CV pharmacology Flashcards
relationship between cardiac AP and ion channel currents
Arrhythmias are caused by ?
abnormal pacemaker activity
abnormal impulse propagation
The aim of therapy of the arrhythmias is to ?
reduce ectopic pacemaker activity
modify conduction or refractoriness in reentry circuits to disable circus movement
what do antiarrhythmic drugs do?
- decrease automaticity of ectopic pacemakers more than that of SA node
- reduce conduction and excitability and increase refractory period
3 subclasses are further defined by the effect of the agents on the Purkinje fiber AP:
class I
- Class Ia: slow rate of rise of AP and prolong duration = slowing conduction and increasing refractoriness (moderate depression of phase 0 upstroke of the action potential)
- Class Ib: shorten AP duration; do not affect conduction or refractoriness (minimal depression of phase 0 upstroke of AP)
- Class Ic: Dissociates from channel with slow kinetics (no change in AP duration)
What is the drug classification for antiarrhythmics
Vaughan-Williams Classification system
- Block fast Na channels (class I)
- BB (class II)
- block K channels (class III)
- CCB (class IV)
what drugs are class Ia?
quinidine, procainamide, disopyramide
what drugs are class Ib?
lidocaine, mexiletine
what drugs are class Ic?
flecainide, propafenone
Quinidine MOA/effect
- potent anticholinergic properties that affect SA and AV nodes = increase SA nodal discharge rate and AV nodal conduction
- may lead to increased ventricular rates with afib or aflutter
- Addition of BB, non-dihydropyridine CCB, or digoxin protects against this
SE of Quinidine
GI-related - N/V/D
Proarrhythmic – torsades
Can interact with CYP3A4 inducers or inhibitors
difference between Quinidine vs Procainamide
Does not have the anticholinergic activity of quinidine
SE of procainamide
- Prolongs QT interval = risk of torsades
- SLE – MC adverse event
- N/V/D and drug fever
disopyramide effect
Potent anticholinergic and negative inotropic effects limits uses clinically
SE/CI of disopyramide
- Prolongs QT = torsades
- CI: reduced LV EF (<40%)
- Precipitation of CHF
- Anticholinergic effects – dry mouth, urinary retention, constipation, blurred vision
lidocaine effect
- Selective to ischemic tissue, and esp to active fast Na channels in bundle of HIS, Purkinje fibers, and ventricular myocardium
- Primarily effective in treating ventricular dysrhythmias, especially those associated with acute MI
- Little effect: non-ischemic tissue, atrial myocardium, and automaticity of the SA node
monitoring for lidocaine
Cleared by hepatic metabolism, therefore, monitor closely for signs of toxicity in patients with liver failure
SE of lidocaine
CNS effects of dizziness, paresthesia, disorientation, tremor, agitation, seizures and respiratory arrest
effect of mexiletine
- Not used as a single agent - combo w/ class IA and III drugs for the tx of refractory ventricular dysrhythmias
- Similar to lidocaine, but in oral form
SE mexiletine
- GI – N/V, limits use
- neurologic - dizziness, confusion, ataxia, and speech disturbances
MOA of Flecainide (Tambacor)
- Slows conduction velocity in Purkinje fibers & AV node
- lengthen PR interval & QRS duration
- MC for afib/flutter
- for VT but it sucks
SE of flecainide
- Rapid VT, resistant to resuscitation, esp with CAD, LV dysfunction, LVH or valvular disease - AVOID in any heart dz
- Blurred vision, dizziness, HA, tremor, N/V
MOA of propafenone
- Class IC
- Slows conduction velocity in Purkinje fibers and AV node; also has a mild nonselective BB effect
- lengthen PR interval and QRS duration = conduction disturbances (bradycardia, blocks)
- MC for afib/flutter
SE of propafenone
- May cause VT similar to flecainide, so avoid in any form of heart dz
- Blurred vision, dizziness, HA, N/V, bronchospasm, and taste disturbances (metallic taste)
MOA of BB
- Decrease automaticity, prolong AV conduction, and prolong refractoriness - Negative chronotropic and inotropic effects
- Suppresses ventricular dysrhythmias + supraventricular dysrhythmias
- esp helpful when used in combination with other AAD
- Metoprolol MC
which BB can be used as a continuous IV infusion for rapid afib/flutter
esmolol
MOA of class III AAD
- Block K channels and prolong repolarization, widening QRS and prolonging QT interval.
- Decrease automaticity and conduction and prolong refractoriness.
Avoid concomitant use of class III AADs with ?
other drugs that can prolong QT interval to minimize the risk of torsades
MOA of amiodarone
- Possesses characteristics of all 4 classes
- Primarily K channel blocker, also blocks Na channels, has non-selective BB activity, weak CCB properties
- Works on all cardiac cells (SA node, AV node, atria, ventricles and Purkinjes) - Minimal/no negative inotropic effects - Can be used w/ LV dysfunction
SE of amiodarone
- Has potential to for its metabolite to accumulate and cause adverse effects in numerous organs, including the lungs, thyroid, eyes, heart, liver, skin, GI tract, and nervous system
- GI common - N/V, anorexia, abd pain (take w/ food)
- Neurologic toxicities occur frequently - Tremors, ataxia, peripheral neuropathy, fatigue and insomnia
- Liver toxicity is rare, but screening LFTs Q6 mo
- Derm - photosensitivity, blue/gray discoloration - Sunscreen + sun exposure avoidance to help
amiodarone is a potent inhibitor of what enzyme?
