antiarrhythmic drugs Flashcards
class I MOA
rhythm control, Na+ channel blockers, not all just block the passage of Na ions through they channel but prolong the inactivation state of the channel. these agents prolong the recovery of the channel to resting state. Membrane-stabilizing drugs
class I agents primarily affect the following
myocytes and purkinje fibers, by binding to voltage gated sodium channels
how is arrhythmic tissue different than normal tissue
has a higher rate of depolarization and spends a lot of time in the inactive and active state and is not in the resting state very much
when does the antiarrhythmic drug bind
inactive/active state, dissociates when in the resting state, AP dec with depolarization
why is it important to take antiarrhythmic medications chronically?
the drug dissociates in the resting state, if the patient stops taking the RX, arrhythmias will come right back
Class 1A
intermediate Tau recovery time 1-10 seconds, not most common
Class 1B
rapid recovery time, Tau less than 1 second
Class 1C
slow recovery time, Tau delayed and greater than 10 seconds, most commonly used, want bc it helps drug not go back to the arrhythmia
does the drug exclusively bind to arrhythmic tissue
arrhythmic not exclusive
what would happen if the drug binds to normal tissue
irregular tracing
possible effects of class 1C agents
remain bound longest, most potential to cause arrhythmias, A and B shorter time bound
class 2 agents
beta blockers, rate control, not for severe arrhythmias
BB ____ sympathetic activity
decrease
BB ____ chronotropy, dromotropy, ionotropy activity
decrease
BB ____ SA nodal depolarization and AV nodal conduction
decrease
when are class 2 agents used
SNS induced arrhythmias - heart attacks
why are class II agents good in treating arrhythmias caused by class I (probs C) agents
slows down the conduction
comes off the tissue in resting
bblockers puts in rest phase for a longer period of time
class III agents
rhythm, dosing is important, causes ventricular arrhythmias and sudden death
class III moa
prolongs the action potential duration, mainly blocks the K+ channels (lengthens phase 3), slows/decreases depolarization, inc in action potential duration and the effective refractory period
what type of arrhythmias does class 3 treat?
reentry arrhythmias, increases the ERP (effective refractory period) when the signal comes in too early with class three and the drug comes in but the tissue doesn’t respond
class III agents effect on EKG
prolongs the QT interval, T wave shifts right, stretches out your tracing, extended prolongation is called Torsades de Pointe (twisting of QRS complex happens if extended repolarization too long)
class IV agents
calcium channel blockers, rate
Class IV agents moa
dec heart rate and dec AV nodal conduction (PR interval increases), negative ionotropic (like CCB - can’t use for a pt in heart failure)
two CCB used for arrhythmias
non-DHP verapamil (calan) and diltiazem (procardia)
Quinidine MOA
class 1A agent, Na+ blocks, has some class III activity and blocks the K+ channels,
Quinidine AE
blocks the alpha 1 receptors significant anti-muscurinic activity (AE constipation, anti-slud, salavation), GI issues in 30-50% of patients (mainly diarrhea), cinchonism (headache, dizziness, ringing in ears), bblocking effects, make sure the pressure doesn’t fall to much
Quinidine metabolism
primarily CYP3A4, inhibits CYP2D6
Quinidine drug interactions
reduces clearance of digoxin by 50% - digoxin needs dose adjustments 30-50%, blocks the alpha 1 receptors
procanimide MOA
class 1A, blocks Na+ channels but does not block the alpha 1 channels like quinidine does so it has fewer antimuscurinic effects
what is procanimide used for
acute care settings for ventricular arrhythmias
why is there a limited use of procainamide
lupus like effects (auto-immune), reversible (goes back to normal)
lidocaine MOA
class 1B, no non-class 1 activity
positive uses of lidocaine
high efficacy, low toxicity (therapeutic range is 2-6 micrograms)
negative uses of lidocaine
poor bioavailability (3%)
when is lidocaine used
acute post-MI setting for the termination of ventricular tachycardia
Perks of 1C agents
Long tau recovery time - pro arrhythmic activity- reserved for supraventricular arrhythmias who have no structural heart disease, 2nd or 3rd line agent, used in hospital, more likely to cause arrhythmias
Flecanide MOA
Class 1C agent, some class III, blocks Na+ and some K+
Metabolism of flecinide
2D6 substrate, dec CL in patients with hepatic & Renal insufficiency, tobacco inc hepatic metabolism
Flecanide AE
Non cardiac: blurred vision, dizziness, edema, abdominal pain, comstipation and headache, I’m first 2-4 weeks. May require dose adjustment
Nausea / vomit - GI
Mild negative chronotropic (contract) effect that exacerbated congestive heart failure
Propafdnone MOA
Similar to flecainide as well as week bblocking activity, B2- affects lungs, B1- no respiratory issues
Propafenone metabolism
Metabolized by cyp 2D6 and inhibits 2D6, cL decreased in patients with hepatic insufficiency
