Transcript estrogens & androgens

Diuretics
Practice Questions
1
Pharmacology Practice Questions
1 - An 80-yr old woman with a history of acute
MI & CHF presents to the ER Dept with a
chief complaint of fever and lethargy. After a
full workup a urinalysis is performed, yielding
a specimen with a pH 5.5 & increased NaCl, K,
& Ca concentrations. Which of the following
drugs would cause results consistent with the
urinalysis findings?
2
Pharmacology Practice Questions
A – Acetazolamide
B – Furosemide
C – Spironolactone
D – Thiazides
E - Triamterene
3
Pharmacology Practice Questions
2.
A 72 yr-old male is treated for CHF,
HTN and diabetes mellitus. He
experienced a MI 2 yrs ago. He
presents to your office saying that he
has developed “cancer” in his right
breast because it has become
enlarged. Which of the following
drugs could be responsible for this
patient’s problem ?
Pharmacology Practice Questions
A. Hydrochlorothiazide
B. Torsemide
C. Aldosterone antagonist
D. Triamterene
E. Acetazolamide
F. Amiloride
G. Na channel blocker
3.
A 65-year-old female is hospitalized
with a hip fracture. Her bone density,
measured by quantitative X-ray
densitometry, corresponds to the
lowest 10%. Her comorbidities include
hypertension; diabetes mellitus, type
2; and congestive heart failure (CHE).
The attending physician suggests that if
this patient had received long-term
treatment with a drug affecting calcium
metabolism her fracture could have
been avoided.
Which drug is most likely
mentioned by the physician ?
A. Furosemide
B. Hydrochlorothiazide
C. Spironolactone
D. Digoxin
E. Enalapril
F. Glyburide
G. Acarbose
ESTROGENS & ANDROGENS
8
.
Quick Review:
Reproductive Physiology
During normal female reproductive years,
 ovulates once per month.
 Before the egg is released, it develops within a
small swelling or follicle or tiny cyst.
 Egg release heavily regulated by Gonadotropins:
LH & FSH and then E & P.
 E & P - assist in breast development and are the
main controllers of the menstrual cycle.
9
The
Menstrual
Cycle
10
Reproductive Loop
11
12
13
Estrogens
• Natural: Estradiol, estrone & estriol
• Conjugated: premarin (estrone and equillin)
• Steroidal synthetic: Mestranol & Ethinyl
estradiol
• Non-steroidal synthetic: Diethylstilbesterol
• Rationale for synthetic: to ↑ oralbioavailability, half-life and ↑ feedback
inhibition on FSH & LH
14
.
• Estradiol – Transdermal patch, IM
• Oral – Premarin ( Estrone + Equilin) , Estinyl
estradiol , Mestranol
• Excretion - Renal
15
.
Estrogens: Clinical Uses
• Contraception: ↓ feedback release of
gonadotropins
• Female Hypogonadism (estrogen + progestin) or
ovarian failure
• Estrogens for HRT - in menopausal women to ↓
bone resorption
• Uterine bleeding
• Dysmenorrhea
• Men with androgen dependent prostate cancer to
16
slow the growth of the cancer cell.
•
•
•
•
•
•
SIDE EFFECT:
Nausea
Breast tenderness
Endometrial hyperplasia
Increased skin pigmentation
Increased blood coagulation at high doses (V, VII,
X, I)
• Increased risk of endometrial cancer unless
progestin is added
• Breakthrough bleeding
• DES in utero - Clear cell adenocarcinoma of
vagina
17
Contraindicated
Patients:
• With estrogen-dependent neoplasm (e.g.
endometrial carcinoma)
• At higher risk for or with breast carcinoma
that are estrogen dependent
• Predisposed to thromboembolic disease (why
???)
18
.
SELECTIVE ESTROGEN RECEPTOR
MODULATOR (SERMS)
• Are non-steroidal compounds that bind to
estrogen receptors.
• They can act as either agonist, partial agonists
and antagonists depending on the tissue
19
.
Tamoxifene
• Tamoxifene:
Has various actions depending on the tissue
• Bone: agonist to prevent bone resorption
• Breast: antagonist
• Endometrium: a partial agonist with the risk of
increasing endometrial cancer
• USES: estrogen dependent breast cancer
• SE: Hot flushes, nausea and vomiting
20
.
Raloxifene
• Bone: agonist
• Uterus and breast: antagonist
• USES: prophylaxis of postmenopausal
osteoporosis.
• SE: increased risk of DVT, pulmonary embolism
21
.
22
Clomiphene
• MOA: ↓ feedback inhibition→ ↑FSH and LH
• USE: for infertility caused by anovulatory cycle
such as those seen in patients with PCOS
• Side effect: multiple pregnancies, ovarian
enlargement
23
.
ANTI ESTROGENS
• Anastrozole:
• MOA: is an aromatase inhibitor, resulting in
decreased estrogen synthesis
• USE: estrogen-dependent postmenopausal
breast cancer.
24
.
