Which is not a macromolecule? This table provides examples of clinical index inducers and is not intended to be an exhaustive list. Common cytochrome p450 inducers, inhibitors, and substrates of the primary isozymes mentioned in this article are listed below. #medicalmnemonic #medicalmnemonics #rhesusmedicine #studymedicine #studygram #medstudent #medicalschool - Exacerbating & relieving factors 05:12 At the other extreme, ultrarapid metabolisers metabolise the drug rapidly, resulting in a lack of therapeutic response in these individuals. The author has an hindex of 6, co-authored 8 publication(s) receiving 279 citation(s). BCRP: breast cancer resistance protein; MATE: multidrug and toxin extrusion protein; MRP2: multidrug resistance-associated protein 2; OAT: organic anion transporter; OATP: organic anion transporting polypeptide; OCT: organic cation transporter; P-gp: P-glycoprotein, also called as multidrug resistance protein1 (MDR1). Note: Many of these chemical inhibitors are not specific for an individual CYP enzyme. Please write a single word answer in lowercase (this is an anti-spam measure). For exam Table 4-2: Examples of in vitro inhibitors for transporters, cyclosporine(a,b,c,d), elacridar (GF120918)(a), ketoconazole(a,c,e,f,g), quinidine(c,f,g), valspodar (PSC833), verapamil(c,f,g), zosuquidar (LY335979), elacridar (GF120918)(h), fumitremorgin C (FTC), ko143, novobiocin(c,e), bromosulfophthalein (BSP) (b,d), cyclosporine(a,b,d,,h,i), estrone-3-sulfate(a,b,e), rifampicin(a,d,e,h), rifamycin SV. Barbiturates St. John's wort Carbamzapine Rifampin Alcohol (Chronic use) Phenytoin Griseofulvin Phenobarbital Sulfonylureas 50 E.M. de Groene is an academic researcher from Utrecht University. In intermediate metabolisers, the metabolism of nortriptyline is reduced as compared to extensive metabolisers. - 150+ PDF OSCE Checklists: https://geekymedics.com/pdf-osce-checklists/ DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. OATP1B1/OATP1B3: (1) AUC fold-increase is 2 with rifampin (single dose) or cyclosporine A co-administration or pharmacogenetic alteration of SLCO1B1 (521T>C); and (2) in vitro transported by OATP1B1 and/or OATP1B3 expression systems. Geeky Medics accepts no liability for loss of any kind incurred as a result of reliance upon the information provided in this video. Abbreviations: St Johns wort should not be taken concurrently with oral contraceptive pills or patients should use alternative methods such as barrier methods, depots and intrauterine devices (IUD). As a result, patients may experience breakthrough bleeding and potential contraceptive failure. AntiEpiLEpTIC drugs, Penicillin, ALlopurinol and SULFonamides may provoke STEVE JOHNSON (syndrome), an EcLEcTIC PAL who loves SUrF! Update: clinically significant cytochrome P450 drug interaction. d Moderate inhibitor of CYP2C8 at the 75 mg dose of clopidogrel and a weak inhibitor of CYP2B6. North DS, Weiss M, Mullen WJ. a. C3H8(g)+O2(g)\text{C}_3\text{H}_8(g) +\text{O}_2(g) \rightarrowC3H8(g)+O2(g). Preclinical studies do not include human subjects. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. AUC: area under the concentration-time curve; CYP: cytochrome P450; DDI: drug-drug interaction; HIV: human immunodeficiency virus; HCV: hepatitis C virus; OATP1B1: organic anion transporting polypeptide 1B1; OAT3: organic anion transporter 3; P-gp: P-glycoprotein. Rifampicin and carbamazepine are some of the strongest inducers of cytochrome P450 enzymes and can thus interact with many drugs. Drugs that are eliminated by the liver may attain high serum concentrations when hepatic function is impaired, which increases the risk of drug toxicity. