Cardiac Drugs and Drug Classes

Question 1

SA node rate

Answer 1

70-80

Question 2

AV node rate

Answer 2

40-60

Question 3

Purkinje fibers rate

Answer 3

15-40

Question 4

classification of arrhythmias (4)

Answer 4

1. site of origin (atrial/junctional/ventricular)
2. complexes on ECG (narrow/broad)
3. heart rhythm (regular/irregular)
4. heart rate is increased or decreased

Question 5

mechanisms of arrhythmia production: altered automaticity

Answer 5

latent pacemaker cells take over the SA node’s role ex) escape beats

Question 6

mechanisms of arrhythmia production: delayed after depolarization

Answer 6

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”

Question 7

mechanisms of arrhythmia production: re entry

Answer 7

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

Question 8

mechanisms of arrhythmia production: conduction block

Answer 8

impulse fail to propagate in non conducting tissue. ex) LBBB, RBBB. usually due to ischemia, scarring, and fibrosis

Question 9

factors underlying cardiac arrhythmias

Answer 9

arterial hypoxemia
electrolyte imbalance
acid base abnormalities
myocardial ischemia
altered SNS activity
bradycardia
administration of certain drugs
enlargement of failing ventricle

Question 10

causes of intraoperative rhythm disturbances: transient imbalances

Answer 10

stress: electrolyte or metabolic imbalance
laryngoscopy, hypoxia, hypercarbia
device malfunction, micro shock
diagnostic or therapeutic interventions (pacers, ICD)
surgical stimulation
CVC

Question 11

when do cardiac arrhythmias require treatment (3)

Answer 11

1. cannot be corrected by removing precipitating cause ex) fluid for FVD
2. hemodynamic instability
3. disturbance predisposes to more serious cardiac arrhythmias or co morbidities

Question 12

non pharmacological treatment options

Answer 12

acute: vagal maneuvers, cardioversion
prophylaxis: ablation (EP lab), implanted defibrilator
pacing: external, temporary, permanent

Question 13

Vaughan Williams Classification of Antiarrhythmic Drugs

Answer 13

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)

Question 14

Class 1 Agents MOA, ion targeted, and uses for tx

Answer 14

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

Question 15

Class 1A Agents MOA, ion targeted, elimination, SE, uses

Answer 15

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

Question 16

Class 1A Agents (3) and note*

Answer 16

Quinidine, Procainamide, Disopyramide. (these drugs are not commonly used due to toxicity and may precipitate heart failure)

Question 17

Disopyramide class, use, route of administration, SE

Answer 17

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

Question 18

Procainamide class, use, dose, therapeutic window, T1/2, protein binding, SE

Answer 18

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

Question 19

Class 1C agents (2)

Answer 19

flecainide (prototype), propafenone (oral)

Question 20

Class 1C Agents MOA, uses

Answer 20

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

Question 21

flecainide chemical structure, class, use, route of administration, SE

Answer 21

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

Question 22

propafenone class, use, route of administration, SE

Answer 22

class 1C
suppression of ventricular and atrial tachyarrhythmias
PO
has pro arrhythmic SE’s (torsades, vfib)

Question 23

Class 1B agents (3)

Answer 23

lidocaine (prototype), mexiletine, phenytoin

Question 24

class 1B agents MOA, uses, unique characteristic of these agents

Answer 24

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.

Question 25

Lidocaine class, uses, dose, route of administration, protein binding, metabolism, elimination

Answer 25

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

Question 26

Lidocaine metabolism considerations

Answer 26

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)

Question 27

Lidocaine adverse effects

Answer 27

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

Question 28

Mexiletine class, route of administration, dose, chemical structure, uses

Answer 28

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

Question 29

Phenytoin class, uses, route of administraton, administration considerations, dose, therapeutic levels, metabolism, elimination, elimination t1/2, adverse effects

Answer 29

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

Question 30

Class II agents MOA, , desirable effects uses

Answer 30

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.

