MOAs Flashcards
1
Q
Long acting GnRH agonists
A
Continuous administration suppresses release of LH and FSH (after initial surge)
2
Q
GnRH antagonists
A
Suppress LH and FSH
3
Q
hMG
A
Used for FSH effects: Induces spermatogenesis (takes months) IVF: 9-12 days stimulates ovaries→ estrogen
4
Q
hCG
A
Used for LH effects:
Increases testosterone (for up to a year)
IVF: single dose to induce ovulation
5
Q
Estrogens act on
A
Nuclear Receptors
6
Q
Estrogen + uterus
A
endometrial growth
7
Q
Estrogen + vaginal epithelium
A
proliferation, maintenance
8
Q
Estrogen + endocervical glands
A
mucus
9
Q
Estrogen + breasts
A
Breast growth in puberty and pregnancy
10
Q
Estrogen + bones
A
Bone maintenance
osteoclast apoptosis.
Osteoblast: decreased IL-6 and RANKL, increased OPG
11
Q
Estrogen + blood
A
Increased synthesis of blood clotting proteins
Increased platelet adhesiveness
12
Q
Estrogen + lipids
A
Increased HDL
Decreased LDL
13
Q
Estrogen + Liver
A
clotting factors, hormone binding proteins: SHBG, CBG, TBG
14
Q
Estrogen + kidney
A
Na+ and H2O retention
15
Q
Estrogen + ovary
A
prepare for ovulation
16
Q
Clomiphene
A
Anti-estrogen at the hypothalamus
Agonist in other tissues
17
Q
Tamoxifen
A
Selective estrogen receptor modulator:
Agonist: uterus, bone
Antagonist: breast
18
Q
Raloxifene
A
Selective estrogen receptor modulator:
Antagonist: breast, uterus
Agonist: bone, liver
19
Q
Fulvestrant
A
Pure estrogen antagonist
20
Q
Toremifene
A
Selective estrogen receptor agonist similar to tamoxifen
Increases HDL
21
Q
Anastrozole
A
Nonsteroidal competitive inhibitor of aromatase
22
Q
Exemestane
A
Steroid, irreversible aromatase inhibitor
23
Q
Letrozole
A
Nonsteroidal competitive inhibitor of aromatase
24
Q
19-Nortestosterones
A
Progestin
Derived from testosterone→ also have androgenic activity
25
Mifepristone
Antiprogestin
| Blocks binding to progesterone receptors and glucocorticoid receptor
26
Danazol
Antiprogestin
| Weak progestin, androgen, and glucocorticoid that suppresses ovarian function
27
Progesterone acts on
Acts on nuclear protein receptors→ DNA→ mRNA synthesis→ protein synthesis
28
Progesterone + uterus
converts endometrium to secretory state→ maintains pregnancy by suppressing uterine contractility
29
Progesterone + endocervical glands
regulates composition of cervical mucus
30
Progesterone + body temp
Increases body temperature (thermogenic)
31
Progesterone + breasts
lobuloalveolar development in mammary ducts, pregnancy, puberty
32
Oral combination pill: estrogen + progesterone
Inhibit LH surge→ no ovulation
Cause changes in cervical mucosa and endometrium that decrease implantation
Discontinuation→ bleeding at the end of the cycle
Low level estrogens reduce mid-cycle bleeding
33
Anabolic effects of androgens
Increased bone density, amino acid incorporation into muscle, red blood cell mass
Antagonize catabolic effects of glucocorticoids
34
Flutamide
Androgen receptor antagonist
35
High doses of spironolactone
Mineralocorticoid antagonist, Androgen receptor antagonist
36
Finasteride, Dutasteride
5 alpha reductase inhibitors→ no DHT→ suppresses male sex accessory organs without affecting libido
37
GLUT1
brain
38
GLUT2
beta cells of pancreas, Km=15-20 (highest Km=lowest affinity)
39
GLUT3
brain
40
GLUT4
Muscle, adipose tissue, Km=5, insulin-mediated
41
Glucagon
Hormone produced by alpha cells of pancreas→ regulates glucose, amino acids, +/- free fatty acid homeostasis
→ Increases blood glucose levels by mobilizing hepatic glycogen when available
42
Diazoxide
Non-diuretic thiazide, vasodilator, hyperglycemic
→ directly inhibiting insulin secretion
→ decreasing peripheral glucose utilization
→ stimulating hepatic glucose production
43
Metformin
Decreases glucose levels, insulin-independent
Increased: glucose removal from blood: AMPK, secretion of GLP-1
Decreased: glucose absorption from GI, glucagon levels, gluconeogenesis (mitochondrial enzyme inhibtion)
44
GLP1 and GIP
increase release of insulin
| released from bowel in response to glucose
45
GLP 1
inhibits glucagon release → decreased hepatic gluconeogenesis
46
DDP-4 (dipeptidyl peptidase)
binds to and degrades GLP-1 and GIP
47
GLP-1 agonists
| "tides"
GLP-1 agonists resistant to DPP-4 degradation
48
DPP-4 inhibitors
| "gliptins"
DDP-4 inhibition potentiates the effect of endogenous incretin hormones
49
SGLT-2 inhibitors
| "flozins"
inhibit sodium-glucose co-transporter 2 (SGLT-2) in the kidney
50
Thiazolidinediones
| "glitazones"
Insulin sensitizers→ specifically target insulin resistance
Ligand of the nuclear PPAR-gamma receptor→ post-receptor insulin mimetic action:
Increased glucose transporter synthesis in adipose
Decreased hepatic glucose production
51
Alpha glucosidase inhibitors
