Antiarrhythmetic Drugs #1

Question 1

Difference between the resting potential of a pacemaker cell and a ventricular myocyte

Answer 1

PM cells normally sit at a more depolarized resting potential

Question 2

PM action potentials are dependent on __ influx

Answer 2

Ca

Question 3

Talk through the ion motion in a PM cell

Answer 3

Phase 0 - Upstroke from L-type Ca channels
Phase 3 - Repolarization by voltage gated K channels
Phase 4 - Depolarization by “funny currents” performed by HCN channels and ACh-gated K chanels

Question 4

beta adrenergic receptor stimularion results in….

Answer 4

increased cAMP, increases HCN channel activity

Incrased PKA, more P of L-type Ca channels, lets channels open at more negative potentials and let more Ca thru

Question 5

What does acetylcholine do to the heart

Answer 5

• Turns on M1, which inhibits cAMP, activated GIRK
• GIRK lets more K inward, hyperpolarizing, clamping membrane potential
• Less cAMP reduces HCN, less amp. of Ca dependent spikes

Question 6

Phases of a myocyte action potential

Answer 6

Phase 0 – Upstroke Potential (Na channels)
Phase 1 – Brief Repo (transient outward notch)
Phase 2 – Plateau (Inward Ca, some Na and K)
Phase 3 – Repolarization (K currents dominate)
Phase 4 – Time btw APs, slight depolarizationg units

Question 7

Explain how the voltage gated Na Channels/Refractory Period works

Answer 7

Volatage gated channels have the m gate and the h gate
When hyperpolarized, M is closed and H is open
When first depolarized, M opens and Na rushes in
Shortly after opening, H gate closes, inactivating channel
Recovery – Close the M, open the H

Question 8

As you move later toward the end of a relative refractory period, a stimulus provides….

Answer 8

Stronger depolarization

Question 9

Scale used to classify anti-arrhythmic drugs?

Answer 9

Vaugn-Williams-Singh Scale

Question 10

Talk trough the Vaugn-Williams-Singh Scale

Answer 10

Class I – Na Channel Blockers
Class II – Beta adrenergic antag.
Class III – K channel blockers, prolonging refrac. period
Class VI – Ca Channel Blockers

Question 11

Effects of Class II antiarythmics?

Answer 11

Beta Blockers slow PM and Ca currents in nodes
Increase the refractoriness of the nodes
Increase PR Interval (protecting vent. rate)
Stop arythmias involving catecholamines

Question 12

Effects of Class IV antiarythmetics (AAs)?

Answer 12

Ca channel blockers increase frequency dependent block.
Increase the refractoriness of AV + PR interval
Protect vent. rate from atrial tachy

Question 13

Beta blockers typically used to treat arythmia

Answer 13

Esmolol, Acebutolol, Propanolol

Question 14

Important Esmolol details

Answer 14

Cardioselective with a short half life

IV

Question 15

Important Acebutolol details

Answer 15

Cardioselective
Sympathetomimetic Partical Agonist
Weak Na channel Blockade

Question 16

Important propanolol details

Answer 16

non-selective, weak Na blockage

Question 17

Why would you pick beta blockers to treat an arrythmia?

Answer 17

Arrythmia involves catecholamines
Atrial Arrhythmia
Post MI – Prevent Ventricular Arr.
Prophylaxis in long QT

Question 18

Two Ca blockers used as AAs?

Answer 18

Verapamil

Diltiazem

Question 19

Verapamil Mechanism of Action

Answer 19

Frequency Dependent Block of Calcium Channels

Accumulation of blockade in rapidly depolarizing tissues (tachy)

Question 20

Diltiazem mechanism of action

Answer 20

Blocks reentrant arrythmias involving the AV (increases refractoriness)
Protects ventricular rate in A Flut and A Fib

Question 21

Ca channel blockers are used chiefly to…

Answer 21

Protect ventricular rate in atrial flut and fib by increasing refrac. of the AV node

