Med Chem 2 Exam 1

Front 1

How do cholesterol-lowering drugs such as statins work? What is their target enzyme and mechanism of action?

Back 1

statins inhibit HMG-CoA reductase. this enzyme catalyzes a rate limiting step in cholesterol biosynthesis.

Front 2

What is the most important class of drug used to treat angina/angina pectoris?

Back 2

nitrovasodilators/organic nitrates

Front 3

Most of the known biological effects of angiotensin II are mediated by which receptor isoform (subtype)?

Back 3

AT1 receptor

Front 4

name the main enzyme inhibited by the anticancer drug methotrexate.

Back 4

dihydrofolate reductase or DHFR

Front 5

which atom of DNA guanine is particularly susceptible to the formation of a covalent bond with bifunctional alkylating agents?

Back 5

N7 atom of guanine

Front 6

How does Cisplatin work as an antineoplastic agent (mechanism of action)?

Back 6

Cisplatin works as an antineoplastic agent by covalently binding to the nucleophilic sites on DNA causing DNA damage, which induces apoptosis.

Front 7

which type of calcium channel is inhibited by the calcium channel blockers/antagonists?

Back 7

L-type or long-lasting calcium channels

Front 8

Why are guanine and uracil analogs administered as nitrogenous bases while adenine, cytosine, and thymine analogs are given with sugar attached to the nitrogenous bases?

Back 8

cells can uptake uracil and guanine and convert them to nucleotides by the addition of deoxyribose and phosphate groups.
Other bases, including cytosine, thymine, and adenine, cannot be activated by mammalian cells (which lack the ability to add the necessary ribose or deoxyribose groups).
Uracil and guanine analogs are synthesized as bases itself, while analogs of cytosine and adenine are synthesized as nucleotides.

Front 9

what is the main chemical difference between nucleotides and nucleosides?

Back 9

nucleotide consists of nitrogenous base, sugar, and phosphate group(s).

nucleoside consists of nitrogenous base and sugar.

Front 10

why are all nitrovasodilator drugs packaged in dark bottles?

Back 10

all nitrovasodilators are nitrate esters (C-O-NO2 and characterized by a sequence of C-O-N bond). Since the nitrate ester bond is highly susceptible to light and moisture, they are packed in dark bottles.

Front 11

what is the difference between "phase-specific" and "phase-nonspecific" drugs? Give one example of each.

Back 11

Phase-specific: acts at a particular phase of cell cycle
ex: any antimetabolite, taxols, vinca alkaloids

phase-nonspecific: does not act at a particular stage of cell cycle
ex: any alkylating agents

Front 12

which cell cycle phase transition is controlled by RB (retinoblastoma) pathway?

Back 12

G1 to S

Front 13

How does the renin-angiotensin system regulate blood pressure? Describe in detail with a detailed diagram.

Back 13

good luck.....

Front 14

What are the main cardiovascular diseases? name any two.

Back 14

atherosclerosis (hyperlipidemia)
coronary artery diseases
angina pectoris
myocardial infarction
congestive heart failure
hypertension

Front 15

what are the main cardiovascular drug classes? name any four.

Back 15

diuretics
alpha blockers
beta blockers
angiotensin converting enzyme (ACE)
angiotensin II receptor blockers (ARBs)
nitrovasodilators
calcium channel blockers
statins

Front 16

how does the renin-angiotensin system regulate blood pressure? describe briefly.

Back 16

renin converts angiotensinogen into angiotensin I, which is converted to angiotensin II by ACE. angiotensin II binds to the AT1 receptor, causing blood vessels to constrict and thus, an increase in blood pressure.

Front 17

what is the characteristic sequence of chemical bonds present in all nitrovasodilator drugs?

Back 17

nitrate ester/C-O-NO2/carbon-oxygen-nitrogen bond

Front 18

general side-effects of antineoplastic drugs include hair loss, nausea, vomiting, constipation, and diarrhea. what is the reason for these side effects?

Back 18

because hair cells and cells in the GI tract divide quickly, and this type of growth is inhibited by antineoplastic drugs.

Front 19

which enzyme is inhibited by statins?

Back 19

HMG-CoA reductase

Front 20

which type of calcium channel is inhibited by calcium channel blockers/antagonists?

Back 20

L-type

Front 21

all naturally occurring statins contain:
1) mevalonic acid-like hydroxy acid moiety,
2) hexahydronapthalene ring, and
3) methylbutyrate ester group.
which of these is the most important group for the activity of statins?

