Pharmacology Flashcards
(78 cards)
1
Q
alkalating agents
A
- produce strong electrophiles→ promote cross linking of DNA strands making them prone to breaking
- Cell Cycle Non-Specific (CCNS)
- side effects: carcinogenic (leukemia),bone marrow, mucosal toxicity,N/V, toxic effects on reproductive systems
- resistance may occur due to decreased permeability or uptake; increased rates of catabolism; enhanced DNA repair; increased glutathione production (inactivates via conjugation)
- classes: nitrogen mustards, nitrosoureas, triazenes, platinum analogs
2
Q
Mechlorethamine (Mustargen)
A
- alkalating agent; nitrogen mustard
- mechanism: spontaneous conversion to active metabolites in body fluids or enzymatically converted in liver
- historically used for hodgkin’s disease, topically for treatment of cutaneous T-cell lymphoma
- don’t use much anymore due to sterility
3
Q
Cyclophosphamide (Cytoxan)
Ifosfaminde (Ifex)
A
- alkalating agents; nitrogen mustard
- produgs converted by hepatic cyt P450→ phosphoramide mustard
- important side effects: hemorrhagic cystitis due to toxic drug metabolite acrolein (hydration and administration of MESNA minimizes problem)
- cyclophosphamide: MC used alkylating agent (broad spectrum): ALL, CLL, non-hodgkin’s lymphoma, breast, lung, ovarian cancer
- ifosfaminde: sarcoma and testicular cancer
4
Q
Carmustine (Gliadel)
Lomustine (Ceenu)
A
- alkylating agent; nitrosureas
- brain tumors (lipophilic→ cross blood-brain barrier)
- important side effects: renal toxicity, pulmonary fibrosis
- other side effects: profound myelosuppression, severe N/V
5
Q
Dacarbazine (DTIC)
Temozolomide (Temodar)
A
- alkylating agent; triazenes
- side effects: nausea/vomiting, myelosuppression, flu-like symptoms (fever, fatigue)
- dacarbazine: prodrug activated by liver cytochromes; part of ABVD for Hodgkin’s disease
- temozolomide: nonenzymatic conversion to methylhydrazine at physiologic pH; treats malignant gliomas
6
Q
Cisplatin (Platinol)
A
- alkylating agent; platinum analog (MC used)
- doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA
- treats: testicular, ovarian, cervical, and bladder cancers
- important side effects: nephrotoxicity, ototoxicity, peripheral motor and sensory neuropathy at high doses, severe N/V, mild to moderate myelosuppression
7
Q
Carboplatin (Paraplatin)
A
- alkylating agent; platinum analog
- mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA
- treats ovarian cancer
- side effects: myelosuppression (thrombocytopenia)
8
Q
Oxaliplatin (Eloxatin)
A
- alkylating agent; class: platinum analog
- mechanism: doesn’t form carbonium intermediate or formally alkylate DNA; covalently bind nucleophilic sites on DNA
- treats: gastric and colorectal cancer
- important: peripheral sensory neuropathy (cold-induced), neutropenia
9
Q
Methotrexate (Trexall)
A
- antimetabolite; folate analog (MC used)
- inhibits DHFR (converts dietary folate to THF; needed for thymidine and purine synthesis); given orally or intrathecally (meningeal leukemia and metastases)
- treats: childhood ALL and choriocarcinoma; combination therapy for Burkitt’s lymphoma and carcinomas of breast, ovary, head and neck, and bladder; high-dose for osteosarcoma
- side effects: renal toxicity (crystallization in urine at high doses), hepatotoxicity (long-term, fibrosis/cirrhosis), reproductive (defective oogenesis or spermatogenesis, abortion)
- leucovorin: prevents toxic effects of MTX (tumor cells cannot uptake folinic acid)
10
Q
Pemetrexed (Alimta)
A
- antimetabolite; folate analog
- inhibits THF-dependent enzymes (e.g., DHFR, TS); metabolized to polyglutamate forms that inhibit THF-dependent enzymes (e.g., DHFR, thymidylate synthase (TS)
- treats: mesothelioma, non-small cell lung cancer
11
Q
5-Fluorouracil (5-FU, Carac)
A
- antimetabolite; pyramidine analog
- 5-FU→active metabolites: 5-FdUMP inhibits TS; inhibits DNA synthesis
