Cardiac Drugs and Drug Classes Flashcards
SA node rate
70-80
AV node rate
40-60
Purkinje fibers rate
15-40
classification of arrhythmias (4)
- site of origin (atrial/junctional/ventricular)
- complexes on ECG (narrow/broad)
- heart rhythm (regular/irregular)
- heart rate is increased or decreased
mechanisms of arrhythmia production: altered automaticity
latent pacemaker cells take over the SA node’s role ex) escape beats
mechanisms of arrhythmia production: delayed after depolarization
normal action potential of cardiac cell triggers a train of abnormal depolarizations. main cause: increased calcium with train action potentials, called an “R on T phenomenon”
mechanisms of arrhythmia production: re entry
refractory tissue reactivated repeatedly and rapidly due to unidirectional block, which causes abnormal continuous circuit. ex) wolf parkinson white syndrome is an example, caused by accessory pathway conduction
mechanisms of arrhythmia production: conduction block
impulse fail to propagate in non conducting tissue. ex) LBBB, RBBB. usually due to ischemia, scarring, and fibrosis
factors underlying cardiac arrhythmias
arterial hypoxemia electrolyte imbalance acid base abnormalities myocardial ischemia altered SNS activity bradycardia administration of certain drugs enlargement of failing ventricle
causes of intraoperative rhythm disturbances: transient imbalances
stress: electrolyte or metabolic imbalance
laryngoscopy, hypoxia, hypercarbia
device malfunction, micro shock
diagnostic or therapeutic interventions (pacers, ICD)
surgical stimulation
CVC
when do cardiac arrhythmias require treatment (3)
- cannot be corrected by removing precipitating cause ex) fluid for FVD
- hemodynamic instability
- disturbance predisposes to more serious cardiac arrhythmias or co morbidities
non pharmacological treatment options
acute: vagal maneuvers, cardioversion
prophylaxis: ablation (EP lab), implanted defibrilator
pacing: external, temporary, permanent
Vaughan Williams Classification of Antiarrhythmic Drugs
Class 1 (A, B, C): sodium channel blockers (Phase 0) Class 2: beta adrenergic blockers (Phase 4) Class 3: potassium channel blockers (Phase 3) Class 4: calcium channel blockers (Phase 2) Class 5: unclassified drugs (unknown mechanisms)
Class 1 Agents MOA, ion targeted, and uses for tx
Class 1 agents are characterized by how quickly they dissociate from Na channel (A, B, C)
Block Na Channels with depresses phase 0 in depolarization of cardiac AP.
Decreases AP propagation, decreases depolarization rate, slows conduction velocity
Binds to sites on alpha subunits
Binds most strongly when Na channels are either in the open or activated state. Less strongly in the inactivated state.
Tx: SVT, Afib, WPW syndrome
Class 1A Agents MOA, ion targeted, elimination, SE, uses
slows conduction velocity and pacer rate
intermediate Na channel blocker (intermediate dissociation)
direct depressant effects on SA and AV node
decreased depolarization rate (phase 0)
prolonged repolarization (because also blocks K channels to some degree)
increased AP duration and effect of refractory period
decreased automaticity, increased QT duration (phase 0 to end of phase 3 in ventricular AP)
elimination: hepatic
se: reversible lupus like syndrome
used for: atrial and ventricular dysrhythmias
Class 1A Agents (3) and note*
Quinidine, Procainamide, Disopyramide. (these drugs are not commonly used due to toxicity and may precipitate heart failure)
Disopyramide class, use, route of administration, SE
class 1A, suppresses atrial and ventricular tachyarrhythmias, oral agent, has significant myocardial depressant effects and can precipitate congestive HF and hypotension. SE can include anticholinergic effects
Procainamide class, use, dose, therapeutic window, T1/2, protein binding, SE
class 1A, used in treatment of ventricular tachyarrhythmias (less effective with atrial)
dose: loading 100mg IV every 5 minutes until rate controlled (max 15mg/kg), then infusion 2-6mg/min
therapeutic window, 4-8mcg/ml
T1/2 2 hours
15% protein bound
SE: myocardial depression leading to hypotension, syndrome that resembles lupus erythematous
Class 1C agents (2)
flecainide (prototype), propafenone (oral)
Class 1C Agents MOA, uses
slow Na channel blocker (slow dissociation), so does not vary much during the cardiac cycle.
