Therapeutics

Question 1

What is arrhythmia?

Answer 1

Abnormal ‘not normal’ cardiac rhythm

Distinct from physiological processes regulating cardiac rhythm, such as slowed heart rate during sleep or increased heart rate during exercise.

Question 2

What are the two broad types of cells found within the heart?

Answer 2

• Contractile
• Conductile

Question 3

What is the role of contractile cells in the heart?

Answer 3

Make up the majority of muscle cells in the heart and generate force for contractions.

Question 4

How does cardiac muscle contraction differ from skeletal muscle contraction?

Answer 4

Cardiac muscle contraction controlled by action potentials within the heart

skeletal muscle is controlled by motor neurons via acetylcholine.

Question 5

What is the critical threshold membrane potential for cardiac action potential initiation?

Answer 5

-60 mV

Question 6

What occurs during Phase 0 of the cardiac action potential?

Answer 6

Rapid depolarization due to inward current of Na+ through voltage-dependent sodium channels.

Question 7

What is the primary event in Phase 1 of the cardiac action potential?

Answer 7

Inactivation gate plugs Na+ channel, preventing another action potential until repolarization occurs.

Question 8

What happens during Phase 2 of the cardiac action potential?

Answer 8

Plateau phase where voltage-sensitive calcium channels open, allowing inward flux of Ca2+ ions.

Question 9

What is the significance of Phase 3 in the cardiac action potential?

Answer 9

Repolarization occurs as calcium channels inactivate and potassium channels open, restoring membrane potential.

Question 10

What characterizes Phase 4 of the cardiac action potential?

Answer 10

Pacemaker potential, typically observed in nodal and conducting tissue.

The slow, automatic rise in voltage that helps trigger a heartbeat — usually seen in the SA node and electrical pathway cells, not the regular muscle cells.

These cells naturally reach threshold on their own without needing outside signals.

Question 11

What is abnormal automaticity in the context of arrhythmias?

Answer 11

Spontaneous Pulse from Non-pacemaker cells

Question 12

What are early afterdepolarizations (EAD) and delayed afterdepolarizations (DAD)?

Answer 12

• EAD: Spontaneous activity that disrupts phase 3 of repolarization
• DAD: Spontaneous action potential after full repolarization

Question 13

What can induce delayed afterdepolarizations (DAD)?

Answer 13

Inotropic agents increasing Na+-Ca2+ exchanger activity, promoting sodium influx.

Question 14

What can cause early afterdepolarizations (EAD)?

Answer 14

Hypokalemia may prolong action potential duration, enabling enough sodium channels to return to resting state for activation.

Question 15

What are disorders of impulse conduction in the heart?

Answer 15

Interference with the propagation of action potentials, leading to conditions like bradyarrhythmias.

Propagation is how a signal travels down a nerve or heart cell so the whole thing knows to fire or contract.

Question 16

What is the difference between atrial fibrillation and atrial flutter?

Answer 16

Fibrillation is sporadic and disorganized, while flutter is more rhythmic and organized.

Question 17

What is the goal of antiarrhythmic therapy?

Answer 17

• Increase or decrease conduction velocity
• Modulate the excitability of cardiac cells
• Suppress abnormal automaticity

Question 18

What are the classes of antiarrhythmic drugs according to the Vaughan Williams classification?

Answer 18

• Class I: Sodium channel blockers
• Class II: Beta blockers
• Class III: Potassium channel blockers
• Class IV: Calcium channel blockers
• Class V: Miscellaneous (e.g., digoxin, adenosine)

Question 19

What is the effect of Class IA sodium channel blockers?

Answer 19

Slows rate of rise (phase 0) of action potential and prolongs action potential.

Question 20

What is the effect of Class IB sodium channel blockers?

Answer 20

Shortens refractory period (phase 3 repolarization) and decreases duration of action potential.

Question 21

What distinguishes Class IC sodium channel blockers?

Answer 21

Markedly slows phase 0 depolarization without affecting refractory period.

Question 22

What is the role of beta-blockers in antiarrhythmic therapy?

Answer 22

Modulate cardiac response to sympathetic stimulation, decreasing inotropy and chronotropy.

Question 23

What is the primary action of Class III potassium channel blockers?

Answer 23

Prolong repolarization and increase refractory period of action potentials.

Question 24

What potential risk is associated with potassium channel blockers?

Answer 24

Can induce torsades de pointes, a lethal form of ventricular tachycardia.

Question 25

What is the action of Class IV calcium channel blockers?

Answer 25

Inhibit currents through L-type channels, slowing conduction in SA and AV nodes.

Question 26

What are the three classes of calcium channel blockers?

Answer 26

* Dihydropyridines (DHP) * Phenylalkylamines (PAA) * Benzothiazepines (BTZ)

Question 27

How do digitalis compounds function in arrhythmia therapy?

Answer 27

Inhibit Na+-K+ ATPase and activate Na+-Ca2+ exchanger to increase intracellular Ca2+.

Question 28

What is the effect of adenosine in antiarrhythmic therapy?

Answer 28

Used to restore normal heart rhythm, particularly in supraventricular tachycardia.

Question 29

What is the role of the parasympathetic ANS in modulating heart rate?

Answer 29

It modulates heart rate by reducing it with doses less than 0.25 mg/day ## Footnote The parasympathetic nervous system primarily uses acetylcholine to exert its effects on heart rate.

Question 30

What is the ratio of Na+ to K+ in the Na+-K+ ATPase?

Answer 30

3:2 ## Footnote This means three sodium ions are exchanged for two potassium ions.

Question 31

What is the ratio of Na+ to Ca2+ in the Na+-Ca2+ exchanger?

Answer 31

3:1 ## Footnote This indicates that three sodium ions are exchanged for one calcium ion.

Question 32

What is the oral availability of Digoxin?

Answer 32

75% ## Footnote Digoxin is a cardiac glycoside used in heart failure and arrhythmias.

Question 33

What is the half-life of Digitoxin?

Answer 33

160 hours ## Footnote Digitoxin is also a cardiac glycoside with a much longer half-life than Digoxin.

Question 34

How is Ouabain eliminated from the body?

Answer 34

Kidneys ## Footnote Ouabain is not orally available and is typically used in a hospital setting.

Question 35

What is the mechanism of action of dipyridamole?

Answer 35

Blocks adenosine uptake into cells to inhibit platelet activation ## Footnote This is achieved through adenosine A2A and A2B receptors.

Question 36

What receptors does adenosine act on to activate potassium channels?

Answer 36

Adenosine A1 receptors ## Footnote Activation of these receptors enhances K+ conductance.

Question 37

What effect does enhanced K+ conductance have on action potential duration (APD)?

Answer 37

Shortens APD ## Footnote This effect also hyperpolarizes membrane potential and reduces atrial contraction.

Question 38

Does adenosine modulate ventricular activity?

Answer 38

No ## Footnote Adenosine primarily affects atrial activity and does not influence ventricular function.