- combination therapy for breast, colorectal, gastric, head and neck, cervical and pancreatic cancer; topically for basal cell carcinoma
- side effects: hand-foot syndrome (erythema, sensitivity of palms and soles), cardiac toxicity (acute chest pains)
- other side effects: anorexia and nausea; mucosal ulcerations, stomatitis, diarrhea; thrombocytopenia and anemia
- leucovorin can potentiate effects of 5-FU
- must be given IV (GI toxicity and rapid degradation + metabolism in gut and liver)
12
Q
Cytarabine (AraC, Depocyt)
A
- antimetabolite; pyramidine analog
- Ara-C converted by deoxycytidine kinase to Ara-CMP→Ara-CTP; terminates DNA synthesis
- treats: AML (most effective treatment), ALL and blast phase CML
- side effects: severe myelosuppression, GI toxicity
13
Q
Gemcitabine (dFdC, Gemzar)
A
- antimetabolite; pyramidine analog
- converted to active metabolites: dFdCDP inhibits ribonucleotide reductase (lowers deoxyribonucleotide); dFdCTP incorporates into DNA
- pancreatic cancer; solid tumors (more effective than cytarabine); NSCLC, ovarian, bladder, head and neck cancer
14
Q
antimetabolites
A
- structural analogs of folic acid or of the purine/pyramidine bases found in DNA; act in S-phase (cell cycle specific)
- classes: folate, pyramidine, and purine analogs
15
Q
6-Mercaptopurine (Purinethol)
A
- antimetabolite; class: purine analog
- prodrug metabolized by HGPRT→ 6-thioinosinic acid (TIMP) which inhibits de novo purine base synthesis, formation of AMP and xanthinylic acid from inosinic acid, (reducing purine levels); TIMP is converted to thio-guanine ribonucleotides inhibiting DNA and RNA synthesis
- maintain remission in acute ALL
- side effects: hepatotoxicity in prolonged use, BMS
- interacts with allopurinol (inhibits xanthine oxidase), decrease 6-MP dose to avoid toxicities
16
Q
Dactinomycin (Actinomycin D, Cosmegen)
A
- DNA intercalating agent
- intercalates G-C base interfering with DNA-dependant RNA pol
- treats: pediatric tumors (Wilms’ tumor, rhabdomyosarcoma Ewing’s sarcoma); choriocarcinoma in women
- side effects: hematopoietic suppression with pancytopenia
17
Q
anthracycline antibiotics
A
- DNA intercalating agents that intercalate between DNA base pairs and donate electrons to O2 → superoxide→ H2O2→ cleaved with Fe→ OH radical→ cleaves DNA
- side effects: irreversible dose-dependent cardiotoxicity (dexrazoxane is cardio-protective)
- daunorubicin/idarubicin: AML
- doxorubicin: broad spectrum (sarcomas, breast, lung, malignant lymphomas)
18
Q
Bleomycin (Blenoxane)
A
- DNA intercalating
- acts in G2 phase; binds to DNA, producing ss- and dsDNA breaks (mechanism similar to anthracyclines)
- treats: combination therapy for testicular tumors or Hodgkin’s disease
- side effects: pulmonary toxicity (pulmonary fibrosis);
- minimally myelo- and immunosuppressive (often used in combo therapy)
- dexrazoxane is cardio-protective
19
Q
Vinca Alkaloids
A
- MT inhibitors that blocks tubulin polymerization into MTs
- resistance
- vinblastine: treats metastatic testicular tumors (+ bleomycin, cisplatin); component of ABVD for Hodgkin’s disease; BMS
- vincristine: treats childhood AL (+ glucocorticoids); dose-limiting neurotoxicity (peripheral neuropathy); low BMS
20
Q
taxanes
A
- MT inhibitors that block MT depolymerization into tubulin
- treats: metastatic breast, ovarian, lung, and head and neck cancers
- side effects: peripheral neuropathy, neutropenia, hypersensitivity reactions
- paclitaxel: metastatic breast, ovarian, lung, head, neck
- docetaxel: hormone refractory prostate cancer
21
Q
epipodophyllotoxinss
A
- inhibits topoisomerase II (breaks and reseals dsDNA)
- side effects: dose-limiting myelosuppression (neutropenia), oral mucositis
- etoposide: broad spectrum (testicular carcinoma, lung cancer, non-Hodgin’s lymphoma)
- teniposide: ALL
22
Q
camptothecin analogs
A
- inhibits topoisomerase I (breaks and reseals ssDNA)
- side effects: severe neutropenia, severe diarrhea
- irinotecan: advanced colorectal cancer
- topotecan: ovarian and SCLC
