Drugs for Midterm 1

Question 1

SERMs

Answer 1

Selective estrogen receptor modulators
Agonists or antagonist actions, depending on the tissue
Occupy estrogen binding site on ER
Ex: tamoxifen, raloxifene, clomiphene
Main side effects are hot flashes and increased risk of DVT

Question 2

Clomiphene

Answer 2

SERM
Used for infertility due to lack of ovulation
Moderate estrogen antagonist
Blocks ER in hypothalamus and pituitary
Prevents estrogen negative feedback
Increases LH and FSH leading to ovulation
Treatment for 5 days at beginning of menstrual cycle
Slight increase for the risk of multiple pregnancies

Question 3

Tamoxifen

Answer 3

SERM
Antagonistic activity at ERs in breast tissue
Used to reduce tumor size in ER positive breast cancer
Non-steroid taken orally
Partial agonist in endometrium tissue and has been linked to endometrial cancer after prolonged use

Question 4

Raloxifene

Answer 4

SERM
Agonist activity at ERs in bone tissue
Used in primary prevention of osteoporosis and bone fracture
Antagonist activity at ERs in breast tissue (alternative to tamoxifen)

Question 5

Fulvestrant

Answer 5

Anti-estrogen
Antagonist at ERs
Inhibits the dimerization of ER
Used in tamoxifen resistant, ER positive breast cancers
Adverse effects: hot flashes, headache

Question 6

Ketoconazole

Answer 6

P450c17 inhibitor
Antifungal
Not typically used due to other systemic effects

Question 7

Danazol

Answer 7

P450c17 inhibitor
Partial agonist of several sex hormone receptors
Can inhibit synthesis of androstenedione
Used to treat endometriosis
Several masculinizing side effects

Question 8

Anastrozole

Answer 8

P450c17 inhibitor
Inhibits aromatase (lower estrogen)
Used to treat ER+ breast cancer

Question 9

Leuprorelin

Answer 9

Agonist/antagonist of GnRH receptor
Same as male system
Disrupt the pulsate release of GnRH to reduce estrogen
GnRH analog
Non-pulsatile application used for precocious puberty and prostate cancer
Subcutaneous implantation of pellet
Undesirable initial “flare” of increased testosterone (antagonist given until levels drop)

Question 10

Micronor

Answer 10

Progestin only pill

Pill needs to be taken at the same time every day to maintain adequate hormone levels

Question 11

Alesse

Answer 11

Combined monophasic oral contraceptive
Estrogen: ethinyl estradiol (0.02 mg/pill)
Progestin: L-norgestrel (levelnorestrel - 0.1 mg/pill)

Question 12

Yasmin

Answer 12

Combined monophasic oral contraceptive
Estrogen: ethinyl estradiol (0.02 mg/pill)
Progestin: drospirenone (3 mg/pill)

Question 13

Triphasil

Answer 13

Combined triphasic oral contraceptive
Estrogen: ethinyl estradiol (stays pretty constant, slight increase for days 7-11)
Progestin: levonorgestrel (increases throughout cycle, highest level days 12-21)
Changing hormone levels more closely mimic physiologic cycles (reduces side effects)

Question 14

Testosterone enanthate

Answer 14

Ester derivative of testosterone
Used for androgen replacement therapy
Administered as an intramuscular injection
Highly lipophilic and diffuses slowly from injection site
Ester group is cleaved by cellular enzyme, then free testosterone enters systemic circulation

Question 15

Degarelix

Answer 15

GnRH antagonist
Synthetic peptide that binds to GnRH receptor
Used to teat advanced prostate cancer
Does not cause initial flare like leuprorelin

Question 16

Spironolactone

Answer 16

Diuretic used for cardiac failure
Can technically be used to suppress androgen levels (but not typically)
Can block biosynthesis of testosterone from cholesterol

