Antidysrhythmics Flashcards
Phase 4 for the working myocardial cells begins when
membrane potential is taken to a transmembrane potential of -90mV
Potassum efflux
Phase 4 for the working myocardial cells ends when
membrane potential reaches -70 mV
Phase 0 represents
rapid depolorization up to 20 mV
Sodium influx
*Vmax (rate of rise) reflects myocardial contractility
Phase 1 represents
Early/fast Repolorization
Fast sodium channels close
Transient Potassium outward current
Phase 2 (plateau) represents
Calcium influx
What are the three functions of the inward calcium current
Prolong refractory period
Delivers calcium to inside of myocardium (electromechanical coupling)
Activates SR to release intracellular calcium stores
Phase 3 represents
Repolarization
Massive reflux of Potassium
When does the relative refractory period begin
during the last half of phase 3
- Calcium channels can reopen at -30 mV if stimulated
- Sodium channels can reopen at -70 mV if stimulated
phase 4 for the myocardial pacemaker cells begins when
cell has reached full repolorization of -70mV
phase 4 for the myocardial pacemaker cells ends when threshold potential reaches
-40 mV
What are three determinants of the frequency of discharge of the cardiac pacemaker cells and what is the effect
rate of phase 4 depolarization
the threshold potential
resting transmembrane potential
- increase in HR
How can you increase the HR while maintaining the rate of depolarization
making the threshold potential more negative or
making the resting transmembrane potential less negative
What effect does the PSNS (AcH) have on the slope of phase 4 myocardial pacemaker cells
decreases the rate of rise»_space;>decrease in HR
What effect does SNS (epi/Norepi) have on the slope of the phase 4 myocardial pacemaker cells
increasing rate of rise»>increase in HR
Dysrhythmias are caused by what two factors
abnormal pacemaker activity or
abnormal impulse spread
What are the four major mechanisms used to tx dysrhythmias
Sodium channel blockade
Calcium channel blockade
Prolonging the effective refractory period
Blocking the Sympathetic autonomic effects
Class I antidysrhythmias largely work by
blocking sodium channels during phase 0 depolarization»>decrease in depolarization and conduction velocity
Class I’s are further subdivided into
Class Ia, Ib, Ic
Class 1a’s inhibit sodium influx and possess what three other unique properties
prolongs AP duration
prolongs the effective refractory period
lengthens repolarization via potassium blockade
*Prodysrhythmic (prolongs QT and depresses conduction)
Class 1b’s inhibit sodium influx and posess what three other unique properties
shortens AP duration in normal cardiac cells
prolongs AP duration in ischemic tissues
decreases spontaneous phase 4 depolorization rate»decreases HR
Class 1c’s inhibit sodium influx and posess what other unique properties
ONLY effects AP duration of purkinje fibers
QRS widens via inhibition of His-purkinje network
*Prodysrhythmic (causes SVT)
Class II’s are
B-adrenergic antagonists
Class II’s work by
decreases rate of phase 4 depolarization
decreases conducton velocity overall
decreases inotropy at higher doses
Class III work by
blocking potassium ion channels resulting in:
prolongation of cardiac repolarization
prolongation of AP duration
prolongation of effective refractory period
- prolongs QT interval
Class IV are
calcium entry blockers
Name the Class Ia antidysrhythmic agents
Procainamide Police
Disopyramide Department
Quinidine Question
What is the MOA for Quinidine
decreases the slope of phase 4 depolarization in PACEMAKER cells
What is Quinidine used to tx
Recurrent SVT
Atrial fibrillation with rapid ventricular response
PVC
VT
Quinidine is mainly metabolized by
liver
*Induces P450 system
What other effects does quinidine have
a-adrenergic blockade»vasodilation»>hypotension
What effect will high doses of quinidine have on the myocardium
depression»decreased contractility
What paradoxical effect can be seen with patients taking quinidine in Sinus rjythm
Increased HR
What effects does quinidine have on neuromuscular transmission
decrease transmission
- potentiates NMB
What are two common SE with quinidine
N/D
What are contraindications to quinidine
VT caused by QT prolongation
AV blocks
Procainamide is an amide analog of
procaine
Procainamide is similar to quinidine except:
less prolongation of QT interval
less antimuscarinic properties
Procainamide is metabolized by
Kidney (40-60%)
Liver (60-40%)»>NAPA (active metabolite that depends on kidney for excretion)
*Beware in Patients with renal disease
Do Plasma cholinesterase effect Procainamide
NO
What are the contraindications to Procainamide
