Arrhythmias
Other Antiarrhythmics: Class III: primarily block potassium channels Dronedarone (Multaq): Boxed Warnings: Contraindications: Warnings: Side Effects: Drug Interactions: Notes:
Boxed Warnings: -*Increased* risk of *death, stroke, and HF* in patients with *decompensated HF* (NYHA Class IV or any Class with a recent hospitalization due to HF) or *permanent AFib* Contraindications: -Pregnancy, 2nd/3rd degree heart block (unless patient has a pacemaker), symptomatic HF, HR <50, concurrent use of strong 3A4 inhibitors and QT prolonging drugs, QT at least 500 msec, PR interval >280 msec, lung or liver toxicity from previous use, hepatic impairment, nursing mothers. Warnings: -*Hepatic failure* (especially in the first 6mos), *pulmonary* disease (including *pulmonary fibrosis* and pneumonitis), marked INC SCr, prerenal azotemia and ARF (usually in the setting of heart failure or hypovolemia), DEC magnesium and DEC potassium with administration of potassium-depleting diuretics. Side Effects: -*QT prolongation*, INC SCr, N/V/D, abdominal pain, diarrhea, bradycardia, asthenia. Drug Interactions: -Dronedarone is a moderate inhibitor of 2D6, 3A4, and P-gp and a major substrate of 3A4. *Avoid use* with *strong inhibitors and inducers of 3A4* and with *drugs that prolong the QT interval.* DEC digoxin dose 50%. Use low doses of statins metabolized by 3A4, or use alternative statin. Monitor INR if on warfarin. Notes: -Unlike amiodarone, dronedarone does *not contain iodine,* and has *little effect on thyroid function*.
Antiarrythmics MOA & Consequence -Class 1: -Class II: -Class III: -Class IV: -Digoxin: -Adenosine:
-Class 1: *Na-channel* blockers: reduces the speed of ion conduction through the sodium channels. Proarrhythmic (higher risk of arrhythmia). *Negative inotrope* potential, which DEC the force of the heart's contraction. -Class II: *beta-blockers*: blocks the sympathetic activity that can trigger an arrythmia; indirectly blocks calcium channels, which DEC ion conduction speed. Used primarily to *slow the rate* in ventricular tachyarrhythmias. -Class III: *K-channel* blockers, primarily: *Amiodarone* and *dronedarone* block K-channels (primarily) and block alpha & beta adrenergic receptors, and Ca & Na channels; Amiodarone is useful for different types of arrhythmias, including *afibrillation,* the most common arrythmia, and is *preferentially used in HF.*; *sotalol* blocks K-channels and is a beta-blocker. -Class IV: *Ca-channel* blockers, *non-DHP*: used primarily to *slow the rate* in *ventricular tachyarrhythmias* (rate control). Negative inotropic effect (DEC contraction force), which can cause cardiac decompensation; *do not use verapamil or diltiazem* with *heart failure* and *reduced ejection fraction (HFrEF)*. -Digoxin: *Na-K-ATPase blocker*: blocking the Na-K-ATPase pump will INC *force* of cardiac conduction (*positive inotrope*) and DEC *heart rate* (*negative chronotrope*). -Adenosine: activates *adenosine receptors* to DEC AV node conduction: used for *paroxysmal supraventricular tachyarrythmias* (PSVTs).
Type of AFIB: -Paroxysmal: -Persistent: -Long-standing Persistent: -Permanent:
-Paroxysmal: AFib that terminates spontaneously or with intervention within 7 days of onset; episodes may recur with variable frequency. -Persistent: Continuous AFib that is sustained >7 days -Long-standing Persistent: continuous AFib of >12 months -Permanent: Term used when a joint decision has been made by the clinician and patient to cease further attempts to restore and/or maintain NSR; this is a treatment choice rather than a characteristic of the arrythmia itself.
Rhythm Control: -Rhythm control consists of: -Conversion to NSR is most effective with: -Meds can be used as well and include: -For maintenance of NSR, recommended options include: -Due to toxicities, amiodarone is recommended only when other agents have failed or are contraindicated (e.g., amiodarone is used in heart failure); despite this, amiodarone is the top-selling antiarrhythmic in the U.S. -*Prior* to *starting* any drug for a non-life threatening arrhythmia:
-consists of 1) methods for conversion to NSR and 2) maintenance of NSR. -effective with direct current cardioversion. -include amiodarone (oral and IV), dofetilide, flecainide, ibutilide, and propafenone. -*electrolytes* and a *toxicology screen* should be checked to identify reversible causes of the arrythmia.