23
Q
hormone therapy
A
- used in the treatment of hormone-dependent neoplasms
- classes: glucocorticoids, SERMs, SERDs, aromatase inhibitors, GnRH blockers, nonsteroidal androgen receptor blockers
24
Q
glucocorticoids
A
- hormone therapy; inhibit mitosis in lymphocytes
- prednisone: ALL (+ vincristine)
- dexamethasone: reduces edema in brain and spinal cord tumors with radiation therapy
25
Tamoxifen (Soltamox)
* hormone therapy; SERM (competes with estradiol for binding to ER)
* treats: ER+ breast cancer and prevention of breast cancer in high-risk patients
* side effects: hot flushes, hair loss; increased risk of endometrial cancer (weak agonist of ER in endometrium); increased risk of thromboembolic events
26
Fulvestrant (Faslodex)
* hormone therapy; class: SERD
* binds with much higher affinity (\>100-fold) to ER vs. tamoxifen, inhibiting dimerization, increasing degradation, and reducing overall ER levels
* treats: posmenopausal women with ER+ metastatic breast cancer
27
aromatase inhibitors
* hormone therapy; class: aromatase inhibitor
* ER + breast cancer in **postmenopausal women**
* **aminoglutethamide:** relatively weak, significant side effects (no longer used)
* **anastrazole/letrozole:** nonsteroidal AI
* **exemestane:** steroidal AI
28
hormone therapy for prostate cancer
* androgen ablation therapy of GnRH analog + AR blocker
* **leuprolide:** GnRH analog (binds GnRH receptor inhibiting FSH and LH but does not inhibit adrenal androgen synthesis)
* **flutamide/bicalutamide:** nonsteroidal AR blockers competes with AR for binding
29
Ima**tinib** (Gleevac)
* tyrosine kinase inhibitor; prevents phosphorylation of Abl-kinase substrate; **metabolized by cyt P450**
* first line therapy for CML
* side effects: N/V, BMS
30
Gefi**tinib** (Iressa)
Erlo**tinib** (Tarceva)
Afa**tinib** (Gilotrif)
* inhibits EGFR tyrosine kinase
* treats: non-small cell lung cancer
* side effects: poddibility of bleeding, interstitial lung disease
* metabolized by CYP3A4 (ketoconazole interacts); PPIs reduce absorption
* **afatinib:** pulmonary toxicity
31
Rituxi**mab** (Rituxan)
* chimeric monoclonal antibody; CD20 B-cell antibody that directly activates apoptosis, complement, or cell-mediated cytotoxicity (e.g., T cells, NK cells)
* treats: non-Hodgkin's lymphomas
* important side effects: **infusion reactions, tumor lysis syndrome (TLS), progressive multifocal leukoencephalopathy (PML)**
* patients need careful monitoring
32
Trastuzu**mab** (Herceptin)
* monoclonal antibody; unknown HER2/neu (ErbB2) receptor antibody mechanism (enhanced receptor endocytosis or blocking homo- or heterodimerization)
* treats: **HER2/neu-overexpressing metastatic breast cancer**
* side effects: **hypersentivity reaction**, ventricular dysfunction, cardiomyopathy, CHF, infusion reactions→ pulmonary toxicity
* usually combined with taxanes; enhances doxorubicin cardiotoxicity
33
Cetuxi**mab** (Erbitux)
* monoclonal antibody that binds to EGFR1 (ErbB1) with similar affinity as EGF or TGF-a
* treats: EGFR+ metastatic colorectal cancer
34
Ipilimu**mab** (Yervoy)
* human monoclonal antibody
* mechanism: Cytotoxic T-Lymphocyte Antigen 4 inhibitor; stimulates immune system
* treats: melanoma
35
Hydroxyurea (Hydrea)
* inhibits ribonucleoside diphosphate reductase (catalyzes ribonucleotides to deoxyribonucleotides)
* treats: myeloproliferative neoplasms, sickle cell disease (increases Hb-F)
36
Retinoids
* all trans retanoic acid (ATRA) induces terminal differentiation in malignant immature promyelocytes, which subsequently apoptose
* treats: APL
37
Arsenic Trioxide (Trisenox)
heavy metal toxin that treats relapsed APL
38
Thalidomide (Thalomid)
treats multiple myeloma and myelodysplastic syndromes
39
Interferons
IFN-a treats hairy-cell leukemia, CML, and AIDS-related Kaposi's sarcoma
40
ABVD
combination therapy of doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine
41
CHOP
