Pharmacology Test 3-Part2

Front 1

what is dysplasia?

Back 1

- abnormal changes in cell size, shape and organization

Front 2

Why is p53 considered a proto-oncogene?

Back 2

it is a benign cellular gene that upon mutation or disruption of normal function results in a protein that can contribute to development of a transformed cellular phenotype (unregulated cell growth or cancer)

Front 3

What's the difference between necrosis and apoptosis?

Back 3

Necrotic cell death is a pathological form of cell death resulting from acute cellular injury which is typified by rapid cell swelling and lysis

Apoptosis is controlled autodigestion by activation of endogenous proteases resulting in cell shrinkage, membrane blebbing and nuclear condensation. This results in DNA fragmentation and DNA “ladder” formation

Front 4

Which type of hyperplasia?
-Involved in regenerative capacity of liver

Back 4

compensatory hyperplasia

Front 5

Which type of hyperplasia?
increase in uterus and mammary tissue in pregnancy

Back 5

hormonal hyperplasia

Front 6

Which type of hyperplasia?

-Edndometriosis is common

Back 6

Pathologic hyperplasia

(Endometriosis: the presence and growth of functioning endometrial tissue in places other than the uterus that often results in severe pain and infertility )

Front 7

What is the name of this transcription factor?
-Regulates cell cycle, functioning as a tumor suppressor. "guardians of the chromosome."

Back 7

p53

Front 8

__(1) causes cells with DNA damage to undergo apoptosis, preventing proliferation of mutated cells.

Back 8

(1) p53

Front 9

Lethal cell injury or accidental cell death in the living organism. Pathological form of cell death resulting from acute cellular injury which is typified by rapid cell swelling and lysis

Back 9

Necrosis

Front 10

Programmed cell death. Control autodigestion by activation of endogenous proteases resulting in cell shrinkage, membrane blebbing and nuclear condensation. This results in DNA fragmentation and DNA "ladder" formation

Back 10

Apoptosis

Front 11

(T/F) apoptosis is energy dependant

Back 11

True. Apoptosis is energy dependent, metabolically active

Front 12

is necrosis regulated by intracellular signals

Back 12

No, necrosis is NOT regulated by intracellular signals

Front 13

What primarily results from a breakdown of fluid homeostasis?

Back 13

Necrosis

Front 14

Which type of Necrosis?

-arises from protein denaturation aggregation, commonly associated with hypoxia due to ischemic (reduced blood perfusion) injury

Back 14

Coagulative Necrosis

Front 15

Which type of Necrosis?

-Often associated with tissues with little connective tissue, brain, release of hydrolytic enzymes extensively degrades lipids and proteins leading to loss of structure, also results from severe bacterial infection of any tissue

Back 15

Liquefactive necrosis

Front 16

Which type of Necrosis?

-Associated with pulmonary infection, clumped cell debris due to lack of complete digestion

Back 16

Caseous necrosis

Front 17

Which type of necrosis?

-Limited to breast, pancreas and abdominal fat due to excess lipolysis and subsequent saponification and formation of lipid micelles

Back 17

Fat Necrosis

Front 18

What makes a cell decide to commit suicide?

Back 18

-withdrawal of positive signals needed for continued survival.
loss of growth factor support or cell-cell interactions.
-increased levels of oxidants within the cell.
-damage to DNA
-accumulation of proteins that failed to fold
-molecules that bind to specific receptors on the cell surface and signal the cell to begin the apoptosis program.

Front 19

Describe the two main apoptotic signaling pathways. include the following terms: Initiation-execution; caspaces; BID.

Back 19

Apoptosis can be initiated by two alternative
pathways: (1) Either through death receptors on the cell surface (extrinsic pathway) or (2) through mitochondria (intrinsic pathway). In both pathways, induction of apoptosis leads to activation of an initiator caspase: caspase-8 and possibly caspase-10 for the extrinsic pathway; and caspase-9, which is activated at the apoptosome, for the intrinsic pathway.

