Pharmacology: Unit 1

Front 1

What is a drug?

Back 1

A chemical or biological agent that affects living processes.

Front 2

What is clinical pharmacology? Toxicology?

Back 2

It is the study of drug administration to and action on patients. Toxicology is the study of adverse effects of drugs.

Front 3

Define pharmacodynamics (PD).

Back 3

The study of what the drug does to the body. Includes study of drug actions, physiochemical actions, receptor interactions, pharmacological effects/side effects and therapeutic window/range. Key focus is on dose-response relationships and drug-receptor interactions.

Front 4

Define pharmacokinetics (PK).

Back 4

The study of what the body does to the drug. Includes study of drug absorption, distribution, metabolism and excretion/elimination (ADME). Key focus is plasma drug concentration as a function of time.

Front 5

Define the term "receptor"

Back 5

A receptor is the component of a cell or organism that interacts with drug and initiates the chain of events leading the drug's effects.

Front 6

Describe the key tenets of Receptor Theory.

Back 6

*Most receptors are proteins (i.e. regulatory proteins, enzymes, transport proteins, structural proteins, intracellular proteins)
*Receptors are part of the normal cell physiologic mechanisms and they interact with endogenous compounds (natural ligand)
*Receptors are specific (re: ligand)
*Receptors act as both ligand binder AND effector
*Receptors may be stimulated (agonist) or inhibited (antagonist)
*Drug-receptor interactions make small, accumulated changes in the cell that lead to changes in cell function. Tissues function is altered by the accumulated changes in cells of that tissue.
*Maximal drug response (Emax) is related to the # drug-receptor interactions and the physiologic capacity of the tissue.
*Structure of the drug determines its fit into the receptor; better fit means better receptor stimulation leading to pharmacological effect
*Major theory assumption: each cell in a tissue contains a large population of receptors that are accessible to drugs.

Front 7

True or false: the cell membrane itself can function as a receptor?

Back 7

True. Changes in electrical potential, membrane fluidity can act as receptor signals.

Front 8

Describe the 6 major types of receptors

Back 8

Membrane bound receptors (i.e. ion channels)
Enzymes--intracellular or extracellular
Structural macromolecules (i.e. microtubules)
Intracellular receptors (i.e. steroid receptors)
Cell membrane

Front 9

Discuss the significance of drug-receptor bonds during their binding interactions.

Back 9

Drug-receptor (DR) interactions are generally brief (fractions of seconds) so the bonds between them are usually reversible (including ionic, van der waals, hydrogen). This facilitates the activation of receptor/effect but also allows for termination of pharmacological effect. Conversely, irreversible or covalent binding is not common (unless used for antagonistic purposes).

Front 10

Describe the mechanism of G protein coupled receptors in transducing and amplifying the drug receptor interaction.

Back 10

Front 11

Define selectivity (of a drug).

Back 11

The property of a drug to cause a specific effect. The primary effect is desired whereas the side effects may be undesired. Note: few drugs produce a single effect.

Front 12

Define the Kd (dissociation constant).

Back 12

A measure of the drug's affinity for a given receptor. The concentration of a drug required in solution to achieve 50% occupancy of its receptors.

The dissociation constant of a drug is equivalent to the EC50 and the 50%Emax.

Front 13

Define the EC50.

Back 13

The concentration of a drug that induces the specified clinical effect in 50% of subjects.

Front 14

Define intrinsic activity.

Back 14

The intrinsic activity is the ability of the drug to stimulate the receptor once it is bound.

Front 15

Define affinity (of drug).

Back 15

Affinity of a drug refers to the strength of binding between a drug and its receptor.

Front 16

Define efficacy (of drug).

Back 16

Efficacy is the ability of the drug to activate the effector portion of the receptor once it is bound. Depends on the structure of a drug (re: intrinsic activity).

Front 17

Define potency (of drug).

Back 17

Potency of a drug relates to the amount of drug needed for effect; The amount of drug depends on the biologic system including receptor density, health of tissue, NRG status and stimulus response system.

Front 18

Define antagonist.

Back 18

Antagonist is a drug that can bind to the receptor but not produce a pharmacological response. In other words, it doesn't stimulate the receptor because it doesn't have the proper structure.

Front 19

Define agonist.

Back 19

A drug that binds to the receptor and produces a pharmacological response.