Shock Myasthenia gravis AV Block Renal failure CHF
Disopyramide has similar electrophysiologic profile as quinidine and procainamide, but differs with the degree of
antimuscarinic effect
*More pronounced
What are SE associated with Disopyramide
More pronounced myocardial depressant effects (negative inotropic)
Serious anticholinergic effects seen in patients with glaucoma, prostated, myasthenia gravis, severe constipation
Disopyramide is contraindicated in
Uncompensated HF Glaucoma Hypotension untreated UTI Significant QT prolongation
Class Ib antidysrhythmics work by
inhibition of fast sodium channels (phase 0)
shortens AP in normal heart tissues
lengthens AP duration in ischemic tissues (thus preventing re-entry and retrograde conduction)
decreases rate of spontaneous phase 4 depolarization
Name the Class 1b antidysrhythmic agents
Tocainide The
Lidocaine Little
Mexiletine Man
Phenytoin Paul
Lidocaine is used to tx
Ventricular dysrhythmias such as:
PVC
VT
V fib prevention
What is the therapeutic plasma concentraton of lidocaine
1-5 mcg/mL
Can lidocaine be given PO
No, extensive first-pass hepatic metabolism
What is the IV bolus therapeutic level of lidocaine
1-2 mg/kg
*immediate IV infusion at 1-4 mg/min
Do not exceed what
3 mg/kg within one hour period
What are contraindications with Lidocaine
SA, AV block
Stoke-Adams Syndrome
WPW syndrome
Sinus bradycardia
Therapeutic levels of Lidocaine will produce what s/s
1-5 mcg/mL Numbness of tongue Light-headedness Tinnitus Visual disturbances
Lidocaine levels reaching 7 mcg/mL will produce what s/s
Muscular twitching
Lidocaine levels of 10 mcg/mL will produce what s/s
Unconsciousness
Convulsions
Lidocaine levels of 15 mcg/mL will produce what s/s
coma
Lidocaine levels of 20 mcg/mL will produce what s/s
Respiratory arrest
Lidocaine levels of 25-30 mcg/mL will produce what s/s
CVS depression
Lidocaine toxicity should be tx by
stopping lidocaine
100% 02
Seizure control
Mexiletine is an orally active amine of
Lidocaine
What is mexiletine used to tx
chronic suprression of VT
What effect does mexiletine have on hemodynamic system
none
What effect does mexiletine have on QT interval
none»>less prodysrythmic
What effect does mexiletine have on vagolytics
none»>no reflex tachycardia
Class Ic antidysrhythmics work by
Inhibition of the His-purkinje fast sodium channels (phase 0)»>QRS widening
*Causes significant Supraventricular prodysrhythmic properties
Name the Class Ic agents
Flecanide For
Propafenone Pushing
Encainide Ecstasy
Flecanide is used to tx ventricula dysrhythmias with what exception
must have normal LV function d/t its negative inotropic effects
Encainide is different than flecanide only in
less negative inotropic activity
What class Ic agent is the only agent useful for supraventricular dysrhythmias
Propafenone
Class II antidysrhythmics are AKA
beta-adrenergic antagonists
SE associated with beta-adrenergic antagonists include
PR interval prolonged brady progressive AV block myocardial depression hypotension bronchospasm (b2)
Although Esmolol is beta 1 selective antagonism, at high doses, what is noted
b2 antagonism
What is the half-life of esmolol
9 minutes (very short acting)
how is esmolol metabolized
ester hydrolysis by red cell esterases
*redistribution half-life is 2 minutes
Name the b1 selective antagonists
AA BB EM
Class III antidysrhythmic agents work by
blocking potassium channels»prolongs repolarization
increases AP duration
QT interval prolonged»>prodysrhythmic
Name Class III antidysrhythmic agents
Bretylium Amiodarone Dronedarone Sotalol Azimilide Dofetilide Tedisamil Ibutilide
*IT BAD, SAD
Bretylium works by
strongly blocking potassium channels in purkinje networks
causes an initial release of NE»>then Inhibits NE release»then inhibits NE reuptake
Amiodarone is a class III antidysrrhythmic with that has wide spectrum of
activity
Amiodarone is used to tx what three dysrhythmias
SVT
Ventricular tachydysrhythmias
WPW
Amiodarone has what effect on ALL cardiac tissues
prolongs the effective refractory period
- SA node, atrium, AV node, HIS-Purkinje system, ventricle, adn accessory bypass tracts
What similarities does amiodarone share with the other classes of antidysrhythmics
blocks sodium channels ( class 1a activity)
noncompetively blocks b-adrenoreceptors (class II activity)
prolongs APD/repolorization of potassium channel blockade (class II activity)
weak calcium channel blocker-class IV activity
- also blocks a-adrenergic receptors»vasodilation
What effect does amiodarone have on coronary arteries
dilates and increases coronary blood flow
*antianginal
Peak plasma concentration of amiodarone is achieve in how many days
