Block 3: Antiarrhythmics
Terms
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- If
-
Na+ inward
Phase 4 - Ica
-
Ca2+ inward
Phase 0 - Ik1
- K+ outward phase 4
- Ina
- Na inward phase 0
- Icat, IcaL
-
Ca inward
Phase 2 - Pacemaker cells
-
Intiate spont. action potential (APs)
Found in SA and AV nodes - All pacemaker cells possess
- Automaticity- ablility to depolarize above threshold in a rhythmic fashion
- Pacemaker cells are also .... cells
- Ca2+ dependent slow-response cells (w/respect to phase 0)
- Conducting cells
- Atrial and ventricular conducting systems: His bundles, bundle branches, Purkinje fibers
- Conducting cells aka
- Na+ dependent fast-response cells
- Non-pacemaker and non-conducting cells
-
Atrial and ventricular myocytes
*can acquire automaticity in pathologic conditions - Are ions distributed equally across the cell membrane?
- No :)
- where do you find If channels
- pacemaker cells
- what do B blockers do to If channels?
- Decrease rate of Na current by (-) cAMP production and PKA activation leading to reduced automaticity and heart rate (HR)
- Where do you find Ica channels
- Pacemaker cells
- How do beta blockers affect Ica
- Decrease Ca current by (-) PKA mediated phosphorylation
- Consequence of beta blockade of Ica channels?
- Decreased automaticity and conduction velocity (esp. in AV node)
- How do Ca channel blockers work?
- slow rise of AP in slow response cells of SA and AV nodes AND prolong repolarization of the AV node
- Consequence of Ca blockade
-
Slowed conduction velocity thru AV node with prolonged repolarization increases the effective refractory period of the AV node
English: It slows the heart down - Two Class IV Ca channel blockers
-
Verapamil
Diltiazem - Is Ik1 opened or closed at resting state? What is the consequence?
-
Open
Membrane resting potential
(-90) of fast response cells is close to the equilibrium potential for K+ (-94) - What is the Nernst equation?
- Ek = -61 * log [ (x)i/(x)o ]
- Explain hyperkalemia via nernst equation?
- If [Ko} is elevated to 10mM (may happen in hyperkalemia) the Ek rises to -70mV, making depolarization easier--arrythymias.
- Where do you find Ina channels?
- Fast-response cells
- What does opening of Ina channels cause?
- Membrane potential moves towards Ena (+70mV)
- What are the 3 conformational states of the Na+ channel?
-
Active
Inactive
Closed/resting - When can the Na channel be reactivated?
- In the closed state
- What is the recovery time dependent on?
- Time and voltage
- Which channel is the major determinant of the velocity of impulse conduction throughout the ventricle?
- Na channel (b.c. of refractory state)
- How do Na channel blockers work?
- Increase threshold voltage for channel activation and thereby increase the refractory period (can't reactivate as quickly)
- What is the fxn of IcaT and IcaL channels?
- Mediate plateau phase (phase 2) by transient (IcaT) and long (IcaL) currents
- How do IcaT and IcaL differ?
- IcaT inactivates with time and is insenstive to blockage by dihydropyridines, whereas IcaL channels are.
- Example of dyhydropyridine
- Nifedipine
- Which Ca channel dominates in cardiac cells?
- L-type Ca channels
- How do Ca channel blockers work
- Prolong refractory period of the fast response cells by decreasing Ca influx (increase phase 2)
- What is the consequence of Ca channel blockade?
- Decreased contractility--- decreased ventricular rate
- Uses for Ca channel blockers?
-
Control ventricular rate
A fib or A flutter - Nifedipine vs. Verapamil and diltiazem
-
All Ca blockers
Nifedipine more effective on vascular smooth muscle
Verapamil and diltiazem more effective on cardiac muscle - Name 3 major pumps and what they do.
-
ATP-dependent Na-K pump: 3Na out 2K in, generates repol
ATP-dependent Ca pump (SERCA): moves Ca back into Sarc reticulum
Na-Ca exchanger (NCX): 3 Na in for 1 Ca out - Which pump does digitalis inhibit?
- ATP-dependent Na-K pump
- Which pump do Beta blockers inhibit? How?
-
ATP-dep. Ca pump
(-) PKA mediated phosphorylation of phospholamban - Where do normal cardiac impulses orginate?
- SA node
- Where do abnormal cardiac impulses orginate
- anywhere, including SA node
- What is refractoriness dependent on in slow-response cells?
- Recovery of Ca channels
- What is refractoriness dependent on in fast-response cells?
- Na channel recovery
- What determines basic HR? What else is important?
-
Automaticity
Conduction Velocity - How is automaticity controlled?
- The ANS controls spontaneous depolarization (phase 4) threshold potential, and resting membrane potential
- 3 categories of arrhythmias
-
Defects in impulse formation
Defects in impulse conduction
Defects in both - Mechanism of defective impulse formation
- SA node automaticity interrupted or altered--missed or ectopic beats
- Can ectopic beats occur w/o SA node alteration or interruption?
- Yes
- MA of defective impulse conduction
- AV node conduction accelerated or decreased--- irregular beats
- Two types of defective impulse formation
-
Altered automaticity
Triggered automaticity: EAD and DAD - Give and example of early after depolarization
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Torsades de pointe
Drugs that prolong QT interval: Amiodarone, procainamide, ibutilide - Give causes of delayed after depolarization
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Mycardial ischemia
Adrenergic stress
Digitalis intoxication - Two types of defective impulse conduction
-
1. Re-entry e.g. Paroxysmal supraventricular tachycardia (PSVT)
2. Conduction block e.g. MI, drugs (Amiodarone, procainamide) - Give an example of a condition that causes both defective impulse formation and conduction.
- Atrial fib w/ AV block