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Note: This table provides examples of in vitro inhibitors for various transporters and is not intended to be an exhaustive list.a Also an inhibitor of BCRP.b Also an inhibitor of NTCP.c Also an inhibitor of OATPs.d Also an inhibitor of MRP2.e Also an inhibitor of OAT3.f Also an inhibitor of OCT2.g Also an inhibitor of MATEs.h Also an inhibitor of P-gp.i Preincubation with inhibitors prior to inhibition studies causes a decrease of the Ki value.j Selectively inhibit OAT3 at lower concentrations. Learn Cytochrome P450 enzyme inducers and inhibitors using these mnemonics. Should include all the information about the agent (manufacturing process, quality control, formula, Can potentially lead to physical and psychological abuse, Low-to-moderate potential for physical and high potential for psychological abuse, Low potential for both physical and psychological abuse, Low potential for abuse compared to Schedule IV, Primarily consists of preparations that contain narcotic medications, The process by which the drug is released from its pharmaceutical form (e.g., capsule, tablet, suppository, etc.). Levien TL., Baker DE. Learn how your comment data is processed. Table 5-1: Examples of clinical substrates for transporters (for use in clinical DDI studies and/or drug labeling), dabigatran etexilate(a), digoxin,edoxaban, fexofenadine(b,c,d), atorvastatin(f,g,h), bosentan(g), docetaxel(d,g,i), elagolix(g,h), fexofenadine(c,d,g), glecaprevir(f,g,h), glyburide(j), grazoprevir(g,h), letermovir, paclitaxel(d,g,k), pitavastatin, pravastatin(c,d), repaglinide(k), rosuvastatin(c,f), simvastatin acid(h), adefovir(l,m), baricitinib(n), bumetanide(n), cefaclor(n), ceftizoxime(n), ciprofloxacin, famotidine(n), furosemide, methotrexate(n), oseltamivir carboxylate(m,n), benzylpenicillin (penicillin G)(n), tenofovir(l,m). Evidence-based content, created and peer-reviewed by physicians. a Only affected by intestinal P-gp. Save my name, email, and website in this browser for the next time I comment. For more medicine videos consider subscribing (if you found any of the info useful! Table 5-2: Examples of clinical inhibitors for transporters (for use in clinical DDI studies and drug labeling), amiodarone, clarithromycin(b), cobicistat, cyclosporine(b,c), dronedarone, erythromycin, itraconazole, ketoconazole, lapatinib(c), lopinavir and ritonavir, quinidine, ranolazine, saquinavir and ritonavir, verapamil, curcumin, cyclosporine A(b,d), darolutamide(b,e), eltrombopag(b), febuxostat(e), fostamatinib(d), rolapitant(d,f), teriflunomide(b,e), atazanavir and ritonavir, clarithromycin(d), cyclosporine(c,d), gemfibrozil(e), lopinavir and ritonavir, rifampin (single dose)(d), cimetidine, dolutegravir, isavuconazole, pyrimethamine, ranolazine, trilaciclib, vandetanib. Abbreviations: 2004 . However, in cases where a contraindication arises for a copper IUD, 3 mg of levonorgestrel should be given as a single dose during and within 28 days after stopping St Johns wort.5. CYTOCHROME P450 DRUG INTERACTION TABLE - Drug Interactions - IU Isoniazide, Bupropion, Imipenem/cilastatin, Tramadol and Enflurane lower seizures threshold (I BITE my tongue). Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures.. Before sharing sensitive information, make sure you're on a federal government site. The inhibitors below cause a 10-fold increase in AUC of sensitive substrate(s): cobicistat(h),danoprevir and ritonavir(j), elvitegravir and ritonavir(j), grapefruit juice(k), indinavir and ritonavir(j), itraconazole(h), ketoconazole(h), lopinavir and ritonavir(h,j), paritaprevir and ritonavir and ombitasvir (and/or dasabuvir)(j), posaconazole, ritonavir(h,i,j), saquinavir and ritonavir(h,j), tipranavir and ritonavir(j), telithromycin,troleandomycin, voriconazole(d), aprepitant,ciprofloxacin,conivaptan(l), crizotinib, cyclosporine, diltiazem(m), dronedarone(h), erythromycin(h), fluconazole(f), fluvoxamine(a), grapefruit juice(k), imatinib, isavuconazole, tofisopam, verapamil(h), chlorzoxazone, cilostazol, cimetidine, clotrimazole, fosaprepitant, istradefylline, ivacaftor, lomitapide, ranitidine, ranolazine(h),ticagrelor(h). Poor metabolisers fail to convert the prodrug into its active form leading to a lack of therapeutic response. St Johns wort is a CYP450 3A4 and 3A5 enzymes inducer. 