Lecture 19: CV Pharmacology Flashcards
How does a SA node action potential look like?
- Sodium influx via funny channels
- Calcium influx
- Potassium efflux
What are the 5 phases of a cardiac myocyte action potential?
What is the effect of hypercalcemia on the cardiac action potential?
Extends the plateau phase
What are the 2 general mechanisms behind arrhythmias?
- Abnormal pacemaker activity
- Abnormal impulse propagation
What do antiarrhythmic drugs tend to focus on?
Ectopic pacemakers, reducing their automaticity.
It does not affect the SA node itself as much.
What do antiarrhythmic drugs do to depolarized tissue primarily?
- Reduce conduction and excitability
- Increase refractory period
Effect is more pronounced in depolarized tissue rather than polarized.
What are the 4 classes of antiarrhythmic drugs?
- Class I: fast sodium channel blockers
- Class II: BBs
- Class III: Potassium channel blockers
- Class IV: CCBs
What are the 3 subclasses of class I antiarrhythmics based on and what are the 3 subclasses?
Defined by their effects on purkinje fiber AP
- Class 1a: slow the rate of rise of the AP and prolong its duration (moderate depression of the phase 0 upstroke) (Quinidine, procainamide, disopyramide)
- Class 1b: Shorten AP (minimal depression of the phase 0 upstroke) (lidocaine, mexiletine)
- Class 1c: Dissociates from channel with slow kinetics (no change in AP duration) (flecainide, propafenone)
What is the main purpose of quinidine and what is it often used with?
- Class 1a drug that works as an anticholinergic on SA and AV nodes.
- Often combined with BBs, non-DHP CCBs, or digoxin to prevent increased ventricular rate.
Proarrhythmic that can cause torsades
What does procainamide do?
- Similar to quinidine but lacks anticholinergic activity.
- Prolongs QT interval = torsades risk
- MC ADE: Lupus
- Main use: WPW
Class 1a
Treats Wolff, can cause wolf
What is the profile of disopyramide?
- Class 1a
- Potent anticholinergic and negative inotrope
- QT prolongation
- CI in pts with HFrEF
What is lidocaine selective for in the heart?
Ischemic tissue, primarily active fast sodium channels below the AV node
Class 1b
Class 1a antiarrhythmic mnemonic
Double Quarter Pounder
- Disopyramide
- Quinidine
- Procainamide
When is lidocaine used?
Ventricular dysrhythmias, especially those associated with MI.
What kind of patients should we be cautious of injecting lidocaine into?
Hepatic impairment
What is the difference between lidocaine and mexiletine?
Mexiletine is oral
class 1b
What is mexiletine often used with combination with?
Class 1a and III for refractory ventricular dysrhythmias
What is the main SE of mexiletine?
GI use (limits the use of them)
What is the profile of flecainide?
- Slows conduction velocity in the purkinje and AV node
- MC use: afib/aflutter
- May cause rapid VT in someone with structural abnormalities
Class 1c
Class 1b antiarrhythmic mnemonic
Lettuce Tomato Mayo
- Lidocaine
- phenyToin
- Mexilitine
Liddy’s Mexican Pub
T is actually for tocainide, but we didn’t learn about it
What is the profile of propafenone?
- Slows conduction velocity in the purkinje fibers and AV node + mild non-selective BB effect
- lengthens PR and QRS => bradycardia or heart block
- MC use: Afib/Aflutter
- Avoid in structural heart disease
- Additional SE of metallic taste
Class 1c
Similar to flecainide
What patients should never get class 1c antiarrhythmics?
Structural Heart Disease
What are BBs mainly used for?
- Decrease automaticity, prolong AV conduction, prolong refractory period
- Suppressing ventricular dysrhythmias and SVTs
Class 1c antiarrhythmic mnemonic
Fries Please
- Flecainide
- Propafenone
What BB is good for IV infusions?
Esmolol
What do class III antiarrhythmics do?
- Block potassium channels and prolong repolarization, widening QRS and prolonging QT.
