Cardac Arrhythmia Drugs Flashcards
What are arrhythmia
Heart condition where disturbances in – Pacemaker impulse formation – Contraction impulse conduction – Combination of the two Results in rate and/or timing of contraction of heart muscle that may be insufficient to maintain normal cardiac output (CO)
Describe thr eating potential
• 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 cell
– 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
Desribe the fats cardiac AP
Ss
Describe how class 1 drugs work
Block Na+ channels — Marked slowing conduction in tissue (phase 0) Minor effects on action potential duration (APD)
Describe how class 2 drugs work
Beta blockers — Diminish phase 4 depolarisation and automaticity
Slightly increasing refractory period. Affects depolarisation
Desribe how class 3 drugs work
Block k channels
Increase action potential duration (APD) (plateau phase increased)
Risky - can overlap with other beats - pro arrhythmic?
Describe how class 4 drugs work
Ccb Calcium channel blockers decrease inward Ca2+ currents resulting in a decrease of phase 4 spontaneous depolarization
Effect plateau phase of action potential
Reduced plateau, effect on phase 4 depolarisation
Describe the slow cardiac ap
Ss
Describ ethe efect of Ca2+ blockers on the slow cap
Slope of phase 0 = Conduction velocity
Reduces slope
Describe drugs affecting automaticity
Change phase 4 - beta blockers may be effective at reducing these affects
Muscarinic agonists, Adenosine
???
Gove an overview of mechanisms of arrythmogenesis
Abnormal impulse generation
- Automatic rhytms
- Triggered rhythms
Abnormal conduction
- COnduction block
- Re-entry
How can absonral conduction occur
Ss
Drive abnormal atomic conduction
Present only in small populations
•Lead to preexcitation→Wolf-Parkinson-White Syndrome (WPW)
Ss
Describe re-entry
S
Describe the actio of drugs to treat abnormal generation
Descrease of phase 4 slope in pacemaker cells - slow the automaticity
Raise the threshold - in order to generate impulse, have to have AP above a certain point
Describe the actio of drugs in the case of abnormal condition
Decrease conduction velocity
Increase ERP so ckd cant be reexcited agai
Descrive pharmacologic rationale ad goals
• Goal:
- restore normal sinus rhythm and conduction
- prevent more serious and possibly lethal arrhythmias from occurring
• Antiarrhythmic drugs are used to:
- decrease conduction velocity
- change the duration of ERP
- suppress abnormal automaticity
Give an overview of the drugs used
Ss
Descrive class 1a agents
Class 1A agents: Procainamide, quinidine, disopyramide
Absorption and elimination (oral or iv)
What are the effects of 1A on cardiac activity
Effects on cardiac activity
^ conduction (v phase 0 of the action potential (Na+))
^ refractory period (^APD (K+) and^Na inactivation)
V automaticity (v slope of phase 4, fast potentials)
^increase threshold (Na+)
Quinidine has anticholinergic (atropine like action) to speed AV conduction used with digitalis, β blocker or Ca channel blocker
Effects on ECG ^ QRS, +/- PR, ^QT
Wat are the uses of 1A
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
What are the side effects of 1A drugs
Hypotension, reduced cardiac output
Proarrhythmia (generation of a new arrhythmia) - eg.Torsades de Points (increased QT interval)
Dizziness, confusion, insomnia, seizure (high dose)
Gastrointestinal effects (common)
Lupus-like syndrome (esp. procainamide)
What are class 1B
Class 1B agents: Lidocaine, mexiletine
Absorption and elimination
Lidocaine: iv only (initially)
Mexiletine: oral (long term)
What are the effects of class 1B drugs on cardiac activity and ECG
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,
Effects on ECG
None in normal, in fast beating or ischaemic increase QRS
What are the uses of class 1B
Uses
acute : Ventricular tachycardia (esp. during
ischaemia)
Not used in atrial arrhythmias or AV junctional arrhythmias
What are the side effects of class 1B
Less proarrhythmic than Class 1A (less QT effect)
CNS effects: dizziness, drowsiness
Abdominal upset (major side effect)
What are class 1C agents
Flecainide and propafenone
Absorption and elimination
oral or iv
2mg/kg
terminate rhytms
What are the effects of class 1C on cardiac activity and ecg
very slow binding offset kinetics (>10 s)
Substantially decrease phase 0 (Na+) in normal
decrease automaticity (increase threshold)
increase APD (K+) and refractory period, esp in rapidly depolarizing atrial tissue.
