22. Drug Action on Ion Channels and Pumps

Question 1

Describe what is happening at Phase 0, 2, and 3.

Answer 1

Phase 0 - the rapid depolarization phase caused by influx of Na+
Phase 2 - repolarization caused by efflux of K+ but balanced by influx of Ca2+ –> remains horizontal line

Question 2

Explain what the responsibility of NAv1.5 is.

Answer 2

NAv1.5 is the voltage-gated Na+ channel that is responsible for intial upstroke of action potential.

Question 3

Identify what maintains the resting potential.

Answer 3

Na+-K+ pump

Question 4

Explain the effective refractory period (ERP).

Answer 4

ERP is the period in time, in which a new action potential cannot be initiated.

Question 5

Identify the 4 classes of antiarrhythmic agents.

Answer 5

Class 1 - Na+ channel blockers
Class 2 - beta blockers
Class 3 - K+ channel blockers
Class 4 - Ca2+ channel blockers

Question 6

Explain how the strength of the inhibitor is going to effect the initial Phase 0.

Answer 6

Inital phase 0 slope is decreased more as the inhibitor gets stronger.

Question 7

Rank the kinetic strength of class 1 antiarrhythmic agents: Na+ channel blockers from strongest to weakest.

Answer 7

Class 1B (strongest - fast kinetics)
* Lidocaine, phenytoin
* decreases ERP

**Class 1A **
* Quinidine, procainamide
* increases ERP

Class 1C (weakest - slowest kinetics)
* flecainide, propafenone
* maintains ERP

Question 8

Explain how Na+ channel blockers can work as antiepileptic agents.
Give examples.

Answer 8

By blocking the voltage-gated Na+ channels, there is no influx of Na+ into the neuronal membranes.
–> results in decreased axonal conduction by increasing the ERP of the neuron
* Phenytoin, carbamazepine, oxcarbazepine

Question 9

Can Na+ channel blockers be used as local anesthetic agents?

Answer 9

Yes! They can be short, medium, or high duration anesthetics.
Short - low potency - procaine, chloroprocaine
medium duration potency - lidocaine, prilocaine
high duration potency - tetracaine, bupivacaine

Question 10

List the three drug actions on sodium channels.

Answer 10

• antiarrhythmic drugs
• antiepileptic drugs
• local anesthetic agents

Question 11

Explain the function of Class 3 antiarrhythmic agents: K+ channel blockers.

Answer 11

Primary role: K+ channels are responsible for cell repolarization
* increases phase 3 of the cardiac action potential (delayed repolarization)
* increases ERP

Question 12

Explain the contribution of Class 3: K+ channel blockers on reducing arrhythmias.

Answer 12

K+ channel blockers inhibit the efflux of K+ ions
* increases the period before a new signal for contraction can be generated
* helps correct arrhythmias by reducing the potential for premature/abnormal contraction of the ventricles
* prolongs the frequency of ventricular contraction –> treats tachycardia

Question 13

List drugs that are K+ channel blocker antiarrhythmic agents.

Answer 13

• amiodarone
• sotalol
• dofetilide

Question 14

List drug actions on calcium channels.

Answer 14

• antiarrhythmic drugs
• antihypertension drugs

Question 15

What are the two types of Ca2+ channel blockers and what are they used for. Give examples.

Answer 15

Dihydropyridine Ca2+ channel blockers
* antihypertension
* amlodipine, nifedipine, fleodipine

Non-dihydropyridine Ca2+ channel blockers
* antihypertension and antiarrhythmics
* verapamil, diltiazem

Question 16

Explain the role of Class 4: Ca2+ channel blockers.

Answer 16

• primarily present in the SA and AV nodes of the heart
• decreases the length of phase 2 in the cardiac action potential
• slows heart rate –> allows left ventricle to fill completely and lowers the heart workload

Question 17

Describe the Na-K pump and its role in membrane potential.

Answer 17

• cells use the Na-K pump to help maintain a negative resting potential and gradients of Na+ and K+
• 3 Na+ ions leave the cell
• 2 K+ ions enter the cell
• each ATP molecule decreases the membrane potential by one charge unit
• Na-K pump is an active transporter

Question 18

Describe the mode of action of Ouabain.

Answer 18

Ouabin is a natural toxin that acts by inhibiting the Na-K pump.
* cardiac glycoside and can be used to treat hypotension and some arrhythmias in low doses

Question 19

Describe how digoxin works as a Na-K pump inhibitor.

Answer 19

Used to treat various heart conditions
* inhibits the Na-K pump in the myocardium
* inhibition causes an increase in intracellular Na+ –> decreased activity of the Na-Ca2+ exchanger
* high intracellular Na+ causes Na-Ca2+ exchanger to pump IN Ca2+ and OUT Na+ –> increase Ca2+ concentration in cell
* result: decreased heart rate bc it contracts stronger

Question 20

What are PPIs used for?

Answer 20

PPI (proton pump inhibitors) are used to turn off proton pumps and reduce acid production in the stomach
* acids are produced by proton pumps (H+-K+ pumps)
* treats GI diseases: GERD, esophagitis
* drugs: –prazole

Question 21

Explain the mechanism of PPIs.

Answer 21

• PPIs irreversibly bind to H+-K+ pumps.
• prevents the movement of H+ ions from the parietal cells to the stomach = achlorhydria (all gastric acid secretion is temporarily blocked)
• to return to normal acid secretion, the parietal cells must create new H+-K+ pumps

Question 22

Answer 22

E. propranolol

Question 23

Answer 23

A. lidocaine

Question 24

Answer 24

E. Flecainide - maintains ERP

Question 25

Answer 25

E. Digoxin leads to an increase in heart rate
* digoxin leads to a slower heart rate bc of the stronger contractions

Question 26

Answer 26

D. Omeprazole prevents the movement of H+ from the stomach to the parietal cells.