Model(s): 3300, D000, D001, D002, D003, D010, D011, D012, D013, D020, D021, D022, D023, D030, D031, D032, D033, D044, D045, D046, D047, D050, D051, D052, D053, D140, D141, D142, D143, D150, D151, D152, D153, D160, D161, D162, D163, D174, D175, D176, D177, E050, E051, E052, E053, E102, E103, E110, E111, E140, E141, E142, E143, E160, E161, E162, E163, F050, F051, F052, F053, F102, F103, F110, F111, F140, F141, F142, F143, F160, F161, F162, F163, G050, G051, G056, G058, G140, G141, G146, G148, G150, G151, G154, G156, G158, G160, G161, G164, G166, G168, G172, G173, G175, G177, G179, J062, J063, J064, J065, J066, J067, J172, J173, J174, J175, J176, J177, J178, J272, J273, J274, J275, J276, J277, J278, J279, K062, K063, K064, K065, K066, K067, K082, K083, K084, K085, K086, K087, K172, K173, K174, K175, K176, K177, K182, K183, K184, K185, K186, K187, K188, K272, K273, K274, K275, K276, K277, K278, K279, K282, K283, K284, K285, K286, K287, K288, K289, L058, L059, L100, L101, L110, L111, L121, L131, L200, L201, L209, L210, L211, L221, L231, L300, L301, L310, L311, L321, L331, N050, N051, N052, N053, N106, N107, N108, N118, N119, N140, N141, N142, N143, N160, N161, N162, N163, N164, N165, P052, P053, P106, P107, P108, P142, P143, P162, P163, P165, S701, S702, S722, U125, U128, U225, U226, U228, V172, V173, V182, V183, V272, V273, V274, V275, V282, V283, V284, V285, W172, W173, W272, W273, W274, W275
In a multi-center 6-week study, Fux et al (2005) examined the impact of CYP2D6 polymorphism on the tolerability of metoprolol in a primary care setting. The adverse effects studied comprised effects related to the central nervous system, cardiovascular effects, and sexual dysfunction. The dosage of metoprolol was determined on an individual basis and could be adjusted on clinical grounds. The indication for treatment was hypertension in about 90 % of cases. CYP2D6 genotyping covered alleles *3 to *10 and *41 and the duplications. Possible ADRs of metoprolol were systematically assessed over the study period using standardized rating scales and questionnaires. The final study population comprised 121 evaluable patients: 5 ultrarapid metabolizers (UMs) ( %), 91 extensive metabolizers (EMs) (75 %), 21 intermediate metabolizers (IMs) (17 %), and 4 poor metabolizers (PMs) ( %). Plasma metoprolol concentrations normalized for the daily dose and metoprolol/alpha-hydroxymetoprolol ratios at steady state were markedly influenced by CYP2D6 genotype and displayed a gene-dose effect. The median of the dose-normalized metoprolol concentration was ng/ml, ng/ml, ng/ml, and ng/ml among UMs, EMs, IMs, and PMs, respectively (p < ). There was no significant association between CYP2D6 genotype-derived phenotype (EMs and UMs combined versus PMs and IMs combined) and ADRs during treatment with metoprolol. There was a tendency toward a more frequent occurrence of cold extremities in the PM plus IM group as compared with the EM plus UM group ( % versus %, p = ; relative risk, [95 % confidence interval [CI]: to ]). These investigators concluded that CYP2D6 genotype-derived phenotype was not significantly associated with a propensity for ADRs to develop during treatment with metoprolol. However, the results concerning tolerability of metoprolol in PMs were inconclusive because of the small number of PMs enrolled.
PATIENTS WITH ATRIO VENTRICULAR BLOCK
AND NORMAL SINUS NODE FUNCTION
In the DDD mode, if the lower rate of the pacer is programmed at a sufficiently low value to permit atrial tracking, the pacemaker stimulates the ventricle synchronous with intrinsic P waves. If a patient does not require atrial pacing, it may be reasonable to implant a dual-chamber pacer with a single tripolar or quadripolar lead that allows atrial sensing and ventricular pacing and sensing ( Fig. 16p ). These VDD pacing systems allow for ease of implant and for bipolar atrial sensing. Atrial sensing may not be as reliable compared to a fixed atrial lead, which may lead to occasional atrial '81 In a recent prospective comparison between single-lead VDD systems to DDD leads, however, there were lower P-wave amplitudes in the group with VDD systems, but no significant clinical differences with respect to atrial undersensing.