Medchem Ii: Exam 3

Front 1

chemical nucleus for estrogens

Back 1

estrane C18

Front 2

chemical nucleus for androgens

Back 2

androstane C19

Front 3

chemical nucleus for progestrogens and corticosteroids

Back 3

pregnane C21

Front 4

chemical nucleus for cholesterol

Back 4

cholestane C27

Front 5

Ring ___ must be aromatic for estrogens
____ hybridization at all carbons in this ring gives estrogens their selectivity.

Back 5

A

sp2

Front 6

Natural estrogens produced by the ovaries:

Back 6

Estradiol (Estrace)
Estrone (Theelin)
Estriol

Front 7

Semi-synthetic estrogens include:

Back 7

Estradiol cypionate (Depo-estradiol)
Ethinyl estradiol (Estinyl)
Mestranol
Estropipate (Ogen)
Conjugated Estrogens (Premarin)

Front 8

Synthetic estrogens (nonsteroidal nucleus)

non-serms

Back 8

Diethylstilbestrol (DES)
Dienestrol (Ortho-dienestrol)
Chlorotrianisene (TACE)

Front 9

SERMs

Back 9

Clomiphene (Clomid)
Tamoxifene (Nolvadex)
Raloxifene (Evista)

Front 10

The hypothalamus releases ____ stimulating the pituitary to release ___ which causes the ovaries to release estrogen. Estrogens are responsible for:

Back 10

FSRH

FSH

maturation of follicles / ovum

Front 11

The hypothalamus releases ____ stimulating the pituitary to release ___ which causes the ovaries to produce progersterone. Progesterone is responsible for

Back 11

LHRF

LH

release ovum, maintaining pregnancy or shedding the endometrium during menstruation

Front 12

Oral contraceptives work via:

Back 12

Negative feedback on the HPA axis

Front 13

Natural estrogen functions

Back 13

Maturation of sex hormones
Regulation of ovulation
Bone growth

Front 14

Potential therapeutic uses of estrogens

Back 14

HRT during menopause
Male prostate cancer
Hirsutism

Front 15

Estrone is produced from the _________ of estradiol

Back 15

Oxidation

Front 16

_________ + _________ of estrone will produce estriol

Back 16

enolization + Hydration

Front 17

Diethylstilbestrol requires _______ bonds at the ethyl groups to maintain activity.

Back 17

Trans

Front 18

This synthetic estrogen led to the development of SERMs which has high affinity for receptors but low intrinsic activity

Back 18

Chlorotrianisene (TACE)

Front 19

SERMs are used to treat _________ and ________

Back 19

breast cancer

osteoporosis

Front 20

Tamoxifen is metabolized via aromatic hydoxylation and N-dealkylation, and its para-hydroxylated metabolite is ________

Back 20

Active

Front 21

Ethinyl Estradiol was developed to prevent

Back 21

First pass oxidation

Front 22

Mestranol is a derivative of ethinyl estradiol that was developed to:

Back 22

Limit phase II metabolism as well as first pass oxidation

Front 23

This semi-synthetic estrogen is a prodrug given PO or by injection, activated via phase II metabolism.

Salt of estrone-sulfate

Back 23

Estropipate (Ogen)

Front 24

True or False

Synthetic estrogens are steroids that have high affinity for estrogen receptors with low intrinsic activity.

Back 24

False

NOT steroids, with variable activity

Front 25

Clomiphene's agonistic effect is used to treat _______ or _______, while its antagonistic effect is good for _________

Back 25

osteoporosis / infertility

cancer

Front 26

Exogenous progestins will cause feedback inhibition of ____

Back 26

LH

Front 27

Side effects of progestins are associated with

Back 27

Androgenic nucleus

acne, hirsutism, decreased bone density, decreased HDL, high LDL

Front 28

Progesterone has high absorption but first pass metabolism.__________ is progesterones active metabolite

Back 28

Hydroxyprogesterone

Front 29

This progestin contains ethinyl group giving it high androgenic activity due to its similarity to androstane nucleus

Back 29

Ethisterone

Front 30

Removal of ______ from position __ on ethisterone will block the androgenic effects.