Front 20

Define Emax

Back 20

The maximal drug effect.

Front 21

Alkylating Agents

Back 21

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Hint 21

Produce strong electrophiles through carbonium or ethyleneimonium ion intermediates, which covalently bond via alkylation of nucleophilic moieties in DNA (mostly N7 position of guanine);Cell Cycle Non-Specific (CCNS)

Front 22

Ifosfamide (Ifex)

Back 22

Nitrogen mustard

Hint 22

Alkylating agent;Prodrug; Conversion by hepatic cytochrome P450 to active metabolite phosphoramide mustard

Front 23

Lomustine (Ceenu)

Back 23

Nitrosoureas

Hint 23

Alkylating agent

Front 24

Dacarbazine (DTIC)

Back 24

Triazenes

Hint 24

Alkylating agent;<br />Prodrug; activated by liver cytochromes

Front 25

Temozolomide (Temodar)

Back 25

Triazenes

Hint 25

Alkylating agent;<br />Nonenzymatic conversion to methylhydrazine at physiologic pH

Front 26

Cisplatin (Platinol)

Back 26

Platinum analogs

Hint 26

Alkylating agents that do not form carbonium ion intermediates or formally alkylate DNA;Covalently bind nucleophilic sites on DNA (e.g., guanine N7);Converted to active cytotoxic forms by reacting with water to form (+)charged, hydrated intermediates that react with DNA guanine, forming inter- and intrastand cross-links

Front 27

Carboplatin (Paraplatin)

Back 27

Platinum analogs

Hint 27

Alkylating agents that do not form carbonium ion intermediates or formally alkylate DNA;<br />Covalently bind nucleophilic sites on DNA (e.g., guanine N7);<br />Converted to active cytotoxic forms by reacting with water to form (+)charged, hydrated intermediates that react with DNA guanine, forming inter- and intrastand cross-links

Front 28

Oxaliplatin (Eloxatin)

Back 28

Platinum analogs

Hint 28

Alkylating agents that do not form carbonium ion intermediates or formally alkylate DNA; <br>Covalently bind nucleophilic sites on DNA (e.g., guanine N7);<br>Converted to active cytotoxic forms by reacting with water to form (+)charged, hydrated intermediates that react with DNA guanine, forming inter- and intrastand cross-links

Front 29

Antimetabolites

Back 29

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Hint 29

Structural analogs of folic acid or of the purine/pyramidine bases found in DNA;<br>Act in S-phase (CCS)

Front 30

Methotrexate (Trexall)

Back 30

Antimetabolite; Folate analogs

Hint 30

Inhibits dihydrofolate reductase (DHFR), which converts dietary folate to tetrahydrofolate (THF) needed for thymidine and purine synthesis;Given orally or intrathecally

Front 31

Pemetrexed (Alimta)

Back 31

Antimetabolite; Folate analogs

Hint 31

Active metabolite are polyglutamate forms that inhibit THF-dependent enzymes (e.g., DHFR, Thymidylate synthase (TS));

Front 32

5-Fluorouracil (5-FU, Carac)

Back 32

Antimetabolite; Pyramidine analogs

Hint 32

Prodrug; Converted to active metabolites:; ; ;5-FdUMP inhibits TS;; ; ;5-FdUTP incorporates into RNA &amp; interferes with RNA function;

Front 33

Capecitabine (Xeloda)

Back 33

Pyramidine analogs

Hint 33

Prodrug converted to 5'-dFdU

Front 34

Cytarabine (AraC, Depocyt)

Back 34

Pyramidine analogs

Hint 34

Ara-C converted by deoxycytidine kinase to Ara-CMP --&gt; Ara-CTP;Terminates DNA synthesis as Ara-CTP

Front 35

Gemcitabine (dFdC, Gemzar)

Back 35

Pyramidine analogs

Hint 35

Converted to active metabolites:; ; ;dFdCDP inhibits ribonucleotide reductase (lowers deoxyribonucleotide);; ; ;dFdCTP incorporates into DNA, terminating DNA synthesis

Front 36

6-Mercaptopurine (Purinethol)

Back 36

Purine analogs (antimetabolites)

