CV Drugs I - Antiarrhythmics Flashcards
Class I Agents
Sodium Channel Blockers
Sodium Channel Blockers MOA
- phase 0 of fast AP
- block sodium channels which depresses phase 0 in depolarization of the cardiac AP
- resultant decrease in AP propagation, decrease in depolarization rate, and slowing of conduction velocity
Sodium Channel Blockers clinical uses
-treat SVT, AF, WPW
Class IA agents
- Quinidine (prototype)
- Procainamide
- Disopyramide
Class IA agents MOA
- slow conduction velocity and pacemaker rate
- intermediate Na+ channel blocker (intermediate dissociation)
Class IA agents PK/PD
-hepatic metabolism
Class IA agents clinical use
-atrial and ventricular arrhythmias
Class IA agents effects
- direct depressant effects on SA and AV node
- decreased depolarization rate (phase 0)
- prolonged repolarization
- increased AP duration
- not commonly used due to toxicity may precipitate HF*
Disopyramide dose/route
oral agent
Disopyramide clinical use
-suppression of atrial and ventricular tachyarrhythmias
Disopyramide effects
-significant myocardial depressant effects and can precipitate CHF and hypotension
Procainamide PK/PD
- 15% protein bound
- elimination ½ is 2 hours
Procainamide dosing/routes
-Loading: 100 mg IV Q5min until rate controlled (max 15 mg/kg); then infusion 2-6 mg/min
Procainamide clinical use
-treatment of ventricular tachyarrhythmias (less effective with atrial)
Procainamide effects
- myocardial depression –> hypotension
- syndrome that resembles lupus erythematous
Procainamide therapeutic level
-therapeutic blood level 4-8 mcg/mL
Class IC Agents
- Flecainide (prototype)
- Propafenone
Class IC Agents MOA
- slow Na+ channel blocker (slow dissociation), so does not vary much during cardiac cycle
- potent decrease of depolarization rate phase 0, decreased conduction rate with increased AP
- markedly inhibit conduction through the His-Purkinje system
Class IC Agents effects
-may have proarrhythmic side effects due to action in different cells
Flecainide route
oral
Flecainide clinical use
- main use = paroxysmal afib
- treatment of suppressing ventricular PVCs and ventricular tachycardia
- atrial tachyarrhythmia treatment
- WPW treatment
Flecainide effects/considerations
- proarrhythmic effects
- no longer recommended for use of treatment of tachyarrhythmias post MI –> high incidence of Vfib and death
Propafenone route
oral
Propafenone clinical use
-suppression of ventricular and atrial tachyarrhythmias
Propafenone effects/considerations
-proarrhythmic effects
Class IB Agents
- Lidocaine (prototype)
- Mexiletine
- Phenytoin
Class IB agents MOA
- fast Na+ channel blocker (fast dissociation)
- alters AP by inhibiting sodium ion influx via rapidly binding to and blocking sodium channels
- produces little effect on maximum velocity depolarization rate, but shortens AP duration and shortens refractory period
- decreases automaticity
Lidocaine PK/PD
- 50% protein bound
- hepatic metabolism
- active metabolite, slows elimination half-time
- metabolism may be impaired by drugs like cimetidine or propranolol or physiologic alter conditions like CHF, MI, liver dysfunction, GA
- can be induced by drugs like barbiturates, phenytoin, or rifampin
- 10% renal elimination
lidocaine dose/route
IV bolus: 1-1.5 mg/kg
IV infusion: 1-4 mg/min
MAX = 3 mg/kg
lidocaine clinical use
- ventricular arrhythmias
- suppression of reentry rhythms – vtach, fibrillation, PVCs
lidocaine effects/considerations
- no longer recommended for preventing v-fib after acute MI –> increased mortality d/t fatal brady arrhythmias
- Adverse effects –> hypotension, bradycardia, seizures, CNS depression, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment preexisting neuromuscular blockade
Mexiletine dose/route
-oral agent
PO dose: 150-200 mg Q8H
