MOA

Question 1

Prostaglandin E1 (alprostadil)

Answer 1

Vasodilation

Question 2

Sildenafil

Viagra

Answer 2

PDE5 inactivates cGMP so viagara blocks this to maintain relaxation and penile erection

Question 3

Anti-ED drugs

Answer 3

relaxation of smooth muscle in corpora cavernosa

Question 4

Calcium

Answer 4

↑ in Ca2+ absoprtion →

↑ bone deposition
and

↓ PTH release

Question 5

Vitamin D

Answer 5

↑ in Vit D →

↑ Ca2+ absorption in GI tract →

↑ bone deposition and

↓ PTH release

Question 6

“Teriparatide

(hPTH 1-34)”

Answer 6

↑ osteoblasts and osteoclasts number

and

Indirectly ↓ osteoclast activation by ↑ RANKL and ↓ OPG

Question 7

Calcimimetic

Answer 7

Binds to Ca2+ sensitizing receptors →

↑ sensitivity of receptor to Ca2+ →

↓ PTH production and release

Question 8

Raloxifen

Answer 8

↓ Osteoclast number
and
↓ osteoclast activation by RANKL

Question 9

Biphosphonates

Answer 9

Incorporated into bone and comes out w/ osteoclast activity → becomes incorporated in osteoclasts→
apoptosis of osteoclasts→

↓ Osteoclast number

Question 10

Denosumab

Answer 10

Binds to RANKL and ↓ RANKL - RANK interaction →
↓ osteoclast activation→

↓ osteoclast #

Question 11

Salmon Calcitonin

Answer 11

↓ plasma Ca2+ levels → 
↓ Ca reabsorption in kidney
and
↓Ca2+ abs in GI tract
and
↑ Ca2+ deposition in bone

Question 12

Cortisol/Glucocorticoids

Answer 12

Binds glucocorticoid receptor (GR)→ dimerizes → goes to nucleus → dimers bind to GRE → transcriptional repression

Suppress T-and B-cell transcription of pro- inflammatory mediator genes and cytokine genes (TNF- a, IL-2)

Suppress inflammatory immune cell (monocytes, macrophages) production of prostaglandins and thromboxane A2 by:

Up-regulating lipocortin gene transcription → Lipocortin protein inhibits PLA2 → preventing arachidonic acid mobilization

Down-regulating COX-2 transcription

Question 13

Cytotixic Antimetabolites

Answer 13

Inhibit clonal expansion of lymphocyte population

Question 14

Azathioprine

Answer 14

Azathioprine taken up in liver → cleaver → converted non- enzymatically to 6-MP (a purine analog) → converted to Thio-dGTP by de novo purine synthesis pathway.

Thio-dGTP incorporated into DNA of replicating immune cells→DNA breaks → suppression of T- and B-cell proliferation

Question 15

Mycophenolate Mofetil

Answer 15

More selective in suppressing B and T cells (less SE)

Prodrug hydrolyzed to mycophenolate (active form)→ taken up by de novo purine pthwy→ inhibits IMP dehydrogenase (IMPDH) in B- and T- cells → decrease purine biosynthesis → Ab formation by B-cells is inhibited and cellular adhesion and migration is inhibited

Question 16

Cyclosporine

Answer 16

Calcineurin inhibitor

Binds to cyclophilin to inhibit calcineurin → inactive NFAT and ↓ IL-2 gene transcription in T-cells

Question 17

Tacrolimus

Answer 17

Calcineurin inhbitor

Binds to FKBP-12 to inhibit calcineurin → inactive NFAT and ↓ IL-2 gene transcription in T-cells

Question 18

Sirolimus

Answer 18

Binds to FKBP-12 to inhibit mTOR → ↓ translation of proteins needed for proliferation of T- cells

Question 19

Abatacept

Answer 19

Fusion protein that neutralizes the co- stimulatory ligand CD80/86 on antigen presenting cells → thus preventing T-cell activation → T-cell hyporesponsiveness → apoptosis
(Anergy)

Question 20

Adalimumab

Humira

Answer 20

Human monoclonal Ab that neutralizes TNF-alpha → ↓ regulation of macrophage and T-cell fn

Question 21

Etanercept

Enbrel

Answer 21

Fusion protein (fusion of TNF receptor and Fc domain of IgG) that neutralizes TNF-alpha by binding to it and preventing its interaction w/ cellular receptor

Question 22

Infliximab

Remicade

Answer 22

Chimeric human/mouse monoclonal antibody that neutralizes TNF-alpha → ↓ regulartion of T cell and macrophage fn

Question 23

Rituximab

Answer 23

Humanized monoclonal Ab against CD20 on the surface of B-cells → depletes →CD20 + B cells

Question 24

Tocilizumab

Answer 24

Humanized monoclonal antibody that neutralizes IL-6 receptor on immune cells → blocks activation of JAK-STAT pthwy → prevents transcription of proinflammatory proteins

Question 25

ALKYLATING AGENTS

Answer 25

CCNS drugs

Greatest anti-ca activity in S phase

Bi-functional

Alkylates guanine
residues → produces
interstrand crosslinks

Guanine has abnrml base-pairing w/ thymine during replication → protein miscoding and apoptosis

Question 26

ANTI-METABOLITES

Answer 26

CCS drugs (active in S-phase of cell cycle)

Structurally similar to endogenous molecules → act as antagonists of biosynthetic pthwys

Ca cells are more sensitive than nrml cells bc of high growth fraction and higher levels of certain enzymes

Question 27

Methotrexate

Answer 27

CCS

Folic acid
analog

Binds to and inhibits
DHFR →
prevents formation of
THF from folate  → prevents
thymidylate, purine &
amino acid synthesis→
interruption of DNA, RNA and protein syntheses

Question 28

5-Fluorouracil

Answer 28

CCS

Analog of uracil

Prodrug → converted to 5FdUMP,
which inhibits TS activity which is required for de novo pyrimidine synthesis → slows ca cell replication and causes DNA damage

Question 29

6-Mercaptopurine

Answer 29

CCS

HGPRT metabolizes 6 mercap into TIMP →

converted to Thio-dGTP

Thio-dGTP is incorporated
into DNA of replicating
cancer cells→ leading to
apoptosis

Question 30

Vinca Alkaloids (Vinblastine and Vincristine)

Answer 30

Binds to β-tubulin→
prevents
polymerization of
microtubules → causes blocking of mitotic spindle formation → tumor cell death

Question 31

Paclitaxel

Answer 31

CCS

Binds with high
affinity to β-tubulin and
stabilizes microtubules
(prevents depolymerization)→ cells blocked at G2/M phase

Question 32

Etoposide

Answer 32

CCS

Inhibits
topoisomerase II → prevents DNA uncoiling → DNA strand breakage

Question 33

Irinotecan

Answer 33

CCS
(CCNS at higher
concentration)

Inhibits topoisomerase I → prevents uncoiling → DNA strand breakage

Question 34

Doxorubicin

Answer 34

CCNS

DNA intercalation that
interferes with DNA &
RNA synthesis

Inhibits topoisomerase II→ DNA fragmentation

Free radical formation
→ DNA scission (responsible for cardiotox)

Question 35

Bleomycin

Answer 35

CCS

 Intercalation,
scission and
fragmentation of DNA due
to oxidation by a DNAbleomycin-Fe(II)
complex

Question 36

Allopurinol

Answer 36

Purine analog

Inhibits XO → prevent uric acid production