Acarbose
Miglitol
Inhibition of alpha glucosidases in small intestine→ delayed carbohydrate digestion and absorption
52
Sulfonylureas
Binding to and blocking ATP-sensitive K+ channel→ depolarization→ Ca++ influx in beta cells→ insulin exocytosis
53
Meglitinides
| “Glinide”
Binding to and blocking ATP-sensitive K+ channel→ depolarization→ Ca++ influx in beta cells→ insulin exocytosis
54
Colesevelam
Bile acid binding resin
| MOA for glycemic effect unknown
55
Bromocriptine
Quick acting dopamine agonist
Augments low hypothalamic dopamine levels→ inhibition of excessive sympathetic tone in CNS→ decreased post meal plasma glucose levels due to enhanced suppression of hepatic glucose production
56
Pramlintide
Synthetic analog of amylin, a hormone co-secreted with insulin
→ regulation of postprandial glucose:
Decreased gastric emptying
Suppression of postprandial glucagon secretion
Centrally mediated modulation of appetite→ decreased caloric intake
57
Oxytocin
Cyclic octapeptide stored in posterior pituitary
| Suckling/cervical pressure→ release
58
Ergot alkaloids
Activation of serotonin receptors and alpha receptors→ contraction of uterine smooth muscle
59
Synthetic prostaglandin E2 (Dinoprostone)
causes:
expulsion of uterine contents
Cervical ripening prior to delivery at term
60
Prostaglandin: PGF2 alpha derivative (15 methyl) (caboprost tromethamine)
Induce abortion in 13th and 20th week
| 3rd line: postpartum bleeding due to uterine atony
61
Tranexamic acid
Inhibits plasminogen activation→ antifibrinolytic
62
Magnesium Sulfate (MgSO4)
Unknown
| Relaxes uterus, probably direct effect
63
Nifedipine
L-type calcium channel blocker→ inhibits Ca++ influx→ inhibits smooth muscle contraction
64
Indomethacin
Inhibits COX enzyme→ reduction of prostaglandin synthesis
65
Prophylactic Progesterone
Maintaining length of pregnancy from 16th week-37 weeks/delivery
→ high risk women with a history of preterm birth
→ approved for use in assisted reproductive technology to maintain the luteal phase following IVF or intracytoplasmic sperm injection
66
Nitroglycerin
100 ug IV bolus → sudden transient cervicouterine relaxation within 45-90 seconds, lasting about 1 minute
67
Ethanol
Direct relaxant effect on myometrium
| Inhibits oxytocin release
68
Thioamides
Inhibits synthesis of T4
| Propylthiouracil: Blocks conversion of T4→ T3
69
Iodide
Decreases synthesis and release of T3/T4
| Short term effect: 2-8 weeks
70
Radioactive Iodine
| I-131
Small amounts microCi=diagnostic
| Large amounts mCi=destroys gland
71
Propranolol
Non-specific beta blocker
| Specifically inhibits conversion T4→ T3
72
OPG=osteoprotegerin
comes from osteoblasts, blocks RANKL
73
RANKL
ligand for receptor for activation of nuclear factor-kB → positive effect on osteoclast, preosteoclast
stimulated by Vit D
74
Calcitonin
Decreases bone resorption of calcium
| Antagonizes PTH
75
PTH drugs
→ more osteoblast activity→ osteoporosis in men/postmenopausal
PTH and PTHrP bind to PTH receptor type 1 (PTHR1) RG conformation on osteoblast→ activation:
Decreased new fractures
Stimulates formation of new bone: ONLY anabolic drugs
rhPTH also binds PTHR1 R0 confirmation→ more osteoclast activity→ hypoparathyroidism tx
76
Denosumab
Antibody against receptor activator of nuclear factor kappa-beta ligand (RANKL)
→ inhibits bone resorption
→ inhibits RANKL-mediated osteoclast maturation
77
Bisphosphonates
P-C-P bond analogs of pyrophosphate→ substitutes for PO4 in Ca++ binding→ incorporates into bone→ inhibit resorption
Mechanism unclear: inhibition of osteoclasts, bone resorption
78
Fludrocortisone
Mimics aldosterone
Has mineralocorticoid and some glucocorticoid activity
Used to treat adrenal insufficiency refractory to glucocorticoids alone: inadequate salt/water retention
79
Hydrocortisone
Slow onset and long lasting: Bind to cytoplasmic receptor (nuclear receptor) → simulate gene transcription
Some rapid actions (poorly understood)
80
Prednisone/Prednisolone
Glucocorticoid>mineralocorticoid
| Prednisone: Must first be activated by liver: converted to prednisolone
81
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Triamcinolone
Methylprednisolone
Betamethasone
Dexamethasone
Fluticasone
```
Newer glucocorticoid drugs→ Virtually no mineralocorticoid activity
82
Ketoconazole
Corticosteroid synthesis inhibitor
Antifungal that inhibits steroid synthesis at very high doses
Non-selective
83
Mitolane
Corticosteroid synthesis inhibitor
| Adrenocrotioclytic→ causes adrenocortical atrophy→ used for primary adrenal carcinoma
84
Metyrapon
Corticosteroid synthesis inhibitor
| Selective inhibitor of terminal enzyme in cortisol synthesis
85
Mifepristone
Antagonist of glucocorticoid and progesterone receptors
