Module C: Drugs for Cardiac Dysrhythmia Flashcards
Pacemaker cells
-have automaticity (depolarize spontaneously), located in: SA node (R atrium, natural pacemaker) AV node Bundle of His Bundle branches Purkinje fibres
Depolarization of SA node
- resting membrane potential approx. -55- -60 mV (phase 4)
- depolarization primarily by influx of Na+ and K+ as efflux of K+ subsides
- RMP becomes less negative
- at threshold potential (TP) of -40mV, depolarization occurs (phase 0) and impulse conducted through heart
Resting Membrane Potential (RMP)
difference in ion concentration between inside of cell compared to outside
Threshold potential (TP)
critical level when all activation gates open instantaneously and there will be a large influx or efflux of an ion
RMP of ventricular myocyte
-85 to -90 mV
Phase 0-4 ventricular polarization
0: SA impulse changes RMP to less negative; when TP o f-65mV is reached, Na+ channels open to max. and Na+ rushes inside until +30mV
-depolarization of ventricles = QRS of EKG
1-2: repolarization of ventricles begins = ST segment
-K+ channels open, K+ exits cells
-this phase slowed by influx of Ca++ (isoelectric potential)
3: inward flow of Ca+ stops, outward flow of K+ increases=inside of cell is negative = T wave
-repolarization complete
4: ion distribution (K+ and Na+) different across cell membrane
-Na+/K+ ATPase pump and Ca2+/Na+ exchanger restore ions to initial and correct compartments (Na+ outside, and K+ inside)
Refractory Periods
- time when cell cannot accept new action potential until repolarization of cell has occurred
- two periods:
1: Absolute or Effective Refractory Period (ERP)- cell cannot conduct action potential, no matter how strong (Phase 0-middle of phase 3) - on EKG = beginning of Q wave to middle of T wave
2: Relative Refractory Period (RRP)- strong stimulus may result in conduction but may not be normal - on EKG = middle of T wave to end of T wave
Arrhythmias
- disturbances to normal rhythm of heart
- caused by coronary schema or hypoxia, electrolyte imbalances, increased sympathetic activity, drugs, etc.
- leads to abnormal impulse formation or abnormal impulse conduction
Abnormal Impulse Formation
- often leads to tachycardia
- due either to increased automaticity or afterdepolarization
Increased Automaticity
-diseases or drugs (ie. sympathomimetics) can make cells depolarize more rapidly
Afterdepolarization
- occurs due to abnormal Ca++ influx into cardiac cells
- occurs during, or immediately after, Phase 3 of ventricular action potential
- can be provoked by Digitalis toxicity
Abnormal Impulse Conduction
- occurs due to reentry (reexcitation of a particular area of cardiac tissue by the same impulse)
- primary cause is a unidirectional block in a bifurcating pathway, where reexcitation happens due to retrograde impulse
- often leads to tachycardia, in particular, paroxysmal supra ventricular tachycardia (PSVT)
Tachycardias
- caused by fever, increased sympathetic activity, stimulants, and pathological conditions
- may be constant or paroxysmal
- ex. PVST (atrial originated), afib, aflutter, vtach,vfib
- flutter - little blood pumped
- fib - no blood pumped
Bradycardias
- not always pathological, (ie. athletes)
- may be caused by a stroke or abnormal electrical impulses
- serious if associated with hypotensive symptoms such as LOC, dizziness, etc.)
