arrhythmia mech 4 Flashcards
How do use-dependent channel blockers prolong the refractory period?
- the drugs block initially by entering the open channel
- they have a higher affinity for the inactivated state of the channel (whether Na channel blocker like lidocaine or Ca2+ channel blocker like verapamil).
- They prolong the time the channel spends in its inactivated state.
- 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.
- there are fewer channels available to open.
- exact percentage available to open depends upon the membrane potential, with depolarization reducing the percentage.
- Depolarization also reduces the percentage of channels available to open in control because of depolarization causes inactivation of these channels.
- drug-treated channels recover from inactivation more slowly than do control channels
- they have a longer time constant for recovery from inactivation.
- This means that the use-dependent channel blocking drug will prolong the refractory period.
Re-entry could be terminated by
- 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.
faster
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.
quickly
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:
- propranolol
- metoprolol
- esmolol
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 ?
- a reduction in the rate of diastolic depolarization in pacing cells,
- reduction in the upstroke rate
- slows repolarization particularly in AV nodal myocytes.
- 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)
increase current
I-f effect on NE (symp)
increase current
I-ks effect on symp (NE)
increase current
I-ca-L effect on parasymp (Ach)
decrease current
I-f effect on parasymp (Ach)
decrease current
I-ks effect on parasymp (Ach)
decrease current
I-k-Ach effect on parasymp (Ach)
opens channel
Class II action
blocking cardiac K+ channels, with ibutilide and dofetilide specifically blocking IKr channels.
The consequences of K+ channel block are
prolongation of fast response phase 2, and a prominent prolongation of refractory period.