potent decrease of the depolarization rate of phase 0 and decreased conduction rate of cardiac impulses with increased AP
markedly inhibit conduction of AP through his-purkinje system
uses: atrial arrhythmias, PVC’s, vtach
flecainide chemical structure, class, use, route of administration, SE
fluorinated local anesthetic analogue of procainamide
class 1C
effective in tx of suppressing vtach, atrial tachyarrhythmias, WPW syndrome, delays conduction in bypass tracts so its good for reentry rhythms and therefore good for afib prophylaxis
PO
has pro arrhythmic SE
propafenone class, use, route of administration, SE
class 1C
suppression of ventricular and atrial tachyarrhythmias
PO
has pro arrhythmic SE’s (torsades, vfib)
Class 1B agents (3)
lidocaine (prototype), mexiletine, phenytoin
class 1B agents MOA, uses, unique characteristic of these agents
fast Na channel blocker (fast dissociation) alters AP by inhibiting Na ion influx via rapidly binding to and blocking sodium channels (fast) produces little effect on maximum velocity depolarization rate, but shortens AP duration and shortens refractory period decreases automaticity shortens repolarization and refractory period, decreases AP binds to open channels and dissociates quickly, in time for the next AP but premature beats still blocked little effect on max velocity and depolarization use: ventricle arrhythmias but not vfib post MI this class is unique because it also binds to ischemic cells to decrease activity in these cells while others dont.
Lidocaine class, uses, dose, route of administration, protein binding, metabolism, elimination
class 1B, used in tx of ventricular arrhythmias, particularly effective in suppression reentry rhythms, vtach, PVC’s, delays phase 4. not good for SVT, vfib after acute MI.
dose: 1-1.5mg/kg IV, infusion 1-4mg/min (max dose 3mg/kg)
extensive 1st pass PO so only given IV
50% protein binding
hepatic metabolism
active metabolite, prolongs elimination T1/2, 10% renal elimination
not pro arrhythmic but dissociates so quickly
Lidocaine metabolism considerations
metabolism may be impaired by drugs such as cimetidine and propranolol, or physiologic altering conditions such as CHF, acute MI, liver dysfunction, GA, or can be induced by drugs like barbiturates, phenytoin, or rifampin (CYP450)
Lidocaine adverse effects
hypotension, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest, and can augment preexisting NMB
Mexiletine class, route of administration, dose, chemical structure, uses
class 1b anti arrhythmic
150-200mg PO q8h
similar to lidocaine, has amine side group to bypass 1st pass effect
can be used for neuropathies, also used for chronic suppression of ventricular cardiac tachyarrhythmias
Phenytoin class, uses, route of administraton, administration considerations, dose, therapeutic levels, metabolism, elimination, elimination t1/2, adverse effects
1B agent, effects resemble lidocaine
can be used in suppression of ventricular arrhythmias associated with digitalis toxicity, can also be used with other tachycardias or torsades
given IV in NS (can precipitate in D5W). can cause pain or thrombophlebitis in peripheral IV
dose 1.5mg/kg IV every 5 minutes up to 10-15mg/kg
therapeutic blood levels 10-18mcg/ml
metabolized by liver
excreted in urine
elimination t1/2 24 hours
adverse effects: CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea, vertigo, ataxia, slurred speech, SJS, severe hypotension if given rapidly
Class II agents MOA, , desirable effects uses
beta antagonists, depress spontaneous phase 4 depolarization resulting in decrease of SA node discharge.
slowing of HR with resulting decreases in MVO2 demands, good for CAD patients
slows speed of conduction of cardiac impulses through atrial tissues and AV node resulting in prolongation of PR interval on ECG, increased duration of AP in atria
decreased automaticity
stops AP’s due to excitation of catecholamines or increased SNS response induced arrhythmias
prevents catecholamines from binding to beta receptors
desirable effects: slows HR, decreases MVO2 requirements
uses: CAD, MI (blocks “adrenergic surges”). used to treat SVT, atrial and ventricular arrhythmias, used to suppress and tx ventricular dysrhythmias during MI and reperfusion. used to tx tachyarrhythmias secondary to digoxin toxicity and SVT. controls rate of atrial fib or flutter.