This hormone is called

Back 30

methyl

C10 (carbon19)

Norethisterone

Front 31

Modified hydroxyprogesterone given as a depot IM injection

Back 31

Hydroxyprogesterone capoate

Front 32

hydroxyprogesterone capoate is no longer used in the US. Instead ____________ was made by removing long chained fatty acid and adding an additional methyl at C6 to resist 1st pass

Back 32

medroxyprogesterone acetate

Front 33

Common ingredient in many oral contraceptives, resists first pass metabolism, sold as a racemic mix

Back 33

norgestrel

Front 34

Plan B

Back 34

levonorgestrel

Front 35

This abortive agent works to block progesterones endometrial effects after ovulation

Back 35

Mifepristone

Front 36

testosterone is metabolized by 5-alpha reductase into

Back 36

dihydrotestosterone

Front 37

Testosterone decanoate is an IM injection indicated for

Back 37

hypogonadism + anemia

Front 38

Effects of testosterone

Back 38

Male sex characteristics
Spermatogenesis
Protein synthesis - anabolic

Front 39

__________ is an oral testosterone derivative designed to avoid first pass metabolism,
7-10X more potent, also sublingual

Back 39

methyltestosterone

Front 40

________ is 20X more potent than testosterone, anabolic effects aid in anemia also used for hypogonadism

Back 40

fluoxymesterone

Front 41

Anabolic steroid lacking a methyl at C____ which is essential for androgenic effects, in order to isolate anabolic effect

Back 41

C10 (carbon19)

Nandrolone

Front 42

1-2 double bonds in ring A, or an additional ring with double bonds will give steroid structures more activity at ________ receptors due to ___ hybridization and flattening structure

Back 42

Anabolic

sp2

Front 43

Explain why dihydrotestosterone is 10 times more active at androgenic receptors than testosterone

Back 43

alpha reductase removes the double bond in ring a creating sp3 hybridization all around the ring (chair) which is more selective towards androgenic receptors

Front 44

Estrogen receptor affinity is associated with ___ double bonds (_______) in ring A

Back 44

3

Benzene

Front 45

Danazol has no effect for hypogonadism. It is an anabolic steroid used to treat ___________. Side effects are caused by its _________ effects.

Back 45

hemolytic anemia

progesterone

Front 46

These steroids have no androgenic activity but will not come up positive on anabolic steroid testing.

Back 46

Oxandrolone + Testolactone

Front 47

Nandrolone (Deca-durabolin) is used for

Back 47

breast cancer + anemia

Front 48

Anabolic steroids ______ nitrogen balance

Back 48

increase

Front 49

Anti-androgens are used for:

Back 49

acne
hirsutism
prostate cancer

Front 50

Cyproterone + Flutamide are:

Back 50

competitive androgen receptor antagonists

acne / hirsutism / prostate cancer

Front 51

Insulin is a ___ amino acid polypeptide consisting of 2 separate chains connected by 2 ______ bonds

Back 51

51

disulfide

Front 52

Chain A of insulin polypeptide is ___ amino acids long and contains an ______molecular disulfide bond.

Back 52

21

INTRA molecular

Front 53

Chain B on insulin is ___ amino acids long

Back 53

30

Front 54

True or False

Insulin has no plasma protein binding when distributed in the body

Back 54

True

Front 55

In order for insulin to be active it must be in its ______ form

Back 55

monomer

Front 56

Insulin metabolism happens where?

Back 56

Liver, kidney, muscles

Front 57

________ cleaves intermolecular disulfide bonds, giving insulin a t1/2 of ___ minutes

Back 57

Insulin-glutathione transhydrogenase

6 minutes

Front 58

Polypeptide hormones produced by gastric mucosa when you eat, stimulating the release of insulin

Back 58

Incretins

GIP (glucose dependent insulin releasing peptide)

GLP-1 (glucagon-like peptide)

Front 59

Glucagon stimulates __________ and ________ through a receptor-mediated action in the liver.

Back 59

glycogenolysis

gluconeogenesis

Front 60

________ serves as a mediator between glucagon and insulin.

Back 60

Somatostatin

Front 61

Iletin = ______ insulin differing from human insulin structure by __ amino acid(s)

Back 61

Pork

1 AA

Front 62

Regular human insulin has an onset of ___ minutes and a duration of ______ hours

Back 62

30 minute onset

5-8 hour duration

Front 63

Rapid acting insulin has an onset of ___ minutes and a duration of ____ hours

Back 63

15-30 minute

2-6 hour duration

Front 64

Lispro is a derivative of regular insulin but dissociates from its hexamer form more rapidly because of alterations at positions ___ + ___

Back 64

28 lysine

29 proline

Front 65

Aspart contains _____ at position 28.

Glulisine contains _____ at position 3 and _____ at position 28

Back 65

Aspartate

Lysine + Glutamate

Front 66

Lispro and Aspart are contained in a _______ buffer, while ________ is contained in distilled water

Back 66

phosphate buffer

glulisine

Front 67

_______ is a fast acting insulin not used in the US. Its amorphous shape provides a larger surface area for dissolution when zinc is low.

