antiarrhythmics Flashcards
class 1 agents
block Na channels which depresses phase 0, in depolarization of the cardiac AP which results in decreased AP propagation–
decrease in depolarization rate, and slowing of conduction velocity
decreasing upstroke of depolarization
blocks excitation of myocardium (which occurs with tachy)
membrane stabilization drugs
(ex: LA also block Na channels)
3 sub types
class 1a
Intermediate Na channel blockers (intermediate dissociation)
decreased depolarization rate
Phase 0 decreased conduction velocity
Prolonged repolarization
Increased AP duration and refractory period of cells
in addition blocking K channels
class 1a drugs
Quinidine- Class 1a prototype, rarely used
Procainamide: not used bc of SE: hypotension
Disopyramide: PO,
Moricizine: PO
Disopyramide
suppresses atrial and ventricular tachyarrhythmias
membrane stabilizing, decreased excitability of cells
PO
SE: has significant myocardial depressant effects and can precipitate congestive Heart failure and hypotension
Class 1b agents
FAST Na channel blockers (fast dissociation) Phase 0 weak or less powerful bc so quick: fast association and dissociation with Na channels alters the AP by inhibiting Na ion influx via rapidly binding to and blocking Na channels (fast) Produces little effect on max velocity depolarization rate (the rate of the rise of phase 0) leaves many channels blocked by time AP reaches the peak but shortens AP duration and shortens refractory period bc fast has different effect that class 1a, advantage can be use for topic and premature beats
class 1b agents
lidocaine- class 1b prototype, still used for arrhythmia
mexiletine
tocainide: no uses in US
phenytoin: torsades
Lidocaine dose, kinetics
Dose: 1-1.5mg/kg IV
gtt: 1-4mg/min (max 3mg/kg)
there is PO but has extensive 1st pass
50% pb
hepatic metabolism: active metabolite which prolongs e1/2t
metabolism may be impaired by drugs: cimetidine and propanolol. conditions: CHF, acute MI, liver dysfunction GA
metabolism my be INDUCED by barbs, phenytoin or rifampin
10% renal
Lidocaine e1/2t, therapeutic plasma [ ], AE
e1/2t 1.4-8hr
[ ] 1-5mcg/ml
lidocaine use
**acute tx/prevention of vent dysrhythmias immediate post MI–raises vent fib threshold
vent tachy, fibs, PVC,
pulseless VT, and VF
lidocaine AE
CNS effects leading to resp depression leading to cardiac arrest
hypotension, brady, sz, decreased CNS, drowsiness, dizziness, tinnitus, condusion, apnea, myocardial depression, sinus arrest, HB, vent depression, cardiac arrest,
Mexiletine
class 1b
for chronic suppression of ventricular cardiac tachyarrhymias
PO
Class 1C
Slow Na channel blocker (slow dissociation) so does not vary much during cardiac cycle
Very Potent
Phase 0: potent decreased of depolarization rate with increased AP and refractory period
markedly inhibit conduction through His-purkinje system
Flecainide
class 1c prototype
effective in tx of suppressing ventricular PVC, Vtach, Atach, WPW(reentry rhythm)
PO
SE: proarrhythmic
Propafenone
class 1c
suppression of vent and atrial tachy
PO
SE: proarrhythmic
Class II
Beta-adrenergic antagonist
depress spontaneous Phase 4 depolarization
depress pacemaker activity
**push threshold down in nodal tissue
decrease in SA node discharge
antiSNS
drug-induced slowing of heart rate results in decreased myocardial O2 demands–desirable in pts with CAD
Slow speed of conduction of cardiac impulses through atrial tissue and AV node resulting in prolongation of the PR interval on ECG, increased duration of the AP in atrial
decreased automaticity
**Slows HR, Decrease force of contractility
Class II drugs
propanolol-prototype, both
metoprolol,
esmolol
labetolol (alpha and beta)
Propanolol class, use
prototype, class II, b-blocker, B1and 2
in heart and bronchial tone
decrease rate of Phase 4 depolarization, which leads to decreased automaticity
decrease SNS activity of heart,
decrease conduction through AV node,
decreased QT interval
use: prevent reoccurrence of tachyarrh–SVT caused by SNS stimulation aka tachys caused by catacolamines and also atrial tachy, decrease mortality after MI
Proparanolol does onset peak e 1/2t cardiac effects
dose: 1mg/min total dose 3-6mg IV or 10-80mg PO
onset: PO
Peak effect 10-15min duration 3-4hr??