Antiarrhythmic Drugs: -These work by affecting the electrical currents in the cells of the heart. -By blocking the movement of ions in different phases of the cardiac action potential, select drugs can: -They can also occasionally worsen the existing arrhythmia or cause other arrythmias. -Ventricular arrhythmias are managed in hospital settings. -AFib is managed inpatient and outpatient, and most pharmacists will be assisting patients with Afib. -Guideline-recommended tx of AFib involves two main strategies:
-drugs can reduce conduction velocity and/or automaticity, or prolong the refractory period, which can slow or terminate the abnormal electrical activity causing the arrhythmia. -two main strategies: *rate control* and *rhythm control*
-A small percentage of arrhythmias are *silent* (asymptomatic), and might be detected during a medical exam. -With most arrhythmias, patients can feel that the heart is beating very fast, or feel a *"fluttering"* in their chest or think that their heart was *"skipping a beat"* -Symptoms can include *dizziness, SOB, fatigue,* lightheadedness and chest pain. -In severe cases, arrhythmias can lead to: -An *electrocardiogram* (ECG) is used to *diagnose* arrhythmias. -An ECG machine records the heart's electrical activity using electrodes placed on the skin. -An ECG recorded in a medical office will pick up an arrhythmia only when it is present at the time the ECG is being conducted. -A *Holter monitor* is an *ambulatory ECG* device that records the heart's electrical activity for 24-48 hours. -It is used to detect arrhythmias that are *intermittent (i.e., the heart goes in and out of normal sinus rhythm (NSR).
-include *dizziness, SOB, fatigue,* lightheadedness and chest pain. -lead to syncope, heart failure, and death.
Ventricular Arrhythmias: -Common ventricular arrythmias include: -PVCs are relatively common and occur in ppl with and without heart disease. -They are referred to as a: -PVCs are generated from within the ventricular tissue. -In some ppl, it can be related to *stress* or too much *caffeine,* nicotine or exercise. PVCs can happen in anyone. -A *series of PVCs* in a row, resulting in a *heart rate of greater than 100 BPM,* is known as *ventricular tachycardia* (VT). -VT is further classified based on: -VT with a pulse is treated with: -Pulseless VT is a medical emergency, and advanced cardiac life support (ACLS) should be initiated. -*Untreated VT* can *degenerate* into *ventricular fibrillation* (completely disorganized electrical activation of the ventricles) which is always a *medical emergency*.
-include *premature ventricular contractions* (PVCs), ventricular tachycardia and ventricular fibrillation. -as a *skipped heartbeat* -based on the presence or absence of a detectable peripheral pulse. -treated with antiarrhythmics
Common Antiarrhythmics: -Commonly used antiarrythmics include: -The other antiarrythmics are used less commonly, but many have toxicities that require careful attention, such as:
-include amiodarone, the non-DHP calcium channel blockers diltiazem and verapamil, digoxin and beta-blockers; common beta blockers used for HF (metoprolol, carvedilol) will treat HF *and* DEC HR. -such as cinchonism with quinidine, DILE with procainamide, and others.
Patient Counseling: Digoxin: -Helps heart beat with more regular rate. -Do not stop taking med without talking to provider. -Avoid becoming overheated or dehydrated as an overdose can occur more easily if you are dehydrated. -Symptoms of overdose may include: -There are many meds that can interact with digoxin. -To be sure that this med is not causing harmful effects, blood may need to be tested on regular basis. Kidney function will also need to be monitored.
-include nausea, vomiting, diarrhea, loss of appetite, vision changes (such as blurred or yellow/green vision), confusion and hallucinations and feeling like you might pass out.
Supraventricular Arrhythmias: -Supraventricular tachyarrhythmias include: -Many patients have ongoing supraventricular arrythmias (especially atrial fibrillation), without realizing it. -*Afib* is the most common type of arrythmia. -Afib results from: -The rapid ventricular rate can result in hypotension and worsen underlying ischemia and heart failure. -D/t the disorganized depolarization of the atria, the atria are not able to adequately contract. -This results in blood stagnation in the atria, which increases the *risk* of *clot* formation. -A clot can embolize to the brain (blocking blood in an artery in the brain), which causes a: -To reduce clotting risk, patients with afribrillation can be taking: -Atrial flutter is usually more organized and regular than atrial fibrillation. -This arrythmia occurs most often with heart disease, and in the first week after heart surgery. -Atrial flutter often leads to AFib.
-include sinus tachycardia, atrial fibrillation, atrial flutter, focal atrial tachycardias and supraventricular re-entrant tachycardias (formerly known as paroxysmal supraventricular tachcardias or PSVTs). -results from multiple waves of electrical impulses in the atria, resulting in an *irregular* and usually *rapid* ventricular response. -which causes a *stroke*. -taking anticoagulants
The Cardiac Conduction Pathway: -The cardiac conduction pathway consists of a group of specialized cardiac cells (myocytes) that send electrical impulses (signals) to the heart muscle, causing it to contract. -The main components include: -The SA node is a cluster of cells located at the: -The electrical impulse begins in the: -Any disruption in the normal sequence of impulse conduction can result in an arrhythmia.