Mexiletine clinical use
-chronic suppression of ventricular tachyarrhythmias
Mexiletine effects/considerations
-need cardiac clearance
Phenytoin PK/PD
- metabolized in liver
- excreted in urine
- elimination ½ time 24 hours
Phenytoin dose/route
IV bolus: 1.5 mg/kg every 5 min up to 10-15 mg/kg
Phenytoin clinical use
- suppression of ventricular arrhythmias associated with digitalis toxicity
- also used for other ventricular tachycardias or torsades de pointes
Phenytoin effects/considerations
- effects resemble lidocaine
- can precipitate in D5W, mix in NS
- can cause pain or thrombosis when given in peripheral IV
- therapeutic blood level 10-18 mcg/mL
- adverse effects CNS disturbances, partially inhibits insulin secretion, bone marrow depression, nausea, hypotension with rapid admin, Stevens Johnson syndrome
- toxicity = CNS disturbance, ataxia, slurred speech
Class II Beta Adrenergic Antagonists (Beta Blockers)
- Propranolol (prototype)
- Metoprolol
- Esmolol
Beta blockers MOA
- phase 4 of slow AP
- depresses spontaneous phase 4 depolarization resulting in SA node discharge decrease
- prevents catecholamine binding to beta receptors at SA node (slow HR, decrease MVO2)
Beta blockers clinical use
- treat SVT, atrial and ventricular arrhythmias
- suppress and treat ventricular dysrhythmias during MI and reperfusion
- to treat tachyarrhythmias secondary do digoxin toxicity and SVT (atrial fib or flutter)
Beta blockers effects/considerations
- drug-induced slowing of HR with resulting decrease in MVO2 – desirable for patients with CAD
- slow 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
Propranolol MOA
non-selective beta adrenergic antagonist
Propranolol PK/PD
- onset: 2-5 min
- peak: 10-15 min
- DOA: 3-4 hours
- elimination ½: 2-4 hours
Propranolol clinical use
-used to prevent recurrence of tachyarrhythmias, both supraventricular and ventricular precipitated by sympathetic stimulation
Propranolol effects/considerations
cardiac effects –> decreased HR, contractility, CO (increased filling, decreased MVO2); increased PVR, coronary vascular resistance, however decreased oxygen demand
Metoprolol MOA
selective beta1 adrenergic antagonist
Metoprolol PK/PD
- onset: 2.5 min
- half-life 3-4 hours
- metabolized by liver
Metoprolol dose/route
IV bolus: 5 mg over 5 min; max 15 mg over 20 min
Metoprolol clinical use
can be used in mild CHF
Esmolol MOA
selective beta1 adrenergic antagonist
Esmolol PK/PD
- DOA: <10 min
- hydrolyzed by plasma esterases
Esmolol dose/route
IV bolus: 0.5 mg/kg over 1 min, then 50-300 mcg/kg/min
Esmolol effects/considerations
- great choice for OR because short DOA
- effects HR without decreasing BP significantly in small doses
Class III: Potassium Channel Blockers
- Amiodarone (prototype)
- Dronedarone
- Ibutilide
- Dofetilide
- Sotalol
Potassium Channel Blockers MOA
- phase 3 of fast AP
- block potassium channels resulting in prolongation of cardiac depolarization, increasing AP duration, and lengthening repolarization
- decrease proportion of the cardiac cycle during which myocardial cells are excitable and thus susceptible to triggering event
Potassium Channel Blockers clinical use
- treat supraventricular and ventricular arrythmias
- preventative therapy in patients who have survived sudden cardiac death who are not candidates for ICD
- control rhythm in Afib
Potassium Channel Blockers effects/considerations
- can prolong QT interval and develop torsades
- prophylaxis in cardiac surgery patients r/t high incidence of Afib
Amiodarone MOA
potassium/sodium/calcium channel blocker, alpha and beta adrenergic antagonist
Amiodarone PK/PD
- prolonged elimination ½ –> 29 days
- hepatic metabolism, active metabolite
- biliary/intestinal excretion
- 96% protein bound
- large Vd
Amiodarone dose/route
