Drugs Modifying Cardiac Rate and Force Flashcards Preview

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3 Major ions to consider in Drugs?



How many types of AP in the heart? What are they called?

2 types
Fast and Slow response


Where is the fast AP response present?

Atrial and ventricular muscle; purkinje fibers


Where is the slow AP response present?

SA node (normal pacemaker)
AV node (normal route of AP conduction between atria and ventricles)


Phases of fast response?

Phase 4 = -90mV
Phase 0 = Rise to +30 mV
Phase 1 = Small decrease from +30mV
Phase 2 = Plateau
Phase 3 = Larger decrease back to -90mV


Phases of the slow response?

Phase 4 = Small incline from -65mV
Phase 0 = Rise up to +10mV
(No distinct phase 1 or 2)
Phase 3 = Decrease back to -65mV


What is the fast response dependent on?

Sodium dependent


What is the slow response dependent on?

Calcium dependent


What can cause significant changes to the duration and phases of an AP?

-Normal, physiological, influences such as autonomic transmitters and some hormones
-Cardiac disease (ischaemia)
-pH of the blood and electrolyte abnormalities
-Drugs, either intentionally, or unintentionally (adverse effects)


Membrane potential in ventricular cardiac muscle cells in phase 4?

-90mV (resting potential)


What is dominant in phase 4 of a fast response?

Outwards flux of K+


What Vm?

Membrane potential


What is significant about resting Vm in phase 4 of FR?

Close to the equilibrium potential for K+ (-94mV) due to K+ conductance via specific voltage-regulated K+ channels conducting an outwards hyperpolarizing current called iK1

However Ek and Vm are not completely the same due to to small inwards depolarizing leak conductance to Na+


How are ion concentration gradients across the membrane maintained? And what drug can affect this?

Na+/K+ ATPase
This can be inhibited by digoxin - which then causes the cell to depolarizes slightly


What is dominant in phase 0 of a FR?

Inward flux of Na+


What is the appearance of phase 0?

Upstroke to +30mV


What triggers ventricular and atrial impulses?

SA node


What does triggering V & A impulse involve?

Rapid activation of voltage-activated Na+ channels at threshold potential (-65mV) generating a Na+ conductance and an inward depolarizing Na+ current that drives Vm towards the Na+ equilibrium potential (-74mV)

This is very brief as the Na+ channels rapidly inactivate during depolarization to non conducting state and they only recover from this at partial repolarization


What is dominant in phase 1 of FR?

Outwards flux of K+


How would you describe phase 1 of FR? Depolarization or repolarization?

Early repolarization


Describe phase 1 of FR?

Most evident in cardiac cells that have predominant phase 2 (plateau) (eg purkinje fibers)


What causes phase 1?

Rapid inactivation of I.Na
-Activation of transient K+ current
called I.to mediated by a specific class if voltage activated potassium channel distinct from the inwards rectifier K+ channels


What is dominant in phase 2?

Inward flux of Ca++ is roughly balanced by outward flux of K+


How would you describe phase 2?



What is phase 2 caused by?

A balance of conductances - inwards depolarizing flow of Ca++ and an outwards repolarizing flow of Na++

Inwards flow of Ca++= via voltage activated Ca++ channels (L-type) (activate relatively slowly in upstroke of the AP [-30mV], inactivate even more slowly = produces long lasting Ca++ current crucial to C. muscle contraction


What effect does any drug which increases the Calcium movement have?

Decrease the force of contraction of the heart


What is the effect of any drug which decreases potassium?

Augment the force of contraction of the heart


What changes occur in potassium conductance in phase 2?

-I (K1) decreases, facilitating the depolarizing effect of I(Ca,L)
-Ito= continues to exert a repolarizing effect initially but reduces with time
-Voltage activated delayed rectifier potassium channels slowly open generating the repolarizing current Ik


How long does the plateau persist for?

For as long as the charge carried by the inward flux of Ca++ is balanced by that carried by the outward flux of K+


What do calcium blockers do to the plateau phase?

Reduce I.Ca,L thus reduce the duration of plateau and force of cardiac contraction