-include the SA node, AV node, bundle of His, bundle branches, and Purkinje fibers. -located at the junction of the superior vena cava and the right atrium. -begins in the SA node (1) and travels through the right and left atria (2), which causes the atria to contract. When the signal reaches the AV node (3), the electrical conduction slows down before traveling through the bundle of His (4) and into the ventricles. The bundle of His divides into the right bundle branch for the right ventricle (5) and into the left bundle branch for the left ventricle (6). The signal spreads through the ventricles via the Purkinje fibers (7), which causes the ventricles to contract.
Verapamil & Diltiazem Drug Interactions: -All CCBs, DHP and non-DHPs, are 3A4 substrates. Use strong 3A4 inducers/inhibitors with caution, and in some cases, avoid. Do not use grapefruit with any CCB. -Diltiazem and verapmil are substrates of P-gp, and *inhibitors of 3A4*. Then can *increase* the conc of many other drugs. *Use with statins not metabolized by 3A4* (pravastatin, rosuvastatin, pitavastatin), or use *lower doses* of statins, such as simvastatin 10-20 mg. -*Additive* effect with other drugs that *decrease HR* including:
-including *amiodarone, digoxin, beta blockers*, dexmedetomidine (Precedex) and clonidine.
Digoxin Drug Interactions: -*Additive* effect with other drugs that *decrease HR*, including: -Digoxin is 50-70% cleared by the kidney (unchanged) and partially cleared hepatically. DEC *renal function* requires: -Digoxin is a substrate of P-gp. Digoxin levels INC with *inhibitors,* including: -*Hypokalemia, hypomagnesemia, and hypercalcemia INC the risk of digoxin toxicity* -Hypothyroidism can INC digoxin levels.
-including *amiodarone, non-DHP calcium channel blockers, beta blockers,* dexmedetomidine (Precedex) and clonidine. -requires a DEC digoxin dose. In acute renal failure, digoxin is held. -including *amiodarone*, dronaderone, quinidine, verapamil, erythromycin, clarithromycin, itraconazole, propafenone and many other drugs. With amiodarone or dronedarone, DEC digoxin dose by 50%.
Amiodarone Drug Interactions: -Amiodarone is often given with drugs that it interacts with including: -Amiodarone can *increase* the level of many drugs; is an *inhibitor* of: -Amiodarone is a *substrate* of: -*When starting amiodarone, DEC digoxin by 50% and DEC warfarin by 30-50%*. Do not exceed *20 mg/day of simvastatin or 40 mg/day of lovastatin;* statin levels will inc. Consider use of alternative statin. -*Additive* effect with other drugs that *decrease HR*, including: -*Sofosbuvir* can enhance the *bradycardic* effect of amiodarone; *do not use together*
-including warfarin, digoxin, and statins. CVD drugs often interact too. -of *2C9 (moderate), 2D6 (moderate), 3A4 (weak), and P-gp* -of 3A4, 2C8, and P-gp. Strong/moderate inhibitors of these enzymes will INC amiodarone and strong/moderate inducers will DEC amiodarone. -including *amiodarone, digoxin, beta blockers,* dexmedetomidine (Precedex) and clonidine.
Arrhythmias: -Abnormalities of the heart or its conduction system can alter the cardiac action potential and lead to arrhythmias. -The most common cause of arrythmias is: -Other conditions resulting in damage to cardiac tissue can cause arrythmias, including: -Non-cardiac conditions can trigger or predispose a patient to arrhythmias. These include: -Arrythmias are generally classified based on their location of origin into two broad categories: -Arrythmias originating in or just below the AV node are called:
-is *myocardial ischemia or infarction*. -including heart valve disorders, hypertension, and heart failure. -these include *electrolyte imbalances (especially potassium, magnesium, sodium and calcium), elevated sympathetic states (e.g., hyperthyroidism, infection) and drugs (including illicit drugs and antiarrhythmics) Two categories: -*Supraventricular* (originating above the AV node) -*Ventricular* (originating below the AV node) -called junctional rhythms, which are less common.
Rate Control: -The *goal resting HR is:* -*Beta blockers* (preferred) or nondihydropyridine (non-DHP) calcium channel blockers are recommended for controlling ventricular rate in patients with AFib. -Of note, *patients with heart failure with reduced ejection fraction (HFrEF) should *not receive* a *non-DHP calcium channel blocker*. -Digoxin is not first-line for ventricular rate control, but an be added for:
-is <80 BPM in patients with symptomatic AFib; however, a more lenient rate-control strategy of *<110 BPM* may be reasonable in patients who are asymptomatic and have preserved left ventricular function. -added for refractory patients or used in those who are not able to tolerate beta blockers or calcium channel blockers.
