專技 - 藥物治療學題庫下載題庫

70.有關慢性骨髓性白血病（chronic myeloid leukemia, CML）之治療，下列何者正確？
(A)費城染色體( (-)Bcr-Abl)是CML的致病因，為第9與第15染色體互換造成的異常~> 22
(B)費城染色體所產生的異常融合蛋白，是一種tyrosine kinase
(C)hydroxyurea的角色為預防血液中的惡性白血球再復發(用來降低白血球數量). 機轉為：抑制ribonucleotide reductase
(D)imatinib應用在dasatinib治療失敗的病人~> 2者互換

65.所有的tyrosine kinase inhibitors（-nib）都會與下列何者產生藥品交互作用？
(A)CYP3A4酵素誘導劑或抑制劑
(B)任何提高胃pH之藥品
(C)P-glycoprotei...

70.有關慢性骨髓性白血病（chronic myeloid leukemia, CML）之治療，下列何者正確？
(A)費城染色體( (-)Bcr-Abl)是CML的致病因，為第9與第15染色體互換造成的異常~> 22
(B)費城染色體所產生的異常融合蛋白，是一種tyrosine kinase
(C)hydroxyurea的角色為預防血液中的惡性白血球再復發(用來降低白血球數量). 機轉為：抑制ribonucleotide reductase
(D)imatinib應用在dasatinib治療失敗的病人~> 2者互換

65.所有的tyrosine kinase inhibitors（-nib）都會與下列何者產生藥品交互作用？
(A)CYP3A4酵素誘導劑或抑制劑
(B)任何提高胃pH之藥品
(C)P-glycoprotein誘導劑或抑制劑
(D)warfarin

INCIDENCE AND RISK FACTORS [Uptodate]

Fluorouracil — The reported incidence of fluorouracil (FU)-related cardiotoxicity ranges from 1 to 19 percent [5-15], although most series report a risk of 8 percent or less.

The variability in incidence rates may be due in part to differences in the definition of cardiotoxicity, but risk estimates may also be influenced by the method of FU administration, the presence of underlying coronary artery disease (CAD), the use of concurrent radiation therapy (RT) or anthracyclines, and how intensively patients were monitored.

The highest rates of cardioto...

INCIDENCE AND RISK FACTORS [Uptodate]

Fluorouracil — The reported incidence of fluorouracil (FU)-related cardiotoxicity ranges from 1 to 19 percent [5-15], although most series report a risk of 8 percent or less.

The variability in incidence rates may be due in part to differences in the definition of cardiotoxicity, but risk estimates may also be influenced by the method of FU administration, the presence of underlying coronary artery disease (CAD), the use of concurrent radiation therapy (RT) or anthracyclines, and how intensively patients were monitored.

The highest rates of cardiotoxicity have been observed in carefully monitored patients, as reflected by the following reports:

●One study evaluated 102 consecutive patients receiving FU, all of whom were monitored using 12-lead electrocardiogram (ECG), echocardiography, and radionuclide ventriculography prior to the first cycle and continuous Holter monitoring during the FU infusion; the same examinations were repeated three months later after the discontinuation of chemotherapy [10].

Reversible symptoms of angina pectoris lasting up to 12 hours were observed in 19 patients (19 percent) within 24 hours of starting FU, and these lasted up to 12 hours after cessation of treatment.

Most symptomatic patients had accompanying ECG changes.

In addition, both bradycardia and ventricular extrasystoles were significantly more frequent during treatment than when assessed in the three months following therapy.

●Asymptomatic ECG changes and arrhythmias, as well as increases in plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), during FU chemotherapy have also been described, suggesting the possibility of subclinical cardiotoxicity [7,10,11,16]. However, the clinical significance of these findings remains uncertain.

Effect of schedule and dose — As with other FU-associated toxicities, the risk of cardiotoxicity is also dependent on the schedule and route of administration.

In general, risk appears higher with infusional (both long-term and short-term schedules) as opposed to bolus FU regimens:

●With bolus regimens, the incidence of cardiotoxicity is between 1.6 and 3 percent [5,6].

●With continuous infusional regimens of five days or longer, the reported range of risk is 2 to 18 percent [8,9,15,17,18].

●The risk with short-term infusional regimens is intermediate and variable:

•In one series of 106 patients receiving short-term infusional FU as a component of the FOLFOX regimen (oxaliplatin plus infusional FU and leucovorin (table 1)), nine (8.5 percent) developed chest pain during treatment [11].

The onset was during courses 1, 2, 6, and 8 in three, four, one, and one patient(s), respectively.

•In a second report, the risk of cardiotoxicity was significantly higher with continuous versus short-term infusional FU (13 of 205 versus 7 of 317, 6.3 versus 2.2 percent, p <0.012) [18].

Rarely, myocardial ischemia has been reported with topical [19] or intraperitoneal [8] administration of FU.

The relationship between cardiotoxicity and FU dose is unclear; the available data are sparse: