Antiarrhythmic Drugs Flashcards
what part of the cardiac action potential do class 1 antiarrhythmic drugs affect
phase 0
what part of the cardiac action potential do class 3 antiarrhythmic drugs affect
phases 2 and 3
what part of the nodal action potential do class 2 antiarrhythmic drugs affect
prolongs phase 4 (delays progression to phase 0)
what part of the nodal action potential do class 4 antiarrhythmic drugs affect
prolongs phase 4 (delays progression to phase 0)
describe phase 0 of the cardiac action potential
voltage-dependent fast Na+ channels open as a result of depolarization and Na+ enters the cells down its gradient
describe phase 1 of the cardiac action potential
K+ exits the cell down its gradient while fast Na+ channels close, causing some depolarization
describe phase 2 of the cardiac action potential
the plateau phase which results from K+ exiting the cells offset by Ca2+ entering the cells through slow voltage- dependent Ca2+ channels
describe phase 3 of the cardiac action potential
Ca2+ channels close and K+ begins to exit more rapidly, resulting in repolarization
describe phase 4 of the cardiac action potential
resting membrane potential is gradually restored by Na+/K+ ATPase and Na+/Ca2+ exchanger
describe phase 4 of the pacemaker action potential
slow spontaneous depolarization; pacemaker current (funny current) opens and lets Na+ into the cell
describe phase 0 of the pacemaker action potential
upstroke of action potential; Ca2+ influx through L-type Ca2+ channels
describe phase 3 of the pacemaker action potential
Repolarization; inactivation of Ca2+ channels with increased K+ efflux
describe resting state of sodium channels
channel closed but ready to generate an action potential
describe activated state of sodium channels
depolarization to the threshold opens m-gates which greatly increases sodium permeability
describe inactivated state of sodium channels
h-gates are closed, inward sodium flux is inhibited, channel not available for reactivation
–> responsible for the refractory period
describe the state-dependent block of class 1 antiarrhythmics
they block activated or inactivated Na+ channels with very little affinity toward channels in a resting state
class 1A antiarrhythmics:
- state dependent block
- binding strength
- effect on ECG
- preferentially bind to open (activated) channels
- dissociate with intermediate kinetics (medium strength)
- prolong QRS and QT
what does procainamide do in addition to Na+ channel block
- directly depresses SA and AV node
- antimuscarinic activity
- reduces PVR and can cause hypotension
non-cardiac adverse effects procainamide
- lupus-like syndrome (arthritis, pleuritis, hepatitis)
- nausea, diarrhea
non-cardiac adverse effects quinidine
- GI stuff
- tinnitus, dizziness, HA
- thrombocytopenia
non-cardiac adverse effects disopyramide
- urinary retention
- dry mouth
- blurred vision
cardiac adverse effects of all class 1A drugs
- QT prolongation
- torsades de pointes
- excessive inhibition of conduction
class 1B antiarrhythmics:
- state dependent block
- binding strength
- effect on ECG
- bind preferentially to inactivated Na+ channels
- dissociate with fast kinetics (weak binding)
- doesn’t block K+ so does not prolong QT or action potential on ECG
how does lidocaine make damaged tissue “electrically silent”
it selectively blocks conduction in depolarized tissue
why do class 1B drugs have no effect on cardiac conductivity in normal tissue
fast kinetics of dissociation from Na+ channels results in recovery from block between action potentials
adverse effects lidocaine
- hypotension in pts with heart failure
- paresthesias, tremor, slurred speech, convulsions
adverse effects mexiletine
- tremor
- blurred vision
- nausea
- lethargy
class 1C antiarrhythmics:
- state dependent block
- binding strength
- effect on ECG
- preferentially bind to activated sodium channels
- dissociate from channel with slow kinetics (strong binding)
- prolongs QRS, does not prolong action potential or QT on ECG
which class 1 drugs also block K+ channels
class 1A class 1C
adverse effects Flecainide
severe exacerbation of ventricular arrhythmias in pts with preexisting ventricular tacchyarrhyhtmias, previous MIs, or ventricular ectopic rhythms
adverse effects Propafenone
- exacerbation of ventricular arrhythmias
- metallic taste (purple phone tastes like metal)
- constipation
sympathetic effect of beta blockers on funny channel and T-type Ca2+ channels in nodal AP
increased slope
sympathetic effect of beta blockers on L type Ca2+ channels in nodal AP
reduced threshold
effect of esmolol on SA and AV node and ECG
SA node: decreases HR (increase RR interval)
AV node: decreases AV conductance (increase PR interval)
based on its half life, how must esmolol be administered
continuous IV infusion with rapid onset and termination of its action
(half life is 10 min b/c hydrolysis by blood esterases)
contraindications beta blockers
- asthma
- PVD
- Raynaud’s
- type 1 DM on insulin
- bradyarrhythmias and AV conductance abnormalities
adverse effects beta blockers
- reduced CO
- bronchoconstriction
- impaired liver glucose mobilization
- increase VLDL and decreases HDL
- sedation, depression
effect of class 3 drugs on ECG
prolong QT
effect of class 3 drugs on refractory period
prolong refractory period
effects of amiodarone on Na+ and Ca2+ channels
blocks Ca2+ and inactivated sodium channels as well as K+ channels
what is amiodarone metabolized by
CYP3A4
effect of cimetidine or rifampin on amiodarone
they inhibit CYP3A4, which affects metabolism of amiodarone
how does amiodarone affect metabolism of other drugs
it inhibits many CYP enzymes
cardiac adverse effects amiodarone
- AV block and bradycardia
- torsade de pointes
extracardiac adverse effects amiodarone
- fatal pulmonary fibrosis
- hepatitis
- photodermatitis (blue-gray skin)
- deposits of drug in cornea
- hypo or hyperthyroidism
adverse effects sotalol
- depression of cardiac function
- torsades de pointes
adverse effects dofetilide and ibutilide
QT interval prolongation and increased risk of ventricular arrhythmias
why are the effects of dofetilide and ibutilide more pronounced at lower heart rates
they specifically block the rapid component of the delayed rectifier potassium current
effect of class 4 drugs on nodal action potential
- decrease slope of phase 0
- increase L-type Ca2+ channel threshold potential
- prolong refractory period in AV node
adverse effects of class 4 drugs
- negative inotropy
- AV block
- SA node arrest
- bradyarrhythmias
- hypotension
non-cardiac adverse effect verapamil
constipation
effect of adenosine on nodal action potential
- inhibits Ca2+ and funny currents
- causes hyperpolarization and suppression of AP in slow cells
- inhibits AV conduction
- increases refractory period
adverse effects adenosine
- SOB
- bronchoconstriction
- chest burning
- AV block
- hypotension
