MOA

Question 1

Thioamides- PTU and MMI

Answer 1

Prevent hormone synthesis by inhibiting TPO-catalyzed rxns to block iodide organification

Block coupling of iodotyrosines

Drug binds to and inactivates TPO

Slow onset (takes 4- wks to deplete), excreted in urine

Question 2

Anion Inhibitors- ClO4- and TeO4-

Answer 2

Compete with sodium ion transporter for uptake

Question 3

Iodide

Answer 3

Inhibit organification and hormone release and ↓ size of hyper plastic gland

Effect reverses with time (escape) if used alone

Question 4

Radioactive Iodine

I131

Answer 4

Taken orally → rapidly
concentrated in thyroid follicle cells, where
β particles selectively destroy gland w/o injury to adjacent cells →
become euthyroid in 6-8 wks

Question 5

Biguanides

Answer 5

Enhances effects of insulin “sensitizer”

Activates AMP-dependent protein kinase (AMPK) causing ↑ glucose uptake by fat and muscle and ↓ production by liver

Question 6

Sulfonylureas

Answer 6

↑ Insulin release from pancreas beta cells by binding to K+ channel (requires functional beta cells)

Mimic Glucose to Close ATP-sensitive K+ Channels and Stimulate Insulin Secretion

Question 7

Non-Sulfonylurea Secretagogues (Meglitinides)

Answer 7

Mimic glucose to close K+ ch and stim insulin secretion

↑ Insulin release from pancreas beta cells by bindi to beta K+ cells (require fn beta cells)

Question 8

Thiazolidenediones (TZDs)

Answer 8

↑ Insulin sensitivity in target tissues by activating receptor gamma (PPAR-gamma) liganda

Question 9

GLP-1 Receptor Agonists

Answer 9

↑ glucose-dependent insulin secretion

Question 10

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

Answer 10

Prolong endogenous GLP-1 action

↑ glucose-mediated insulin secretion

Question 11

α-Glucosidase Inhibitors

Answer 11

Stays in intestine and ↓ GI glucose absorption

↓ Postprandial glycemia (must be taken with meal)

Question 12

Canagliflozin

Answer 12

Glucose co-transporter inhibitor

Inhibition of SGLT-2 → suppresses renal glucose re-absorption → lowers blood glucose

Question 13

Estrogen/progestin combo pill

Answer 13

Hypothal
↓ GnRH pulses (P) → no LH surge

Pituitaty
↓ responsiveness to GnRH (combo)

↓FSH/LH release (E) → ↓ follicular devel

Other
thickening of cervical mucus (P) → ↓ sperm penetration

Atrophic endometrium ( P) to implantation

↓ transport of sperm/egg through fallopian tub (combo)

Overall blocks ovulation, atrophies endometrium, thick cervical mucus, altered traans in fallopian tube

Question 14

Ulipristal

Answer 14

Selective

Delays ovulation

Alters cervical mucus and endometrium

Question 15

Mifepristone

RU486

Answer 15

Competitive antagonist

Blocks uterine progesterone receptors → decidual breakdown → blastocyst detachment (↓hCG)

↑ sensitivity of myometrium to PG → contractile, softens cervix

Question 16

Generally how do combo estrogen/progestins work?

Answer 16

by suppressing follicle development, thickening cervical mucus, and inhibiting ovulation

Question 17

Copper IUD

Answer 17

reduces sperm motility and viability

Question 18

LNG-IUD

Answer 18

inhibits ovulation, thickens cervical mucus, reduces sperm motility and viability

Question 19

Hormonal EC

Answer 19

acts by delaying ovulation and may also interfere with sperm migration and fn at all levels of genital tract

Question 20

Tamoxifen

Answer 20

Metabolized by CYP2D6 to active metabolites endoxifen and 4- hydroxyTAM that bind to ER-alpha, acting as antagonists in breast tissue to inhibit gene transcription, inhibit cell proliferation and promote apoptosis

Acts as a partial agonist in endometrium to promote endometrial hyperplasia

Question 21

Toremifene

Answer 21

Active antagonist at ER-alpha/beta

Does NOT require activation by CYP2D6

Insufficient clinical data at this time, but may act as partial agonist in endometrium to promote endometrial cancer

Question 22

Leuprolide

Answer 22

Disrupts normal pulsatile stimulation of GnRH receptor by endogenous GnRH
→ desensitization of GnRH receptor in the pituitary→ ↓ release of FSH and LH from the pituitary→ ↓ estrogen synthesis in the ovaries

Question 23

Anastrozole

Answer 23

Reversible inhibitor

Prevent conversion of testosterone to estrogen by inhibiting aromatase (CYP19A1) in adipose tissue

Question 24

Exemestane

Answer 24

Suicide inhibitor

Prevent conversion of testosterone to estrogen by inhibiting aromatase (CYP19A1) in adipose tissue

Question 25

Trastuzumab

Answer 25

“Armed” monoclonal Ab that has been coupled with DM1 (emtansine) Ab binds to HER2 extracellular domain IV → Ab is internalized into lysosomal stores → DM1 is released DM1 is a mitotic spindle poison, binds beta-tubulin to inhibit microtubule polymerization

Question 26

Pertuzumab

Answer 26

Monoclonal Ab binds HER2 extracellular domain II to prevent ligand-dependent dimerization with EGFR

Question 27

ALKYLATING AGENTS (Cyclophosphamide and Cisplatin)

Answer 27

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 28

ANTI-METABOLITES

Answer 28

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 29

Methotrexate

Answer 29

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 30

5-Fluorouracil

Answer 30

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 31

6-Mercaptopurine

Answer 31

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 32

Vinca Alkaloids (Vinblastine and Vincristine)

Answer 32

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

Question 33

Paclitaxel

Answer 33

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

Question 34

Etoposide

Answer 34

CCS Inhibits topoisomerase II → prevents DNA uncoiling → DNA strand breakage

Question 35

Irinotecan

Answer 35

CCS (CCNS at higher concentration) Inhibits topoisomerase I → prevents uncoiling → DNA strand breakage

Question 36

ANTIBIOTICS

Answer 36

Insert btwn base pairs of DNA → Δ DNA configuration → strand breakage/ enzyme interference

Question 37

Doxorubicin

Answer 37

CCNS DNA intercalation that interferes with DNA & RNA synthesis Inhibits topoisomerase II→ DNA fragmentation Free radical formation → DNA scission (responsible for cardiotox)

Question 38

Bleomycin

Answer 38

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

Question 39

Allopurinol

Answer 39

Inhibits XO → prevent uric acid production