Question 17

Finasteride

Answer 17

Similar structure to testosterone
Competes for binding to 5alpha reductase
Decreases the levels of DHT
Used to treat BPH (reduces prostate size and resolves urinary retention) and male pattern baldness

Question 18

Flutamide

Answer 18

Synthetic, non-steroidal anti-androgen
Androgen receptor antagonist (competitive)
Used in combination with GnRH antagonists (leuprorelin) in prostate cancer

Question 19

Cyproterone

Answer 19

Used to treat excess sex drive

Androgen receptor antagonist (competitive)

Question 20

Metformin

Answer 20

Drug of first choice for type 2 diabetes
Activates AMP-dependent kinase, which is a key regulator of energy metabolism in most cell types
Decreases basal and post-prandial blood glucose

Question 21

Insulin secretagogues

Answer 21

Ex: sulfonylureas, meglitinides
Stimulate insulin release from pancreatic beta cells
Inhibit ATP-sensitive K+ channels in pancreatic beta cells (stimulates the GSIS pathway without glucose)
Uncouples insulin release from blood glucose levels
Increased circulating insulin levels can partially/completely compensate for tissue insulin resistance

Question 22

Incretins

Answer 22

Gastrointestinal derived hormones that regulate pancreatic insulin and glucagon release
Reduced glucagon release and glucose production
Increases insulin release and glucose uptake
Short duration of action - only get action with high glucose levels (not basal insulin secretion)

Question 23

Incretin agents: DPP-4 inhibitors

Answer 23

Reduce GLP-1 degradation (so increase their levels)
Increases pancreatic GSIS insulin release, and reduced glucagon release
Can partially/fully overcome tissue insulin resistance
Usually used in combo with metformin and/or secretagogues

Question 24

Incretin agents: Incretin mimetics

Answer 24

Activate pancreatic GLP-1 receptors (agonists)
Increase pancreatic GSIS release, reduce glucagon release
Can partially/fully overcome tissue insulin resistance
Usually used in combo with metformin and/or secretagogues
Requires subcutaneous injection

Question 25

Gliflozins

Answer 25

Inhibit renal glucose reabsorption
Used in combo with metformin
Inhibitors of sodium-glucose transporter linked transporter 2 (SGLT2)
Gliflozins block reabsorption and lead to greater urinary glucose excretion

Question 26

Thiazolidinediones

Answer 26

Improve insulin sensitivity in many tissues
PPARy agonists
Normalization of adipose tissue function
Improve insulin sensitivity in many tissues (liver, skeletal muscle, adipose)
Some evidence for a preventative effect
Protective role in mortality from CV disease

Question 27

Curare

Answer 27

Paralyzes you by stopping skeletal muscle movement
Competitive antagonist at the ACh receptor at the NMJ
Competitively and reversibly inhibit the nAChR

Question 28

Myasthenia Gravis

Answer 28

Muscle weakness (ptosis)
Caused by antibodies that block, alter or destroy receptors
Gets worse with exercise because as muscles work more they get hotter and with the antibodies present they cause the receptor to internalize
Treatment: cholinesterase inhibitors (not very selective though, will get too much ACh in lots of places, resulting in excess body fluids from the stimulation of parasympathetic NS)

Question 29

Botulism

Answer 29

Caused by Clostridium botulinum
Flaccid paralysis
Neurotoxin interferes with the release of ACh at the NMJ
Interference is permanent, so to regain muscle function they must grow a new axon

Question 30

Succinylcholine

Answer 30

Dimer of 2 ACh molecules
Binds to ACh receptors (particularly at the NMJ)
Causes flaccid paralysis (because Ca is still removed from the cell so the muscles relax)
Activates the receptor and uses up all the ACh
Prevents cells from repolarizing

Question 31

How do benzodiazepines vs barbiturates work?

Answer 31

Benzos: makes the channel easier to open - has to work with GABA
Barbs: increase the length of time that the channel stays open - at high doses can work without GABA