Propanolol class, use, onset, peak, duration, elimination t1/2, cardiac desirable effects
class II, nonselective BB
used to prevent reoccurrence of tachyarrhythmias, both supra ventricular and ventricular precipitated by sympathetic stimulation
onset: 2-5m
peak effect: 10-15min
duration: 3-4h
elimination t1/2: 2-4h
cardiac effects: decreased HR, contractility, CO, increased PVR, coronary vascular resistance, MVO2
metoprolol class, dose, onset, duration, metabolism, use
class II B1 antagonist dose: 5mg IV over 5 minutes, max dose 15mg over 20 min onset: 2.5 min duration t1/2: 3-4h metabolism: liver use: mild CHF
esmolol class, dose, duration, elimination effects
class II B1 antagonist (choice in OR if you dont want an extended response, short acting)
dose: .5mg/kg IV bolus over 1min, then 50-300mcg/kg/min
duration: <10min
metabolism: hydrolyzed by plasma esterase’s, therefore eliminated much faster
effects: effects HR without decreasing BP significantly in small doses
Class III Agents MOA
block potassium ion channels resulting in prolongation of cardiac depolarization and increasing AP duration and lengthening repolarization. decreases proportion of cardiac cycle during which myocardial cells are excitable and thus susceptible to a triggering event. reduction excitability of all myocardial tissue
-also works on Na/Ca channels, non competitively blocks alpha and beta channels as well
Class III Agents uses, consideration
used to treat supra ventricular and ventricular arrhythmias
can prolong QT interval and develop torsades (proarrhythmic)
prophylaxis in cardiac surgery patients related to high incidence of afib (controls afib well)
preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD
almost all class III’s are proarrhythmics
Class III Agents (5)
amiodarone, dronedarone, ibutilide, dofetilide (oral), sotalol
Amiodarone structural consideration, class, MOA, uses
iodine containing composition
class III with class I, II, IV properties
potassium, sodium, calcium channel blocker, alpha and beta adrenergic antagonist
used for prophylaxis or acute tx in treatment of atrial and ventricular arrhythmias, 1st line drug for VT/VF when resistant to electrical defibrillation
used when not ICD candidate
most effective in arrhythmia prevention in HF patients
Amiodarone dose, t1/2, metabolism, elimination, therapeutic levels, Vd, protein binding
dose: bolus 150-300mg IV over 2-5min, up to 5mg/kg. then 1mg/hr x 6 hours, then .5mg/hr x 18 hours t1/2: 29 DAYS metabolism: hepatic. active metabolite elimination: biliary/intestinal therapeutic plasma level: 1-3.5mcg/mL protein binding 96% Vd large
amiodarone adverse effects and administration considerations
pulmonary toxicity (similar to fibrosis) pulmonary edema ARDS photosensitive rashes grey/blue discoloration of skin thyroid abnormalities r/t iodine (hyperthyroidism) corneal deposits CNS/GI disturbances pro-arrhythmic effects (torsades, monitor K level) heart block hypotension sleep disturbances abnormal LFT's inhibits CYP450 may prolong muscle relaxants -admin through a central line r/t thrombophlebitis risk
Sotalol class, use, SE, caution, excretion
class II and III. nonselective beta antagonist and ccb. prolongs AP, works on phase 3 to extend refractory period. torsades possible.
