Metoprolol Amiodarone

M KCl were performed on the PCA 101 titrator. .. at 25 °C for amiodarone, metoprolol and ramipril and at 37 °C for atenolol. The pKa values of metoprolol, atenolol, and ramipril were determined in 0.15M KCl. For die extrapolation of the aqueous pKa of amiodarone, we used the Yasuda-Shedlovsky plot (4). Apparent pKa values (+ log [H2O]) in the medianol/O.lSM KCl mixtures at ratios between 47 and 71%(w/w) methanol were plotted against the inverse dielectric constant... and the pKa of the molecule in 100% aqueous solution was extrapolated by linear regression." surface H2O Ferreira J, Brasseur R, Chatelain P and Ruysschaest J, Properties of... 

Methimazole (Tapazole) [Antithyroid Agent] Uses Hyperthy-roidism, thyrotoxicosis, pr for thyroid surgery or radiation Action Blocks T3 T4 formation Dose Adults. Initial 15-60 mg/d PO tid Maint 5-15 mg PO daily Peds. Initial 0.4-0.7 mg/kg/24 h PO tid Maint V h- U h of initial dose PO daily w/ food Caution [D, +/-] Contra Breast-feeding Disp Tabs SE GI upset, dizziness, blood dyscrasias Interactions t Effects OF digitalis glycosides, metoprolol, propranolol X effects OF anticoagulants, theophylline X effects W/ amiodarone EMS None OD May cause N/V, HA, abd pain, fever, and pale skin symptomatic and supportive... 

AMIODARONE BETA-BLOCKERS Risk of bradycardia (occasionally severe), 1 BP and heart failure. Also, t plasma levels of metoprolol Additive negative inotropic and chronotropic effects. In addition, high-dose amiodarone is associated with t plasma levels of metoprolol due to inhibition of CYP2D6 For patients on beta-blockers, monitor BP closely when loading with amiodarone... 

In the Spanish Study of Sudden Death (SSD) amiodarone reduced all-cause mortality from 15.4 to 3.5% compared with metoprolol however, the mortality in those receiving no antidysrhythmic drugs at all was only 7.7%, and in those the effect of amiodarone was not significant (39). 

Navarro-Lopez F, Cosin J, Marrugat J, Guindo J, Bayes de Luna A. Comparison of the effects of amiodarone versus metoprolol on the frequency of ventricular arrhythmias and on mortahty after acute myocardial infarction. SSSD Investigators. Spanish Study on Sudden Death. Am J Cardiol 1993 72(17) 1243-8. 

Clinically important, potentially hazardous interactions with acebutolol, amiodarone, aspirin, atenolol, atorvastatin, betaxolol, carbamazepine, carteolol, celiprolol, donidine, dabigatran, dantrolene, digoxin, dofetilide, epirubicin, eplerenone, erythromycin, esmolol, eucalyptus, everolimus, lovastatin, metoprolol, mistletoe, nadolol, oxprenolol, penbutolol, pindolol, propranolol, quinidine, ranolazine, sibutramine, simvastatin, timolol, trabectedin... 

CYP2D6 5 25 S-metoprolol Carvedilol Dextromethorphan Nortriptyline Propanolol Odansetron Chlorpromazine Codeine Flecainide Fluoxetine Haloperidol Amiodarone Fluoxetine Methadone Celecoxib Doxorubicin ... 

Noninterfering acetaminophen, acetylmorphine, amiodarone, amobarbital, amphetamine, bendroflumethiazide, benzocaine, benzoylecgonine, benzthiazide, butalbital, carbamaze-pine, chlorothiazide, clonazepam, cocaine, codeine, cotinine, cyclosporine, cyclothiazide, desalkylflurazepam, diamorphine, dicumerol, ephedrine, ethaciynic acid, ethanol, eth-chlorvynol, ethosuximide, furosemide, glutethimide, hydrochlorothiazide, hydrocodone, hydroflumethiazide, hydromorphone, lorazepam, mephentermine, meprobamate, meth-amphetamine, metharbital, methoxsalen, methoxyphenteramine, methsuximide, meth-ylcyclothiazide, metoprolol, MHPG, monoacetylmorphine, morphine, normethsuximide, oxazepam, oxycodone, oxymorphone, pentobarbital, phencyclidine, phenteramine, phenylephrine, phenytoin, polythiazide, primidone, prochlorperazine, salicylic acid, sulfanilamide, THC-COOH, theophylline, thiazolam, thiopental, thioridazine, tocainide, trichlo-romethiazide, trifluoperazine, valproic acid, warfarin... 

Hypotension, bradycardia, ventricular fibrillation and asystole have been seen in a few patients given amiodarone with propranolol, metoprolol or sotalol (for sotalol, see also Drugs that prolong the QT interval + Other drugs that prolong the QT interval , p.2S7). However, analysis of clinical trials su ests that the combination can be beneficial. Amiodarone may inhibit the metabolism of beta blockers metabolised by CYP2D6, such as metoprolol, which might be a factor in the interaction. 

A 64-year-old woman was treated for hypertrophic cardiomyopathy with amiodarone 1.2 g daily and atenolol 50 mg daily. Five days later the atenolol was replaced by metoprolol 100 mg daily. Within 3 hours she complained of dizziness, weakness and blurred vision. On examination she was found to be pale and sweating with a pulse rate of 20 bpm. Her systolic blood pressure was 60 mmHg. Atropine 2 mg did not produce chronotropic or haemodynamic improvement. She responded to isoprena-line (isoproterenol). Severe hypotension has been reported in another patient taking sotalol when intravenous amiodarone (total dose 250 mg) was given. Another report describes cardiac arrest in one patient on amiodarone, and severe bradycardia and ventricular fibrillation (requiring defibrillation) in another, within 1.5 and 2 hours of starting to take propranolol. ... 

In one study, 10 elderly patients (9 with symptomatic atrial fibrillation and one with an implanted defibrillator and frequent ventricular tachycardia) taking metoprolol (mean daily dose 119 mg) were also given amiodarone 1.2 g daily for 6 days. The metoprolol AUC and plasma levels were increased by about 80% and 75%, respectively, by the amiodarone, the extent varying by CYP2D6 genotype. None of the patients included in the study were poor metabolisers. 

Dronedarone is structurally related to amiodarone, which is known to inhibit the cytochrome P450 isoenzyme CYP2D6, by which metoprolol is metabolised (see Amiodarone + Beta blockers , p.246). This study also shows that dronedarone inhibits CYP2D6, effectively making extensive metabolisers into poor metabolisers. For more information on metaboliser status see Genetic factors , (p.4). 

---