Back 67

Semilente

Front 68

Ultralente is long acting. When _____ levels are high it is crystalline with less surface area for dissolution.

Back 68

zinc

Front 69

Intermediate acting insulins have an onset of ____ hours and a duration of _____ hours

Back 69

3-4 hour onset

18-24 hour duration

Front 70

Aspart is more negative due to aspartic residue which aids in ________ rate

Back 70

dissolution

Front 71

Ultra-lente is contained in a ______ buffer

Back 71

Acetate

Front 72

4 Major classes of anti-diabetics

Back 72

Secretagogues

Glucosidase inhibitors

Biguanides

Insulin Sensitizers

Front 73

Secretagogues include

Back 73

Sulfonylureas

Meglitinides

GLP-1 agonists / DPP-IV inhib

Front 74

________ is the longest acting of the 1st generation sulfonylureas with QD dosing.

Back 74

Chlorpropamide (Diabenese)

Front 75

2nd generation sulfonylureas are 100x more potent than first generation. __________ allows for qd dosing

Back 75

enterohepatic circulation

Front 76

Adverse effects associated with 2nd generation sulfonylureas.

Back 76

hyperinsulinemia

hypoglycemia

Front 77

Normal glucose levels should be

Back 77

90-110mg/dL

Front 78

Meglitinides are 5-10x more potent than sulfonylureas and work via the same mechanism. They have a _____ onset and _____ duration and do not cause __________

Back 78

rapid onset

shorter duration

hyperinsulinemia

Front 79

True or False

Stronger effect:

Meglitinides > Sulfonylureas

Back 79

False

Front 80

________ only work when glucose is high. (Antihyperglycemics)

Back 80

Biguanides

Front 81

While metformin is the safest to use, biguanides adverse effects can include:

Back 81

Muscle ache, lactic acidosis

Front 82

Biguanides work by:

Back 82

Inhibit gluconeogenesis
Inhibit glycogenolysis
Promote glycolysis

Front 83

True or False

Biguanides are excreted unchanged

Back 83

True - very polar

Front 84

True or False

Thiazolidindiones when used alone, effectively increase insulin release

Back 84

False

PPARγ agonist / insulin sensitizer! need to be used in combo to have any effect

Front 85

True or False

Sulfonylureas can be used in combination with biguanides

Back 85

True

Front 86

_________ metabolite has a similar structure to vitamin E, it can cause severe hepatotoxicity.

Back 86

Troglitazone

Front 87

metformin + rosiglitazone

Back 87

Avandamet

Front 88

metformin + glipizide

Back 88

Metaglip

Front 89

metformin + glyburide

Back 89

Glucovance

Front 90

Metformin has _______ oral absorption due to its polarity

Back 90

low

food decreases absorption too

Front 91

These antidiabetic drugs are very safe for elderly because they are not absorbed

Back 91

Glucosidase Inhibitors

Front 92

Thyroid functions include:

Back 92

Regulating metabolism BMR
Growth
Homeostasis

Front 93

Another name for hyperthyroidism

Back 93

Graves Disease

Front 94

True or False

Hyperthyroidism or Hypothyroidism can cause goiter

Back 94

True

Front 95

Thyroid hormones are iodinated amino acids derived from ________. They are synthesized in the thyroid gland and stored as amino acid residues of _________.

Back 95

tyrosine

thyroglobulin

Front 96

T3 and T4 tyrosine rings are perpendicular to eachother due to

Back 96

Steric hinderance from Iodination - required conformation for receptor activity

Front 97

T4 is _____ acidic and lipophilic than T3. T4 undergoes enterohepatic circulation and has a t1/2 of about ____

Back 97

more

7 days

Front 98

Which is more active at thyroid receptor?

T3 vs. T4

Back 98

T3 more active, higher affinity for receptor, low ppb, no enterohepatic circulation

Front 99

The overall ratio of T4:T3 in the body

Back 99

4:1

Front 100

After uptake of iodide into the thyroid gland via iodide pump, iodide is ________ by peroxidase into elemental iodine.

Back 100

oxidized

Front 101

Goitrin found in cabbage exists as a tautamer that can interfere with peroxidase enzyme leading to _______

Back 101

goiter

Front 102

hypothyroidism is also called

Back 102

myxedema

Front 103

Types of Anti-thyroid drugs

Back 103

Peroxidase inhibitors

Iodide pump inhibitors