The initiator caspases then activate executioner caspases. Active executioner caspases cleave the death substrates, which eventually results in apoptosis. There is crosstalk between these two pathways. For example, cleavage of the BCL2-family member BID by caspase-8 activates the mitochondrial pathway after apoptosis induction through death receptors, and can be used to amplify the apoptotic signal.

Front 20

As a biochemical marker of Apoptosis, what happens during the INDUCTION OF THE MITOCHONDRIAL PERMEABILITY TRANSITION?

Back 20

a) loss of mitochondrial inner membrane potential.
b) release of cytochrome c

Front 21

As a biochemical marker of Apoptosis, what happens during the ACTIVATION OF PROTEASE CASCADE?

Back 21

a) members of interleukin-1ß converting enzyme(ICE) family of proteases, these proteases called CASPACES, family of cysteine proteases which cleave after aspartate residues, i.e. DEVD, YVAD)
b) granzyme B
c) calpain

Front 22

What kind of drug would would cause the following effects in cellular processes:
1. This kind of drug disrupts DNA structure.
2. Disrupts cell division.
3. Affect nucleotide synthesis.
4. disrupt DNA uncoiling

Back 22

1. DNA Alkylating Agents
2. Microtubule Stabilizers
3. Antimetabolites
4. Topoisomerase Inhibitors

Front 23

Antimetabolites:
-Explain the different ways antimetabolites can inhibit nucleotide synthesis.

Back 23

1. Inhibitors of folate metabolism
2. Inhibitors of purine synthesis and metabolism.(block de novo synthesis or conversion from salvage pathway).
3. inhibitors of ribonucleotide reductase(blocks synthesis of deoxyribonucleotides)
4. inhibitors that are incorporated into DNA.

Hint 23

Analogs of folate, purines, and pyrimidines that inhibit enzymes involved in nucleotide synthesis

Front 24

Match the following Anti-Metabolite Drug classes with diagram:

-Sulfonamide DHFR inhibitors
- 6-Mercaptopurine Thioguanine(2 locations)
- Hydroxyurea
Fludarabine, Cytarabine, and Cladribine

Back 24

Harder question, but it's a hard test

Front 25

requirement for nucleotides met by both dietary intake or ___(1)

Back 25

(1) de novo synthesis

Front 26

The salvage pathways are a major source of nucleotides for synthesis of DNA, RNA, and __(1)

Back 26

(1) enzyme co-factors

Front 27

if the nucleosides and/or bases are not re-utilized the purine bases are further degraded to __(1) and the pyrimidines to __(2) and __(3), NH3 and CO2

Back 27

if the nucleosides and/or bases are not re-utilized the purine bases are further degraded to uric acid(1) (urate crystals) and the pyrimidines to b-alanine(2) and b- aminoisobutyrate(3), NH3 and CO2

Front 28

Allopurinol inhibits __(1)

Back 28

Xanthine oxidase

Front 29

What enzyme salvages guanine and hypoxanthine

Back 29

HGPRTase(if insufficient amount is salvaged, gout development ensues)

Front 30

Folic acid is critical for what step in de novo purine synthesis?

Back 30

Essential cofactor in the synthesis of inosine monophosphate(IMP)

Front 31

Folic acid is critical in what part of pyrimidine de novo synthesis?

Back 31

Folate required for the methylation of deoxyuridylate(dUMP)

Front 32

major site of purine synthesis is...

Back 32

Liver

Front 33

___(1) is a rate limiting step, first step of De Novo Purine synthesis. Feedback inhibited by end products of de novo synthesis, AMP and/or GMP.
-Inhibited by ___(2) metabolite

Back 33

(1) PRPP synthetase
(2) Mecaptopurine

Front 34

purine base is built upon the ribose by __(1) and __(2) reactions.

Back 34

purine base is built upon the ribose by aminotransferase(1) and transformylation(2) reactions.