Hint 36

Prodrug metabolized by hypoxanthine-guanine phosphoribosyl transferase (HGPRT) to 6-thioinosinic acid (TIMP);TIMP inhibits first step of de novo purine base synthesis and the formation of AMP and xanthinylic acid from inosinic acid, reducing purine levels;As well, TIMP is converted to thio-guanine ribonucleotides, inhibiting DNA and RNA synthesis

Front 37

DNA Intercalating Agents

Back 37

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Hint 37

Bind DNA through intercalation between specific bases, blocking DNA, RNA or both synthesis;Cause DNA strands to break and interfere with cell replication;CCNS

Front 38

Dactinomycin (Actinomycin D, Cosmegen)

Back 38

Antitumor antibiotic; DNA Intercalating agent

Hint 38

Intercalates G-C base pairs of DNA; interfering with DNA-dependant RNA polymerase (inhibits DNA transcription);;Also causes ssDNA breaks

Front 39

Daunorubicin (Cerubidine)

Back 39

Anthracyclines

Hint 39

Intercalate between DNA base pairs and donate electrons to O2 to form superoxide;Superoxide reacts with itself to form H2O2 --&gt; cleaved in the presence of Fe to form OH radical, which cleaves DNA

Front 40

Idarubicin (Idamycin)

Back 40

(antitumor antibiotic); Anthracyclines; DNA Intercalating agent

Hint 40

Intercalate between DNA base pairs and donate electrons to O2 to form superoxide;<br>Superoxide reacts with itself to form H2O2 --&gt; cleaved in the presence of Fe to form OH radical, which cleaves DNA

Front 41

Doxorubicin (Doxil)

Back 41

(antitumor antibiotic); Anthracyclines; DNA Intercalating agent

Hint 41

Intercalate between DNA base pairs and donate electrons to O2 to form superoxide (ROS);<br />Superoxide reacts with itself to form H2O2 --&gt; cleaved in the presence of Fe to form OH radical, which cleaves DNA

Front 42

Epirubicin (Ellence)

Back 42

Anthracyclines

Hint 42

Intercalate between DNA base pairs and donate electrons to O2 to form superoxide;<br>Superoxide reacts with itself to form H2O2 --&gt; cleaved in the presence of Fe to form OH radical, which cleaves DNA

Front 43

Mitoxantrone (Novantrone)

Back 43

(antitumor antibiotic); Anthracyclines; DNA Intercalating agent

Hint 43

Intercalate between DNA base pairs and donate electrons to O2 to form superoxide;<br />Superoxide reacts with itself to form H2O2 --&gt; cleaved in the presence of Fe to form OH radical, which cleaves DNA

Front 44

Bleomycin (Blenoxane)

Back 44

antitumor antibiotic; DNA Intercalating agent

Hint 44

Binds to DNA, contributes to free radical formation producing ss- and dsDNA breaks

Front 45

Microtubule Inhibitors

Back 45

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Hint 45

Inhibit mitosis and cause metaphase arrest by interfering with microtubule function (tubulin (de)polymerization);<br>CCS

Front 46

Vinblastine

Back 46

Vinca alkaloids

Hint 46

Block tubulin polymerization into microtubules

Front 47

Vincristine (Oncovin)

Back 47

Vinca alkaloids; Microtubule inhibitor (MTI)

Hint 47

Block tubulin polymerization into microtubules; CCS: M-phase (mitotic arrest)

Front 48

Paclitaxel (Abraxane);

Back 48

Taxanes; Microtubule Inhibitor (MTI)

Hint 48

Block microtubule depolymerization into tubulin; CCS: M-phase

Front 49

Docetaxel (Taxotere)

Back 49

Taxanes; Microtubule Inhibitor

Hint 49

Block microtubule depolymerization into tubulin

Front 50

Topoisomerase Inhibitors

Back 50

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Hint 50

Prevent the resealing of topo I (ssDNA) and topo II (dsDNA);CCS

Front 51

Etoposide (Etopophos)

Back 51

Epipodophyllotoxins

Hint 51

Inhibits topoisomerase II

Front 52

Teniposide (Vumon);

Back 52

Epipodophyllotoxins; Topoisomerase Inhibitor(TI)

Hint 52

Inhibits topoisomerase II; results in DNA damage

Front 53

Irinotecan (Camptosar)

Back 53

Camptothecin analogs

Hint 53

Inhibits topoisomerase I

Front 54

Topotecan (Hycamtin)