-The term *conduction* means to *transmit electrical charges* (or heat) through a substance. -The *cardiac conduction system* is the electrical signaling system that causes the *ventricles to contract*. -The "lub-dub" sounds heard through *auscultation* (listening to the heart by placing a stethoscope on the chest) are made by: -Blood flows in one direction, from chamber to chamber, or to the lungs (to pick up oxygen) or to the body (to provide oxygen and nutrients). -The first heart sound (S1) signals the beginning of: -The second heart sound (S2) signals the end of: -A normal heart beats with a relatively steady rate and a regular, coordinated rhythm. -Sounds other than S1 and S2 (e.g., S3, which is more common in heart failure, and murmers) are abnormal. -Murmurs are caused by turbulent blood flow or regurgitation (i.e., blood flowing in the wrong direction). -An *arrhythmia* is: -Any change from the normal sequence of electrical impulses can cause an arrhythmia. -When the electrical impulses are too fast, too slow, or erratic, the heart cannot pump blood efficiently, and sxs can develop.
-made by the closing of heart valves that occur in sequence with each heart beat. -beginning of ventricular systole (systole means to contract). -end of ventricular systole. -is an *abnormal heart rhythm*, which can cause the heart to *beat* too *slow (bradycardia)* or too *fast (tachycardia)*.
QT Prolongation & Torsades de pointes: -The QT interval is measured from the beginning of the: -It reflects: -The QT interval varies with the heart rate, so a QT interval corrected for heart rate (QTc) is reported. -A QTc interval is considered prolonged when it is >440 msec, but is more worrisome when: -*Prolongation of the QT interval* is a risk factor for: Drugs that can cause QT Prolongation: The risk of drug-induced QT prolongation increases with:
-reflects ventricular depolarization and repolarization. Drugs that can cause QT Prolongation: The risk of drug-induced QT prolongation increases with: -Higher *doses*; (the risk is concentration-dependent) -Reduced drug *clearance* (e.g., with renal or liver disease) -*Multiple* QT-prolonging *drugs* (additive effect) -Drug *interactions* that decrease clearance (with enzymes inhibitors) -With low potassium (*hypokalemia*) and/or low magnesium (*hypomagnesemia*) -Other *cardiac conditions*; cardiac damage is a risk for arrhythmias, including TdP
Patient Counseling: Amiodarone: -Read the Medguide. This med can cause severe: -Get immediate help if you experience any of these serious side effects: -Your blood will need to be checked, and possibly a chest X-ray, during treatment. -This med is used to treat certain types of serious (possibly fatal) irregular heartbeat problems called arrhythmias. It is used to restore and maintain the normal heart rhythm and keep a regular, steady heartbeat. Amiodarone works by blocking certain electrical signals in the heart that can cause an irregular heartbeat. This med has not been shown to help ppl with arrythmias live longer. -Take this med by mouth, usually once or twice daily. If stomach upset, take with food. -Like other meds for irregular heartbeats, amiodarone can infrequently cause them to become worse. Seek attention if heart continues to pound or skip beats. -This may cause serious vision changes. You will need to get eyes checked before and during tx. -You may develop "pins and needles" or numbness in legs, hands, and feet, or muscle weakness or trouble walking. -This drug can change how your thyroid gland works and may cause metabolism to speed up or slow down. Tell provider if develop any symptoms of: -This drug may cause skin to be *more sensitive to the sun*. Stay out of sun during mid-day and use protective clothing and broad-spectrum sunscreen. -Infrequently this med has caused skin to become blue-gray color. Not harmful and usually goes away months after stopping drug. -Avoid grapefruit. -Drug interactions. -If miss dose, do not double it.
-severe lung or liver problems in some rare instances. -cough, fever, chills, chest pain, difficult or painful breathing, coughing up blood, severe stomach pain, nausea, vomiting, fatigue, yellowing eyes or skin, or dark-colored urine and new SOB. -symptoms of low or overactive thyroid including cold or heat intolerance, unexplained weight loss/gain, thinning hair, unusual sweating, nervousness, irritability or restlessness.
Electrical signaling: The cardiac action potential -The cardiac *action potential* refers to the movement of ions through: -In essence, the *action potentials* provide the *electricity* needed to power the heart. -The *SA (pacemaker) cells* have *automaticity*; this means that unlike other myocytes, the pacemaker cells: -The cells spontaneously depolarize. -The action potential is triggered when a threshold voltage is reached. -This occurs in 5 phases:
-through channels in the myocytes that cause the *electrical* impulses in the cardiac conduction pathway. -pacemaker cells *initiate* their own *action potential*; they do not require external stimulation. 5 phases: -Phase 0: Rapid ventricular depolarization initiates a heartbeat in response to an influx of Na; this causes ventricular contraction (represented by the QRS complex on the ECG) -Phase 1: Early rapid repolarization; Na channels close -Phase 2: Plateau in response to an influx of Ca and efflux of K. -Phase 3: Rapid ventricular repolarization in response to an efflux of K (represented by the T wave on the ECG) -Phase 4: Resting membrane potential; atrial depolarization occurs (represented by the P wave on the ECG)
Cardioversion: -An attempt to return the heart to: -Cardioversion is done with: -The shock breaks the incorrect cycle, stops the arrythmia and allows the sinus node to begin firing again with NSR. -The most common arrythmia treated with the procedure is AFib. -A fibrillation has a high rate of thromboembolism. -If the patient is not already using therapeutic anticoagulation, it must be started at least 3 weeks *before* cardioversion, and *continued* for *at least 4 weeks* after successful cardioversion to NSR. -The INR should be at the therapeutic level:
-with drugs, or with a medical procedure that delivers a high-energy shock through the chest wall. -level (2-3)
The heart's natural pacemaker and arrhythmias: -The rate and rhythm of the heartbeat is set by the rapidly firing cells in the sinoatrial (SA, or sinus) node. -The SA node is called the heart's natural pacemaker. -An arrhythmia is caused by a disruption somewhere in the conduction (electrical signaling) system:
An arrhythmia is caused by a disruption somewhere in the conduction (electrical signaling) system: -The SA node can be firing at an abnormal rate or rhythm -Scar tissue from a prior heart attack can block and divert signal transmission. -Another part of the heart may be acting as the pacemaker.
Other Antiarrhythmics: Class 1a: block sodium and potassium channels Quinidine -Dosing: IR: 400 mg PO Q6h; ER: 300-648 mg PO Q8-12hrs; *take with food or milk to dec GI upset*; different salt forms are not interchangeable (267 mg of gluconate = 200 mg of sulfate form) Boxed Warnings: Contraindications: Warnings: Side Effects: Notes:
Boxed Warnings: -May INC mortality in treatment of AFib or flutter; control AV conduction before initiating. Contraindications: -Concurrent use of quinolones that prolong the QT interval or ritonavir; 2nd/3rd degree heart block or idioventricular conduction delays (unless patient has a functional artificial pacemaker), thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), myasthenia gravis. Warnings: -Proarrhythmic, hepatotoxicity, *drug-induced lupus erythematosus (DILE), hemolysis risk* (avoid in *G6PD* deficiency), can cause positive *Coombs* test. Side Effects: -*Diarrhea (35%), stomach cramping (22%),* lightheadedness, N/V, *cinchonism* (sxs of cinchonism include tinnitus, hearing loss, blurred vision, headache, delirium), rash Notes: -Avoid changes in Na intake; DEC Na intake can INC quinidine levels -Alkaline foods/ alkaline urine INC quinidine levels and can lead to toxicity.
Other Antiarrhythmics: Class III: primarily block potassium channels Dofetilide (Tikosyn) Boxed Warnings: Contraindications: Side Effects:
Boxed Warnings: -Must be *initiated* (or reinitiated) in a setting with *continuous ECG monitoring*, experienced staff and ability to *assess CrCl for a minimum of 3 days; proarrhythmic,* with QT prolongation Contraindications: -Patients with congenital or acquired long QT syndromes; concurrent use of cimetidine, dolutegravir, hydrochlorothiazide, itraconazole, ketoconazole, megestrol, prochlorperazine, trimethoprim, verapamil; HR<50, CrCl <20 mL/min, QTc >440 msec Side Effects: -HA, dizziness, ventricular tachycardias (e.g., TdP), INC QT interval
Other Antiarrhythmics: Class 1a: block sodium and potassium channels Procainamide -Dosing: *Active metabolite, N-acetyl procainamide (NAPA)* is *renally cleared*; DEC dose when CrCl <50 mL/min Therapeutic levels: -Procainamide: 4-10 mcg/mL -NAPA: 15-25 mcg/mL -Combined: 10-30 mcg/mL -Draw levels 6-12 hrs after IV infusion has started Boxed Warnings: Warnings: Side Effects:
Boxed Warnings: -Potentially fatal blood dyscrasias (e.g., *agranulocytosis)*; monitor patient closely in the first 3 mos and periodically thereafter. -Long-term use leads to positive *antinuclear antibody (ANA)* in 50% of patients which can result in *drug-induced lupus erythematosus (DILE)* in 20-30% of patients. Warnings: -Proarrhythmic Side Effects: -Hypotension, rash
Other Antiarrhythmics: Class III: primarily block potassium channels Ibutilide (Corvert) Boxed Warnings: Side Effects: Notes:
Boxed Warnings: -Proarrhythmic; confirm that benefits of maintaining NSR outweigh the risks. Side Effects: -Ventricular tachycardias (e.g., TdP), headache, hypotension, QT prolongation. Notes: -Correct *hypokalemia* and *hypomagnesemia* prior to use and throughout treatment.
