Drugs for Arrhythmias - Konorev Flashcards
Sodium channel gates in a voltage-gated Na channel
M gates = open during activation (depolarization)
H gates = close during inactivation (repolarization)
The resting membrane potential is largely regulated by ____ channels
Potassium
In the resting (polarized) state, ____ potassium channels are open.
Is there a current through them?
Inwardly-rectifying
NO current - electric gradient in equilibrium with concentration gradient
During phase 3 of the action potential (repolarization), ____ potassium channels open up.
Function?
Voltage-gated
Limit the frequency and duration of action potentials and refractory period
Which cardiac tissues use a FAST action potential?
Myocytes and purkinje fibers
Which cardiac tissues use a SLOW action potential?
SA and AV nodes
Flow of which ion (channel) is responsible for phase 2 (plateau) of the fast action potential?
Slow voltage-dependent calcium (inward flow)
Flow of which ion is responsible for phase 0 (rise) of the fast action potential?
Sodium
Phase 0 channels
Voltage-gated fast Na+
Phase 1 ion flow (brief repol.)
Voltage-gated K+ OPEN
Fast Na+ CLOSE
Phase 3 ion flow (start of rapid repol.)
Ca+ channels close
K+ begins to exit more rapidly
Restoration of resting membrane potential (refractory period)
Na/K ATPase and Na/Ca exchanger
Phase 4 channels of pacemaker potential
Funny Na+ current (open during hyperpolarization)
Slow Ca+ T-type channels (just before depolarization)
Phase 0 channels of pacemaker potential
L-type (long-acting) Ca+ channels
Phase 3 of pacemaker potential
K+ efflux, closing of Ca+ channels
3 factors that influence the rate of the pacemaker
- Rate of spontaneous depolarization in phase 4
- Threshold potential (more negative = easier to depol.)
- Resting potential (less negative = easier to depol.)
Function of sympathetics on pacemaker rate (pathway of events) - KNOW THIS
Beta-1 –> increased AC –> increased cAMP –> increased funny channel flow rate and decreased calcium channel threshold –> increased pacemaker speed
Function of parasympathetics on pacemaker rate (pathway of events) - KNOW THIS
M2 –> decreased AC and increased K+ opening –> slower funny currents, higher threshold (via less cAMP/PKA for Ca++ channels), and lower resting potential
What is an early afterdepolarization? Cause?
Another rapid depolarization during phase 2 or 3 of the previous action potential – caused by impaired K+ channels and prolonged repolarization period
Torsades de pointes - will see ______
Long QT syndrome (prolonged repolarization)
Do not give a Torsades de Pointes (long QT) inducing drug IF ______
Which ones are long-QT inducing?
QT is > 450 ms
- Class 1A or Class C antiarrhythmics
What is a delayed afterdepolarization? Cause?
Another partial depolarization during phase 4 (hyperpol.) DUE TO INCREASED CYTOSOLIC Ca++
3 causes of increased cytosolic Ca++
Digoxin toxicity, catecholamine excess, myocardial ischemia/reperfusion
A patient is on Digoxin, but starts experiencing heart beat issues. Explain.
Digoxin –> spontaneous Ca++ release from SR after an action potential –> 3Na/Ca exchanger –> net depolarization of membrane –> premature ventricular beats (bigeminy)
Class 1 antiarrhythmic drugs - function
Sodium channel blockers
Class 1A drugs - names
- Quinidine
- Procainamide
- Disopyramide
Class 1B drugs - names
- Lidocaine
- Mexiletine
Class 1C drugs - names
- Flecainide
- Propafenone
Class 2 antiarrhythmic drugs - function
Names?
Beta blockers
- Esmolol
- Propranolol
Class 3 antiarrhythmic drugs - function
Names?
K+ channels blockers
- Amiodarone
- Dronedarone
- Sotalol
- Dofetilide
Class 4 antiarrhythmic drugs - function
Names?
Cardioactive CCBs
- Verapamil
- Diltiazem
Miscellaneous antiarrhythmic agents
- Adenosine
- Magnesium
State-dependent blocks
Drugs block ion channel during certain stage in the cycle (active, inactive, resting)
Functions of class 1A antiarrhythmics
- Slow impulse conduction and reduce rate of pacemaker cells
- Binds ACTIVE sodium channels
- Blocks potassium channels
- Prolong action potential, QRS duration, and QT interval
Procainamide
- Uses? (6)
- Function?