Back 54

Camptothecin analogs; Topoisomerase Inhibitor

Hint 54

Inhibits topoisomerase I; results in DNA damage

Front 55

Hormone Therapy

Back 55

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Hint 55

Treatment of hormone-dependent neoplasms

Front 56

Prednisone (Meticorten)

Back 56

Glucocorticoids

Hint 56

Inhibit mitosis in lymphocytes

Front 57

Dexamethasone (Decadron)

Back 57

Glucocorticoids

Hint 57

Inhibit mitosis in lymphocytes

Front 58

Tamoxifen (Soltamox)

Back 58

Selective estrogen-receptor modulators (SERMs)

Hint 58

Competes with estradiol for binding to estradiol receptor

Front 59

Fulvestrant (Faslodex)

Back 59

Selective estrogen-receptor downregulators (SERDs)

Hint 59

Binds with much higher affinity (&gt;100-fold) to estrogen receptor than tamoxifen, inhibiting dimerization, increasing degradation, and reducing overall ER levels

Front 60

Aminoglutethamide (Cytadren)

Back 60

Aromatase inhibitors

Hint 60

Inhibit function of aromatase (converts androstenedione and testosterone to estrone and estradiol)

Front 61

Anastrozole (Arimidex)

Back 61

Aromatase inhibitors

Hint 61

Inhibit function of aromatase (converts androstenedione and testosterone to estrone and estradiol)

Front 62

Letrozole (Femara)

Back 62

Aromatase inhibitors

Hint 62

Inhibit function of aromatase (converts androstenedione and testosterone to estrone and estradiol)

Front 63

Exemestane (Aromasin)

Back 63

Aromatase inhibitors

Hint 63

Steroidal inhibitor of aromatase

Front 64

Leuprolide (Lupron)

Back 64

GnRH analogs

Hint 64

Binds GnRH receptor; inhibits release of FSH &amp; LH

Front 65

Goserelin (Zoladex)

Back 65

GnRH analogs

Hint 65

Binds GnRH receptor; inhibits release of FSH &amp; LH

Front 66

Flutamide (Eulexin)

Back 66

Nonsteroidal androgen-receptor blockers

Hint 66

Competes with androgen for AR binding

Front 67

Bicalutamide (Casodex)

Back 67

Nonsteroidal androgen-receptor blockers

Hint 67

Complete with receptor for hormone

Front 68

Imatinib (Gleevac)

Back 68

Tyrosine Kinase inhibitor

Hint 68

Inhibits Abl kinase by binding where ATP should go;Also inhibits PDGFR and c-kit;Metabolized by cytochrome P450

Front 69

Gefitinib (Iressa)

Back 69

Tyrosine Kinase inhibitor

Hint 69

Inhibit epidermal growth factor receptor (EGFR) tyrosine kinase

Front 70

Erlotinib (Tarceva)

Back 70

Tyrosine Kinase inhibitor

Hint 70

Inhibit epidermal growth factor receptor (EGFR) tyrosine kinase

Front 71

Nilotinib (Tasigna)

Back 71

Tyrosine Kinase inhibitor

Hint 71

Inhibits Abl kinase;

Front 72

Dasatinib (Sprycel)

Back 72

Tyrosine Kinase inhibitor

Hint 72

Inhibits Abl &amp; Src kinases

Front 73

Rituximab (Rituxan)

Back 73

Monoclonal antibody

Hint 73

CD20 B-cell antibody that can directly activate apoptosis, activate complement, or activate cell-mediated cytotoxicity (e.g., T cells, NK cells)

Front 74

Trastuzumab (Herceptin)

Back 74

Monoclonal antibody

Hint 74

Unknown HER2/neu (ErbB2) receptor antibody mechanism (enhanced receptor endocytosis or blocking homo- or heterodimerization)

Front 75

Cetuximab (Erbitux)

Back 75

Monoclonal antibody

Hint 75

EGFR1 (ErbB1)

Front 76

Hydroxyurea (Hydrea)

Back 76

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Hint 76

Inhibits ribonucleoside diphosphate reductase

Front 77

Retinoids

Back 77

---

Hint 77

ATRA induces terminal differentiation in malignant immature promyelocytes, which subsequently apoptose

Front 78

Arsenic Trioxide (Trisenox)