Question 22

Which classes of drugs influence myocyte action potentials

Answer 22

Class 1 – Na channel blockers

Class 3 – K channel blockers

Question 23

Review the appearance of the curves on page 26

Answer 23

pretty please

Question 24

Effects of Class 1A

Answer 24

Mixed Na/K block
Blocks open state
Moderate, Incomplete dissociation
Widened QRS, Prolonged QT

Question 25

Effects of Class 1B

Answer 25

Na channel Block Blocks Open and Inactivated State Rapid, Complete dissociation Narrowed AP, normal EKG

Question 26

Effects of Class 1C

Answer 26

Strong Na channel block Blocks Open State Very slow dissociation Marked QRS widening

Question 27

Important examples of 1A

Answer 27

Quinidine Procainamide Disopyramide

Question 28

Important examples of 1B

Answer 28

Lidocaine Tocainide Mexilitine

Question 29

Important examples of 1C

Answer 29

Propafenone | Flecainide

Question 30

Risks of Class 1A drugs

Answer 30

Quinidine - Torsades de Pointes, Anti Musc. Procainamide - Lupus-like, Gang. blocker Disopyramide - Anti-musc.

Question 31

Risks of Class 1B drugs

Answer 31

Lidocaine - IV, rapidly control of vent. arr.

Question 32

Risks of Class 1C

Answer 32

Propafenone - Vent and Sup. vent use. beta-blocking activity

Question 33

How do class 3 AAs work?

Answer 33

Block K channels, prolonging action potential + QT interval | Increase in Effective Refractory Period, which can terminate reentry in a re-entrant circuit

Question 34

Significance of Torsade de pointes (TDP)

Answer 34

Arrhythmia that can develop because of Class 3 agent administration or use of a drug that blocks HERG channel.

Question 35

Early after depolarizations (EAD) are capable of...

Answer 35

Giving Rise to triggered upstrokes and ectopic action potentials, potentially setting up a re-entry arrhyth.

Question 36

The five given Class 3 anti-arrhythmetic drugs

Answer 36

``` Amiodarone Dronedarone Ibutilide Sotalol Dofertilide ```

Question 37

Important details for Amiodarone/Dronedarone

Answer 37

Effects like all classes, but mostly 3 Used in emergency ventricular + atrial arr, A fib prev. Long half life (weeks) Amiodarone -- Can cause hypothyroid, pulm fibrosis Dronedarone is similar, but with less toxicitiy

Question 38

Important Ibutilide details

Answer 38

Can cause TDP | Rapid Conversation of A Fib/Flut to normal rhy

Question 39

Important details for Sotalol

Answer 39

Can cause TDP One isomer as beta-blocking activity Life threatening vent. arr. or maintenence of normal rhy.

Question 40

Important details about dofetilide

Answer 40

High risk of TDP, drug restricted, used infrequently Atrial arrythmia Requires special training/certification to administer/monitor

Question 41

Sources of Long QT Syndrome (LQTS)

Answer 41

Drug Induced Electrolyte Imbalances Bock of HERG Channel

Question 42

Some drugs that are associated witi TDP

Answer 42

antiarr, antibiotics, antineoplastics, Ca blockers, opiates, antihistamines, antipsychotics

Question 43

Clinical use of Amiodarone

Answer 43

A-fib | Suppression post-MI vent arr.

Question 44

Clinical use of Dronedarone

Answer 44

A fib

Question 45

Clinical use of Sotalol

Answer 45

Prevent A fib reoccurance

Question 46

Clinical use of Ibutilide

Answer 46

Convert A fib to sinus rhythm

Question 47

Important digoxin details?

Answer 47

Direct inhibition os AV node

Question 48

Important Magnesium Chloride details?

Answer 48

Treat hypomagnesemia Convert TDP Prevent MI and Digoxin Arr.

Question 49

Important details of Potassium Chloride

Answer 49

Hypokalemia reduces Ikr current | Prolong action potentials and can be proarrhythmetic

Question 50

Important details of Adenosine

Answer 50

Similar to M2 muscarinic activiation, depresses PM Suppresses Atrial tachycardia Short half-life, given IV