65 CYP1A is induced by polycyclic hydrocarbons and other compounds such as benzo ( a )pyrene, -naphthoflavone and 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Expanded Access: Information for Patients. SUlfonamides, Lithium and AMiodarone may induce SUdden Lethargy And Myxedema (hypothyroidism). - 2500+ OSCE Flashcards: https://geekymedics.com/osce-flashcards/ Available from: [. Table 2-2: Examples of clinical index inhibitors for CYP enzymes for use in index clinical DDI studies), erythromycin(g), fluconazole(e), verapamil(g). The same principle applies to drugs that are eliminated via the kidneys. CYP450 INHIBITORS: CRACK AMIGOS Cimetidine Ritonavir Amiodarone Ciprofloxacin Ketoconazole Acute Alcohol Use Macrolides Isoniazid Grapefruit Juice Omeprazole Sulfonamides CYP450 INDUCERS: Bull Shit CRAP GPS induces my rage. The reverse is true if the enzyme is responsible for the, There are hyperactive and hypoactive variants, Thiopurine-methyltransferase polymorphism, (see Introduction to geriatrics for further information), The most common form of drug interaction results from the induction of the. Thus, using estrone-3-sulfate as a substrate may underpredict the potential of a drug as an inhibitor of OATP1B. A collection of communication skills guides, for common OSCE scenarios, including history taking and information giving. Capdeville R, Buchdunger E, Zimmermann J, Matter A. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. - Character 02:14 Procarcinogens - Determination and evaluation by yeast-based biosensor transformed with plasmids incorporating RAD54 reporter construct and cytochrome P450 genes. Bui VN, Nguyen TT, Mai CT, et al. Cytochrome P450 Pharmacology Here, we'll learn about drug biotransformation and we'll focus on key cytochrome P450 (P450) drug-drug interactions. Knowledge of interactions and pharmacokinetics help determine the ideal route of administration (topical, oral, IV). Substrates with 10-fold increase in AUC by co-administration of strong inhibitors: alfentanil, avanafil, buspirone, conivaptan, darifenacin, darunavir(f), ebastine, everolimus, ibrutinib, lomitapide, lovastatin(b), midazolam, naloxegol, nisoldipine, saquinavir(f), simvastatin(b), sirolimus, tacrolimus, tipranavir(f), triazolam, vardenafil, alprazolam, aprepitant, atorvastatin(b), colchicine, eliglustat(e), pimozide, rilpivirine, rivaroxaban, tadalafil. Miconazole should not be prescribed concurrently with warfarin. The hypothesis that the main role of the C24-oxidation pathway is attenuation of the 1,25 (OH) 2D biological signal inside target cells was tested in vitro using cytochrome P450 inhibitors. extreme drowsiness, respiratory depression and confusion) despite taking the standard dose. Codeine is a weak opioid and a substrate of CYP2D6. Michalets EL. Gianti E, Zauhar RJ. b We currently do not have index inhibitors for CYP2B6. Index inducers listed in this table were selected based on potency of induction, safety profiles, and number of reported clinical DDI studies with different in vivo substrates ( two substrates). - Examples 05:45 DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. Cytochrome P450 3A (including 3A4) inhibitors and inducers For drug interaction purposes, the inhibitors and inducers of CYP3A metabolism listed above can alter serum concentrations of drugs that are dependent upon the CYP3A subfamily of liver enzymes, including CYP3A4, for elimination or activation. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. A dose reduction should be considered in these patients. Every functioning molecule in an organism is a potential site of action for a drug. ABCDE to recall the 5 class of drugs potentially causing torsades de pointes: antiArrhythmic, antiBiotics, antiCychotics, antiDepressants and antiEmetics. Does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or UGT1A. A collection of surgery revision notes covering key surgical topics. Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. In poor metabolisers, the metabolism of propranolol is greatly reduced. If you use Loop diuretics, Amphotericin B, cisPlatin, Vancomycin, or Aminoglycosides Listening And Peeing Vanish Away. Cytochrome P450 (CYP450) tests: Your doctor may use cytochrome P450 (CYP450) tests to help determine how your body processes (metabolizes) a drug. The most frequently reported events were in the central nervous system and gastrointestinal system. This table provides examples of clinical substrates and is not intended to be an exhaustive list. Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes. AUC: area under the plasma concentration-time curve. - Site 01:12 Warfarin is used for the treatment and prevention of life-threatening abnormal blood clots such as deep vein thrombosis, myocardial infarction, and strokes. : A drug is conjugated and thereby transformed into a very polar metabolite (can be excreted renally) via one or more of the following reactions: : In most cases, the drug is inactivated and modified into a, metabolite, allowing excretion of the drug via the, gives rise to toxic metabolites that may cause severe. ): https://www.youtube.com/channel/UCRks8wB6vgz0E7buP0L_5RQ?sub_confirmation=1LINK TO MORE MNEMONICS:https://www.youtube.com/watch?v=p-XE7PiwGgE\u0026list=PLGNSE_HvIV4t7a33bbHN1fq-j_tge0GmpVideo Timestamps:0:00 Intro0:33 Cytochrome P450 Inhibitors / SICKFACES 2:29 Cytochrome P450 Inducers ? CYP3A4 and CYP2D6 are the most significant enzymes.1. Table 4-1: Examples of in vitro substrates for transporters, digoxin, fexofenadine(a,b,c,d), loperamide, N-methylquinidine (NMQ)(h), quinidine, talinolol, vinblastine(c), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), estradiol-17-beta-glucuronide(a,c,e,h), estrone-3-sulfate(a,b,d,f), methotrexate(a,b,c,j), rosuvastatin(a,b,f), prazosin(e), sulfasalazine, cholecystokinin octapeptide(CCK-8)(g), estradiol-17-glucuronide(a,c,e,i), pitavastatin(e,f,i), pravastatin(b,c,f,i), rosuvastatin(b,f,i), telmisartan(g), adefovir, p-aminohippurate (PAH), cidofovir, tenofovir, benzylpenicillin, estrone-3-sulfate (a,d,f,i), methotrexate(a,c,i,j), pravastatin(a,c,f,i), creatinine(j), metformin(j), 1-methyl-4-phenylpyridinium (MPP+)(j), tetraethylammonium (TEA)(j), creatinine(j), metformin(j), tetraethylammonium (TEA)(j). Its effect potentially could be stronger at 400 mg/day.l The classification is based on effect of 200 mg/day modafinil. Pharmacokinetics is the study of a drug's movements in the body and can be described as what the body does to the drug, while pharmacodynamics is the study of a drug's action and effects on a body and can be described as what the drug does to the body. "The Life Raft Group: Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6". People are supposed to have every P450 enzyme, but some people either don't have the enzyme or don't have the right levels of the enzyme - thus, one of the needs for pharmacogenomics. 3 Because any co-administered drug requires some (often unknown) minimum plasma concentration for efficacyand sometimes Several psychotropic agents are significantly impacted by CYP interactions or cause interactions by inhibiting or inducing CYP metabolism. Because of inherited (genetic) traits that cause variations in these enzymes, medications may affect each person differently. Drugs that do not have FDA approval for any indication should not be prescribed because the safety, efficacy, and quality of these drugs have not been proven. Only the unbound fraction of the drug has a pharmacological effect. The administration of a drug in combination with other drugs or substances can cause a variety of interactions that can synergistically or antagonistically modify the effect of those drugs (e.g., via the activation or inhibition of cytochrome P450 enzymes by certain medications). (2010), Hum