation to normal sinus rhythm
Ivabradine
Administration
Mechanism
Cardiac effects
Side effects
Uses
Admin = orally in 2.5 mg bolus dose up to 10mg
Mechanism = blocks If ion currently that is highly expressed in Sinus node
Cardiac effects = slows the sinus node but does not affect BP
Side effects = flashing lights / teratogenicity not known so avoid in pregnancy
Uses = reduce inappropriate sinus tachycardia
* reduce HR in heart failure and angina - as it avoids BP drops
Digoxin
Mechanism
Uses
Mechanism
- enhances vagal activity - increased K+ currents, decreases Ca2+ currents and increases refractory period
- slows AV conduction and slows HR
Uses
* treatment to reduce ventricular rates in atrial fibrillation and flutter
Atropine
Mechanism
Cardiac effects
Uses
Mechanism = selective muscarinic antagonist
Cardiac effects = block vagal activity to speed AV conduction and increase HR
Uses = treats vagal bradycardia
Which anti-arrhythmic drug has the most efficacy?
Amiodarone
Which anti arrhythmic drug is the worst in terms of safety and tolerability? And the best?
Worst = amiodarone
Best = beta blockers
Which drugs should be used in AF?
- rate control - slow conduction though AV node to reduce heart back to normal levels
= bisoprolol
= verapamil
= diltiazem +/- digoxin - rhythm control
= sotalol
= flecainide with bisoprolol
= amiodarone
Which drugs for VT?
Depends on what drugs already prescribed!
- metoprolol/bisoprolol
- lignocaine/mexiletine
- amiodarone
IV metoprolol/lignocaine or amiodarone
Should flecainide be used alone in atrial flutter?
No
Give AV nodal blocking’s drugs to reduce ventricular rates in atrial flutter
Best drug for treatment of WPW?
Flecainide
Amiodarone
List drugs that could be used in re-entrant NCT
Acutely (IV)
- adenosine
- verapamil
- flecainide
Chronic (repeated episodes - orally)
- bisoprolol, verapamil
- sotalol
- flecainide, procainamide
- amiodarone
Which drugs for ectopic beats?
- bisoprolol = first line
Then flecainide, sotalol or amiodarone
Which drugs to treat sinus tachycardia?
- Ivabradine (no drop in BP!)
* bisoprolol, verapamil
