Verapamil Amiodarone

Digoxin Inhibits AV nodal conduction by 1. Vagal stimulation 2. Directly slowing AV nodal conduction and prolonging AV nodal refractoriness 0.25 mg every 2 hours up to 1.5 mg 0.125-0.25 mg PO once daily Amiodarone, verapamil, quinidine inhibit digoxin elimination... 

Ezetimibe/Simvastatin (Vytorin) [Antilipemic/HMG CoA Reductose Inhibitor] Uses H rp cholest olemia Action X Absorption of cholesterol phytost ol w/ HMG-CoA reductase inhibitor Dose 10/10-10/80 mg/d PO w/ cyclosporine or danazol 10/10 mg/d max w/ amio-darone or verapamil 10/20 mg/d max -1- w/ sev e renal insuff Caution [X, -] w/ CYP3A4 inhibitors (Table VI-8), gemfibrozil, niacin >lg/d, danazol, amiodarone, verapamil Contra PRG/lactation livCT Dz, t LFTs Disp Tabs SE HA, GI upset, myalgia, myopathy (muscle pain, weakness, or tendOTiess w/ CK 10 x ULN, rhab-domyolysis), Hep, Infxn Interactions t Risk of myopathy W7 clarithromycin, erythromycin, itraconazole, ketoconazole EMS None OD Sxs unknown symptomatic and supportive... 

This occurs in otherwise healthy individuals, who possess an anomalous (accessory) atrioventricular pathway they often experience attacks of paroxj mal AV re-entrant tachycardia or atrial fibrillation. Drugs that both suppress the initiating ectopic beats and delay conduction through the accessory pathway are used to prevent attacks e.g. flecainide, sotalol or amiodarone. Verapamil and digoxin may increase conduction through the anomalous pathway and should not be used. Electrical conversion may be needed to restore sinus rhythm when the ventricular rate is very rapid. Radiofrequency ablation of aberrant pathways will almost certainly provide a cure. 

Toxicity is increased by i K, A Mg, T Ca (note effects of diuretics on electrolytes) and by quinidine, NSAIDs, amiodarone, verapamil, sympathomimetics, and some antibiotics (e.g., erythromycin). Avoid digitalis in Wolff-Parkinson-White arrhythmias. 

Describe the mode of action of the following drugs used to treat cardiac arrhythmia amiodarone, verapamil and lidocaine. 

Verapamil, diltiazem, amiodarone Diminished renal and nonrenal excretion ... 

Numerous drugs ((1-blockers, diltiazem, verapamil, digoxin, and amiodarone) can cause bradyarrhythmias (sinus bradycardia and AV nodal blockade). 

Ventricular Rate Control is achieved by inhibiting the proportion of electrical impulses conducted from the atria to the ventricles through the AV node. Therefore, drugs that are effective for ventricular rate control are those that inhibit AV nodal impulse conduction P-blockers, diltiazem, verapamil, and digoxin (Tables 6-5 and 6-6). Amiodarone also inhibits AV nodal conduction, but is not a preferred drug for ventricular rate control in AF due to its unfavorable adverse-effect profile (Table 6-6). 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Fig. 20.13. Potential H-bonding energy, released upon interaction with the transmembrane domains of P-gp (in arbitrary energy units, EU) for progesterone (1), propranolol (2), amitriptyline (3), diltiazem (4), amiodarone (5), colchicine (7), gramicidin S (8), daunorubicin (9), vinblastine (10), cyclosporin A, in comparison with verapamil...

Maintenance dose 0.125-0.25 mg PO/IV qd low potassium or magnesium levels potentiate toxicity reduce dose in renal failure toxicity indicated by nausea, headache, visual disturbances (yellow-green halos), ventricular arrhythmias. Quinidine, verapamil, and amiodarone elevate digoxin level. 

The enzyme is the principal participant in N-demethylation reactions where the substrate is a tertiary amine. The list of substrates includes erythromycin, ethylmor-phine, lidocaine, diltiazem, tamoxifen, toremifene, verapamil, cocaine, amiodarone, alfentanil and terfenadine. Carbon atoms in the allylic and benzylic positions, such as those present in quinidine, steroids and cyclosporin A, are also particularly prone to oxidation by CYP3A4, a range of substrates is illustrated in Figure 7.10. 

Drugs that may affect flecainide include amiodarone, cimetidine, cisapride, disopyramide, propranolol, ritonavir, urinary acidifiers/alkalinizers, and verapamil. Smoking may also have an effect. Drugs that may be affected by flecainide include cisapride, propranolol, and digoxin. 

Concomitant amiodarone or verapamil (immediate-release only) - In patients taking amiodarone or verapamil concomitantly with lovastatin, the dose should not exceed 40 mg/day. 

Drugs that may affect HMG-CoA reductase inhibitors include alcohol, amiodarone, antacids, azole antifungals, bile acid sequestrants, cimetidine, cyclosporine, diltiazem, erythromycin, gemfibrozil, isradipine, nefazodone, niacin, nicotinic acid, omeprazole, phenytoin, propranolol, protease inhibitors, ranitidine, rifampin, St. John s wort, and verapamil. 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Antibacterials Ciprofloxacin Erythromycin Isoniazid Antidepressants Flnoxetine Huvoxamine Paroxetine Antifungal drugs Fluconazole Itraconazole Ketoconazole Miconazole Antiviral drugs Indinavir Ritonavir Saquinavir Cardiovascular drugs Amiodarone Diltiazem Quinidine Verapamil... 

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