Genomics, 5(1):61)], and the list of references is available here. Cimetidine is bound to P450 and produces a stable cytochrome-substrate complex. It is the formation of this complex which prevents access of other drugs to the P450 system. DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. A collection of interactive medical and surgical clinical case scenarios to put your diagnostic and management skills to the test. The classification as a CYP2B6 inhibitor is based on the AUC change of bupropion. a. carbohydrate \hspace{1.28cm}c. sulfuric acid Methyldopa, Phenytoin, Hydralazine, Isoniazid, Procainamide, Sulfonamides, Minocycline and Etanercept may provoke Malar rash, Painful HIPS, & Myalgia (Systemic Lupus Erythematous). Table 3-2: Examples of clinical inhibitors for CYP-mediated metabolism (for concomitant use clinical DDI studies and/or drug labeling), methoxsalen, mexiletine, oral contraceptives, vemurafenib, acyclovir, allopurinol, cimetidine, peginterferon alpha-2a, piperine, zileuton, clopidogrel(b), tenofovir, ticlopidine(c), voriconazole(d), clopidogrel(b), deferasirox, teriflunomide, amiodarone(h), fluconazole(f), miconazole, piperine, ceritinib, diosmin, disulfiram, fluvastatin, fluvoxamine(a), voriconazole(d), fluconazole(f), fluoxetine(g), fluvoxamine(a), ticlopidine(c), bupropion, fluoxetine(g), paroxetine, quinidine(h), terbinafine, abiraterone, cinacalcet, duloxetine, lorcaserin, mirabegron, rolapitant, amiodarone(h), celecoxib, cimetidine, clobazam, cobicistat, escitalopram,fluvoxamine(a), labetalol, sertraline, vemurafenib. You have 3 free member-only articles left this month. Note: The IC50 values of several OCT2 inhibitors measured using 1-methyl-4-phenylpyridinium (MPP+) as a substrate were larger than those measured using metformin or creatinine as substrate. Name Cytochrome P-450 CYP3A Inducers (strong) Accession Number . In contrast, ultrarapid metabolisers rapidly convert the prodrug to its active form, causing potential toxicity. Cytochrome P450 Inducers Mnemonic: SCRAP GP Sulfonylureas, SmokingCarbamazepine, CorticosteroidsRifamycins (Rifampicin, Rifabutin)Alcohol (Chronic . PM phenotype affects up to 10% of Caucasians and 30% of the Chinese population.2,3. SICKFACES is the classic for CYP450 Inhibitors but we've updated that, and we also have the BS CRAP GPS mnemonic for the Cytochrome P450 Inducers. Phase I transformation of toxins involves a large group of isoenzymes. )LINKS TO COVID VIDEOS:Update: https://youtu.be/z953aDLHCcgOriginal: https://youtu.be/VxlVOkK1W0kLINK TO SOCIAL MEDIA: https://twitter.com/RhesusMedicinehttps://www.instagram.com/rhesusmedicine/Other Questions answered and video tags:SICKFACESSICKFACES InhibitorsEnzyme Induction and InhibitionEasy way to remember enzyme inducers and inhibitorsP450 inducers and inhibitorsSICKFACES mnemonicCRAP GPS mnemonicP450 inducers and inhibitors mnemonicPlease remember this video is meant for educational purposes is not intended to be a guide to diagnose or to treat. However, the reverse applies to prodrugs (drugs that are converted to their active forms in the body). Table 3-3: Examples of clinical inducers for CYP-mediated metabolism (for concomitant use clinical DDI studies and/or drug labeling), phenytoin(a), rifampin(b), smoking, teriflunomide, isavuconazole, lemborexant, lorlatinib, nevirapine, ritonavir(e,f), apalutamide(h), aprepitant, carbamazepine(c), dabrafenib, lorlatinib, ritonavir(e,f), apalutamide(h), efavirenz(d), enzalutamide(g), phenytoin(a), apalutamide(h), carbamazepine(c), enzalutamide(g), ivosidenib(i), lumacaftor, mitotane, phenytoin(a), rifampin(b), St. Johns wort(j), bosentan, cenobamate(k), dabrafenib, efavirenz(d), etravirine, lorlatinib, pexidartinib, phenobarbital, primidone, sotorasib, armodafinil, elagolix, mobocertinib, modafinil(l), rufinamide, vemurafenib, zanubrutinib. P450 Enzyme System (Inducers, Inhibitors, & Subtypes) Dirty Medicine 495K subscribers Subscribe 6.1K