E1/2t 2-4hr
Cardiac effects: decreased HJR, contractility, CO, Increased PVR, coronary vascular resistance, however, O2 demand lowered
Proparanolol kinetics SE
90-95%pb hepatic metabolism, with weak metabolite. therapeutic plasma level 10-30mcg/ml
SE: brachy, hypotension, myocardial depression, fatigue, **worse brochospasm, drug fever, rash,N, worse raynauds, interferance with glucose metabolism, caution with: reactive airway disease, **CHF, AV block
Metoprolol
class II, bblocker, selective b1 dose: 5mg IV over 5min max 15mg, over 20min onset:2.5m E1/2t 3-4hrs hepatic metab can be used in mild CHF
Esmolol
class II bblocker selective B1
dose: 0.5mg/kg bolus over 1min the 50-300mcg/kg/min
duration: <15m
effects HR without decreasing BP significantly in small doses
Rapidly hydrolyzed by plasma esterases
not the same as sux, so NO effect on sux metabolism
Class III
block potassium ion channels, resulting in prolongation of cardiac depolarization (refractory period) which
increasing AP duration
lengthening repolarization
decreased conduction velocity
decrease the proportion of the cardiac cycle during which myocardial cells are excitable and thus susceptible to triggering event
increased QT interval
decrease automaticity
class III use
tx SVT, vent arrhythmias
prophylaxis in cardiac surgery pts r/t high incidence of Afib
preventative therapy in pts who have survived sudden cardiac death who are not candidates for ICD
control rhythm in Afib
**re-entery tachy, effective at control of arrhythmia and rate
Prevent more serious arrhythmias from rate control
Class III drugs
amiodarone - prototype
Dronedarone
Sotalol
Amiodarone class use
class III prototype, has class I, II, IV too. K/Na/Ca channel blocker α and β antagonist Use: prophylaxis or acute tx of atrial and vent arrhy: refractory SVT, refractory VT/VF, Afibcan revert arrhy back, Anti angina -dialate coronaries
Amiodarone dose, e1/2t, kinetics
dose: bolus 150-300mg over 2-5m up to 5mg/kg then 1mg/hr X6h then 0.5mg/h X18h e1/2t: 29DAYS, up to 100 days Heaptic metabolism--ACTIVE metabolite Biliary/GI excretion Theraprutic plasma level 1.0-3.5mcg/ml 96%pb Large VD
Amiodarone SE
Bc of large VD and tissue binding
**MOST concerning: Pulmonary toxicity bc of free radicals in lungs, high O2 may accelerate so restrict O2 concentrations with this drug
● Pulmonary edema
● ARDS
● Photosensitive rashes
● Grey/blue discolouration of skin
**Thyroid abnormalities 2% can effect thyroid metabolism, hypo or hyper
● Corneal deposits
● CNS/GI disturbance, peripheral neuropathy
**Pro-arrhythmic effects lengthen QT (torsades de pointes)
● Heart block
**Hypotension
● Nightmares 25%
● Abnormal LFT 20%
** Inhibits hepatic P450
Class IV
Ca channel blockers
*primary site AV node,
block inward slow Ca mvmt
decreased conduction through AV does and shortens Phase 2, (plateau)
shortens AP of ventricular myocyte
decrease contractility, smooth muscle relax
Coronary art vasodilation, and systemic arterier–hypotension
neg inatrop
Class IV use
used for SVT, vent rate control in Afib/flutter
not for vent arrhy
Class IV drugs
Verapamil
Diltiazem
Verapamil class, dose kinetics
Class IV CCB *neg inotrop and hypotension dose: 2.5-10mg IV over 1-3min max 20mg gtt: 5mcg/kg/min, rare high PB hepatic metab with ACTIVE metabol excreted in urine and bile
Verapamil drug interactions and SE
