Pharmacology - Arrhythmias Part 2 Flashcards
true or false
class Ia sodium channel blockers have vagolytic properties and this is a positive effect
FALSE - negatve effect
vagolytic properties will result in increased heart rate and conduction which is udnesirable in arrhythmia patients
differentiate between the metabolism of procainamide/quinidine/disopyramide
procainamide goes directly to phase 2 acetylation to form NAPA
quinidine and disopyriamide undergo phase 1 by CYP3A4 — watch for DDI!!!!
true or false
quinidine slows conduction through the heart
true
true or false
quinidine can cause QT prolongation and thus torsades de pointes
true
name some unique AE of quinidine
cinchonism - tinnitus, headache, dizziness
also watch for low potassium (electrolytre imbalance) - contraindicated in hypokalemia
true or false
rifampin is a CYP3A4 inhibitor
FALSE - inducer
which class IA sodium channel blocker has the HIGHEST vagolytic activity
disopyramide
which 1A sodium channel blocker has similar anticholinergic side effects like atropine
disopyramide
disopyrimide is only given in….
LIFE THREATENING ventricular arrhythmia
CI disopyramide
may cause or worsen CHF! or severe hypotension
name 2 types of drugs that quinidine is CI with
drugs that prolong QT or drugs that cause electrolyte imbalance (specifically hypokalemia)
true or false
lidocaine blocks both activated and inactivated sodium channels with rapid kinetics
true
lidocaine is highly effective in what specific arrhythmias
those associated with acute MI
explain HOW lidocaine is an antiarrhythmic
increases the threshold
true or false
lidocaine is most effective on atrial cells
FALSE - greater effects on cells with long action potentials like purkinje and ventricular cells
true or false
lidocaine can be given oral or IV
FALSE - only IV
extensive 1st pass
explain lidocaine dose adjustments
its highly protein bound to alpha acid glycoprotein - need to MONITOR and adjust dose accordingly to prevent AE
decrease the dose in drugs like propranolol that decrease liver perfusion and thus decrease metabolism
metabolism of lidocaine
1A2 AND 3A4
CI lidocaine
in patients with preexisting condction abnormalities like SA, AV block
true or false
lidocaine is one of the LEAST cardiotoxic sodium channel blockers
TRUE !!!! weakly bound - fast dissociation kinetics
can lidocaine cause hypotension
yes - by depressing contractility
true or false
lidocaine does not have CNS AE
FALSE - it does
bc of the hypotension can cause lightheadedness and also sodium channel blocking in general
lidocaine plasma levels should be kept below ____ to avoid side effects
9 micrograms/mL
true or false
mexiletine is given orally
true
metabolism of mexiletine
CYP2D6
general AE mexelitine
CNS (like lidocaine)
tremor, blurred vision, etc
effect of flecainide on APD
DOES NOT PROLONG
true or false
flecainide has SLOW unbinding kinetics
true
true or false
out of all of the Na channel blocking classes, flecainide has the most anticholinergic effects
FALSE - has no anticholinergic effects!
metabolism of flecainide
2d6
is flecainide given orally
yes
in which patients can class IC sodium channel blockers NOT BE GIVEN TO
patients with structural heart disease!!!!!!!!!!!!! higher mortality
true or false
flecainide is proarrhythmogenic
true
unique mechanism of propafenone
structurally similar to propranolol so has weak beta blocking action!!
DDI concerns propafenone
3A4 AND 2D6 inducers/inhibitors
also increases concentrations of digoxin, warfarin, and propranolol! need to decrease their doses!
name 5 class 3 potassium channel blockers/multichannel blockers
amiodarone
dronedarone
dofetilide
sotalol
ibutilide
major effect of class 3
increased APD and ERP (effective refractory period)
true or false
no 1C sodium channel blockers should be used in heart disease patients
true
true or false
class III blocks repolarization
TRUE
blocks potassium channels in phase 3 – preventing repolarization
true or false
class III shortens the ERP
FALSE - prolongs
true or false
class III does not show reverse use dependence
FALSE - it does
what does it mean that potassium channel blockers show reverse use dependance
effect is low at higher heart rates (higher heart rate is when the action is really needed!!!)
true or false
ALL class III causes QT prolongation
true
what does amiodarone structurally resemble
thyroxine (T4)
explain the hydrophilic/lipophilic properties of amiodarone
VERY LIPOPHILIC!!!
accumulates in adipose and thyroid tissue and can cause toxicity
to increase absorption, take with food!!!
name a scenario in which amiodarone has been shown to benefit patients
shown to decrease the frequency of cardioverter-defibrillator discharges (shock delivered to heart_
true or false
amiodarone is widely used and useful against most arrhythmias
true
**true or false
the major action of amiodarone is as a class III potassium channel blocker
TRUE
minor action is sodium channel blocking
in what state does amiodarone block sodium channels
in the inactivated state
true or false
amiodarone shows NO reverse use dependence
true
true or false
amiodarone does not cause QT prolongation
false - all the class III do. however, risk of torsades is low
does amiodarone have any effects outside of the heart?
YES - causes vasodilation and decreased blood pressure when given IV
route of administration amiodarone
explain how route changes the action
oral and IV
oral - takes 1-3 weeks to see effect. usually more used for prevention
IV - you see rapid effects. usually used for treatment
true or false
amiodarone has a low Vd
FALSE - high Vd. accumulates in adipose and thyroid tissue
excretion of amiodarone
biliary (fecal)
true or false
amiodarone has a short half life
FALSE - very long. takes several weeks for the action of the drug to stop
DDI concerns with amiodarone
metabolized by 3A4!
amiodarone + statin
increased statin levels and thus increased risk of myopathy
cyclosporine/digoxin + amiodarone
increased levels of cyclosporine/digoxin
bc amiodarone inhibits Pgp (efflux protein)
digoxin dose needs to be decreased by half!
5 things that INHIBIT CYP3A4 and thus increase toxicity of amiodarone
“CLAP G”
cimetidine
loratidine
antidepressent (trazodone)
protease inhibitors
grapefruit juice
2 CYP3A4 inducers
what is their effect on amiodarone
rifampin and st john’s wort
decreased efficacy of amiodarone
3 drugs that increase risk of QT prolongation when given with amiodarone
azole antifungals
macrolides
fluoroquinolones
fentanyl/lidocaine/dextromethorphan + amiodarone
increase levels of fentanyl/lidocaine/DM
cholestyramine + amiodarone
decreased amiodarone levels (only applies to oral!)
mechanism of amiodarone thyroid toxicity
blocks conversion of T4 to T3 (active) - hypothyroidism (WOLFF-CHAIKOFF EFFECT) or hyperthyroidism
areas with high diet of iodine + amiodarone…
hyperthyroidism
amiodarone toxicities
thyroid toxicity
skin gray-blue discoloration
loss of vision
pulmonary toxicity
bradycardia
worsened arrhythmias
structural analog of amiodarone
dronedarone
differences between amiodarone and dronedarone
the iodine was removed
has NO EFFECT on thyroxine metabolism like amiodarone does
true or false
dronedarone doesnt accumulate as much as amiodarone
true - shorter half life
true or false
unlike amiodarone, dronedarone has NO thyroid effects and NO pulmonary toxicity
true
true or false
dronedarone has liver toxicity
true
DDI concern with dronedarone
cyp3a4 substrate and inhibitor
BBW of dronedarone
DO NOT USE IN HEART FAILURE PATIENTS
