Steroid-based drugs

Question 1

Aldosterone

Answer 1

• Stimulated by ATCH and Angiotensin 2
• Produced by Zona Glomerulosa of adrenal cortex
• C21 no C17 hydroxylation, Pregnenolone rate limiting step for steroid synth., C21 hydroxylase prevents C17 hydroxylation of progesterone-> mineralocorticoids

Question 2

Glucocorticoid

Answer 2

• Stimulated by ACTH
• Produced by Zona Fasciculata of adrenal cortex
• C21 with hydroxylation at C17 by C17 hydrolylase

Question 3

Androgens

Answer 3

• Produced by Zona reticular is

- Testosterone->C19 with C17 hydroxylation by P450C17alpha hydroxylase-> 17-keto-steroids, also C3 keytone

Question 4

Estrogen

Answer 4

-C18, C17 hydroxylation or keytone, C3 hydroxylation

Question 5

Effects of Glucocorticoids

Answer 5

• Promotes fetal lung development
• inhibits NFkB nuclear translocation-> production of inflammatory mediators
• Upregulates lipocortin-> inhibits PLA2-> no PG and LT production

Question 6

Negative effects of Glucocorticoids

Answer 6

• immune suppressant
• increased glucose release and subsequent fat production
• increased protein catabolism-> muscle atrophy
• Decreased ACTH-> decrease aldosterone-> water retention-> hypertension
• Osteoperosis

Question 7

Addison’s disease

Answer 7

• Failure of adrenal cortex
• Chronic fatigue and muscle weakness
• Loss appetite, inability to digest food, weight loss
• Increased production of Aldosterone-> diuresis-> hypotension
• No negative feedback-> increased ACTH-> Increased melanin->Blotchy,dark tanning and freckling of the skin
• Inability to cope with stress
• Blood sugar abnormalities

Question 8

Cushing’s Syndrome

Answer 8

• Tumor in the adrenal cortex, GC overproduction
• Upper body obesity, “buffalo hump”
• Red, round “moon face”
• Hypertension
• Water retention
• Thin skin and bruising, poor healing

Question 9

Hydrocortisone

Answer 9

• Cortisol
• Main glucocorticoid in humans
• Binds Mineral corticoid receptor as well(cortisone doesn’t)
• Uses: Replacement therapy for Addison’s disease, Mostly topical application due to sodium retaining effects
• Dosage should be taken in the morning to not effect circadian rhythm

Question 10

Prednisone

Answer 10

• Glucocorticoid, Inactive until converted to Prednisolone

- Drug of choice for systemic application, lower sodium retaining effects

Question 11

Triamcinoline

Answer 11

• GC, 5x stronger anti-inflamitory than Cortisol

- No Na retaining effects

Question 12

Betamethasone

Answer 12

• Halogenated GC
• 30x more potent than cortisol, no Na or water retention effects
• Dexamethasone

Question 13

Effects of Estrogen

Answer 13

• Brest development
• Improve bone density
• Growth of uterus
• Accelerated bone maturation and epiphysis closure
• Development of endometrium
• Promote vaginal mucus thickening
• Increase HDL

Question 14

Three main endogenous estrogens

Answer 14

• Estradiol(primary estrogen), Estrone, Estriol(made by fetus)
• Estradiol not suitable for oral administration, Hepatic elimination
• Estrogens used for replacement therapy(turner syndrome, menopause), contraception, cancer therapy

Question 15

Ethinylestradiol

Answer 15

-Stable estrogen derivative protected from hepatic elimination by Alkyne

Question 16

Diethyl-Stilbestrol

Answer 16

• Stable estrogen derivative

- Stilbene derivative, 2 benzene rings connected by ethylene

Question 17

Mestranol

Answer 17

• Used in oral contraceptives

- Ethinylestradiol with C3 Methoxy group, inactive until cleaved

Question 18

Raloxifen

Answer 18

• Selective estrogen receptor modifier(SERM)
• Estrogenic effects on bone and lipid metabolism
• Antiestrogenic effects on breast and endometrium
• Used in post menopausal ostioperosis

Question 19

Tamoxifen

Answer 19

• Antiestrogen effects on mammary tissue
• Weak estrogenic effects on bone and lipid metabolism
• Used to treat breast cancer

Question 20

Clomiphene

Answer 20

• Antiestrogen, Inhibits estrogen binding in the pituitary-> prevention of negative feed back-> ovulation
• Used to treat infertility

Question 21

Hydroxyprogesterone

Answer 21

• Progesterone derivative, avoid hepatic elimination, older formulation
• Inhibits rhythmic contractions of myometrium
• Medroxyprogesterone

Question 22

Norgestol

Answer 22

• Testosterone derivative with progesterone activity

- Norethindrone, Desogestrel

Question 23

Mifepristone

Answer 23

-RU486, Progesterone receptor antagonist-> Endometrial decidual degeneration, followed a few days later by prostaglandin administration-> abortion

Question 24

Testosterone

Answer 24

• Oral administration hepatic elimination, also Fluoxymesterone
• Short half-life after injection-> etser derivatives, Proprionate

Question 25

Nandrolone

Answer 25

• Testosterone with anabolic effects dominant
• Injection
• Stanozolol: oral administration

Question 26

Flutamide

Answer 26

• Anti-androgen, Non-steroidal receptor antagonist

- Used in prostate cancer treatment

Question 27

Finasteride

Answer 27

• 5alpha reductase inhibitor-> prevent DHT production

- Used to treat prostate gland enlargement and hair loss

Question 28

Danazol

Answer 28

• Inhibit GnRH release-> block LH/FSH production-> no steroid production
• used to treat endometriosis

Question 29

Gonadorelin

Answer 29

• Synthetic GnRH 200x more potent than GnRH
• given in pulses-> gonadotropin release-> ovulation
• Continuous application desensitizes GnRH receptors-> gonadal suppression-> medical castration
• Used in sex hormone dependent conditions (prostate, breast cancer, endometriosis,uterine fibrosis)
• Side effect: menopausal symptoms

Question 30

Contraception Mechanism

Answer 30

• Estrogen inhibits FSH-> suppresses follicle development
• Progesterone inhibits LH-> suppresses ovulation and increases mucus viscosity
• Both effect endometrium-> implantation

Question 31

Mini Pill

Answer 31

• Contains only estrogen, levonorgestrel
• Used with patients with estrogen contraindications, thrombosis
• Taken daily without interruption, less reliable
• Acts mainly by increasing mucus, cough medicine cause failure

Question 32

Combination birth control pill

Answer 32

• Highly effective
• Ethinylestdiol or mestrnol
• Progesterone component varies
• 21 day with 7 day break, bleeding
• Can be mono or bi-phasic

Question 33

Postcoital contraceptives

Answer 33

• High doe of progesterone (levonorgestral)
• Must be taken within 72 hrs
• Nausea and vomiting are common

Question 34

Depot and patch formulations

Answer 34

• Injection of oily depot formulation every 3 months

- Transdermal formulation

Question 35

Birth control side effects

Answer 35

• Thrombosis
• Hypertension
• Nausea
• Weight gain
• Loss of libido
• Intermittent bleeding
• Depression