Le Journal canadien de la pharmacie hospitaliere Volume 48, N° 6, decembre 1995 360 PHARMACY PRACTICE Therapeutic Alternatives in Atrial Fibrillation William John Perks, Carmine Stumpo, Brian Jurewitsch and Christian Klem INTRODUCTION verting to normal sinus rhythm in equipotent doses to control the Atrial Fibrillation (AF) is the most (NSR); and, VRR. Esmolol was considered the common sustained dysrhythmia. It is maintaining NSR after initial prototype because of its short half­ more prevalent in the elderly and is a conversion; life, and ease of titration. Use of common complication of cardiac sur­ b) onset of effect; esmolol can demonstrate how a patient gery. Treatment of AF is often based c) usual dosing regimens; will respond to a beta-blocker in terms on previous experience and the most d) pharmacoki netics; of causing hypotension or brady­ appropriate therapeutic regimen for e) toxicity; cardia. The short half-life of esmolol each patient may not be selected. f) drug interactions; and should ensure a short duration of the Therefore, this Therapeutic Alterna­ g) availability/cost. adverse effect. Other less expensive tive Chart for AF was developed to These agents were also classified beta-blockers such as metoprolol, help both medical and pharmacy clin­ into groups by their pharmacologic propranolol, atenolol, and others may icians choose and utilize the most effects which: be substituted for longer-term control appropriate therapy for the treatment i) only control VRR (i.e., beta­ of VRR once response to a beta­ of AF in a specific patient. Currently blockers, calcium channel blocker has been demonstrated. For the chart is used by practicing phar­ blockers, digoxin); the post-operative patient, the macists at St. Michael's Hospital as a ii) only convert to NSR (i.e., pro­ intravenous forms of these drugs arc tool in providing pharmaceutical care. cainamide, quinidine, disopyra­ used initially because of their more Additionally, it is used as an educa­ mide); rapid onset; the parenteral forms can tional tool for pharmacists, residents, iii) control both VRR and convert be substituted with oral agents once students, and other health profes­ to NSR (i.e., sotalol, amio­ the patient is stabilized and is sionals. darone, flecainide, propa­ absorbing enterally. Similar oral fenone). conversions for other anti-arrhyth­ METHODS Disopyramide was not included in mic drugs can also be made. A thorough review of the current the chart as the authors felt that its use Although no column in the chart biomedical literature was undertaken is quite infrequent secondary to its was set aside specifically for the using a Medline search of the primary negative inotropic and anticholinergic duration of action, the overall duration literature back to 1984. All effective effects. of action of a drug is a function of the agents captured in this literature pharmacokinetic half-life (listed on search were then reviewed specif­ DISCUSSION the chart under kinetics), pharma­ ically for: While the therapeutic chart only codynamic half-life, and receptor includes esmolol under the beta­ response (i.e., up or down regulated). a) efficacy in: controlling ventri­ blocker row, other beta-blockers The duration of effect may, therefore, cular response rate (VRR); con- would be equally effective when used differ depending on the patient, the William John Perks, B.Sc.Phm. is a Staff Pharmacist, Department of Pharmacy, St. Michael's Hospital, Toronto, Ontario. Carmine Stumpo, B.Sc.Phm, at time of writing, Mr. Stumpo was a Pharmacy Resident, St. Michael's Hospital, Toronto, Ontario. Currently Mr. Stumpo is a Pharm.D. candidate at the College of Pharmacy, Wayne State University, Detroit, Michigan. Brian Jurewitsch, B.Sc.Phm., is a Staff Pharmacist, Department of Pharmacy, St. Michael's Hospital. Christian Klem, Pharm.D. at time of writing, Dr. Klem was Clinical Coordinator, Critical Care at St. Michael's Hospital. Currently Dr. Klem is a Pharmacotherapy Specialist, Tampa General HealthCare and Assistant Professor, University of South Florida, Tampa, Florida. Address Correspondence to: Mr. Wm. Perks, B.Sc.Phm., Department of Pharmacy, St. Michael's Hospital, 30 Bond Street, Toronto, Ontario M5B IWS. Acknowledgements: The authors would like to thank Dr. Al Rasymas, Pharm.D., Clinical Coordinator, St. Michael's Hospital for his guidance and coordination in the preparation of this paper. U.,) Table I: Therapeutic Alternatives in Atrial Fibrillation °'._ Drug Efficacy Onset Dose Kinetics Toxicity Drug Interactions Comments Availability/Cost 8-Blockers VRR = excellent (similar to PO= l-2hrs Complex (multiple bolus infusions) Ester hydrolysis by RBC bradycardia, symptomatic calcium channel blockers, -little risk of proarrhythmic effects / IV: IOOmg/JOml = $9.48 verapamil)1 500 mcg/kg over I min then 300 esterases. hypotension (10%) 1· 4· 34 digoxin, disopyramide torsades des pointes 2.5G/10ml = $134.10 2 E~molol CONY = similar to placebo IV= 2-5 min (may mcg/kg/min x 3 min then 50-300 tl/2=9min .J. contractility, .J. conduction, -may aggravate asthma, AV block, 11 (Brevibloc®l -may be higher than placebo take longer to mcg/kg/min bronchospasm, .J. glycogenesis diabetes, CHF Metoprolol if hyperadrenergic state 1 titrate)30 (quick offset with esmolol) -benefit in hyperadrenergic post-op Others patients 4 30 Diltiazem VRR = 94% bolus3• IV= 2-5 min3 0.25 mg/kg over 2 min. Hepatic elimination symt hypotension 3%3. B-blockers, digoxin - .J. HR is dose-related IV: 25mg/5ml = $13.00 (Cardizem®l = 76% infusion3· 4 (duration 3 hours)30 If no response in 15 min tl/2=3-5h bradycardia, less -ve inotropic - Calcium infusion may decrease 50mg/10ml = $24.00 CONY= similar to placebo5 PO= 1-2 hrs then O.35 mg/kg over 2 Active metabolites:4 effects vs. verapamiJ 35·38 hypotension PO: 60mg = $0.33 min then 5-15mg/hr11 desacetyl/N-desmethyldiltiazem -Use dependent effects46 120mg SR= $0.58 Verdpamil* VRR = excellent IV= 2-5 min 2.5-10 mg IV (0.0375-0.15mglkg) Hepatic elimination symt hypotension (10%)1.30.39, 8-blockers - Calcium infusion may decrease IV: 5mg/2ml = $17.80 7 (lsoptin®) (similar to diltiazem)4 (30-90 min duration over 2 min then 2.5-10 mg/hr bradycardia. diltiazem hypotension39.4 PO: 80mg = $0.20 2 11 CONY = similar to placebo post bolus) .J. contractility, .J. conduction warfarin 120mg=$0.33 PO= l-2hrs 80-120 mg PO Q6-8h 11 constipation. digoxin 240mg SR= $1.33 Digoxin* VRR = moderate (loss of effect IV= 3-4 hrs IV loading = I 0-15 mcg/kg (7-11 Renal elimination bradycardia, nausea, GI effects, quinidine, verapamil, -beneficial effect~ in LV dysfunction IV: 0.5mg/2ml = $3.27 (Lanoxin®J with i adrenergic states)6-7 PO =4-6 hrs mcg/kg if renal dysfunction) in (May require dose adjustment arrhythmias, i PR interval, diltiazem, amiodarone, -may require higher plasma level PO: 0.125mg = $0.09 26 CONY = similar to placebo - ,8 divided doses over 24 hours and/or closer monitoring with .J. AV block, CNS effects cholestyramine, antacids, for effect 1-2.6 nmol/L 0.25mg = $0.09 then 0.0625-0.25 mg/day 11 renal function interactions)32 propafenone32 (0.8-2 ng/ml)32,48 40 Procainamide t VRR=poor IV= 10-30 min 10-15 mg/kg IV (max 50 mg/min) Hepatic & renal (50%) proarrhythmia (9%) digoxin, amiodamne, -requires prior VRR control IV: lg/lOml = $10.15 ~ (Pronestyl®J CONY= 38-80%2·9·13 PO= 2-4 hrs then 2-4 mg/min elimination. cimetidine, lrimethoprim -levels: 4-8 mcg/ml (17-34 µmol/L) PO: 250mg = $0. I 8 (1:, MAINT=? tl/2 = 2.5-5 hrs nausea/vomiting, tremors, -NAPA-toxic/activemet(l4-29µmol/L) 375mg = $0.23 ~ 250-750 mg PO Q3-4h hypotension (IV), ANA (SLE- (may require dose adjustment/ 500mg SR= $0.48 ;:::: 1 500-1000 mg SR PO Q6h I NAPA is primarily renally like symptoms) (20-30%), monitoring of levels with .J. renal ~ eliminated. blood dyscrasia.~ (0.5% )11 function) ~ ;:::: Quinidinet VRR=poor IV= 1-2 hrs 5-10 mg/kg IV over 30 min Hepatic elimination proarrhythmia (15% )40 digoxin, amiodarone, -requires prior VRR control IV: 190mg/lml=$4.98(sulfate) (Quinate®, CONY= 60-80%2·12·14 PO= 4-24 hrs (infuse 0.9% NaCl concomitantly to tl/2 = 5-9 hrs Torsades des JX>intes ()-8%)41 warfarin, verapamil -3% mortality with use 15 800mg/10ml (gluconate) ~ :::: Cardioquin®) MAINT = 50% 15 maintain preload).May repeat 400mg F=0.7 pain with IV admin./phlebitis -levels: 2-6 mcg/ml (6-18 µmo1!L)48 ~ iv q2h to max 3g daily. Vo=3L/kg nausea/vomiting, diarrhea, cinchonism PO: sulfate 200mg = $0.05 dizziness, tinnitus, nystagmus (22%) gluconate 375mg = $0.26 :2.. 200-300 mg PO Q6-8h 11 blood dyscrasia, 19 ~ 17 16 40 ~ Propafenone1 VRR = moderate to good 16- IV = 10-30 min 18 2 mg/kg JV then 2mg/min Hepatic elimination (saturnble) proarrhythmia (4-8%) - 8-blockers, calcium -<lose-related 8-blockade (genetic IV: 70mg/20ml =? 'ij (Rhythmol®l CONY= 5J-9J<)15,12.13.16.18 PO=l-3hrs tl/2 = 2-10 hrs (fa~l) (90%) channel blockers, disposition) (emergency relea~e) MAINT = 30-78% 16-19 150-300mg POQ8h 11 12-32 hrs (slow) (10'1) .!.contrnctility, AV block, digoxin, warfarin, -active metabolite 5-0H propafenone [ hypotension. dil.Ziness(l0%), nausea cimetidine PO: 300mg = $1 .26 (efficacy may be dose dependent) 16 F = 0.1- 0.2 (non-linear) (9%), constipation, tremor, 150mg=$0.71 ""Cl parnsthesia, taste changes, (15% )42 ~ 40 43 ~ Aecainide'JI VRR = modc·rate20 IV = 10-60 min 2 mg/kg JV over IO min. Renal (25%) & hepatic proarrhythmia (4-12% ) - procainamide. sotalol, -use-<lependent effects IV:') ~ CONY= _92%5.9.12-14.19 48 (Tambocor®J 52 PO=l-3hrs 100-200 mg PO Q12h elimination.