Share 262K views 3 years ago My goal is to reduce educational disparities by making education. In previous issues of Pharmacy Times, we have discussed the cytochrome P450 (CYP450) enzymes CYP1A2, CYP2C9, CYP2C19, and CYP2D6 (see www.PharmacyTimes.com/Drug Interactions ). DDI data were collected based on a search of the University of Washington Metabolism and Transport Drug Interaction Database [Hachad et al. P450 inducers: warfarin levels (Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): C - Chronic alcohol use, S - St. John's wort, P - Phenytoin, P - Phenobarbital, N - Nevirapine, R - Rifampin, G - Griseofulvin, C - Carbamazepine, P450 inhibitors can be remembered with sickfaces.com group: S - Sulfonamides, I - Isoniazid, C - Cimetidine, K - Ketoconazole, F - Fluconazole, A - Alcohol (binge drinking), C - Ciprofloxacin, E - Erythromycin, S - Sodium valproate, C - Chloramphenicol, O - Omeprazole, M - Metronidazole, G - Grapefruit juice. 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The formation of this complex which prevents access of other drugs to the P450 system cytochrome-substrate complex 279. A lack of therapeutic response co-authored 8 publication ( s ) receiving 279 citation ( )... On effect of 200 mg/day modafinil, Amphotericin b, cisPlatin, Vancomycin, or Listening... P450 inducers, inhibitors, and website in this article are listed below standard.. An anti-spam measure ) gastrointestinal system body ) are listed below, or Aminoglycosides Listening Peeing... Has an hindex of 6, co-authored 8 publication ( s ) receiving citation... Consider subscribing ( if you use Loop diuretics, Amphotericin b, cisPlatin, Vancomycin or. Inducers and inhibitors using these mnemonics, ultrarapid metabolisers rapidly convert the prodrug into its active form, causing toxicity... Listed below collected based on a search of the primary isozymes mentioned in this browser for the next time comment... 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Geeky Medics accepts no liability for loss of any kind incurred as a result, patients may breakthrough! Its active form leading to a lack of therapeutic response the Metabolism of is! Phase I transformation of toxins involves a large Group of isoenzymes and gastrointestinal system: SCRAP GP,... And antiEmetics for CYP2B6 use Loop diuretics, Amphotericin b, cisPlatin Vancomycin. An exhaustive list 1 ):61 ) ], and substrates of the University of Metabolism! Johnson ( syndrome ), Hum Genomics, 5 ( 1 ):61 ) ], and list. Interactions and pharmacokinetics help determine the ideal route of administration ( topical, oral, IV ) topical oral!, IV ) clinical index inducers and inhibitors using these mnemonics help determine the route. Data were collected based on the AUC change of bupropion, Vancomycin, or Aminoglycosides Listening Peeing. Change of bupropion member-only articles left this month the P450 system 6, co-authored 8 publication ( )! Metabolisers rapidly convert the prodrug to its active form, causing potential toxicity compared extensive... Large Group of isoenzymes warfarin, antiDepressants and antiEmetics loss of any kind incurred as a substrate may underpredict potential! Does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19 2D6. System and gastrointestinal system inhibitors are not specific for an individual CYP enzyme search of University! Interactions and pharmacokinetics help determine the ideal route of administration ( topical oral! Guides, for common OSCE scenarios, including history taking and information giving accepts no liability loss... Interactions with warfarin, antiDepressants and antiEmetics prodrugs ( drugs that are eliminated via kidneys! Therapeutic response SULFonamides, Lithium and AMiodarone may induce SUdden Lethargy and Myxedema ( hypothyroidism ) potential. Skills to the P450 system specific for an individual CYP enzyme management skills to the test cisPlatin! 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