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Markboguski.net0031-6997/04/5602-159 –159$7.00PHARMACOLOGICAL REVIEWS Copyright 2004 by The American Society for Pharmacology and Experimental Therapeutics PharmGKB Update:
II. CYP3A5, Cytochrome P450, Family 3, Subfamily A,
E. G. SCHUETZ, M. V. RELLING, S. KISHI, W. YANG, S. DAS, P. CHEN, E. H. COOK, G. L. ROSNER, C. H. PUI, J. G. BLANCO, M. J. EDICK, M. L. HANCOCK, N. J. WINICK, T. DERVIEUX, M. D. AMYLON, R. O. BASH, F. G. BEHM, B. M. CAMITTA, S. C. RAIMONDI, B. C. GOH, S. C. LEE, L. Z. WANG, L. FAN, J. Y. GUO, J. LAMBA, R. LIM, H. L. LIM, A. B. ONG, H. S. LEE, P. KUEHL, J. ZHANG, Y. LIN, M. ASSEM, J. SCHUETZ, P. B. WATKINS, A. DALY, S. A. WRIGHTON, S. D. HALL, P. MAUREL, C. BRIMER, K. YASUDA, R. VENKATARAMANAN, S. STROM, K. THUMMEL, AND M. S. BOGUSKI St. Jude’s Children’s Research Hospital, Memphis, Tennessee Category: Genotype
itative overlap in substrate specificity, although thereare differences among substrates in the relative im- PharmGKB
portance of CYP3A5 versus CYP3A4. CYP3A5 is the PS115406, PS114503, PS200420, PS201057, PS115245 predominant form for extrahepatic CYP3A expression.
Whereas CYP3A4 is expressed in all adult human livers, CYP3A5 hepatic expression is polymorphic.
Date of Submission: May 19, 2003
Potential Drug Interactions: erythromycin, midazo-
lam, prednisone, itraconazole, ketoconazole, fluconazole,
Project: Pharmacogenetics of Anticancer Agents, St.
etoposide, teniposide, vincristine, vinblastine, pacli- taxel, topotecan, docetaxel, cyclosporine, tacrolimus,grapefruit juice, ritonavir, clarithromycin, quinidine, al- HGNC Symbol: CYP3A5
prazolam, diazepam, midazolam, triazolam, indinavir, HGNC Name: cytochrome P450, family 3, subfamily A,
saquinavir, cisapride, astemizole, chlorpheniramine, amlodipine, diltiazem, felodipine, nifedipine, isoldipine, Synonyms: CYP3A5
nitrendipine, verapamil, atorvastatin, cerivastatin, lo-vastatin, buspirone, haloperidol, methadone, pimozide, Gene Ontology Terms: GO:0004497 monooxygenase ac-
quinine, sildenafil, tamoxifen, trazodone, vincristine, tivity, GO:0005783 endoplasmic reticulum, GO:0005792 indinavir, nelfinavir, ritonavir, saquinavir, amiodarone, microsome, GO:0006118 electron transport, GO:0008202 cimetidine, fluoxetine, fluvoxamine, itraconazole, keto- steroid metabolism, GO:0015034 cytochrome P450 activ- conazole, mibefradil, nefazodone, troleandomycin, vera- ity, GO:0016020 membrane, GO:0016712 oxidoreductase pamil, isoniazid, carbamazepine, phenobarbital, phenyt- activity, acting on paired donors, with incorporation or oin, rifabutin, rifampin, St. John’s wort, troglitazone reduction of molecular oxygen, reduced flavin or flavopro-tein as one donor, and incorporation of one atom of oxygen Function Characteristics: Liver microsomes from in-
Locus ID: 1577
dividuals homozygous for the nonfunctional *3 genotype GenBank Accession: J04813
have about half the overall CYP3A catalytic activitytoward midazolam, which is a substrate for CYP3A5 and Pharmacogenetic Significance: An AG SNP in in-
CYP3A4, than individuals with at least one wild-type tron 3 of CYP3A5 results in the introduction of an alter- native exon 3A, that introduces a premature stop codon Summary of Data Submitted:
and lack of CYP3A5 protein expression. The nonfunc-tional homozygous *3 genotype is present in 70% of Size of Sample Set Assayed: 386 (772 chromosomes)
Number of gene regions assayed: 1
Total bases assayed: 2760
Pharmacological Significance: CYP3A4 and CYP3A5
Number of variant sites: 3
together account for approximately 50% of hepatic cyto- PCR Primers Reported: 6
chrome P450 and approximately half of medications thatare metabolized by P450 are CYP3A substrates. The two Available online at http://pharmrev.aspetjournals.org/ forms are often linked because they have substantial qual-
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