PB of propafenone
85-97% PB
Special considerations propafenone
Contraindications in patients with acute bronchospasms, bioavailability of rhythmol 325mg twice daily is equal to IR of propafenone 150mg PO 3x daily
Class 2 uses
SNS-induced arrhythmias, catecholamine induced arrhythmias (pheochrpmocytoma)
AE class 2 agents
Hypotension and Brady Cardiac- avoid I’m low BP, can cause heart block, avoid in bradycardia
Class 2 agents contraindication
Use with caution in patients with asthma/COPD and diabetes (masks signs of hypoglycemia
Esmolol half life
Ultra short acting - t1/2 10 mind, no titration needed bc half life is so short and there’s s short term control of the arrhythmia, IV only
Uses of esmolol
B1 selective so can be given to pets with respiratory issues, used in acute care setting for rapid short term control of supraventricular arrhythmia (sinus tachycardia, afib)
Propranolol MOA
Blocks B2 and B1, some class 1 activity
Propranolol admin
PO and IV
Class 3 agents MOA
Prolongs phase 3 by blocking K+ channels, small number of agents increase inward current of Na and Ca, K increases, good for reentry arrhythmias, blocks efflux, becomes more positive inside the cell
Amiodarone MOA
K+ channel blocker (3), Na+ channel blocker (1), bblocker (2), Ca+ channel blocker (4), inhibition of cell cell coupling, thyroid hormone/receptor effects (channel expression)
Amiodarone pharmaco kinetics
highly lipophilic, crosses everything easily, derivative of thyroid hormone
Amiodarone - half life
complex elimination half life. rapid component of 3-10 days, slower component of several weeks
implications of amiodarone
AE, 7-8 months to eliminate from the body, have to give a loading dose, agressive
loading dose amiodarone oral
1g/day divided doses over two weeks then 200-400mg per day
IV loading dose
acute treatment of ventricular arrhythmias: 150mg IV bolus followed by 1mg/min x 6hrs, then 0.5mg/min x 18hrs; followed by 200mg/day oral starting dose
metabolism of amiodarone
CYP 3A4, inhibits CYP 2C9 (inc warfarin), inhibits PGP (dec digoxin)
why would patients be on warfarin along with amiodarone?
afib puts them at risk for clots, atria is not pumping properly and the blood pools, make sure the patient doesn’t have a clot before putting them on meds - put on warfarin and then put them on amiodarone - make dose adjustments
AE/toxicity of amiodarone
pulmonary fibrosis (shortness of breath) 10%, most significant type of effect thyroid dysfunction corneal diposits (most pts experience) photodermatitis (rash, sensitive to sunlight, sunscreen and layers)
donedarone uses
same benefit of amiodarone but not as many AE (iodine groups are removed, amiodarone still works so much better, dec thyroid toxicity, lipophilicity, tissue accumulation and half-life goes down
PB bound donedarone
98%
metabolism donedarone
inhibits C2D6 and 3A4
implications of donedrone
patients > 65 have 23% greater exposure than those <65, females have 30% greater exposure than males
bioavailability inc with high fat meals
AE dronedrone
GI common, worsen HF, skin and soft tissue reaction (pruritis, rash, eczema, atopic dermatitis)
special considerations of donederone
pregnancy category X, twice daily with meals, dispense MedGuide with each prescription and refill, contraindicated in severe hepatic impairment
sotalol moa
class III (blocks K+), prolongs the QT interval: torsades de pointe, t wave shifts to the right, generally well tolerated
why sotalol and what happens if stop sotalol
generally well tolerated, fast ventricular arrhythmias if taking off sotalol
elimination of sotalol
eliminated mostly by the kidneys (dose adjustments), few drug interactions
dofetilide moa
class III agent
implications of dofetilide
last choice selection: patients with AF who are highly symptomatic (works well, lots of safety considerations), other AA helf for 3 half lives prior to admin
admin of dofetilide
admin by a cardiologist
elim of dofetilide
renally eliminated, contraindicated with CrCl < 20
contraindication dofetilide
avoid other drugs that prolong QT interval
ibutalide implications
prolongation of QT interval, dose dependent (give lowest dose), torsades de pointe
ibutalide rout of admin
extensive 1st pass metabolism
CCBs
class IV agents, verapamil and diltiazem
what are class IV agents good for
rate control, monitor reflex tachycardia and increased activation of the AV node, often with CCB
metabolism of class IV agents
CYP 3A4, drug interactions
class IV disease contraindications
HF
adenosine half life
10 seconds, admin 3 seconds
why adenosine
code situation of severe tachycardia, IV, induces but transient AV nodal block, patient may go into transient ventricular a-systole
digoxin moa
inhibits the Na/K ATPase, increases intracellular Ca, increases vagal activity, rate control drug, mimics PNS (parasympathomimetic), ability to decrease the AV nodal conduction (vagal like effect),
digoxin - why?
favored over class II and IV agents in treating patients with supra-ventricular arrhythmias who also have heart failure, + inotropic effect, has become a third line agent