used to tx severe sustained vtach and VF, to prevent reoccurrence of tachyarrhythmias, esp aflutter and afib
se: prolonged QT interval, bradycardia, myocardial depression, fatigue, dyspnea, AV block
caution in patients with asthma
excreted in urine
dofetilide and ibutilide class, uses, se
class III used for conversion of afib or aflutter to NSR. used for maintenance of SR after fib or conversion of fib to sinus pro arrhythmic- prolongs QT interval
class IV agents (3)
verapamil
diltiazem
nifedipine
calcium channel ions are present in
cell membranes of skeletal muscle vascular smooth muscle cardiac muscle mesenteric muscle neurons glandular cells platelets, affecting coagulation
Class IV agents ion affected and result
CCB’s bind to receptor on VgCa ions maintaining channels in inactive or closed state. although there are many different types of Ca channels, we are talking specifically about L type calcium channels.
selectively interfere with inward calcium ion movement across myocardial and VSMC’s
Structural Classifications for class IV agents
Verapamil: phenyl-alkyl-amines, AV node
Diltiazem: benzothiazepin, AV node
Nifedipine: 1,4 dihydroppyridines-arterial beds
vascular uses for CCB’s
angina systemic HTN pHTN cerebral arterial spasm ex) post bleed raynauds migraine
non vascular uses for CCB’s
bronchial asthma
esophageal spasm
dysmenorrhea
premature labor
class IV MOA (not focusing on solely ion), uses
blocks slow (L type) calcium channels (keeps intracellular Ca low), primary site of AV node, decreases conduction through AV (and SA) node and shortens phase 2 (plateau) of the action potential in ventricular myocytes. contractility of heart decreases.
decrease in AP’s impairs impulse propagation in nodal tissues
also decreases rate of spontaneous phase 4 and phase 4 depolarization
good for reentrant tachycardias at AV node
VSMC’s relax and vasodilate, which decreases systemic BP
positive effects of CCB’s
decreases contractility, chronotropy, inotropy
decreases activity of SA node
decreased rate of conduction of impulses via AV node
arterial>venous VSMC relaxation to decrease SVR and BP
decreases MVO2 demand
uses of CCB’s
second line for stable angina. used for angina, CAD used in tx of SVT and ventricular rate control in afib and aflutter used to prevent recurrence of SVT NOT**** used in ventricular dysrhythmias
Verapamil class, chemical structure, site of action, other actions, clinical uses
class IV CCB (prototype)
synthetic derivative of papaverine
levoisomer is specific for slow Ca channel
primary site of action is AV node (depresses AV node)
also: negative chronotropic effect on SA node, negative inotropic effects on myocardial muscle, moderate vasodilation on coronary as well as systemic arteries
clinical uses: SVT, vasospastic angina, HTN, hypertrophic cardiomyopathy, maternal and fetal tachydysrhythmias, premature onset of labor
(not as much dilation on smooth muscle of coronary arteries, that is why it is primarily utilizes as an anti arrhythmic)
Verapamil protein binding, dose, route of administration, t1/2, metabolism, excretion, SE
highly protein bound, presence of other agents such as lidocaine, diazepam, propranolol will increase its activity
PO: extensive hepatic 1st pass, PO peak 30-45m, t1/2 6-12h
IV: 2.5-10mg IV over 1-3m (max dose 20mg), continuous infusion 5mcg/kg/min, t1/2 6-8h
hepatic metabolism with active metabolite norverapamil
excreted in urine
SE: myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of NMB and can antagonize effects of NMB reversal as well. possible toxicity if given with regional anesthetic
what can you give to decrease the SE of hypotension with verapamil
1g ca gluconate
diltiazem chemical structure, MOA, clinical uses, dose, route of admin, onset, protein binding, t1/2, excretion, SE
benzothiazepine derivative
principal site of action AV node, binds at subunit of alpha type L Ca channel. intermediate potency b/t verapamil and nifedipine, minimal CV depressant effects
uses: 1st line for SVT’s. also used for HTN, vasospastic angina, hypertrophic cardiomyopathy, maternal and fetal tachydysrhythmias
