Flashcards in 7, 8. Molecular Mechanisms of Arrhythmias and Drugs Deck (54):
Cardiac arrhythmias are acquired subsequent to what 7 things?
MI, ischemia, acidosis, alkalosis, electrolyte abnormalities, drug toxicitiy, or excessive catecholamine exposure
Name a cardiac glycoside that can cause arrhythmias.
Name some antihistamines that can cause arrhythmias.
Name an antibiotic that can cause arrhythmias.
What are the 1a targets of antiarrhythmic drugs?
1. cardiac Na+ channels (INa)
2, Ca2+ channels (ICa-L)
3. K+ channels (IKs and IKr)
4. β-adrenergic receptors
What drugs can reduce the incidence of sudden cardiac death?
What is familial long QT syndrome?
a genetic prolongation of the duration of the cardiac AP (phase 2 plateau phase in the QT interval) that can lead to ventricular arrhythmia and death
What is torsades de pointes?
a polymorphic ventricular tachycardia that can degenerate into v-fib
What triggers torsades de pointes?
an abrupt increase in sympathetic tone
How are long QT patients treated?
β-adrenergic receptor blockers (β-blockers)
What is Brugada syndrome?
an inherited v-fib with only 40% survival to age 5- caused by mutations in Na+ channels
What is yotiao?
a protein that normally targets PKA, the effector of β receptors in cardiac Ca and K channels
What are the 2 general mechanisms of arrhythmia generation?
1. inappropriate impulse initiation at the SA node or ectopically
2. disturbed impulse conduction in nodes, Purkinje cells, or myocytes
Why do ectopic foci occur?
SA nodal pacemaker is abnormally slow or ectopic focus is abnormally fast; infarct
What does EAD stand for?
When do EADs occur?
in late phase 2 or early phase 3
What causes EADs?
re-activation of Ca2+ channels in response to elevated Ca2+
What does DAD stand for?
When do DADs occur?
during early phase 4
What causes DADs?
initiated by elevated [Ca2+]in and elevated Na+/Ca2+ exchange
What is NCX?
the sodium-calcium exchanger
What is the current the NCX generates?
Re-entrant arrhythmias require what two conditions?
1. uni-directional conduction block in a functional circuit
2. conduction time around the circuit is longer than the refractory period
In many cases, arrhythmia is triggered by _____ but is maintained by _____.
Why does increased sympathetic tone increase the likelihood of triggered afterdepolarizations?
Ca2+ influx is enhanced by β-adrenergic receptor activity
What is the mechanism of action of Class I Anti-arrhythmic Drugs?
voltage-gated Na+ channel blockers
All Na+ channel blockers decrease _____ and
nearly all increase _____.
conduction rate; refractory period
All _____ decrease conduction rate and nearly all increase refractory period.
Na+ channel blockers
Class I action results in _____.
_____ action results in slowed upstroke.
_____ drugs slow upstroke and also decrease action potential duration.
Class Ib drugs slow _____ and also decrease _____.
upstroke; action potential duration
_____ and _____ drugs delay phase 3 onset by blocking K+ channels.
Class Ia; class Ic
Class Ia and class Ic drugs delay ____ onset by blocking K+ channels.
Class Ia and class Ic drugs delay phase 3 onset by blocking _____.
Name 3 specific class 1a Na+ channel blockers.
quinidine, procainamide, disopyramide
All ____ drugs slow the upstroke of the fast response, and they also delay the onset of repolarization.
All class Ia drugs slow the _____, and they also delay the ____.
upstroke of the fast response; onset of repolarization
Class Ia drugs prolong the refractory period via two processes: _______ and _____.
1. classic, use-dependent mechanism, similar to local anesthetics in action
2. depolarization (phase 2 duration) is prolonged
Quinidine has important effects not related to Na+ channel block, including ____, ____, and ____.
1. blocks K+ channels particularly well, thereby prolonging action potential duration
2. it is a vagal inhibitor (anti-cholinergic)
2. it is an α-adrenergic receptor antagonist
Name 3 specific Class Ib Na+ channel blockers.
lidocaine, mexiletine, phenytoin
Lidocaine, mexiletine, and phenytoin are all what kind of drug?
Class Ib Na+ channel blockers
How are class 1b drugs similar to class 1a drugs?
they are use-dependent blockers of voltage-gated Na+ channels
In contrast to class Ia drugs, ____ drugs do not prolong phase 2 of the action potential.
In contrast to class Ia drugs, class Ib drugs do not ____.
prolong phase 2 of the action potential
What is the most important class 1b drug for the treatment of arrhythmias?
Name 3 specific Class Ic Na+ channel blockers.
propafenone, flecainide, encainide
Propafenone, flecainide, and encainide are all what kind of drug?
Class Ic Na+ channel blockers
_____ produce the most pronounced slowing of upstroke rate; the net effect is powerful prolongation of tissue refractory period.
Class Ic drugs
Class Ic drugs produce the most pronounced slowing of upstroke rate; the net effect is powerful ____.
prolongation of tissue refractory period
What does it mean that class 1c drugs preferentially target cells?
Na+ channels in myocytes with abnormally high firing rates or abnormally depolarized membranes will be blocked to a greater degree than are Na+ channels in normal, healthy myocyte
What is the mechanism of action for class 1c drugs that allows their preferential targeting?
the channel must be open
_____ is the fundamental mechanism of prolongation of cellular refractory period.
Prolongation of channel inactivation