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37 Cards in this Set
- Front
- Back
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Beta blocker receptors
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β-1 receptors in heart
β-2 receptors in vascular smooth muscle, bronchial smooth muscle |
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Beta blocker mechanism
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Practically speaking, all cardiac effects are indirect – work by blocking effects of catecholamines
If taking a beta blocker makes your heart rate slow down – well, that means that your sympathetic tone was speeding it up previously Negative chronotropic effect -Slows automaticity in sinus node and AV node by slowing phase 4 depolarization -slows sinus rhythm, also slows junctional escape rhythm Negative dromotropic effect -Slows velocity of conduction through AV node -Especially useful to slow ventricular response rate during atrial tachyarrhythmias Can interrupt any reentrant loop that uses the AV node as part of the circuit (AVNRT, AVRT) -By slowing conduction through the AV node Negative inotropic effect They are the only antiarrhythmic drugs that actually improve survival in patients with heart disease |
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Cardioselective vs nonselective beta blockers
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Cardioselective – only block β-1 receptors
-Atenolol -Metoprolol -Esmolol Nonselective – block β-1and β-2, some also block alpha receptors -Propranolol -Labetalol – also α-block -Carvedilol – also α-block Some also have intrinsic sympathomimetic activity -Simultaneously stimulate and block beta receptors -More useful for SN dysfunction Not everything that ends in “–ol” is a beta blocker! Isoproterenol is not a beta blocker -It’s a beta agonist! -It is the exact opposite of a beta blocker |
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Cardioselective vs nonselective beta blockers: why does it matter
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Asthma
-Nonselective beta blockers block β-2 receptors, can cause bronchospasm -Rarely can be life-threatening (I’ve seen it) Peripheral vascular disease and Raynaud’s -Severe PVD and Raynaud’s syndrome can be exacerbated by nonselective beta blockers -Sometimes even selective β-blockers are a problem Additional alpha blockade can be helpful -IV Labetalol useful in hypertensive emergencies |
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Beta blocker: adverse effects
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Really just too much of a good thing
Negative chronotropic effect -Sinus bradycardia Negative dromotropic effect -AV block Negative inotropic effect -Can worsen patients who are already having severe, acutely decompensated heart failure -In most heart failure patients, beta blockers are a good thing When beta blockers make a heart failure patient worse, negative inotropy usually isn’t the reason -The problem is usually bradycardia (negative chronotropic and dromotropic effects) |
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Calcium channel blockers: classes
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Dihydropyridine (DHP)
-Nifedipine, Amlodipine, Felodipine, etc., etc. Nondihydropyridine (non-DHP) -Diltiazem -Verapamil Only diltiazem and verapamil have clinically relevant effects on cardiac action potential -DHP-CCBs are such potent vasodilators that no one can take a high enough dose to actually affect the cardiac Ca++ channels |
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Calcium channel blockers: Mechanism
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Diltiazem and Verapamil
Block L-type calcium channels Only affect Sinus and AV nodal cells -AV node most of all Effects on sinus and AV nodes are similar to beta blockers Negative chronotropic effect Sinus Node -Usually do not cause significant sinus bradycardia unless patient already has sinus node dysfunction -If patient does have sinus node dysfunction, the effect can be profound AV node -Can “shut down” a junctional escape rhythm Negative dromotropic effect on AV node -This is the primary use for these drugs -Especially useful to slow ventricular response rate during atrial tachyarrhythmias --Atrial fibrillation, Atrial flutter, Atrial tachycardia… -Can interrupt any reentrant loop that uses the AV node as part of the circuit (AVNRT, AVRT) Negative inotropic effect -Unlike beta blockers, this really is a problem -These drugs are relatively contraindicated in patients with systolic heart failure |
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Calcium channel blockers: adverse effects
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Diltiazem and Verapamil
Too much negative chronotropy -Sinus node dysfunction -“shut down” a junctional escape rhythm Too much negative dromotropy -AV block Too much negative inotropy -Systolic heart failure Hypotension Peripheral edema Various drug interactions |
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Digoxin terminology
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Digoxin is a form of digitalis
It is a cardiac glycoside |
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Digoxin mechanism
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As a positive inotrope
1. Digoxin poisons the Na+-K+ pump 2. Increases Na+ concentration inside cell 3. Na+-Ca++ exchanger keeps more Ca++ in cell to balance this 4. More Ca++ enters SR more Ca++ available for contraction Therefore Digoxin acts as a positive inotrope (more contraction) As an antiarrhythmic Primary effect on cardiac rhythm is through augmentation of vagal tone Primarily affects Sinus and AV nodes -Like verapamil and diltiazem, sinus node is not usually affected, but can be profoundly supressed in patients with pre-existing sinus node dysfunction -AV node is the primary target --Slows conduction velocity through the AV node |
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Digoxin adverse effects
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No hypotension
Digoxin is a (mildly) positive inotrope Much less effective in slowing AV nodal conduction than verapamil and diltiazem Narrow therapeutic index – much easier to reach toxic levels Almost never the best first choice for any arrhythmia – especially bad in elderly patients Toxicity: Nausea / vomiting, visual disturbances (seeing yellow-green halos around things) High-grade AV block along with atrial tachycardias Ventricular tachyarrhythmias due to delayed afterdepolarizations Digoxin is cleared by the kidney, so must keep track of renal function -Severe toxicity may need digibind and dialysis |
