Flashcards in Antiarrhythmetic Drugs #1 Deck (50):
Difference between the resting potential of a pacemaker cell and a ventricular myocyte
PM cells normally sit at a more depolarized resting potential
PM action potentials are dependent on __ influx
Talk through the ion motion in a PM cell
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
beta adrenergic receptor stimularion results in....
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
What does acetylcholine do to the heart
- 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
Phases of a myocyte action potential
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
Explain how the voltage gated Na Channels/Refractory Period works
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
As you move later toward the end of a relative refractory period, a stimulus provides....
Scale used to classify anti-arrhythmic drugs?
Talk trough the Vaugn-Williams-Singh Scale
Class I -- Na Channel Blockers
Class II -- Beta adrenergic antag.
Class III -- K channel blockers, prolonging refrac. period
Class VI -- Ca Channel Blockers
Effects of Class II antiarythmics?
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
Effects of Class IV antiarythmetics (AAs)?
Ca channel blockers increase frequency dependent block.
Increase the refractoriness of AV + PR interval
Protect vent. rate from atrial tachy
Beta blockers typically used to treat arythmia
Esmolol, Acebutolol, Propanolol
Important Esmolol details
Cardioselective with a short half life
Important Acebutolol details
Sympathetomimetic Partical Agonist
Weak Na channel Blockade
Important propanolol details
non-selective, weak Na blockage
Why would you pick beta blockers to treat an arrythmia?
Arrythmia involves catecholamines
Post MI -- Prevent Ventricular Arr.
Prophylaxis in long QT
Two Ca blockers used as AAs?
Verapamil Mechanism of Action
Frequency Dependent Block of Calcium Channels
Accumulation of blockade in rapidly depolarizing tissues (tachy)
Diltiazem mechanism of action
Blocks reentrant arrythmias involving the AV (increases refractoriness)
Protects ventricular rate in A Flut and A Fib
Ca channel blockers are used chiefly to...
Protect ventricular rate in atrial flut and fib by increasing refrac. of the AV node
Which classes of drugs influence myocyte action potentials
Class 1 -- Na channel blockers
Class 3 -- K channel blockers
Review the appearance of the curves on page 26
Effects of Class 1A
Mixed Na/K block
Blocks open state
Moderate, Incomplete dissociation
Widened QRS, Prolonged QT
Effects of Class 1B
Na channel Block
Blocks Open and Inactivated State
Rapid, Complete dissociation
Narrowed AP, normal EKG
Effects of Class 1C
Strong Na channel block
Blocks Open State
Very slow dissociation
Marked QRS widening
Important examples of 1A
Important examples of 1B
Important examples of 1C
Risks of Class 1A drugs
Quinidine - Torsades de Pointes, Anti Musc.
Procainamide - Lupus-like, Gang. blocker
Disopyramide - Anti-musc.
Risks of Class 1B drugs
Lidocaine - IV, rapidly control of vent. arr.
Risks of Class 1C
Propafenone - Vent and Sup. vent use. beta-blocking activity
How do class 3 AAs work?
Block K channels, prolonging action potential + QT interval
Increase in Effective Refractory Period, which can terminate reentry in a re-entrant circuit
Significance of Torsade de pointes (TDP)
Arrhythmia that can develop because of Class 3 agent administration or use of a drug that blocks HERG channel.
Early after depolarizations (EAD) are capable of...
Giving Rise to triggered upstrokes and ectopic action potentials, potentially setting up a re-entry arrhyth.
The five given Class 3 anti-arrhythmetic drugs
Important details for Amiodarone/Dronedarone
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
Important Ibutilide details
Can cause TDP
Rapid Conversation of A Fib/Flut to normal rhy
Important details for Sotalol
Can cause TDP
One isomer as beta-blocking activity
Life threatening vent. arr. or maintenence of normal rhy.
Important details about dofetilide
High risk of TDP, drug restricted, used infrequently
Requires special training/certification to administer/monitor
Sources of Long QT Syndrome (LQTS)
Bock of HERG Channel
Some drugs that are associated witi TDP
antiarr, antibiotics, antineoplastics, Ca blockers, opiates, antihistamines, antipsychotics
Clinical use of Amiodarone
Suppression post-MI vent arr.
Clinical use of Dronedarone
Clinical use of Sotalol
Prevent A fib reoccurance
Clinical use of Ibutilide
Convert A fib to sinus rhythm
Important digoxin details?
Direct inhibition os AV node
Important Magnesium Chloride details?
Prevent MI and Digoxin Arr.
Important details of Potassium Chloride
Hypokalemia reduces Ikr current
Prolong action potentials and can be proarrhythmetic