Class III Antiarrhythmics: Block Potassium Channels: Amiodarone (Pacerone, Nexterone): tablet, injection Dosing: -Pulseless VT/VF 300 mg IV push x 1, may repeat 150 mg x 1 if needed. -VT with pulse 150 mg IV bolus, 1 mg/min x 6 hrs, then 0.5 mg/min x 18 hrs or longer -Ventricular arrhythmias 800-1,600 mg/day x 1-3 weeks, then 600-800 mg/day x 4 weeks, then 400 mg/day -AFib: Cardioversion (off label) 600-800 mg/day for a 10 g loading dose, followed by 200 mg daily -AFib: Maintenance of NSR (off label) 400-600 mg/day for 2-4 weeks; then 100-200 mg daily -*T1/2 = 40-60 days* Boxed Warnings: Contraindications: Warnings: Side Effects: Monitoring: Notes:
Boxed Warnings: -Proarrythmic, *pulmonary toxicity* and *hepatotoxicity*, use *only* for *life-threatening arrhythmias* d/t toxicities. Patients should be *hospitalized when loading dose* is given. Contraindications: -Severe sinus-node dysfunction causing marked DEC HR, 2nd/3rd degree heart block (unless patient has artificial pacemaker), DEC HR that is causing syncope, cardiogenic shock, iodine hypersensitivity. Warnings: -*Hyper- and hypo-thyroidism* (hypo is more common) - amiodarone partially *inhibits* peripheral *conversion* of T4 and T3, *optic neuropathy* (visual impairment), *photosensitivity (slate-blue skin discoloration)*, neurotoxicity (peripheral neuropathy), severe skin reactions (SJS/TEN). Side Effects: -*Hypotension, bradycardia, corneal microdeposits, dizziness, ataxia, N/V, constipation, tremor,* skin *photosensitivity*, drug-induced lupus erythematosus (DILE) Monitoring: -*ECG, BP, HR, electrolytes, pulmonary function* (including chest X-ray) at baseline and annually, *LFTs* at baseline and every 6 months, *thyroid* function at baseline and Q3-6 mos, eye exams. Notes: -Infusions longer than 2 hrs must be administered in a *non-polyvinyl chloride (PVC) container such as polyolefin or glass. Premixed Nexterone comes in GALAXY containers (non-PVC and non-DEHP)* that can be stored up to 24 months at room temp. PVC tubing is fine to use. Use a *0.22 micron filter.* Incompatible with *heparin* (flush with saline). -*Premixed IV bag advantages:* longer stability, non-PVC, comes in common concentrations. -*Slow the infusion rate or discontinue if hypotension or bradycardia occurs.* -Recommended as *antiarrhythmic drug of choice* in patients *with heart failure*. -Oral and IV amiodarone can provide rate control (d/t beta blocking properties) when other measures are unsuccessful or contraindicated. -Amiodarone (chemical struncture of drug) contains *iodine* (thyroid hormones also contain iodine).
Other Antiarrhythmics: Class III: primarily block potassium channels Sotalol (Betapace AF, Betapace, Sotylize, Sorine): *Non-selective beta blocker* -Dosing: *CrCl <60 mL/min:* DEC frequency; CrCl <40mL/min: varies by formulation Boxed Warnings: Contraindications: Side Effects:
Boxed Warnings: -To minimize risk of life-threatening ventricular arrhythmias (TdP), initiation (or reinitiation) and dosage increase should be down in a hospital with continuous ECG monitoring and experienced staff. -*Adjust dosing interval* based on *creatinine clearance* to DEC risk of proarrhythmia; QT prolongation is directly related to *sotalol concentration* -Betapace should not be substituted with Betapace AF since Betapace AF is distributed with educational information specifically for patients with AFib/ Atrial flutter. Contraindications: -2nd/3rd degree heart block (unless patient has a functional artificial pacemaker), congenital or acquired long QT syndrome, sinus bradycardia, uncontrolled HF, cardiogenic shock, asthma. -For Betapace AF, Sotylize, sotalol injection Qtc >450 msec, bronchospastic conditions, CrCl <40 mL/min, K<4 mEq/L, sick sinus syndrome Side Effects: -Bradycardia, palpitations, chest pain, dizziness, fatigue, dyspnea, N/V, TdP, HF, bronchoconstriction.