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Adenosine: overview
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It is a natural substance
It is given as a rapid IV push It is cleared very quickly after administration -Half-life = about 10 seconds Can precipitate bronchospasm in asthmatics -Bronchospasm may continue even after adenosine has been eliminated Rarely can precipitate atrial fibrillation -Not common with usual doses (6 mg to 12 mg) |
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Adenosine: purpose
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Cause AV nodal block:
-Great for terminating any reentry involving AV node – usually the first-line drug for this -It also usually slows the sinus node a bit --Direct effect on automaticity --But then indirectly speeds it up a few seconds later, sinus tachycardia is a compensatory response to hypotension (adenosine is a vasodilator) -It has no noticeable effect on ventricular cardiac cells |
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Na channel blocking drug: mechanism
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Slow upstroke of phase 0
Prolong QRS duration: not always noticeable on EKG Blockade of sodium channels -Fewer Na+ channels available for conduction -Raise the threshold for initiation of action potential -Slow the upstroke of phase 0 -May also decrease slope of phase 4 in cells with abnormal automaticity |
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Na channel blocking drug: effects
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Effect on automaticity:
Takes a larger stimulus to excite each cell Slows or terminates automaticity -May slow enough that sinus node now becomes dominant rhythm (“fastest one wins”) Sinus node automaticity not usually affected unless already have sinus node dysfunction Effect on conduction velocity: Na+ channel blockade causes each cell to activate a bit more slowly Cumulative effect is to slow conduction through the affected tissue Good effect on reentry: Alter conduction properties so that spiral waves and rotors can’t keep on going Convert unidirectional block to bidirectional block at critical heart rate Slow the “slow pathway” so much that it no longer conducts at all Bad effect on reentry: Slow either pathway just enough to make the reentrant circuit virtually incessant This is the primary danger of type 1 antiarrhythmic drugs – incessant VT Patients with prior myocardial infarction should not take type 1 drugs unless they already have an ICD |
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Class 1A Drugs and Effects
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Na channel blockers
Class 1A -Quinidine -Procainamide -Disopyramide Also block K+ channels -QT prolongation can cause arrhythmias --“Torsades de pointes” (aka Polymorphic Ventricular Tachycardia) Lots of noncardiac side effects -Nausea and vomiting -Diarrhea in up to ⅓ of patients -“cinchonism” = tinnitus, confusion, visual disturbance, etc. -Autoimmune thrombocytopenia -Major interaction with digoxin --Raises digoxin level |
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Procainamide
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Only 1A (Na blocker) drug used intravenously
Breakdown product = NAPA (N-acetyl procainamide) -An active metabolite -Metabolism depends on rate of acetylation --Patients can be “slow” or “rapid” acetylators -Blood level = check both Procainamide + NAPA Lupus-like syndrome in up to ⅓ of patients -Fever, rash, arthralgias, etc. -Requires stopping the drug |
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Disopyramide
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1B (Na blocker)
Strong anticholinergic effect -Dry mouth, urinary retention, constipation, exacerbation of glaucoma Negative inotrope -unlike procainamide and quinidine, which are not negative inotropes -Has been used as a “good side effect” in patients with hypertrophic cardiomyopathy |
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Class 1B Drugs and Effects
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Na channel blockers
Lidocaine Mexiletine Shorten the QT interval -Not usually enough to be noticeable on EKG Target ventricular cells only -No effect on atrium Preferentially affect ischemic tissue -Can be useful for ventricular arrhythmias in AMI --Lidocaine was once recommended prophylactically during AMI (was proven false) |
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Lidocaine
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1B
Intravenous only Cleared by liver, so careful in: -Liver disease (obviously) -Heart failure means less hepatic perfusion CNS side effects -Can be serious if levels get too high -Confusion: seizures If prolonged infusion needed, must check levels frequently |
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Mexiletine
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1B
Oral only Practically speaking, probably okay to consider this an oral form of lidocaine Not very effective, but mixes well with certain other antiarrhythmics when needed |
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Class 1C Drugs and Effects
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Flecainide and Propafenone
The most potent Na+ channel blockers Markedly decrease upstroke of phase 0 “Clean” drugs – no effect on K+ channels -No direct effect on QT interval -Can cause bad arrhythmias, but not Torsades Negative inotropes -contraindicated in systolic heart failure Primarily used for atrial arrhythmias (AFib) -Also can be used to “shut down” accessory pathways (i.e. Wolff-Parkinson-White syndrome) |
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Flecainide side effects
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1C
Side effects are common, but not usually severe enough to stop the drug if it’s working -Fatigue is very common -Visual disturbances fairly common --Complaints are vague but consistent |
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Propafenone side effects
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1C
Has beta blocking properties -How much depends on individual patient’s metabolism -Think of as getting broken down into propanolol (not really accurate) Mild CNS symptoms -Dizziness |
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Na channel blocking drugs use dependence