15-30 (orally)
How long does the pharmacological effects of amiodarone last after being D/C’d
45-60 days
Amiodarone is extensively metabolized into what ACTIVE form
desethylamiodarone
Desethylamiodarone is excreted by the
lacrimal glands
skin
biliary tract
*NO renal excretion
What is the IV loading dose of amiodarone
150 mg over 10 minutes
How much amiodarone should be given over next 6 hours
360 mg
How much amiodarone should be given over next 18 hours
540 mg
What is the maintenance infusion of amiodarone
0.5 mg/min
How much amiodarone should be given as a supplemental infusion for breakthrough dysrhythmias
150 mg
What is the major SE associated with amiodarone
Pulmonary toxicity
*predisposed to ARDS, must keep Fi02 < 0.3
What endocrine gland is effected by amiodarone
thyroid (hyper/hypo thyroidism)
*inhibits peripheral conversion of T4 to T3
What hematologic component is effected by amiodarone
directly depresses vitamin K-dependent clotting factors (II, VII, IX, X)
Sotalol at low doses behaves as a ——–, and at high doses behaves as a ——–
b-blocker
class III antidysrhythmic
*prolongs the APD in the atria, ventricles, and accessory bypass tracts
Is sotalol a prodysrhthmic
YES
*because of this, it is restricted to use in life threatening situations
What are unique features of the pharmacokinetics of sotalol
does not bind to plasma proteins and is not metabolized
excreted unchanged by kidneys (lower with renal failure)
Ibutilide is a class III antidysrhythmic that is indicated for
a-fib
a-flutter
*slows repolarization and prolongs APD
Name the three Class IV antidysrthmics and their MOA
Verapamil
Diltiazem
Nefedipine
*calcium channel blocker
Phenylalkylamines and benzothiazepines are calcium channel blockers that are selective for
AV node
Dihydropyridines are CCB taht are selective for
arteriolar beds
What is the MOA of
selectively blocks the inward transfer of calcium through slow calcium channels in heart and vasculature
What is the effect of CCB on the heart
decreased HR
decreased contractility
decreased SA/AV nodal conduction
- prevents recurrent SVT
- reduces the ventricular rate in a. fib
What is the effect of CCB on the vascular smooth muscles
vasodilation»relaxation
Verapamil and diltiazem also block
fast sodium channels
Verapamil is a
phenylalkylamine
Verapamil binds to which portion of the L-type calcium channel
intracellular portion when the channel is in an OPEN state (occludes the channel)
What are two isomer of verapamil and their MOA
dextro-isomer act upon fast sodium channels
levo-isomer acts upon the calcium channels
What effect does verapamil have on the SA node
direct depressant
What is verapamil effective in treating
SVT (a fib, a-flutter with RVR)
Nifedipine is a
dihydropyridine calcium antagonist
Nifedipne binds to which side on the calcium channel
outer gate of the slow calcium channel
Nefedipine primarily acts on the
arterial smooth muscles
Nefedipine is used to tx what four conditions
prinzmetal’s angina
raynaud’s phenomenon
essential HTN
pulmonary HTN
Nifedipine is rapidly oxidized by
light
*must be given immediately if drawn into a syringe
What is the MOA of digoxin
inhibition of sodium-potassium ATPase pumpe
What is the effect of blocking the NA/K+ atpase pump
increases intracelluar sodium
decreases extrusion of calcium leading to greater intracellular calcium availability»>greater contractility (INOTROPISM)
What effect does digoxin have on phase 0
decreased d/t inhibition of outward transport of sodium
What effect does digoxin have on the APD
decreases it d/t shortened phase 2
By enhancing PSNS tone, digoxin has what three effects on the heart
decreased SA node activity
prolongs absolute (effective) refractory
suppresses conduction across AV node
What percentage of digoxin is excreted unchanged by the kidneys
75%
Digoxin competes with what electrolyte
potassium
*with low level of potassium, digoxin activity increases
What are the three main body systems effected by digoxin toxicity
Heart- brady, dysrhythmias r/t increased SNS tone secondary to arterial hypoxemia
GI- d/t increased vagal tone, increase Ach activity in the gut
Nervous system- d/t blocking Na/KATPase dependent photoreceptors (amblyopia, scotoma, trigeminal neuralagia)
Name four methods of correcting digoxin toxicity
d/c digoxin
correct hypoxemia/hypokalemia
treat dysrhythmias
Give DIGIBIND
What is the three MOA of adenosine
slows conduction through AV node
interrupts re-entry pathways through AV node
restores SR in SVT and WPW patients
What is the initial dose of adenosine and the repeat dose
6 mg IV RAPID (1-2 seconds)
12 mg repeat dose with refractory dysrhythmia