Avoid combining with other QT prolongation drugs. May cause TORSADES
What is the profile of amiodarone?
- Characteristics of all 4 antiarrhythmic classes! (primarily Class III)
- Works on all cardiac cells, but is primarily a potassium channel blocker
- OK to use in LV dysfunction (mild negative inotrope effect)
- Can buildup in toxicity
Amiodarine should be avoided in bradycardic patients
How do we screen for pulmonary toxicity in amiodarone?
- Annual CXR
- Stop Amiodarone ASAP
What mineral effect can amiodarone mimic?
- Iodine, so it can induce hypo or hyperthyroidism.
- Q6months TSH checks
What are the toxicities that amiodarone can cause?
- Pulmonary
- Thyroid (iodine)
- Ocular (deposits)
- Neurologic (tremors, ataxia)
- Dermatologic (blue/gray discoloration & photosensitivity)
- Liver
Derm = smurf looking
What does amiodarone interact with?
CYP3A4 inhibitor: can potentiate warfarin and digoxin
Doubles digoxin levels
What is the profile of sotalol?
- Primarily a potassium channel blocker but also has non-selective BB properties (negative inotrope)
- Prolongs atrial and ventricular refractoriness
- ADE: QT prolongation (d/c if QT interval > 550ms)
Class III drug since it is primarily a potassium channel blocker.
What is the profile of dofetilide?
- Prolongs AP and QT interval (OK to use in LV dysfunction)
- Mainly atrial focused
- MC ADE: Torsades, gotta monitor IP.
- 3 days, 6 doses inpatient, EKG 2 hrs after every dose.
What concomitant drug use CIs usage of dofetilide?
- Cimetidine
- Ketoconazole
- Megestrol
- Prochlorperazine
- Bactrim
- Verapamil
Also Renal impairment
What is the profile of dronedarone?
- Similar to amiodarone with less efficacy but less SEs also
- CI: Symptomatic CHF or recent decompensation, Permanent AF, Hepatic impairment
Class III antiarrhythmic
What is the profile of ibutilide/corvert?
- Similar to sotalol
- IV only, used solely for afib/aflutter cardioversion
- Can cause torsades
- Avoid in LV dysfunction and lyte abnormalities
What are the two Class IV antiarrhythmics?
Verapamil and diltiazem
What do class IV antiarrhythmics do and their main weakness?
- Decrease automaticity and AV conduction
- negative inotrope = avoid in pts with LV dysfunction.
What does digoxin do?
- Inhibition of Ca channels in AV node and activates K+ channels.
- Slows conduction through AV node, prolonging refractoriness
- Slows ventricular rate in afib/aflutter and terminating AVNRTs
What are the EKG changes associated with digoxin?
- PR prolongation
- ST segment depression
Pt in afib
What is the concern with oral digoxin?
- Poor bioavailability
- Toxicity can occur if ABX are also administered. (microflora metabolize it)
What are the pharmacokinetics of digoxin?
- Half life of 36hrs
- Renal elimination
- Clearance is decreased by: Amiodarone, quinidine, verapamil, diltiazem, itraconazole, propafenone, and flecainide
What is the therapeutic range of digoxin?
0.5-2 NANOgrams/mL
What does digoxin toxicity cause?
- Visual disturbances, dizziness, weakness, N/V/D, anorexia
- Any dysrhythmia can occur
How do you treat digoxin toxicity?
- IV hydration + lyte correction
- Digoxin immune Fab can be used to bind
What does adenosine do?
- Activate potassium channel and hyperpolarizes membrane, decreasing SA node depolarization
- Short-term AV nodal blocker
- Use: conversion of SVT to sinus rhythm
What is the dosing for adenosine?
6, 6, 12 mg
What does atropine do?
- Parasympatholytic drug that enhances sinus nodal automaticity and AV nodal conduction
- Use: Emergent bradycardia
- Caution: MI pts that get converted into tachycardia will have a worse supply-demand mismatch.
What is the paradoxical effect of atropine?
Slows HR in pts with mobitz type II AVB and 3rd deg AVB.