Other Antiarrhythmics: Class 1c: block sodium channels Flecainide: 50-100 mg PO Q12h; max 400 mg/day; store in tight, light-resistant container Boxed Warnings: Warnings: Contraindications: Side Effects:
Boxed Warnings: -When treating atrial flutter, 1:1 atrioventricular conduction may occur; pre-emptive negative chronotropic therapy (e.g., digoxin, beta blockers) can DEC the risk. Warnings: -*Proarrythmic,* especially in permanent (chronic) afib; do not use for afib tx (appropriate use in aflutter). Contraindications: -2nd/3rd degree heart block (unless patient has a functional artificial pacemaker), cardiogenic shock, structural heart disease (e.g., *heart failure, myocardial infarction*), concurrent use of ritonavir. Side Effects: -Dizziness, visual disturbances, dyspnea
Vaughan Williams Classification: -The *Vaughan Williams* classification system is the most commonly used. -Here, drugs split into categories based on *dominant electrophysiological effect*. Class 1: Class II: Class III: Class IV: Memory tool:
Class 1: -Ia: Disopyramide, Quinidine, Procainamide -1b: Lidocaine, Mexiletine -1c: Flecainide, Propafenone Class II: beta blockers Class III: Dronedarone, Dofetilide, Sotalol, Ibutilide, Amiodarone Class IV: Verapamil, Diltiazem Memory Tool: Double Quarter Pounder, Lettuce, Mayo, Fries Please! Because Dieting During Stress Is Always Very Difficult
Other Antiarrhythmics: Class 1b: block sodium channels. Useful for *ventricular arrhythmias only* (no efficacy in afib) Lidocaine (Xylocaine): used for *refractory VT/cardiac arrest* Mexiletine: capsule -Dosing: 200 mg PO Q8h; max 1.2 g/day; take with food Contraindications: Warnings:
Contraindications: -2nd/3rd degree heart block (unless patient has a functional artificial pacemaker) -Lidocaine: Wolff-Parkinson-White syndrome, Adam-Stokes syndrome, allergy to corn or corn-related products or amide type anesthetic. -Mexiletine: cardiogenic shock, blood dyscrasias, severe skin reactions (DRESS). Warnings: -Caution in the elderly, hepatic impairment and in patients with HF.
Other Antiarrhythmics: Class 1a: block sodium and potassium channels Disopyramide (Norpace, Norpace CR) -Dosing: take on empty stomach Contraindications: Warnings: Side Effects:
Contraindications: -2nd/3rd degree heart block (unless patient has a functional artificial pacemaker), cardiogenic shock, congenital QT syndrome, sick sinus syndrome. Warnings: -Proarrythmic, HF, BPH/urinary retention/ narrow-angle glaucoma, myasthenia gravis (d/t *anticholinergic* effects). Side Effects: -*Anticholinergic effects (10%)* (dry mouth, constipation, urinary retention), hypotension.
Drugs not included in Vaughan Williams Classification: Adenosin (Adenocard): -Dosing: 6mg IV push (may increase to 12 mg if not responding); T1/2: *less than 10 sec*; used in *paroxysmal supraventricular tachycardia (PSVTs)*; do not use for converting AFib/ Atrial flutter or ventricular tachycardia. Contraindications: Side Effects:
Contraindications: -2nd/3rd degree heart block, sick sinus syndrome or symptomatic bradycardia (except in patients with a functional pacemaker), bronchospastic lung disease. Side Effects: -Transient new arrhythmia, facial flushing, chest pain/pressure, neck discomfort, dizziness, headache, GI distress, transient DEC in blood pressure, dyspnea.
Class IV Antiarrhythmics: Block Calcium Channels; Used to slow ventricular HR Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cartia XT, Dilt-XR, Diltzac, Tiazac, Taztia XT): tablet, capsule, injection -Dosing: 20-360 mg PO daily Verapamil (Calan, Calan SR, Covera HS, Verelan, Verelan PM): tablet, capsule, injection -Dosing: 180-480 mg PO daily Contraindications: Warnings: Side Effects: Monitoring: Notes:
Contraindications: -Severe hypotension (SBP <90 mmHg), 2nd/3rd degree heart block/ sick sinus syndrome (unless the patient has a pacemaker), cardiogenic shock, systolic HF, Wolff-Parkinson-White syndrome with AFib. Warnings: -1st degree AV block with sinus bradycardia, INC LFTs. Side Effects: -*Edema, HA, dizziness, hypotension, arrhythmias, HF, constipation (> with verapamil), gingival hyperplasia.* Monitoring: -ECG, BP, HR, electrolytes, LFTs, renal function. Notes: -Only *Non-dihydropyridine CCBs* are used as antiarrhythmics.
Other Antiarrhythmics: Class 1c: block sodium channels Propafenone (Rythmol, Rythmol SR) Contraindications: Warnings: Side Effects: Notes:
Contraindications: -Sinoatrial and atriventricular disorders (unless patient has a functional artificial pacemaker), sinus bradycardia, cardiogenic shock, hypotension, structural heart disease (e.g., *heart failure, myocardial infarction*), bronchospastic disorders. Warnings: -*Proarrhythmic* Side Effects: -*Taste disturbance (metallic)*, dizziness, visual disturbances, N/V Notes: -Propafenone has significant beta-adrenergic receptor blocking effects. Negative inotropic and proarrhythmic properties (contraindicated in HF).