combination therapy of cyclophosphamide, hydroxydoxorubicin, vincristine (oncovine), prednisone
42
MOPP
combination therapy of mechlorethamine, vincristine (oncovine), procarbazine, prednisone
43
CMF
combination therapy of cyclophosphamide, methotrexate, 5-fluorouracil
44
FEC
combination therapy of 5-fluorouracil, epirubicin, cyclophosphamide
45
Diethylstilbestrol (DES)
* non-steroidal synthetic estrogen
* increased risk of clear cell adenocarcinoma of vagina & cervix
46
Tamoxifen citrate (Nolvadex)
* non-steroidal anti-estrogen; selective estrogen receptor modifier
* ER competitive antagonist (use in high doses because estrogen has much higher binding affinity)
* **anti-estrogenic effect on mammary epithelium** (treats ER+ breast cancer)
* **pro-estrogenic effect on uterine epithelium** (increase risk of endometrial cancer), bone, and endometrium
47
Clomiphene citrate (Clomid)
* non-steroidal anti-estrogen
* **ER competative antagonist in hypothalamus (no estradiol negative feedback)→ increased secretion of FSH/LH→ ovulation**
* trans-isomer is a potent estrogen antagonist (dominant isoform), cis-isomer is a weak estrogen agonist
48
Levonorgestrel (Plan B)
* synthetic progestogen
* mechanism of action is unknown
* prevents implantation (must be taken within 72 hours of coitus)
* side effects are likely the same as OCPs
49
Mifepristone (RU-486, Korlym)
* anti-progestin; glucocorticoid receptor antagonist
* **competitively binds to PR (leading to detachment of fetus)**; glucocorticoid receptor antagonist
* "the abortion pill", also sed for cushing's syndrome
* must take early (by day 49)
* PO but must be given in medical facility (surgery if abortion incomplete)
50
erectile dysfunction drugs
* PDE5 inhibitors (inhibits PDE5 breakdown of cGMP→ decreased Ca→ smooth muscle relaxation→ erection)
* **silden*_afil_* citrate, verden*_afil*_ HCl, tada_*lafil_***
* improves response to sexual stimulation (does not trigger erection)
* important side effects: headache, dizziness, change in vision **(NAION due to sudden decreased blood flow to optic nerve)**
* PO (once/day max)
* contraindicated if on nitrates or α-blockers (unsafe drop in BP)
51
Indomethacin (Indocin)
Naproxen (Aleve)
* non-selective NSAID used as symptomatic treatment of RA and acute gouty arthritis
* eliminate pains and reduces inflammation but **does not slow RA disease progression**
* side effects: gastric and duodenal ulcers
52
COX-2 inhibitors
selective NSAID that is superceding conventional NSAIDs for symptomatic treatment of RA due to reduced side effects (50% fewer gastric and duodenal ulcers)
53
glucocorticoids (corticosteroids)
* DMARD for RA and acute gouty arthritis
* inhibits phospholipase A2 (inhibiting release of arachidonic acid and formation of prostaglandins) and inhibits cytokine production (prevents induction of COX-2)
* given orally or intraarticular injection; not for long term use
* started initially (fast acting) before other drugs become effective
54
Methotrexate (Trexall) for RA
* DMARD (immunosuppressive)
* **gold standard for RA;** low dose used (vs. cancer treatment; hepatotoxicity is rare)
* inhibition of AICAR transformylase and thymidylate synthetase which effects PMN chemotaxis; causes adenosine accumulation (inhibits inflammation)
* takes several weeks to start working
55
Colchicine (Colcrys)
* treats acute gouty arthritis
* prevents tubulin polymerization→ inibition of leukocyte migration, phagocytosis, and release of cytokines
* **small therapeutic window;** N/V/D**,** long-term use causes peripheral neuropathy & neutropenia
* works in 12-24 hours
56
Probenecid (Benemid)
* treats chronic tophaceous gout
* uricosuric agent (competes with urate at anionic transport site of renal tubule to inhibit urate reabsorption→ **increased rate of urate excretion, decreased plasma levels**)
* decreased secretion of some weak acids (e.g., penicillin)
* urate crystal mobilization can lead to acute gouty arthritis; GI irritation
57