IV bolus: 150-300 mg IV over 2-5 min; up to 5 mg/kg then 1 mg/hr x 6 hours, then 0.5 mg/hr x 18 hours
Amiodarone clinical uses
- prophylaxis or acute treatment of atrial and ventricular arrhythmias (refractory SVR, refractory VT/VF, AF)
- 1st line for VT/VF when resistant to electrical defibrillation
Amiodarone considerations
- therapeutic plasma level 1.0-3.5 mcg/mL
- lengthens refractory period so susceptible to torsades (monitor Mg)
- can give PO preop to decrease incidence of Vfib post CT surgery
- many adverse effects, especially if given in high doses or over a long period of time
Amiodarone adverse effects
-adverse effects – pulmonary toxicity (fibrosis develops), pulmonary edema, ARDS, photosensitive rashes, grey/blue discoloration of skin, thyroid abnormalities, corneal deposits, CNS/GI disturbances, pro-arrhythmic (torsades), heart block, hypotension, sleep disturbances, abnormal LFT, inhibits CYP450
Sotalol class
- II and III
- beta adrenergic antagonist (non-selective) and potassium channel blocker
Sotalol PK/PD
excreted in urine
Sotalol clinical use
treat severe sustained VT and VF
Sotalol effects/considerations
- side effects –> prolonged QT, bradycardia, myocardial depression, fatigue, dyspnea, AV block
- caution with asthma (because of beta2 blockade)
Dofetilide & Ibutilide clinical use
conversion of AF or aflutter to NSR
Dofetilide & Ibutilide effects/considerations
proarrhythmic side effect (prolong QT)
Class IV Calcium Channel Blockers
- Verapamil (prototype)
- Diltiazem
- Nifedipine
Calcium Channel Blockers MOA
- phase 2 of fast AP
- bind to the alpha1 subunit on the L type voltage-gated calcium ion channel maintaining an inactive or closed state
- selectively interfere with inward calcium ion movement across myocardial and vascular smooth muscle cells
- decreases conduction through AV node and shortens phase 2 of AP in ventricular myocytes
- decreased contractility
Calcium Channel Blockers clinical use
Vascular –> angina, systemic HTN, pulmonary HTN, cerebral arterial spasm, Raynaud’s disease, migraine
Non-vascular –> bronchial asthma, esophageal spasm, dysmenorrhea, premature labor
-treatment of SVT and ventricular rate control in Afib and Aflutter
-prevent recurrence SVT
Calcium Channel Blockers effects
- decreased contractility
- decreased HR
- decreased activity of SA node
- decreased rate of conduction of impulses via AV node
- vascular smooth muscle relaxation (decreased SVR & BP)
Calcium Channel Blockers drug interactions
- myocardial depression and vasodilation with inhalational agents
- can potentiate NMBD
- verapamil and beta-blockers
- verapamil increases risk of local anesthetic toxicity
- verapamil and dantrolene can cause hyperkalemia d/t slowing of inward movement of K+ ions can result in cardiac collapse
- interact with Ca2+ mediated platelet fxn
- increase plasma dig concentration by decreasing clearance
- H2 antagonists alter hepatic enzyme activity and increase plasma level of CCB
Calcium Channel Blockers adverse effects
vertigo, HA, flushing, hypotension, paresthesias, muscle weakness, can induce renal dysfunction, coronary vasospasm with abrupt discontinuation
Calcium channel blocker toxicity treatment
can be reversed with IV admin of calcium or dopamine
Verapamil MOA
- phenyl-alkyl-amines (AV node)
- intracellular pore blocking of channel at binding site
Verapamil PK/PD
- 87-98% protein bound
- presence of lidocaine, diazepam, and propranolol increase activity
- extensive 1st pass hepatic metabolism
- peak: oral 30-45 min, IV 15 min
- elimination ½: 6-12 hrs
- hepatic metabolism, active metabolite (norverapamil)
- excreted in urine/bile
Verapamil dose/route
IV bolus: 2.5-10 mg over 1-2 min (max is 20mg)
IV infusion: 5 mcg/kg/min
Verapamil clinical uses
- SVT
- vasospastic angina