Digoxin blocks: Digoxin (Digitek, Digox, Lanoxin): tablet, solution, injection Dosing: -Typical dose: *0.125-0.25 mg* PO daily -Tablet strengths: 0.0625, 0.125, 0.1875, 0.25 mg -Loading dose (called total digitalizing dose (TDD)) is: 8-12 mcg/kg. Give 1/2 of the TDD as the initial dose, followed by 1/4 of the TDD in 2 subsequent doses at 4-8 hr intervals. Alternatively, give 0.25 mg IV and repeat dosing to a max of 1.5 mg over 24 hrs. -*Therapeutic rnage for AFib = 0.8-2 ng/mL* (lower range for heart failure) -When *CrCl <50 mL/min, DEC dose or DEC frequency* -DEC dose by *20-25%* when going from *oral to IV* -*Antidote: DigiFab* Contraindications: Warnings: Side Effects: Monitoring: Toxicity: Notes:
Contraindications: -Ventricular fibrillation Warnings: -2nd/3rd degree heart block without a pacemaker, Wolff-Parkinson-White syndrome (WPW) with AFib, vesicant - avoid extravasation. Side Effects: -Dizziness, mental disturbances, headache, N/V/D Monitoring: -ECG, HR, BP, electrolytes, renal function and digoxin level (drawn 12-24 hrs after dose). Toxicity: -*Initial s/sx of toxicity are N/V, loss of appetite and bradycardia.* -*Severe s/sx of toxicity include *blurred/double vision*, altered color perception, *greenish-yellow halos* around lights or objects, abdominal pain, confusion, delirium, prolonged PR interval, arrythmias. Notes: -Not usually given alone for rate control (used in *combination* with a beta blocker or CCB)
QT Risk Requires Assessment: -In addition to recognizing the drugs that prolong the QT interval, an assessment of the patient's risk for TdP will be required. -If low-dose amitriptyline is being used for neuropathic pain, the dose is not particularly risky; but if the same patient is admitted to the hospital with hypokalemia and started on fluconazole and ondansetron, the level of concern would be heightened. Key Drugs:
Key Drugs: Antiarrhythmics: -Class 1 (especially *Class 1a*) and *Class III* Antibiotics: -*Quinolones* and *macrolides* Azole antifungals: -*Not* isavuconazole (Cresemba) Antidepressants: -*Tricyclics* (amitriptyline, clomipramine, desipramine, doxepin, imipramine), SSRIs (*citalopram, escitalopram,* others), SNRIs, mirtazapine and trazodone; *sertraline* is *preferred* in *cardiac* patients. Antiemetic agents: -*5-HT3 receptor antagonists, droperidol* and phenothiazines Antipsychotics (most): -Notably chlorpromazine, clozapine, *haloperidol*, olanzapine, paliperidone, quetiapine, risperidone, *thioridazine, ziprasidone* Other agents: -*Fingolimod, methadone,* donepezil OTHERS: -Antibiotics: Foscarnet, telavancin, and others -Oncology Agents: Arsenic, bortezomib, bosutinib, ceritinib, crizotinib, dasatinib, lapatinib, nilotinib, sorafenib, sunitinib -HIV agents: Protease inhibitors (atazanavir, saquinavir) and rilpivirine -Other agents: Alfuzosin, apomorphine, atomoxetine, buprenorphine, chloroquine, diphenhydramine, ezogabine, galantamine, mirabegron, pentamidine, propofol, quinine, ranolazine, sevoflurane, solifenacin, tacrolimus, tizanidine.
Normal Sinus Rhythm: -A *NSR* is a normal heart rhythm, with a normal heart rate (60-100 BPM). -A NSR will *originate* (begin) in the *SA node.* -The SA node is called the *heart's natural pacemaker*; this is where the electrical signal for a heartbeat begins, and the frequency of the signals determines the pace, or heart rate. -A normal rhythm on an ECG is seen with the characteristic appearance of consecutive heartbeats shown on an ECG printout.
No extra info
AFib: Rate vs Rhythm Control: Rate Control: Rhythm Control: Stroke Prophylaxis:
Rate Control: -Patient remains in AFib and takes *meds* to *control ventricular rate (HR)* -*Beta blockers or non-DHP CCBs (sometimes Digoxin)* Rhythm Control: -The goal is to restore and maintain NSR -1a, 1c, or III antiarrhythmic, or electrical cardioversion. -If AFib is permanent, avoid rhythm-control antiarrhythmic drugs (risk > benefit) Stroke Prophylaxis: -*Clots* can form *when a patient is in AFib* and *embolize (causing stroke)* when the patient *returns to NSR.* Studies show that, for many patients, it is safer to remain in AFib with proper stroke prophylaxis and rate control than to try to restore NSR. -A rate control strategy requires anticoagulation or aspirin (indefinitely) for stroke prevention (in most patients) -When a rhythm control strategy is chosen, restoration and maintenance of NSR is not guaranteed. Long-term anticoagulation decisions depend on the patient's clot risk.