Exam 2: Arrhythmias Flashcards
Class 1 Medications are _______ and act on phase _________
Sodium channel blockers, 0
Class 2 Medication are __________
and act on phase ________
propranolol and metoprolol, 4
Class 3 Medications are _______ and act on phase _________
Potassium channel blockers (amiodarone, sotalol), 3
Class 4 Medications are _______ and act on phase __________
Calcium channel blockers, 2
Electrical Conduction in the Heart Steps
- SA node fires
- Excitation spreads through atrial myocardium
- AV node fires
- Excitation spreads down AV bundle
5: Purkinjie fibers distribute excitation though ventricular myocardium
What influences nodal firing?
Pacemakers have automaticity
+
input from SNS and PSNS
Important Ion Channels in the Heart
sodium channels
calcium channels
potassium channels
HCN channels
hERG channel
Significance of hERG channels
an important channel to avoid being targeted when developing new drugs
Membrane Potential Outside of Cell
0 mV
Electrolyte Concentrations Outside of Cell
K = 5 mM
Na = 142 mM
Ca= 5 mM
Cl = 103 mM
Membrane Potential Inside of Cell
-70 mV
Electrolyte Concentrations Inside of Cell
K = 148 mM
Na = 10 mM
Ca= < 1 uM
Cl = 4 mM
Concentration Gradient: Sodium
flows inside of cell (142 -> 10)
Electrical Gradient: Sodium
flows inside of cell (+ to -)
Concentration Gradient: Potassium
flows outside of cell (5 <- 148)
Electrical Gradient: Potassium
inside of cell (+ to -)
Pacemaker Cells
calcium dependent spikes
non contractile cells
depolarized
high automaticity
Ventricular Myocytes
sodium dependent spikes
contractile cells
hyperpolarized
Currents for pacemaker APs: iCa
carries AP upstroke (phase 0)
Currents for pacemaker APs: iK
repolarizing K+ current (phase 3)
Currents for pacemaker APs: if
diastolic pacemaker current (phase 4)
HCN channel
Currents for pacemaker APs: iK(ACh)
K+ current activated by vagus (phase 4)
Acetylcholine
decreased HCN and calcium current
hyper-polarization (GIRK)
Atrium and SA/AV nodes
Myocyte AP Currents: iNa
carries ap upstroke (phase 0)
Myocyte AP Currents: iKto
transient outward repolarizing current (phase 1)
Myocyte AP Currents: iCa(L)
plateau Ca2+ current critical for muscle contraction (phase 2)
Myocyte AP Currents: iK
repolarizing K+ current (phase 3)
Myocyte AP Currents: if
pacemaker current (phase 4, very minimal)
No _______ channel involved in myocytes
calcium channels
neuronal action potential
The Refractory Period
result of a 2nd stimulus on ability to elicit an AP is greater as you progress through the RRP (relative refractory period)
Re-entry requirements
multiple parallel pathways
unidirectional block
conduction time greater than ERP (effective refractory period)
Class 2 Drugs
beta AR blockade
shifts the timing of the peak
HCN channel slows down the pacemaker cell, longer phase 4
useful for arrhythmias involving catecholamines (epi, norepi, etc)
increases refractoriness of SA, AV node
Class 4 Drugs
calcium channel blockades
lower the mV of the peak
frequency dependent block
protect ventricular rate from atrial tachycardia
increases refractoriness of AV node and PR interval
Class 2 Change in EKG
increases PR interval
beta blockers used in antiarrhythmics: esmolol
cardioselective B1
very short half life ~9 min due to plasma esterase hydrolysis
given iv
beta blockers used in antiarrhythmics: acebutolol
cardioselective
weak partial agonist at B1AR (sympathomimetic)
weak sodium channel blockade
beta blockers used in antiarrhythmics: propranolol
non selective
weak sodium channel blockade
clinical uses of bAR blockers
arrhythmias involving catecholamines
atrial arrhythmias
post mi prevention of ventricular arrhythmias
prophylaxis in long QT syndrome
Calcium channel blockers in arrhythmias: MOA
frequency dependent block of calcium channels
selective block for channels opening more frequently
accumulation of blockade in rapidly depolarizing tissue
clinical uses of CCBs in arrhythmias
block re-entrant involving AV node
protect ventricular rate in aflutter and afib
Class 1A effect on AP
prolonged qt interval
Class 1B effect on AP
no clinically significant effect on ECG
Class 1C effect on AP
strong sodium channel block
widens QRS
Class 1A Drug
quinidine
Class 1B Drug
lidocaine
mexiletine
Class 1C
flecainide
ventricular and supra-ventricular
orally available
Class 3 MOA
block IKr
prolong action potential duration and QT interval
increases effective refractory period
increased ERP above conduction time around circuit will terminate re-entry
Class 3 Drugs
Amiodarone
blocks IKr the most
top choice prevention of afib
suppresses emergency ventricular and atrial arrhythmias
Adverse Effects: Amiodarone
hypothyroidism
pulmonary fibrosis
photosensitization
Digoxin
inhibition of AV node
also increase intropy, used for CHF
Adenosine
leads a brief but potent slowing of the heart
Questions to ask when looking at an EKG?
P wave in front of every QRS?
QRS after P wave?
Intervals are the same?
What is the rate?
PR interval normal
0.12-0.20 seconds (120-200 ms)
QTc interval in men
360-450 ms
QTc interval in women
360-460 ms