Flashcards in arrhythmia mech 4 Deck (28):
How do use-dependent channel blockers prolong the refractory period?
1. the drugs block initially by entering the open channel
2. they have a higher affinity for the inactivated state of the channel (whether Na channel blocker like lidocaine or Ca2+ channel blocker like verapamil).
3. They prolong the time the channel spends in its inactivated state.
4. This prolongation of channel inactivation is the fundamental mechanism of prolongation of cellular refractory period.
High affinity for the inactivated state of the channel means that
these use-dependent blockers stabilize the inactivated state.
What is a vital part of the mechanism by which re-entrant arrhythmias are suppressed by these drugs?
prolongation of channel inactivation is the fundamental mechanism of prolongation of cellular refractory period, whether with Na+ channels in non-pacemaker cells or with Ca2+ channels in SA nodal or AV nodal cells.
Use-dependence: mechanism of drug action.
1. there are fewer channels available to open.
2. exact percentage available to open depends upon the membrane potential, with depolarization reducing the percentage.
3. Depolarization also reduces the percentage of channels available to open in control because of depolarization causes inactivation of these channels.
4. drug-treated channels recover from inactivation more slowly than do control channels
5. they have a longer time constant for recovery from inactivation.
6. This means that the use-dependent channel blocking drug will prolong the refractory period.
Re-entry could be terminated by
1. converting unidirectional block into bi-directional block
2. by prolonging the refractory time.
Unidirectional block can be converted to bi-directional block by?
(1) by slowing action potential conduction velocity or
(2) by prolonging refractory period.
Terminating re-entry by slowing conduction velocity will cause?
reducing upstroke rate.
Unidirectional block can be converted to bi- directional block via this mechanism.
The steeper the upstroke of the action potential, the ___ the action potential will propagate.
because the steeper upstroke corresponds to a steeper voltage gradient along the conduction pathway, which in turn makes a larger flow of action current.
larger action current pushes the adjacent, previously resting section of the conduction pathway, up to firing threshold more ____ than would a smaller action current.
A drug-induced reduction in upstroke rate therefore results in ?
slower conduction velocity.
Slower conducting action potentials are more likely to fail to propagate through a ?
depressed region, for the simple reason that the underlying action current density is smaller and therefore may fail to actively re-excite tissue beyond the depressed region.
Thus slowed conduction velocity is an ____
easy-to-measure reporter of drug-mediated block of some of the Na+ channels in the re-entrant circuit.
partial block of INa by drugs such as lidocaine means that?
in a depressed region, retrograde or circus conduction is more likely to fail, which is the intent with the use of these kinds of drugs
Prolonged refractoriness can help suppress re-entrant arrhythmias because?
the refractory tissue will not generate an action potential, and so the re-entrant wave of excitation is extinguished.
slowing conduction velocity makes it?
less likely that conduction time around the circuit will be shorter than the refractory period.
Class II Antiarrhythmic Drugs: β-blockers Drugs:
The action of class II drugs — β-adrenergic receptor blockers:
reduce If current, L-type Ca2+ current, and K+ current.
Reduction of If, ICa-L and IKs will cause ?
1. a reduction in the rate of diastolic depolarization in pacing cells,
2. reduction in the upstroke rate
3. slows repolarization particularly in AV nodal myocytes.
4. If pacing rate is reduced and refractory period is prolonged in SA and AV nodal cells.
β-blockers are thus used to ?
terminate arrhythmias that involve AV nodal re-entry, and in controlling ventricular rate during atrial fibrillation.
I-Ca-L effect on symp (NE)
I-f effect on NE (symp)
I-ks effect on symp (NE)
I-ca-L effect on parasymp (Ach)
I-f effect on parasymp (Ach)
I-ks effect on parasymp (Ach)
I-k-Ach effect on parasymp (Ach)
Class II action
blocking cardiac K+ channels, with ibutilide and dofetilide specifically blocking IKr channels.