Back 78

---

Hint 78

---

Front 79

Thalidomide (Thalomid)

Back 79

---

Hint 79

---

Front 80

Interferons

Back 80

---

Hint 80

---

Front 81

Asparaginase (Elspar)

Back 81

---

Hint 81

Deaminates asparagine --&gt; inhibition of protein synthesis

Front 82

ABVD

Back 82

Combination therapy

Hint 82

Doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine

Front 83

CHOP

Back 83

Combination therapy

Hint 83

Cyclophosphamide, hydroxydoxorubicin, vincristine (oncovine), prednisone

Front 84

MOPP

Back 84

Combination therapy

Hint 84

Mechlorethamine, vincristine (oncovine), procarbazine, prednisone

Front 85

CMF

Back 85

Combination therapy

Hint 85

Cyclophosphamide, methotrexate, 5-fluorouracil

Front 86

FEC

Back 86

Combination therapy

Hint 86

5-fluorouracil, epirubicin, cyclophosphamide

Front 87

Ipilimumab (Yervoy)

Back 87

Human monoclonal antibody

Hint 87

Cytotoxic T-Lymphocyte Antigen 4 inhibitor; stimulates immune system

Front 88

Vemurafenib (Zelboraf)

Back 88

Serine/threonine kinase inhibitor

Hint 88

Inhibits oncogenic BRAF kinase

Front 89

Dabrafenib (Tafinlar)

Back 89

Serine/threonine kinase inhibitor

Hint 89

Inhibits oncogenic BRAF kinase

Front 90

Trametinib (Mekinist)

Back 90

---

Hint 90

Inhibits MEK

Front 91

List the 6 mechanisms of acquired drug resistance.

Back 91

1. Decreased cellular uptake2. Abnormal transport of the drug (i.e. efflux by P-glycoprotein)3. Increased cellular activation (binding/metabolism)4. Altered target protein5. Reduced affinity for the drug6. Enhanced repair of DNA damage

Front 92

List the 7 most common side effects of chemotherapy.

Back 92

1. Neutropenia2. Thrombocytopenia3. Anemia4. Nausea &amp; Vomiting5. Stomatitis6. Alopecia (hair loss)7. Secondary leukemia (due to long term CTX tx)

Front 93

List the 4 subclasses of alkylating agents.

Back 93

1. Nitrogen mustards2. Nitrosoureas3. Triazenes4. Platinum analogs

Front 94

List the 3 Nitrogen mustards

Back 94

1.Mechlorethamine2. Cyclophosphamide3. Ifosfamide

Hint 94

Alkylating

Front 95

List the 2 Nitrosoureas drugs

Back 95

1. Carmustine2. Lomustine

Hint 95

Alkylating

Front 96

List the 2 Triazenes

Back 96

1.Dacarbazine2. Temozolomide

Hint 96

Alkylating

Front 97

List the 3 Platinum analogs

Back 97

1. Cisplatin2. Carboplatin3. Oxaliplatin

Hint 97

Alkylating

Front 98

For;Mechlorethamine (Mustargen):;1. Pharmacologic class/subclass

Back 98

Alkylating agent; Nitrogen mustard

Front 99

For Mechlorethamine (Mustargen):-Indicate its MOA

Back 99

--

Hint 99

Spontaneously converted to active metabolites in body fluids or enzymatically converted to metabolites in liver.;

Front 100

Cyclophosphamide (Cytoxan)--Indicate pharmacological class/subclass

Back 100

Alkylating agent; Nitrogen mustard

Front 101

Cyclophosphamide (Cytoxan)--Indicate MOA

Back 101

Prodrug; Converted to active metabolite phosphoramide mustard by hepatic cytochrome P450 enzymes. Alkylates DNA;

Front 102

Ifosfamide (Ifex):--Indicate pharmacological class/subclass

Back 102

Alkylating agent; Nitrogen mustard

Front 103

Ifosfamide (Ifex):--Indicate MOA

Back 103

Prodrug; MOA same as cyclophosphamide

Front 104

Carmustine (Gliadel):--Indicate pharmacological class/subclass

Back 104

Alkylating agent; Nitrosoureas

Front 105

Carmustine (Gliadel):--Indicate MOA

Back 105

Alkylating agent; highly lipid-soluble; can cross BBB