Metoprolol Verapamil

Antiarrhythmics (e.g., disopyramide, flecainide, and others) P-Blockers (e.g., propranolol, metoprolol, atenolol, and others) Calcium channel blockers (e.g., verapamil and others)... 

Class I compounds have both good solubility and permeability and generally offer no problems with regard to having a good absorption profile (e.g., acetaminophen, disopyramide, ketoprofen, metoprolol, nonsteroidal anti-inflammatory agents, valproic acid, verapamil). In general, one would not expect the presence of food to influence the absorption of this class... 

VERAPAMIL DILTIAZEM PROMETHAZINE PHENAZOPYRIDINE DESIPRAMINE PROGESTERONE IMIPRAMINE CHLORPROMAZINE GRISEOFULVIN PROPRANOLOL CARBAMAZEPINE QUININE IBUPROFEN PIROXICAM PRIMAQUINE CAFFEINE ANTIPYRINE METOPROLOL NAPROXEN KETOPROFEN SULPIRIDE TERBUTALINE FUROSEMIDE SULPHASALAZINE RANITIDINE HYDROCHLOROTHIAZIDE ATENOLOL AMIOLORIDE... 

Figure 7.41 Gradient pH profiles for three weak bases with double-sink conditions, 20% wt/vol soy lecithin in dodecane (a) verapamil (pKa 9.07) (b) propranolol (pKa 9.53) (c) metoprolol (pKa 9.56).

If patients are hemodynamicaUy stable, the focus should be directed toward control of ventricular rate. Drugs that slow conduction and increase refractoriness in the AV node should be used as initial therapy. In patients with normal LV function (left ventricular ejection fraction >40%), IV j3-blockers (propranolol, metoprolol, esmolol), diltiazem, or verapamil is recommended. If a high adrenergic state is the precipitating factor, IV /J-blockers can be highly effective and should be considered first. In patients with left ventricular ejection fraction <40%, IV diltiazem and verapamil... 

Acebutorol, arotinolol, atropine, bupivacaine, clorprenaline, denopamine, eperisone, epinastine, etirefline, fenoterol, homatropine, ketamine, metanephrine, metoprolol, mexiletine, nicardipine, oxyphencyclimine, phenylephrine, pindolol, primaquine, promethazine, sulpiride, ter-butaline, tolperizone, trihexyphenidyl, trimebutine, trimetoquinol, trimipramine, verapamil 81... 

Nitrates are required for symptomatic relief of chest pain they are not proven to improve hard outcomes such as MI or death. Nitrates should be given initially sublingually or by spray, followed by oral or transdermal routes if pain is relieved. Lack of pain relief mandates i.v. administration. Beta-blockers such as metoprolol are used and may reduce the risk of subsequent MI. Calcium channel blockers such as dilfiazem, verapamil, or long-acting di-hydropyridines can be added for symptom control if nitrates and beta-blockers do not suffice they do not improve outcomes. In fact, they may worsen outcomes in the presence of left ventricular dysfunction or CHF in acute coronary syndrome. 

L A. Verapamil is an L-type calcium channel blocker. Nitroglycerin and isosorbide are both organic nitrates and have no direct effect on L-type calcium channels at the SA node, while propranolol and metoprolol are (3-adrenoceptor blockers and will slow heart rate by blocking the actions of norepinephrine and epinephrine on (3-receptors at the SA node. 

Figure 6.3 Plot of the fraction of dose absorbed (in %) of various drugs as a function of the permeability estimates in the Caco-2 system. Key 1 D-glucose 2 verapamil 3 piroxicam 4 phenylalanine 5 cyclosporin 6 enalapril 7 cephalexim 8 losartan 9 lisinopril 10 amoxicillin 11 methyldopa 12 naproxen 13 an-tipyrine 14 desipramine 15 propanolol 16 amiloride 17 metoprolol 18 terbu-taline 19 mannitol 20 cimetidine 21 ranitidine 22 enalaprilate 23 atenolol 24 hydrochlorothiazide.

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

Propranolol, verapamil, nifedipine, diltiazem, metoprolol, nicardipine, or labetolol. 

There is some anecdotal evidence that atrioventricular nodal blockade with verapamil or a beta-blocker can also be effective. However, in two cases the addition of a beta-blocker (either atenolol or metoprolol) to treatment with class I antidysrhythmic drugs (cibenzoline in one case and flecainide in the other) did not prevent the occurrence of atrial flutter with a 1 1 response (47). However, the author suggested that in these cases, although the beta-blockers had not suppressed the dysrhythmia, they had at least improved the patient s tolerance of it. In both cases the uses of class I antidysrhythmic drugs was contraindicated by virtue of structural damage, in the first case due to mitral valvular disease and in the second due to an ischemic cardiomyopathy. 

Hyldstmp L, Mogensen NB, Nielsen PE. Orthostatic response before and after nitroglycerin in metoprolol-and verapamil-treated angina pectoris. Acta Med Scand 1983 214(2) 131-4. 

D Rifampin significantly reduces the plasma concentrations of the calcium channel blockers verapamil, diltiazem, and nifedipine. Diltiazem is a substrate of Gi P3A4 and rifampin is an inducer of CYP3A4. Rifampin does not interact with metoprolol, aspirin, pravastatin, or nitroglycerin. However, if the patient had been on another HMG-CoA reductase inhibitor such as atorvastatin, lova-statin, or simvastatin instead of pravastatin, rifampin would have reduced the plasma concentrations of these agents since they are also metabolized via CYP3A4. 

Clinically important, potentially hazardous interactions with acebutolol, amitriptyline, amoxapine, atenolol, betaxolol, carteolol, clomipramine, desipramine, dexmethylphenidate, doxepin, esmolol, imipramine, insulin detemir, insulin glulisine, metoprolol, nadolol, nortriptyline, oxprenolol, penbutolol, pindolol, propranolol, protriptyline, sulpiride, timolol, tricyclic antidepressants, trimipramine, verapamil... 

PAMPA-pKa fiux optimized design (pOD)-permeabiiity Iso-pH mapping unstirred PAMPA was used to measure the effective permeability, Pe, as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, Po, the UWL permeability, Pu, and the apparent pKa (pKa.fiux) were determined from the pH dependence of log Pg. The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases, and ampholytes. The average thickness of the UWL on each side of the membrane was estimated to be nearly 2000 p, somewhat larger than that found in Caco-2 permeability assays (unstirred). As the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g., pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log Pe-pH plots, a method to improve the selection of the assay pH, called pOD-PAMPA, was described and tested. From an optimally selected assay pH, it is possible to estimate Pg, as well as the entire membrane permeability-pH profile. 

Singh N, Mironov D, Goodman S, et al. Treatment of silent ischemia in unstable angina A randomized comparison of sustained-release verapamil versus metoprolol. Clin Cardiol 1995 18 653-658. 

Cardiodepressant drugs, including beta blockers and cardioactive CCAs like verapamil, have usually been avoided in management of heart failure. Recently, survival benefits in heart failure have been demonstrated for specific drugs, including metoprolol. 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

---