dose: .25-.35mg/kg over 2min, can repeat in 15min. IV infusion 10mg/h
route of admin: PO or IV
onset: PO, 15 min and peaks in 30
70-80% protein bound
t1/2: 4-6h
liver disease may require a decreased dose
excreted in bile and urine (inactive metabolite)
SE: bradycardia, constipation, hypotension, myocardial depression
Nifedipine structure, MOA, effects, uses, route of admin, onset, peak, protein binding, metabolism, excretion, t1/2
dihydropyridine derivative ("different than others")
primary site of action is peripheral arterioles, coronary and peripheral vasodilator properties >verapamil
little to no effect on SA or AV node
decreased SVR or BP
used for angina
IV, PO, or SL
oral: onset 20 min, peak 60-90min
90% protein bound
hepatic metabolism
urine excretion
t1/2 3-7 hours (shorter)
SE: reflex tachycardia, can produce myocardial depression in patients with LV dysfunction or on BBgeneral CCB SE’s
cancer, cardiac problems (blocks, esp if on BB), bleeding prolongation, constipation
general CCB drug interactions (5)
potentiates myocardial depression and vasodilation with inhalational agents
can potentiate NMB’s, monitor
verapamil with BB can create heart block
verapamil increases risk of local anesthetic toxicity
verapamil and dantrolene can cause hyperkalemia due to slowing of inward movement of potassium ions and can result in cardiovascular collapse
CCB’s interact with calcium mediated platelet function
CCB’s can increase plasma concentration of digoxin by decreasing plasma clearance
ranitidine and cimetidine (H2 antagonists) alter hepatic enzyme activity and thus could increase plasma levels of CCB
CCB toxicity reversal
IV calcium or dopamine, to increase inotropy
general SE’s of CCB’s
vertigo, HA, flushing, hypotension, paresthesias, muscle weakness, can induce renal dysfx, coronary vasospasm can happen with abrupt discontinuation
adenosine MOA, uses, dose, route of administration, elimination, SE’s, contraindications
binds to A1 purine nucleotide receptors (activates adenosine receptors to open K channels and increase K currents, which means there is an increase in K conductance and a decrease in AP. slows AV nodal conduction and stops arrhythmias from occurring. essentially causes a hyperpolarization to decrease excitability
slows AV nodal conduction
used for termination of SVT or diagnosis of VT
dose 6mg IV rapid bolus, repeated q3m 6-12mg IV
t1/2 10 seconds
eliminated by plasma and vascular endothelial cell enzymes in RBC’s. taken by nucleoside transporter cells on surface of endothelium of vasculature
SE: excessive AV or SA node inhibition, facial flushing, HA, dyspnea, chest discomfort, nausea, bronchospasm.
contraindicated in asthma, heart both
where is endogenous adenosine found
heart muscle, nerve tissue, platelets, breathing effects
Digoxin class, MOA, use, dose, onset, t1/2, TI, protein binding, excretion, dose considerations
cardiac glycoside
increases vagal activity, thus decreasing activity of SA node and prolongs conduction of impulses through AV node.
binds Na/K/atpase pump to increase calcium concentration and slow extrusion.
decreases HR, preload, after load
slows AV conduction by increasing AV node refractory period and increasing force of contraction.
used to tx CHF, positive inotrope. used for atrial tachycardias, afib, flutter.
dose: .5-1mg in divided doses over 12-24h
onset: 30-60m
t1/2 36h
narrow TI: .5-1.2mg/dL
weak protein binding
90% excreted in kidneys
reduce dose in elderly/renal impairment
Digoxin Adverse Effects
arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation. potentiated by hypokalemia and hypomagnesemia.
digoxin toxicity treatment
phenytoin for ventricular arrhythmias, pacing, atropine
magnesium MOA, uses, dose
works at Na/K/Ca channels, can be used for torsades in ACLS
dose: 1gm IV over 20 min, can be repeated.
originally used in dig induced arrhythmias for patients with low magnesium
atropine class, use, dose, onset, duration, metabolism, dosing caution
muscarinic antagonist used for unstable bradyarrhythmias .4-1mg, repeat as necessary metabolized by liver onset <1min doa 30-60min caution dosing
