arrhythmia mechanism Flashcards
Almost all arrhythmias are
acquired:
1. myocardial infarction (MI)
2. ischemia
3. acidosis
4. alkalosis
5. electrolyte abnormalities.
Drug toxicity is a common cause of arrhythmia: including
- cardiac glycosides
- some antihistamines (astemizole, terfenadine)
- antibiotics (sulfamethoxazole)
Cardiac Arrhythmia Suppression Trial (1989):
post-MI patients treated with flecainide or encainide had a 2-3x >mortality compared to placebo.
Consequence of CAST trial:
catheter ablation of ectopic foci and implantable cardioverter- debrillator devices (ICDs) are very often used in place of drugs.
Drugs
(1) remain useful in treating some arrhythmias, like ____
(2) are used with_____
(3) would be more useful if we ____
- supraventricular
- ICDs to
- understood the mechanism of action AND molecular targets better
The primary targets of antiarrhythmic drugs are:
1. cardiac Na+ channels (current = INa) 2. cardiac Ca2+ channels (current = ICa-L) 3. cardiac K+ channels (currents = IKs and IKr) 4. B -adrenergic receptors (BAR)
direct drug targets
- Na+ channels
- Ca2+ channels
- K+ channels
- B adrengeric receptors
indirect targets of antiarrhythmic drug action.
Via the B adrenergic pathway
only ____ have been demonstrated to reduce the incidence of sudden cardiac death
B blockers
prolonged ST interval corresponds to
increased AP duration
APs in which Ikr channels are partially blocked result in
prolongation of plateau phase
at ___% block, ____ are observed.
75%
after-depolarization
torsades de pointes
degenerate to ventricular fibrillation
Ina is the
cardiac Na+ channel
Ica-L is the
cardiac Ca2+ channel
INCX is the
electrogenic Na:Ca exchanger
Ikr is the
rapidly activated cardiac delayed rectifier K+ channel
Iks is the
slowly activated cardiac delayed rectified K+ channel
Ik1 is the
hyperpolarization activated K+ channel largely responsible for resting potential in ventricular myocytes
Ito is a
very rapidly activated K+ channel that is responsible for phase 1 of the fast response
voltage sensor
S4
NaV =
voltage- gated Na+ channels
familial long QT syndrome results in a
a prolongation of the duration of the cardiac action potential (QT interval) that can lead to ventricular arrhythmia and sudden death
In Familial long QT syndrome, prolongation of the plateau phase of the fast response action potential in ventricular myocytes initiates ____
a polymorphic ventricular tachycardia (called torsades de pointes) which can degenerate into ventricular fibrillation followed by syncope and sudden cardiac death.