Front 35

__(1) is necessary to turn Dihydrofolate into Tetrahydrofolate. What drugs block this pathway?

Back 35

(1) DHFR(Dihydrofolate reductase)
-Inhibiting drugs: Trimethoprim, Methotrexate, Pyrimethamine

Front 36

This drug is selective for bacterial DHFR; bacteriostatic; often used in combination with sulfonamides to sequentially inhibit folate metabolism; since it is a reversible DHFR inhibitor, less competition, increased efficacy

Back 36

Trimethoprim

Front 37

inhibiting folate synthesis decreases substrate for __(1)

Back 37

(1) DHFR-dihydrofolate reductase

Front 38

What substance inhibits Ribonucleotide synthesis?

Back 38

Hydroxyurea

Hint 38

it's an antineoplastic

Front 39

What chemo drug prevents DNA synthesis' insertion?

Back 39

Cytarabine

Hint 39

It's a metabolite

Front 40

__(1) is a Non-selective inhibitor of Dihydrofolate reductases.

Back 40

Methotrexate

Front 41

__(1) is an irreversible inhibitor of thymidylate synthase and is a pro-drug.

Back 41

(1) 5-FU(5-Fluorouracil)

Front 42

FdUMP forms a covalent ternary complex with __(1) and ___(2)
and blocks __(3) formation, dominate mechanism of anti-metabolite

Back 42

FdUMP forms a covalent ternary complex with methyleneTHF(1) and thymidylate
synthase(2) and blocks dTMP(3) formation, dominate mechanism of anti-metabolite

Front 43

hydroxyurea block reduction of the __(1) to __(2)

Back 43

(1) ribose
(2) deoxyribose

-also used in treatment of sickle cell anemia.

Front 44

What four drugs inhibit inosine monophosphate dehydrogenase? (dehdrogenase responsible for changing IMP to XMP during purine synthesis)

Back 44

(1)6-mercaptopurine
(2) Azathioprine(AZA)
(3) Thioguanine
(4) Mycophenolic acid

First two can also inhibit Adenylsuccinate sunthetase

Front 45

__(1) is a feedback inhibitor of PRPP synthase(first enzyme in de novo purine synthesis.)

Back 45

(1) T-IMP

Front 46

Allopurinol blocks degradation of __(1)

Back 46

6-MP(Mercaptopurine). Co-administration of allopurinol lowers the dose of 6-MP required but increases the half-life and possible toxicity of the drug.

Front 47

This nucleoside analog inhibits purine metabolism via Adenosine Deaminase(inhibits it).

Back 47

Pentostatin

Front 48

What happens if there is an increase in intracellular adenosine and deoxyadenosine.

Back 48

Increases the metabolite S-adenosylmethionine which is especially toxic to lymphocytes.

Front 49

What does pentostatin normally treat?

Back 49

Hairy cell leukemia.

Front 50

Converted to GHPRTase to 6-thioGMP

Back 50

Thioguanine

Front 51

-Once incorporated into DNA,
interferes with transcription
and DNA replication, also decreases GMP synthesis.
- Used to treat myelocytic leukemia but strongly suppresses bone marrow function and has gastrointestinal toxicity issues.

Back 51

Thioguanine

Front 52

Triphosphorylated form inhibits
DNA polymerase and ribonucleotide
Reductase, reduces nucleotide synthesis

also can be incorporated into DNA, causes
chain termination

Used in treating lymphocytic leukemia
and B-cell lymphomas

Back 52

Fludarabine-5-Phosphate (Fludara)

Front 53

Phosphorylated by deoxycytidine kinase in cells with a high ratio of deoxycytidine kinase to deoxynucleotidase there is little deoxynucleotide deaminase in lymphocytes and monocytes,
aids conversion to active triphosphate deoxynucleotide, 2-chloro-dATP.

-When incorporated into DNA causes strand breaks
used in treating hairy cell leukemia
both Fludara and Leustat are resistant to deamination by adenosine deaminase.

Back 53

Cladribine (Leustat)

Front 54

-Metabolized to araCTP and
competes with CTP for incorporation
into DNA

-Results in chain termination since steric interaction of 2’-OH on ribose disrupts base stacking.

Back 54

Cytosine Arabinoside
(Cytarabine or AraC)

Front 55

Interferes with DNA methylation which is a critical feature in regulating gene expression.

-Both reagents used in treating myelocytic leukemias.

Back 55

5-Azacytidine