Back 21

mevalonic acid-like hydroxy acid moiety

Front 22

why is cancer difficult to treat?

Back 22

cancer is a common name used for more than 100 different tumors.
Cancer cells are very similar to normal cells. Unlike bacterial cells, there are not major differences in biochemical processes between normal and cancerous human cells.
Immune response plays a minor role in eradicating tumors. cancer drug toxicity limits dosage.

Front 23

what role is played by normal/wild-type p53 during chemotherapy by alkylating agents?

Back 23

alkylating agents create DNA damage, which is recognized by p53. p53 tries to fix the damage, but if it can't then it induces apoptosis/cell death

Front 24

which atom in guanine is most susceptible to alkylation?

Back 24

N7/ nitrogen 7

Front 25

alkylated guanine pairs with which nitrogenous base instead of cytosine in DNA?

Back 25

tymine

Front 26

what is the mechanism of action of platinum complexes?

Back 26

platinum complexes covalently bind to nucleophilic sites on DNA causing DNA damage.

Front 27

name any one antimetabolite drug which inhibits dihydrofolate reductase (DHFR).

Back 27

methotrexate
trimetrexate
5-fluoroucil (5FU)

Front 28

name any one antineoplastic agent which is specific for the S-phase of the cell cycle.

Back 28

methotrexate
trimetrexate
5FU
cytarabine
6-mercaptopurine (6-MP)
6-thioguanine (6-TG)

Front 29

vinca alkaloids are anti-cancer drugs. they bind to beta-tubulin and inhibit its ability to polymerize with alpha-tubulin into microtubules/spindle. based on this proposed mechanism of action of vinca alkaloids, which phase of the cell cycle to you think this drug will be most effective?

Back 29

M phase/ mitosis

Front 30

what are the six classes of drugs used to treat hypertension?

Back 30

diuretics
vasodilators
alpha blockers
beta blockers
calcium channel blockers
ACE/ARBs

Front 31

angiotensin II binds to which receptor to control arterial blood pressure?

Back 31

AT1

Front 32

what is the mechanism of action of organic nitrates or nitric oxide (NO)?

Back 32

relaxation of vascular smooth muscle leading to vasodilation

Front 33

what are the low molecular-mass organic nitrates such as nitroglycerin administered with an inert carrier such as lactose?

Back 33

because they are volatile and oily liquid

Front 34

what are the five classes of calcium channel antagonists?

Back 34

phenylalkylamines
benzothiazepines
dihydropyridines
diphenylpiperazines
diarylaminopropylamine

Front 35

what are the most effective drugs for the reduction of LDL levels?

Back 35

statins

Front 36

how do the cholesterol lowering statins work? what is their target and mechanism of action?

Back 36

statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes an early, rate-limiting step in cholesterol biosynthesis?

Front 37

why are some statins like lovastatin and simvastatin less water soluble than other statins?

Back 37

because they are lactone prodrugs

Front 38

suggest and one main difference between normal and cancer cells

Back 38

1. loss of control of cell growth
2. decreased cellular differentiation
3. ability to invade surrounding tissue
4. ability to establish new growth at ectopic sites (metastasis)

Front 39

suggest one phase specific and one phase non-specific cancer drug/drug class.

Back 39

s phase specific: cytosine arabinoside
phase non-specific: alkylating drugs

**there is a good diagram on page 4 of the 2011 exam

Front 40

what are the five types of alkylating agents?

Back 40

nitrogen mustards
ethyleneimines
alkyl sulfonates
nitrosoureas
triazenes

Front 41

alkylated guanine (at N7) pairs with which nitrogenous base instead of cytosine in DNA?

Back 41

thymine

Front 42

why is cisplatin most effective in patients with testicular or ovarian cancers?

Back 42

because testicular or ovarian cancers express higher amounts of transporter (Cu ion).

Front 43

Camptothecins are anti-cancer drugs. they bind to and stabilize the normally transient DNA-topoisomerase I cleavable complex. based on the proposed mechanism of camptothecins, during which phase of the cell cycle do you think this drug will be most effective?

Back 43

S phase

Front 44

which enzyme converts angiotensin I into angiotensin II?

Back 44

ACE

Front 45

most of the known biological effects of angiotensin II are mediated by which receptor isoform?

Back 45

angiotensin 1/ AT1 receptor

Front 46

analysis of the dipeptide cleaved by ACE lead to which classes of orally active drugs (two classes of ACE inhibitors)?

Back 46

carboxy- and mercapto-alkanoyl derivatives

Front 47

what was the first clinically used angiotensin II receptor blocker developed?

Back 47

losartan

Front 48

name any two classes of drugs used in the treatment of angina

Back 48

beta adrenergic receptor anatagonists
nitrovasodilators
calcium channel antagonists
statins

Front 49

name any four classes of calcium channel antagonists used in the treatment of cardiovascular diseases.

Back 49

phenylalkylamines
benzothiazepines
dihydropyridines
diphenylpiperazines
diarylaminopropylamine

Front 50

name any four types of alkylating antineoplastic agents

Back 50

nitrogen mustards
ethyleneimines
alkyl sulfonates
nitrosoureas
triazenes

Front 51

what is the present working hypothesis of alkylating agents?

Back 51

alkylating agents produce cytotoxic, mutagenic, and carcinogenic effects by reacting with cellular DNA.
Alkylating agents become strong electrophiles through the formation of carbonium ion intermediates (due to the presence of 2-chloroethyl group).
The 7 nitrogen atom of guanine is particularly susceptible to the formation of a covalent bond with bifunctional alkylating agents.

Front 52

which atom of DNA guanine is particularly susceptible to the formation of a covalent bond with bifunctional alkylating agents?

Back 52

7 nitrogen atom of guanine

Front 53

how does cisplatin work as an antineoplastic agent?

Back 53

platinum complexes enter cells either by diffusion or by an active Cu++ transporter. these become activated intracellulary by the aquation of one of the two chloride leaving groups, and subsequently covalently binds to DNA, forming DNA adducts.

Front 54

how does cytabarine work as an antineoplastic agent?

Back 54

this compound is an analog of 2'-deoxycytidine with the 2'-hydroxyl in a position trans to the 3'-hydroxyl of the sugar. Ara-C penetrates cells by a carrier-mediated process shared by physiological nucleosides.
The 2'-hydroxyl hinders rotation of the pyrimidine base around the nucleosidic bond and interferes with base stacking. The incorporated Ara-CMP residue is also a potent inhibitor of DNA polymerase, both in replication and repair.

Front 55

name any one purine analog which is used as an antineoplastic drug.

Back 55

6-mercaptopurine (6-MP) and 6-thioguanine (6-TG)

Front 56

which enzyme is inhibited by hydroxyurea?

Back 56

ribonucleoside diphosphte reductase

Front 57

which cell cycle phase transition is controlled by RB (retinoblastoma) pathway?

Back 57

G1 to S

Front 58

what is the difference between phase-specific and phase-nonspecific drugs? give one example of each.

Back 58

phase-specific: acts at a particular phase of cell cycle
ex: any antimetabolite, taxols, vinca alkaloids

phase-nonspecific: does not act at a particular stage of cell cycle
ex: any alkylating agents

Front 59

which normal tissues are generally damaged by antineoplastic drugs and why?

Back 59

any rapidly dividing cell (such as bone marrow, lymphoid tissue, GI tract, reproductive organs, embryonic tissue). most cancer drugs are not specific and inhibit the growth of normal cells as well.

Front 60

what are the five major classes of cancer drugs?

Back 60

alkylating agents
antimetabolites
natural products
miscellaneous agents
hormones and antagonists

Front 61

how does mechlorethamine work as an anticancer agent? you can either write the answer or draw a scheme.

Back 61

see diagram on page 2 of 2009 exam

Front 62

what is the main cellular protein target of methotrexate and at which cell cycle phase does it exert its anticancer effects?

Back 62

DHFR
S phase

Front 63

how does angiotensin II work?

Back 63

binds to its heptahelical GPCR, AT1, and causes arteries to constrict. it is a vasoconstrictor.

Front 64

what are organic nitrates? how do they work?

Back 64

NO donors.
relaxation of vascular smooth muscle leading to vasodilation.
relaxation of smooth muscle in the bronchi and GI tract.

Front 65

how doe calcium channel blockers work? what do they do?

Back 65

Ca++ channel antagonists produce their effects by binding to the alpha 1 subunit of the L-type Ca++ channel and reducing Ca_++ influx thru the channel, causing relaxation

Front 66

what is the cellular protein target of statins?

Back 66

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase

Front 67

what is the name of the chemical group/pharmacophore/central scaffold of statins which inhibits its cellular protein target?

Back 67

hydroxy acid, mevalonic acid-like moiety