ECG: increase PR, QRS and QT
What are the uses of class 1C
Wide spectrum
Used for supraventricular arrhythmias (fibrillation and
flutter)
Premature ventricular contractions (caused problems)
Wolff-Parkinson-White syndrome
What are the side effects of class 1c
Side effects
Proarrhythmia and sudden death especially with chronic use (CAST study) and in structural heart disease
increase ventricular response to supraventricular
arrhythmias (flutter)
CNS and gastrointestinal effects like other local anesthetics
What are Class II agents
Class II agents: propranolol, bisoprolol, metoprolol
and esmolol
Absorption and elimination
Propranolol: oral, iv
Metoprolol 5mg IV, orally too (shorter acting BD or TDS
regime)
bisoprolol: oral
Esmolol: iv only (very short acting T1⁄2, 9 min)
What are the cardiac effects of Class II
Increase APD and refractory period in AV node to slow AV
conduction velocity
decrease phase 4 depolarization (catecholamine
dependent)
ECG: increase PR, decrease HR
What are he uses of class II
treating sinus and catecholamine dependent tachycardia
converting reentrant arrhythmias at AV node
protecting the ventricles from high atrial rates (slow AV
conduction)
What are the side effects of class II
bronchospasm
hypotension
don’t use in partial AV block or acute heart failure (are
used in stable heart failure)
What are Class III agents
Class III agents: amiodarone, sotalol
Amiodarone
Absorption and elimination
high efficacy but high side effects
oral or iv (T 1/2 about 3 months)
What are the cardiac and ecg effects of amiodarone
- increase refractory period and Ç APD (K+)
- decrease phase 0 and conduction (Na+)
- increase threshold
- decrease phase 4 (β block and Ca++ block)
- decrease speed of AV conduction
ECG: increase PR, QRS and QT
Decrease HR
What are the uses of amiodarone (cIII)
Amiodarone (cont.)
Uses
Very wide spectrum: effective for most arrhythmias
What are the side effects of amiodarone
Side effects: many serious that increase with time
Pulmonary fibrosis Hepatic injury Increase LDL cholesterol Thyroid disease Photosensitivity optic neuritis (transient blindness)
May need to reduce the dose of digoxin and monitor warfarin more
closely
Dronaderone (no iodine) not widley used despite new drug, failed to
live up to expectation
What are the cardiac effects of sotalol
Cardiac effects
- Increase APD and refractory period in atrial and ventricular tissue
- Slow phase 4 (β blocker)
- Slow AV conduction
ECG: increase QT, decrease HR
What are the uses of sotalol
Wide spectrum: supraventricular and ventricular tachycardia
What are the side effects of sotalol
Proarrhythmia, fatigue, insomnia
What are class IV agents
Class IV agents: verapamil and diltiazem
Administration
verapamil: oral or i.v.
diltiazem: oral
What are cardiac effects of class IV
- slow conduction through AV (Ca++)
- increase refractory period in AV node
- inrease slope of phase 4 in SA to slow HR
Effects on ECG: increase PR,
- increase or decrease HR (depending of blood pressure response and baroreflex)
What are the uses of class IV
Uses
control ventricles during supraventricular tachycardia
convert supraventricular tachycardia (re-entry around AV)
What are the side effects of class IV
Caution when partial AV block is present. Can get asystole
if β blocker is on board
Caution when hypotension, decreased cardiac output or
sick sinus
Some gastrointestinal problems (constipation)
What are some additional antiarrythmic agents
SEE TABLE
Which drugs could be used in AF
Rate control:
– Bisoprolol, verapamil, diltiazem + digoxin
Rhythm control:
– Sotalol, flecainide with bisoprolol, amiodarone
– (dronedarone hardly used)
Which drugs coulkd be used in VT
– Metoprolol/bisoprolol
– Lignocaine/mexiletine
– amiodarone
Should flecainide be used alone in AF?
No
– Give AV nodal blocking drugs to reduce
ventricular rates in atrial flutter
Best drug for WPW
Flecainide
amiodarone
What could be used in re entrant SVT
• Acutely (IV) – Adenosine – Verapamil – flecainide • Chronic (repeated episodes, orally) – Bisoprolol, verapamil – sotalol – Flecainide, procainamide – amiodarone
What is best for ectopic beats
- Bisoprolol first line
* Flecainide, sotalol or amiodarone
Sinus tachycardia?
Ivabradine
Bisoprolol, verapamil
