PMT - Konorev Antiarrhythmic Drugs Flashcards
Explain function of sodium channel and relationship to concentration gradients.
What is the Na concentraiton gradient?
140mmol/L outside, 10-15mmol/L inside
What are the 3 sodium channel states?
- Resting state - channel closed
- Activated State - depol to threhold opens m-gates
- Inactivated state - h-gates closed, inward sodium iflux inhibited, channel is not available for reactivation - responsible for refractory period
What is the potassium concentration gradient?
4mmol/L outside, 140mmol/L inside
Describe the function of K and Na regulation of membrane potential?
What is the function of K+ channels?
- At resting state - Inward rectifying K+ channels open during resting state.
- Regulation of action potential - VGKC regualte repolarization of cell.
Cardiac AP - what has fast AP, what has slow AP?
- Fast AP - Ventricle, artium, Purkinje
- Slow (pacemaker) AP - SA node, AV node
Fast action potential in cardiac muscle. Phases
Phase 0 - INa(fast)
Phase 1 - IK = repol
Phase 2 - plateau phase, IK and ICa(slow)
Phase 3 - Ca channels close, K exits faster
Phase 4 - Resting membrane potential restored by Na/K-ATPase and Na/Ca-exchanger
Fast action potential in cardiac muscle - deconvolution of cationic fluxes of cardiac AP
Pacemaker AP Phases
Phase 4 - slow, spontanous depol = ICa(T-type, slow) and If
Phase 0 - Upstroke of AP = Ca influx thorugh ICa(L-type)
Phase 3 - repolarization, inactivation calcium channels with increased IK
What is the mechanism of arrhythmia?
Altered automaticity of the SA node due to
The two types of abnormal pulse formations.
-
Early afterdepolarizations - in phases 2 or 3 of AP
- Prolonged repol d/t impaired function of K-channels
- Abnormal depol d/t Ca or Na channel opening
-
Delayed afterdepolarizations - in phase 4 of AP
* increased cytosolic Ca
Torsade de point - what is it?
What is a proarrhythmia?
What rarely induces TdP?
Drug-induced new arrhythmia or worsening of pre-existing arrhythmia.
Due to: antiarrhythmic drugs (groups 1A and 3), antipsychotics, antihistamines, antibiotics, antidepressants
Amiodarone rarely induces TdP
Do not give TdP-inducing drugs if QTc is less than what?
How is QTc calculated?
QTc = less than 450ms
QTB= (QT)/(square root of RR)
What can cause delayed afterdeloparizations?
Digitalis toxicity, cat excess, myocardial ischemia
What are digoxin-induced arrhythmias?
Spontaenous Ca release fromSR activates 2Na/2Ca exchange, leading to net depolarizing current.
Digoxin induced bigeminy NSR, PVB, and ST
List the 5 classes of drugs
- Class 1 - Na Channel blocker
- Class 2 - Beta Blockers
- Class 3 - Potassium Channel Blockers
- Class 4 - Calcium Channel Blockers
- Unclassified