CYP3A4
- Many DDI
- Potentiates the anticoagulation effects of warfarin; close monitoring is essential
- Can double serum digoxin concentrations
MOA of sotalol
- Class III that also has nonselective beta-adrenergic blocking properties
- May decrease cardiac contractility and therefore should be avoided in patients with LV dysfunction - Prolongs atrial and ventricular refractoriness
SE of sotalol
- QT prolongation common - monitored for closely
- DC if QT interval > 550 ms
- Avoid combining with other QT prolonging drugs - Most SE from BB properties
MOA of dofetilide
Results in prolonged AP and an increased QT interval
- Affects atria > ventricles
- No negative inotropic effects = safe in LV dysfunction
SE of dofetilide
torsades de pointes - Admit, telemetry Q12 hr EKG’s for first 3 days of loading to monitor QT interval and adjust dose
CI with dofetilide
- Cimetidine, ketoconazole, megestrol, prochlorperazine, Bactrim, or verapamil - Avoid inhibitors of the CYP3A4 isoenzyme
- Renally cleared, avoid if CrCl < 20 mL/min
MOA of dronedarone
- Exact MOA unknown; exhibits AA properties of all 4 classes
- Some considered it the “safe cousin of amiodarone”; but not nearly as effective, and side effects and toxicities are still common
SE of dronedarone
CHF exacerbation
QT prolongation
bradycardia
hepatotoxicity
pulmonary toxicity
photosensitivity
N/D
pruritis
dyspepsia
CI of dronedarone
- Symptomatic CHF & recent decompensation requiring hospitalization
- Permanent AF
- Severe hepatic impairment
monitoring for dronedarone
BUN/Cr; EKG q 3 mos; LFT’s during 1st 6 mos of Tx
effect and indication for ibutilide
Ibutilide - Corvert
- Structurally similar to sotalol, but no BBing activity
- IV only, and indicated only for afib/flutter cardioversion
SE of ibutilide
torsades
- Monitored on telemetry following IV infusion
- Avoid: LV dysfunction and electrolyte abnormalities (esp hypokalemia and hypomagnesemia)
verapamil
CCB
diltiazem
CCB
MOA of CCB
- Decrease automaticity and AV conduction
- Potent negative inotropic effects - avoid LV dysfunction
MOA of digoxin
Predominant AA effect is on AV node
- Inhibits Ca currents in AV node and activates Ach-mediated K+ currents in atrium
- Slows conduction thru AV node and prolongs AV nodal refractory period
- Therefore, mainly used for slowing the ventricular rate in afib/flutter, as well as terminating reentrant arrhythmias involving AV node
On EKG you see PR prolongation and ST segment depression, what is going on?
digoxin effect
toxicity of digoxin is a risk if ____ are administered that destroy intestinal microflora
antibiotics
PK of digoxin
- Half-life - 36 hrs = once daily dosing
- Renal elimination = reduced dose/dosing intervals with renal insufficiency
- IV or oral - Tablets are incompletely bioavailable
- intestinal microflora may metabolize digoxin = reduced bioavailability = need higher doses
- Slow distribution to effector sites - Even w/ IV
- Requires loading dose 0.6-1 mg x 24 hrs, then reduce to maintenance dose
what drugs specific can decrease digoxin clearance?
Amiodarone
quinidine
verapamil
diltiazem
itraconazole
propafenone
flecainide
dose should be decreased if combining with these drugs
signs of digoxin toxicity?
- declining renal function, electrolyte abnormalities, hypoxia or DDI
- Visual disturbances, dizziness, weakness, N/V/D, anorexia
- Essentially ANY dysrhythmia can result from digoxin toxicity
tx of digoxin toxicity
- IV hydration and electrolyte correction
- Digoxin immune Fab - an immunoglobulin fragment with specific and high affinity for digoxin molecules
MOA of adenosine
- Activates K channels and by increasing outward K current hyperpolarizes the membrane potential, decreasing spontaneous SA nodal depolarization
- Inhibits automaticity and conduction in the SA and AV nodes
adenosine is used for converting what abnormality to sinus rhythm?
SVT to sinus rhythm; essentially causing sinus arrest
SE of adenosine
Chest discomfort, dyspnea, flushing, HA
what is atropine
- Parasympatholytic drug that enhances both sinus nodal automaticity & AV nodal conduction through direct vagolytic action
- Blocks Ach at parasympathetic neuroeffector sites
when is atropine used?
emergent setting of symptomatic bradycardia
SE of atropine
- tachycardia - may result in poor outcomes in pts with MI, so use cautiously
- paradoxical slowing HR with Mobitz type II AVB and 3rd degree AVB - monitor
which AADs are safe for LV dysfunction
- amiodarone
- dofetilide
which AADs should be avoided in LV dysfunction
- Flecainide
- sotalol
- ibutilide
- CCB