- HTN
- hypertrophic cardiomyopathy
- maternal and fetal tachyarrhythmias
- premature onset of labor
Verapamil effects/considerations
- primary site of action is AV node depresses AV node, negative chronotropic effect on SA node, negative inotropic effect on myocardial muscle, moderate vasodilation on coronary as well as systemic arteries
- do not use in combination with beta-blocker (can induce heart block)
- side effects –> myocardial depression, hypotension, constipation, bradycardia, nausea, prolongs effects of NMBDs
Diltiazem MOA
- benzothiazepines (AV node)
- unclear mechanism
- principal site of action is AV node
Diltiazem PK/PD
- onset: oral 15 min, peak 30 min
- 70-80% protein bound/excreted in bile and urine
- elimination ½: 4-6 hrs
- liver disease may require decreased dose
Diltiazem dose/route
-PO or IV
IV bolus: 0.25-0.35 mg/kg over 2 min (can repeat in 15min)
IV infusion: 10 mg/hr
Diltiazem clinical use
- SVT (1st line treatment)
- vasospastic angina
- HTN
- hypertrophic cardiomyopathy
- maternal and fetal tachyarrhythmias
Diltiazem effects/considerations
- intermediate potency between verapamil and nifedipine
- minimal CV depressant effects
- side effects –> constipation, hypotension, bradycardia
Nifedipine MOA
- 1,4-dihydropyridines (arterial beds)
- extracellular allosteric modulation of channel at binding site
- primary site of action = peripheral arterioles
Nifedipine PK/PD
- oral onset 20 min
- oral peak 60-90 min
- 90% protein bound
- hepatic metabolism
- excreted in urine
- elimination ½: 3-7 hrs
Nifedipine dose/route
IV, oral, or sublingual
Nifedipine clinical use
angina pectoris
Nifedipine effects/considerations
- coronary and peripheral vasodilator properties (decreases SVR and BP)
- little to no effect on SA or AV node
- reflex tachycardia
- can produce myocardial depression in patients with LV dysfunction or beta blockers
- side effects –> cancer, cardiac problems, bleeding, constipation, heart block
Adenosine MOA
binds to A1 purine nucleotide receptors – activates adenosine receptors to open K+ channels and increase K+ currents
Adenosine PK/PD
- t ½ < 10 seconds
- eliminated by plasma and vascular endothelial cell enzymes
Adenosine dose/route
IV RAPID bolus: 6 mg; repeat after 3 min 6-12 mg IV
Adenosine clinical use
acute treatment, termination of SVT
Adenosine effects/considerations
- slows AV nodal conduction
- side effects –> excessive AV or SA nodal inhibition, facial flushing, HA, dyspnea, chest discomfort, nausea, bronchospasm, impending doom
- contraindicated –> asthma, heart block
Digoxin MOA
increases vagal activity, decreasing activity of SA node, prolongs conduction of impulses through AV node
Digoxin PK/PD
- onset: 30-60 min
- t ½: 36 hrs
- weak protein binding
- 90% excreted by kidneys
- reduce dose in elderly or renal impairment
Digoxin dose/route
0.5-1 mg in divided doses over 12-24 hrs
Digoxin clinical use
- CHF
- management of afib or aflutter, especially with impaired heart function
Digoxin effects/considerations
- decreases HR, preload, and afterload
- slows AV conduction by increasing AV node refractory period
- positive inotrope
- narrow therapeutic index (0.5-1.2 mcg/mL)
- adverse effects arrhythmias, heart block, anorexia, nausea, diarrhea, confusion, agitation
digoxin toxicity treatment
phenytoin (vent arrhythmias), pacing, atropine
Magnesium
- works at sodium, potassium, and calcium channels
- treatment –> torsades de pointes
- IV bolus: 1 g over 20 min; can be repeated
Atropine
-muscarinic receptor antagonist
atropine PK/PD
- metabolized in liver
- onset <1 min
- DOA: 30-60 min
atropine dose
IV bolus: 0.4-1 mg; repeat as necessary
atropine clinical use
unstable bradyarrhythmias
atropine considerations
caution dosing <0.4 mg –> can have paradoxical response