Allopurinol (Zyloprim)
* treats chronic tophaceous gout
* **r****educes uric acid synthesis** by inhibiting xanthine oxidase (competitive inhibition)→ alloxanthine (non-competitive inhibitor of xanthine oxidase)
* mobilization of urate crystals can leads to acute gouty arthritis
58
Pegloticase (Krystexxa)
* recombinant, stabilized uricase
* mechanism: converts uric acid to allantoin
* treats: chronic tophaceous gout
59
Ado-trastuzumab emtansine (Kadcyla)
* Ab-drug conjugate: trastuzumab + DMI (MT inhibitor)
* mechanism: conjugate undergoes receptor-dependent internalization & drug released inside cell
* treats: HER+ metastatic breast cancer patients with prior treatment history of trastuzumab and/or taxane
* side effects: ventricular dysfunction, hepatotoxicity
60
Panitumumab (Vectibix)
* fully human monoclonal antibody EGFR (ErbB1)
* treats: EGFR-expressing metastatic colorectal cancers resistant to fluoropyrimidine, oxaliplatin, and irinotecan regimens
* side effects: skin toxicities
61
Rheumatoid Arthritis
* chronic, inflammatory autoimmune disease
* MC systemic inflammatory disease
* activated macrophages→ **TNF-a and IL-1→** activate synovial fibroblasts→ recruitment of other inflammatory cells→ release of metalloproteinases→ bone and cartilage degradation
* **nonbiologic DMARD** in **early RA with low disease** to prevent progression
* patients with **high disease and poor prognostic features** may be started on **anti-TNF therapy w/or w/out methotrexate**
62
DMARDs
* disease modifying anti-rheumatic drugs
* **quinolones:** historically used, less efficacious than other DMARDs
* **glucocorticoids (corticosteroids)**
* **sulfasalazine:** used in europe
* **methotrexate:** gold standard immunosuppressive DMARD
* **leflunomide:** newer immunosuppressive DMARD prescribed if patient is becoming insensitive to methotrexate
63
biological response modifiers for treatment of RA
* highly specific therapeutics to target cytokines and surface molecules
* **TNF as target:** Etanercept, Infliximab, **Adalimumab,** Golimumab, Certolizumab
* IL-1 as target: Anakinra
* IL-6 as target: Tocilizumab
* T-cell as target: Abatacept
* B-cell as target: Rituximab
* **JAK as target: Tofacitinib**
64
gout
acute, often recurrent arthritis mediated by crystallization of uric acid within joints, typically associated with hyperuricemia
65
therapeutic strategies for gout
* **acute gouty arthritis:** deposits of uric acid in joint, pain subsides after a few days if untreatment; affects big toe (podagra)
* NSAIDs and lifestyle changes/drug alteration
* colchicine
* corticosteroids (if NSAIDs, corticosteroids contraindicated)
* **chronic tophaceous gout:** deposits of urate (tophi) in tissues that persist and cause destruction
* lifestyle changes/drug alteration
* **uricosuric agent:** probenecid
* **reduce uric acid synthesis:** allopurinol, febuxostat
66
synthetic estrogens
* absorbed through skin, mucous membranes, GI tract and widely distributed
* used for contraception, primary hypogonadism, postmenopausal hormone therapy, prevention of osteoporosis
* **contraindicated in breast or endometrial cancers, endometriosis, undiagnosed vaginal bleeding,** prenancy, thromboembolic disease, HTN, hepatic disease, FH of breast or uterine cancer
* **steroidal:**
* ****estradiol esters: estradiol valerate/ cypionate
* conjugated estrogens: estrone/ equilin sulfate
* alkyl estrogens: ethinyl estradiol, mestranol
* **nonsteroidal:** less commonly used (e.g., DES)
67
progestins
* used for contraception, hormone replacement therapy (counter endometrial stimulator effects of estrogen)
* suppresses LH secretion preventing ovulation, thickens cervical mucus, develops endometrial atrophy
* contraindicated in thromboembolic disorders, liver disease/dysfunction, undiagnosed vaginal bleeding, pregnancy
* **natural:** minimal side effects
* micronized and transvaginal progesterone
* **synthetic:** strong androgenic activity