- Adverse effects?
- WPW, PAC, PVC, A fib, V tach, A flutter
- Depress SA and AV nodes (sodium channel blocker)
- QT prolong (TdP), lupus-like syndrome, hypersensitivity reactions
Quinidine
- Functions? (3)
- Uses?
- Adverse effects?
- Slows velocity of conduction system, decreased automaticity of ectopic foci, and prolongs refractory period in heart
- MAT, PAC, PVC, A. fib, V. tach.
- QT prolongation (TdP), many neural symptoms, thrombocytopenic purpura
Disopyramide
- Uses? (3)
- Adverse effects?
- A fib, V tach, PAC
- QT prolongation (TdP), excess sympathetics effects
Functions of class 1b antiarrhythmics
Benefit of these?
- Binds INACTIVE sodium channels, mostly in depolarized (damaged) tissue
- Shorten action potential
- Do NOT block K+ channels –> no prolonging QT or AP
Lidocaine
- Uses? (4)
- Functions?
- Adverse effects?
- WPW, V tach, PVC, V fib
- Silences ectopic foci, increases conduction in His-Purkinje system
- Hypotension via inhibited contractility, neurologic deficits
Mexiletine
- Uses? (2)
- Functions?
- Adverse effects?
- Life-threatening ventricular arrhythmias (VT), PVC
- Silences ectopic foci and slows AV node, prolongs refractory period for junctional and ventricular pathways
- Hepatotoxicity, seizures
Functions of class 1c antiarrhythmics
Binds ACTIVE sodium channels and some potassium channels
ECG effect of class 1c drugs
- LONG QRS
Flecainide
- Clinical use?
- Chronic therapy for long-term V. tach, supraventricular arrhythmias
Propafenone - adverse effects
- Metallic taste
- Constipation
- Exacerbation of ventricular arrhythmias or HF
Propafenone - MoA (2)
- Increase refractory period and decrease conduction velocity through heart
- Weak BETA-BLOCKING ability
Functions of beta blockers (class 2 drugs) (2)
- Slow action potential (slow down SA and AV nodes)
- Prevent delayed afterdepolarizations (decrease Ca++ overload)
Uses of Propranolol and Esmolol with arrhythmias
- Stress-associated sinus tach.
- AV nodal re-entrant tachycardia
- A fib, A flutter
- WPW syndrome
Function of class 3 drugs
- Block potassium channels – prolong AP and QT
Amiodarone
- Use?
- Adverse effects?
- Ventricular arrhythmias
- AV block, bradycardia, pulmonary fibrosis, hepatitis, blue-gray skin discoloration, optic neuritis, thyroid problems
Dronedarone
- Functions?
- Use?
- Adverse effects?
- CONTRAINDICATION?
- Blocks K+ channels, Na+ current, L-type Ca++ current
- A. fib/flutter
- Worsening heart failure, GI stuff
- INCREASED MORTALITY w/ decompensated HF
Sotalol
- Functions?
- Uses?
- Adverse effects?
- Beta-blocker AND AP prolonger
- Vent. arrhythmias, maintianing sinus rhythm w/ A. fib.
- Cardiac depression, TdP INDUCTION
Dofetilide
- Function?
- CAUTION?
- Use?
- Adverse effect?
- Blocks rapid part of rectifier K+ current (lower HRs)
- NARROW THERAPEUTIC WINDOW
- Converts AF to sinus rhythm
- QT prolongation, risk of ventricular arrhytmias
Function of class 4 drugs
- Blocks all L-type calcium channels
- Decreased slope of phase 0 depolarization
- Prolong SA and AV node APs and refractory periods
Uses of Cardiogenic CCBs
- Prevent paroxysmal SVT
- Control rate in AF and A. flutter
Adverse effects of cardiogenic CCBs
- AV block, weaken contractility, hypotension, CONSTIPATION (VERAPAMIL)
Function of Adenosine
- Activate K+ current, inhibit Ca++ and funny currents –> hyperpolarization of SA and AV nodes
Use of Adenosine
Adverse effects?
- Convert paroxysmal SVT to sinus rhythm
- SoB, bronchoconstriction, chest burning
Uses of magnesium
- Digitalis arrhythmia
- TdP