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Na+ channel blocking drugs bind preferentially to open(active) channels
-The more the channels are open/active (in-use), the greater the blockade -This means that Na+ channel blockers are even more effective at faster heart rates During atrial fibrillation, atrial rates are very fast (300-400 bpm) -This is one reason why Na+ channel blockers can actually stop AFib (convert it to sinus rhythm) |
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Class 3 K channel blockers: Reverse use-dependence
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K+ channel blocking drugs have a greater effect during slower heart rates
This makes them less useful in terminating atrial fibrillation (when atrial rates are very fast) Also means that bad arrhythmias such as Torsades are more likely during slower heart rates if the QT is prolonged -“pause-dependent Torsades” = Polymorphic VT occurring after a sinus pause |
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Class 3 K channel blockers: effect on cardiac potential and EKG
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K+ channel blocking drug will:
-prolong AP phase 3 --This prolongs the Effective Refractory Period of the cell --Makes cell unable to sustain faster heart rates -prolong QT |
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K channel blockers adverse effects
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Again, these all prolong the QT interval
Torsades (polymorphic VT) is a risk with most (exception = amiodarone) Torsades is more likely when: -Too much drug on board --Renal or hepatic failure, depending on drug -Hypokalemia -Bradycardia and especially sinus pauses Despite all this, K+ channel blockers can be used in patients with prior AMI |
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Sotalol
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Class 3 K blocker
Also has beta blocker activity -Can be good or bad depending on patient Cleared by the kidney -Can accumulate in renal failure and cause Torsades (I’ve seen this quite a few times) QT must be monitored periodically |
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Defetilide and Ibutilide
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Class 3 K blocker
Ibutilide = intravenous; Dofetilide = oral -Otherwise, basically same characteristics Ibutilide is given IV to convert Afib -Torsades in up to 10% --Can partially prevent by giving IV magnesium first Dofetilide is cleared by liver and kidney -Renal clearance seems especially important Dofetilide is relatively safe in heart failure -Not a negative inotrope QT must be monitored periodically |
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Amiodarone: overview
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Class 3 K blocker
Amiodarone is the “safest antiarrhythmic drug for your heart, and most dangerous one for every other part of your body” Amiodarone has a LOT of iodine in it -This plays a major role in its noncardiac toxicities Prolongs QT but very rarely causes Torsades -Not usually thought of as a risk for Torsades -Don’t need to monitor QT Almost never causes ventricular arrhythmias -But also can’t be counted upon to prevent them -Only ICDs have been shown to improve mortality in patients at risk for fatal arrhythmias |
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Amiodarone: toxicity
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Class 3 K blocker
Eyes – corneal deposits; rare optic neuropathy - serious Hypothyroidism – common, easily remedied Hyperthyroidism – rare, can be serious Hepatic injury Pulmonary toxicity – irreversible, but usually only after several years Skin photosensitivity – bluish discoloration of skin only after years of fairly high-dose therapy Major interaction with warfarin Amiodarone makes you “blue, blind, and coughing up your liver and thyroid” Most toxicities will be detected by routine monitoring and will resolve or at least not progress once the drug is stopped Pulmonary toxicity is probably the most serious, and usually takes up to 10 years to develop Patient age and life expectancy are very important considerations when considering amiodarone -This is not a drug for young people |
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Amiodarone: mechanism
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Amiodarone has some properties of all four antiarrhythmic drug classes
-Some Na+ channel blocking properties -Some β-blocking properties -A lot of K+ blocking properties -Some Ca++ channel blocking properties This is probably why it can be used for just about every arrhythmia -Not magic, but statistically more effective than the other antiarrhythmic drugs |
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Dronedarone: overview
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Class 3 K blocker
Structurally similar to Amiodarone -Without the iodine Activity supposedly similar to amiodarone except: -Without the awful toxicities -May not be as protected from Torsades --QT does have to be monitored, but Torsades risk is probably low -Not as effective as amiodarone (not even close!) -1/3 of patients have GI side effects Interferes with creatinine secretion – raises serum creatinine level -But GFR is actually not affected |
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What to use for systolic heart failure
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Usually okay to use:
Beta blockers -Just don’t give too much Amiodarone Dofetilide Sotalol, but its beta blocking properties might be a problem Dronedarone, but contraindicated in severe CHF Digoxin Relatively contraindicated: Verapamil and diltiazem -Due to negative inotropy -Sometimes you have no choice but to use them Definitely contraindicated: Any type 1 antiarrhythmic -Unless already have ICD |
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What to use for prior MI with myocardial scar but without systolic heart failure
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Okay to use:
Beta blockers Amiodarone Dofetilide Sotalol Dronedarone Digoxin Verapamil and diltiazem -But beta blockers are better Definitely contraindicated: Any type 1 antiarrhythmic -Unless already have ICD |
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What to use with healthy ventricles
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Everything is okay (hooray!)
Type 1 antiarrhythmics (especially 1C – flecainide and propafenone) may actually be safer than type 3 drugs in patients with a structurally normal ventricle (no scar, normal systolic function) |