* medroxyprogesterone, norethindrone, norgestrel, megestrol
68
contraceptive types
* **estrogen-progestin combination:** most effective, estrogenic and progestin effects
* mono/bi/triphasic orthonovum (fixed estrogen, progestin increases in phases)
* **progestin-only:** less effective than combination preparations, useful when estrogens are contraindicated; irregular menstrual cycle
* minipill
* **post-coital:** take within 72 hours of coitus
* levonorgestrel (plan B)
69
clonal evolution vs. cancer stem cell theory
* **clonal evolution:** all tumors arise from a single transformed clone; new subclones differ from original clone (e.g., become more aggressive, metastatic, and acquire ability to evade host defenses)
* **cancer stem cells:** sub-population of cells with ability to self-renew and differentiate; have cancer initiating potential
* important because conventional therapy targets differentiated cells NOT stem cells so there remains the ability for the tumor to regrow
70
stages of cell cycle
* G1: cell growth before DNA duplication; Cdk4-cyclinD
* S: DNA synthesis; Cdk2-cyclinA
* G2: preparation for division; Cdk1-cyclinB
* M: mitosis; Cdk1-cyclinB
* G0: postmitotic cells exit cycle and enter into non-proliferative phase
71
resistance to anticancer drugs
* **intrinsic:** dysregulation of one or both apoptotic pathways; hyperactivity of survival or antiapoptotit genes/proteins; host factors
* **aquired:** dysregulation of one/bone apoptotic pathways during chemotherapy; aquired ability to rapidly and efficient repair DNA damage; gene amplification; **increased expression of energy-dependent efflux pumps (p-glycoprotein); decrease drug uptake because transporters stop working;** dysregulation in drug metabolism
72
log kill hypothesis
chemotherapeutic agents follow 1st order kinetics (a given dose of drug kills a constant fraction of cancer cells rather than a constant number of cells)
* give chemotherapy based on body weight
73
verapamil
Ca2+ channel blocker that inhibits p-glycoprotein (efflux transporter in gut that pumps drugs back into the lumen, decreasing their absorption)
74
stages of drug development
* preclinical study
* investigational new drug application
* phase I: determine safe and appropriate dose
* phase II: determine effectiveness and side effects
* phase III: effectiveness of new drug vs. standard of care
* new drug application
* FDA approval
* phase IV: long-term safety and effectiveness
75
CML and treatment
* clonal hematopoietic stem cell disorder
* presence of Ph in more thant 90%; t(9:22) fuses BCR with ABL→constituitely active tyrosine kinase
* treat with tyrosine kinase inhibitors:
* **imatinib (gleevac): prevents phosphorylation of substrate**
* nilotinib/dasatinib/bosutinib: imatinib resistant CML
* **ponatinib:** prior CML therapy resistance and patients with T315I mutation
76
melanoma and treatment
* BRAF genes in 45-50 of cutaneous melanomas, more common in those associated with sun-induced damage
* use the following drugs for unresectable stage III and IV or BRAF+ metastatic melanomas; do not give to melanomas with wt BRAF
* **vemurafenib:** inhibits BRAF kinase; long QT and SCC
* **dabrafenib:** inhibits BRAF kinase; serious febrile drug reactions, higher risk of developing cutaneous SCC
* **trametinib:** inhibits MEK (downstream of BRAF); serious skin toxicities
77
CYP enzymes
* major enzymes inolved in drug metabolism; perform phase 1 redox reactions
* have central heme that moves electrons
* interact with \>250 drugs
* known inducers: smoking, st. john's wart
* known inhibitors: grapefruit juice, macrolides
78
CYP polymorphism
* based on number of functional alleles
* **2C9 (warfarin):** 1-3% are poor metabolizers
* **2C19 (clopidogrel, diazepam):** 20% AAs and asians are poor metabolizers
* has the most common loss of function alleles in the US
* **2D6 (codeine, psych):** 5-10% whites are poor metabolizers; 30% ethiopians are ultra metabolizers