Question 31

Propanolol class, use, onset, peak, duration, elimination t1/2, cardiac desirable effects

Answer 31

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

Question 32

metoprolol class, dose, onset, duration, metabolism, use

Answer 32

``` 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 ```

Question 33

esmolol class, dose, duration, elimination effects

Answer 33

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

Question 34

Class III Agents MOA

Answer 34

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

Question 35

Class III Agents uses, consideration

Answer 35

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*

Question 36

Class III Agents (5)

Answer 36

amiodarone, dronedarone, ibutilide, dofetilide (oral), sotalol

Question 37

Amiodarone structural consideration, class, MOA, uses

Answer 37

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

Question 38

Amiodarone dose, t1/2, metabolism, elimination, therapeutic levels, Vd, protein binding

Answer 38

``` 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 ```

Question 39

amiodarone adverse effects and administration considerations

Answer 39

``` 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 ```

Question 40

Sotalol class, use, SE, caution, excretion

Answer 40

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

Question 41

dofetilide and ibutilide class, uses, se

Answer 41

``` 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 ```

Question 42

class IV agents (3)

Answer 42

verapamil diltiazem nifedipine

Question 43

calcium channel ions are present in

Answer 43

``` cell membranes of skeletal muscle vascular smooth muscle cardiac muscle mesenteric muscle neurons glandular cells platelets, affecting coagulation ```

Question 44

Class IV agents ion affected and result

Answer 44

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

Question 45

Structural Classifications for class IV agents

Answer 45

Verapamil: phenyl-alkyl-amines, AV node Diltiazem: benzothiazepin, AV node Nifedipine: 1,4 dihydroppyridines-arterial beds

Question 46

vascular uses for CCB's

Answer 46

``` angina systemic HTN pHTN cerebral arterial spasm ex) post bleed raynauds migraine ```

Question 47

non vascular uses for CCB's

Answer 47

bronchial asthma esophageal spasm dysmenorrhea premature labor

Question 48

class IV MOA (not focusing on solely ion), uses

Answer 48

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

Question 49

positive effects of CCB's

Answer 49

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

Question 50

uses of CCB's

Answer 50

``` 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 ```

Question 51

Verapamil class, chemical structure, site of action, other actions, clinical uses

Answer 51

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)

Question 52

Verapamil protein binding, dose, route of administration, t1/2, metabolism, excretion, SE

Answer 52

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

Question 53

what can you give to decrease the SE of hypotension with verapamil

Answer 53

1g ca gluconate

Question 54

diltiazem chemical structure, MOA, clinical uses, dose, route of admin, onset, protein binding, t1/2, excretion, SE

Answer 54

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

Question 55

Nifedipine structure, MOA, effects, uses, route of admin, onset, peak, protein binding, metabolism, excretion, t1/2

Answer 55

``` 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 BB ```

Question 56

general CCB SE's

Answer 56

cancer, cardiac problems (blocks, esp if on BB), bleeding prolongation, constipation

Question 57

general CCB drug interactions (5)

Answer 57

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

Question 58

CCB toxicity reversal

Answer 58

IV calcium or dopamine, to increase inotropy

Question 59

general SE's of CCB's

Answer 59

vertigo, HA, flushing, hypotension, paresthesias, muscle weakness, can induce renal dysfx, coronary vasospasm can happen with abrupt discontinuation

Question 60

adenosine MOA, uses, dose, route of administration, elimination, SE's, contraindications

Answer 60

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

Question 61

where is endogenous adenosine found

Answer 61

heart muscle, nerve tissue, platelets, breathing effects

Question 62

Digoxin class, MOA, use, dose, onset, t1/2, TI, protein binding, excretion, dose considerations

Answer 62

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

Question 63

Digoxin Adverse Effects

Answer 63

arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation. potentiated by hypokalemia and hypomagnesemia.

Question 64

digoxin toxicity treatment

Answer 64

phenytoin for ventricular arrhythmias, pacing, atropine

Question 65

magnesium MOA, uses, dose

Answer 65

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

Question 66

atropine class, use, dose, onset, duration, metabolism, dosing caution

Answer 66

``` muscarinic antagonist used for unstable bradyarrhythmias .4-1mg, repeat as necessary metabolized by liver onset <1min doa 30-60min caution dosing ```