do not use IV verapamil with blocker–Heart block
myocardial depression and vasodilation with inhalation agents
can potentiate NMB
with Dantrolene can cause hyperkalemia
cause decreased clearance of dig
SE: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of neuromuscular block
Diltiazem class, dose, kinetics SE
Class IV, CCB *neg inotrop and hypotension less cardio depressant effects unlikely to interact with bblocker dose: 5-20mg IV (0.25-0.35mg/kg) over 2min gtt: 10mg/hr e1/2t 4-6h high PB hepatic metab excreted in urine SE: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of neuromuscular block
Other agents aka Class V
adenosine
Digoxin
Phenytoin
Atropine
Adenosine class, MOA, use
most important, doesn’t if in vaughan williams class
Binds to A1 purine nucleotide receptors (activates adenosine receptors to open K+ channels and increase K+ currents)
Slows SA/AV nodal conduction, and atrial conduction
Used for acute tx only
Used for termination of SVT/ diagnosis of VT
NOT for tx of fib/flutter, only to diagnosis
Adenosine dose, kinetics SE
Dose 6mg IV, rapid bolus
Repeated if necessary after 3 minutes, 6-12 mg IV
T1/2 < 10 seconds
**Eliminated by plasma and vascular endothelial
cell enzymes
Side effects: excessive AV or SA nodal inhibition, facial flushing, headache, dyspnea, chest discomfort, nausea, bronchospasm
Contraindicated in asthma, heart block
Digoxin class, MOA
Not in Vaughan Williams class
Cardiac glycoside, Na/K/adenosine triphosotase inhibitors
increase [Ca] which increases inoptorpe,
Increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses thru the AV node
Decreases HR, preload and after load
Slows AV conduction by increasing AV node
refractory period
Positive inotrope- used to treat CHF
Digoxin use, kinetics
Used for the management of atrial fibrillation or flutter (controls ventricular rate), especially with impaired heart function
Dose: 0.5-1 mg in divided doses over 12-24 hrs
Onset of action 30-60 minutes
T1/2 36 hours
Narrow therapeutic index, takes 7days to reach
– Therapeutic levels 0.5-1.2 ng/mL
Weak protein binding
90% Excreted by kidneys
Reduce dose in elderly/renal impairment
Digoxin SE
Arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
– potentiated by hypokalemia and hypomagnesaemia
Toxicity treatment
– Phenytoin for ventricular arrhythmias – Pacing
– Atropine
– Antidote: digoxin immune Fab
Phenytoin class, use does
Effects resemble Lidocaine
Class IA agent
Used in suppression of ventricular arrhythmias associated with digitalis toxicity
Can also be used other ventricular tachycardias or torsades de pointes
Given IV (can precipitate in D5W; mix in NS)
Can cause pain or thrombosis when given in
peripheral IV
Dose: 1.5 mg/kg IV every 5 min. up to 10-15 mg/kg
Therapeutic blood levels 10-18 mcg/ml
Phenytoin kinetics and SE
Metabolized by liver
Excreted in urine
Elimination 1⁄2 time @24 hours
Adverse effects: CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea
Atropine class, use, dose, kinetics
Muscarinic receptor antagonist Used to treat unstable bradyarrhythmias – Option for asystolic patients; PEA 0.4 to 1.0 mg IV and repeat as necessary Onset less 1 min; duration 30-60 minutes Metabolized by liver Caution dosing less than 0.4 mg – Potential to evoking a paradoxical response – Penetrates the BBB, CNS effects