Irregular Rhythms
- due to atrial or ventricular ectopic foci taking over SA node normal function resulting in:
- > premature or extra contractions (PAC- premature atrial contractions)
- > blockade of impulse transmission (AV block)
Non-pharmacological therapies
- defibrillation or implantable cardioverter-defibrillator (ICD)
- transcatheter ablation (uses high frequency wavelengths, freezing or heat)
- pacemaker implantation
Purpose of Antiarrhythmic Drugs
- suppress ectopic impulse generation and restore control to normal pacemaker cells
- normalize heart rhythm as much as possible
classifications of antiarrhythmic drugs
- based on mechanism of action
- Vaughan-Williams (V-W) classifications: Class I,II,III,IV
- 3 drugs do not meet classifications: Adenosine, Mag Sulfate, Digoxin (sometimes known as class V)
Class I Antiarrhythmics
-basic mode of action
SODIUM CHANNEL BLOCKERS
- greatest effect on myocardial cells actively firing (where Na+ channels are open)
- blockade of channels results in reduced action potential or amplitude of myocardial cells (delayed conduction and prolonged refractory time)
- minimal effects on pacemaker cells
Subclasses of Sodium Channel Blockers
- Class IA Pronestyl (Procainamide)
- Class IB Xylocaine (Lidocaine)
- Class IC Rythmol (Propafenone)
Class IB agent: Xylocaine (Lidocaine)
- greater effect on inactivated Na+ channels (non-firing cells), especially ventricular myocardial cells
- used for refractory ventricular arrhythmias
- local anesthetic with anti arrhythmic properties that slows down reentry impulses in ischemic tissue, so normal impulses can “take over”
- has low toxicity and high degree of effectiveness
- used for vtach/vfib in cardiac arrest situations where Amiodarone is ineffective
Class II Antiarrhythmics
B-ADREERGIC BLOCKERS
- block B adrenergic receptors, inhibiting physiologic response that would normally occur with stimulation of B receptor, by Norepi or by B agonists
- result in decreased automaticity (decreased HR), decreased AV node conduction (prolonged PR), increased AV node refractory time, and decreased inotropic effect
- used for non-life threatening arrhythmias, in particular atrial arrhythmias
- useful in preventing cardiac modelling post MI
-selective B blockers, non-selective B blockers, or combination of a+B blockers
Selective B blockers
Tenormin (Atenolol)
Brevibloc (Esmolol)
Lopressor (Metoprolol)
Non-selective B blocker
Inderal (Propanolol)
a+B blockers
Coreg (Carvedilol)
Class III Antiarrhythmics
POTASSIUM CHANNEL BLOCKERS
- primarily affect K+ channel, but also block Na+, Ca++ channels and B1 receptors
- block efflux of K+ = slowed repolarization or increased ERP and decreased HR
- aka increased refractory time agents
- drug ex. Cordarone (Amiodarone)
Cordarone (Amiodarone)
- slows down both atrial and ventricular rates
- long onset of action and extremely long T1/2 (weeks)
- can have serious toxic effects: hypothyroidism, neuropathy, hepatic dysfunction, pulmonary fibrosis
- has replaced Lidocaine as first-line anti arrhythmic in ventricular arrhythmias
Class IV Antiarrhythmics
CALCIUM CHANNEL BLOCKERS
- block entry of Ca+ ions into cell, especially at SA and AV nodes = decreased HR
- little effect on ventricular conduction and QRS duration = more useful for atrial or supra ventricular tachycardias
- drugs ex. Cardizem (Diltiazem) and Isoptin (Verapamil)
Cardizem (Diltiazem)
- slows rise of Phase 4 and 0 of SA node = increased P-P interval and slows AV node conduction velocity so PR interval is increased, HR decreased
- used as antiarrhythmic, antianginal, and as vasodilatory
Adenosine
- endogenous nucleoside, A1 receptors on myocytes in atria, SA and AV node
- ENDOGENOUS levels increase during hypoxia = vasodilation and decreased cardiac work = promotes increased O2 supply and decreased cardiac work (antiadrenergic effect)
- as EXOGENOUS, similar effects, stimulates A1 receptors = decreases HR, decreased SV, decreased response to Epi
- at A2 receptors, causes vasodilation especially of coronary arteries
- short T1/2 (10 sec) with minimum side effects
- very useful in Tx of PSVT, but no effect on ventricular tachycardias and therefore is often used to Dx arrhthmia
Magnesium Sulfate
- 2nd most common intracellular ion
- used in various cardiac functions, such as ATPase pump (used to pump Na+ and K+ into its respective compartments)
- deficiency can result in arrhythmias and CHF
- used to Tx various life-threatening ventricular arrhythmias
Digoxin
-increases parasympathetic stimulation of SA and AV node, and decreases sympathetic activity =decreased HR and AV node conduction (dromotropic effect)