25
Progestin's
• Progestins can be androgenic and antiestrogenic in
action
• Progesterone: major natural progesterone
• Medroxyprogesterone
• Norethindrone
• 17α-Hydroxyprogesterone
• Norgestrel
• Desogestrel: devoid of androgenic and
antiestrogenic actions
26
.
Clinical Uses: Progestins
Major uses:
• hormone contraception : ↑ feedback inhibition
esp LH → no ovulation
• hormone replacement treatment along with
estrogen to decrease endometrial cancer
• dysmenorrhea
27
.
Adverse Effects: Progestins
reduce plasma HDL ↑LDL = ↑↑ atherosclerosis
• Breakthrough bleeding - (mid-cycle bleed)
• Acne, weight gain and hirsutism (androgenic
effect)
28
.
ANTIPROGESTIN
• Mifepristone (RU-486):
• Used as an abortifacient, administered with
misoprostol (PGE₁)
• Also an antiglucocorticoid
• SIDE EFFECT: bleeding, GI effects(nausea,
vomiting) and abdominal pain
29
.
Hormonal Contraception
• Progestins (Mini pill) only (norethindrone or
norgestrel)
• Estrogens and progestins (combination pills)
• Progestin implants
• Post-coital contraception uses estrogen
(mestranol or etinyl estradiol)
Mechanism of Action: contraception
• ovulation-inhibition by suppressing
gonadotropins
• change in cervical mucus(progesterone)
30
.
• Drug interaction: p450 inducers ↓ contraceptive
effectiveness
• Can result in unwanted pregnancies
• Be careful of anti-epileptics
• Is there anti-epileptic drug that does not induce
p450 ?
31
.
• P450 Inhibitors
Don't join this group it will make your spirit go down...
SICKFACES.COM Group
.
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol..binge drinking
Chloramphenicol
Erythromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Grapefruit juice
P450 Inducers
CRAP GPS induce me to
madness!!
Carbemazepines
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbitone
Sulphonylureas
32
Combined oral contraceptive pill
ADVANTAGE
DISADVANTAGE
Reliable (<1% failure)
Taken daily
↓ risk of endometrial and ovarian cancer No protection against STDs
↓ pelvic infections
↑ triglycerides
↓ risk of osteoporosis
Depression, weight gain, nausea,
hypertension
No dysmenorrhea
Hypercoagulable state
33
SIDE EFFECTS
•
•
•
•
•
•
•
•
•
.
ESTROGENS:
Nausea
Bloating
Headache
Mastalgia
Increase skin pigmentation
Weight gain
Breakthrough bleeding
Withdrawal bleeding
34
•
•
•
•
•
PROGESTIN:
Weight gain
Hirsutism
Acne
Increase LDL
35
.
Adverse Effects of combined
ocps
• Venous Thromboembolic Disease
• breakthrough bleeding
• Withdrawal bleeding
• RISK FACTORS: Smoking, Increased age
36
.
ANDROGENS
• Testosterone - Cypionate,
Enanthate,Propionate
• dihydrotestosterone
• Fluoxymesterone
• Danazol
• Androstenedione
• Nandrolone
37
.
•
•
•
•
USES:
Male hypogonadism (e.g. 47 XXY)
For anabolic actions to increase muscle mass
Illicit use in athletes
38
.
Replacement therapy in men
•
•
•
•
•
Acne
excessive libido & erections,
increased muscle & bone mass,
aggravation of pre existing prostate cancer.
Reduce plasma HDL and increase LDL
39
.
Gynecological Disorders: Androgens
• Danazol
• used in the treatment of endometriosis which is
the growth of endometrial tissue outside the
uterus, especially in the pelvis.
40
.
SIDE EFFECTS OF ANDROGENS
•
•
•
•
•
•
SE:
Excessive masculinization
Premature closure of epiphysis
Aggression
Dependence and abuse
Depression of menses and hirsutism in women
41
.
She is Gorgeous … Yes !!!
42
Contraindications: Androgenic
Steroids
• Pregnant women: its teratogenic
• Children Androgens - Not used in children,
why???
• Men with prostatic carcinoma
43
.
Anti-Androgen
•
•
•
•
Cyproterone acetate
Flutamide
Finasteride
Leuprolide
44
.
Androgen Suppression &
Antiandrogens
Androgen Suppression:
• Symptomatic Management of prostatic
carcinoma
• Management of BPH
45
.
Antiandrogens
Conversion Inhibitors
Finasteride:
• Inhibits 5 alpha reductase
• decreases dihydrotestosterone levels in the
prostate
• Uses – BPH to reduce the size of the prostate
and male pattern baldness
• Has been replaced by α1 blockers in the
symptomatic treatment of BPH e.g. prazosin
.
46
Antiandrogens
Competitive androgenic Receptor Inhibitors:
• Cyproterone & Cyproterone acetate
Clinical use:
• Women - hirsutism
• Men - reduction of sexual drive
47
.
Antiandrogens
Flutamide
• Competitive inhibitor of androgens
• Used in androgen receptor positive Prostatic
Carcinoma
48
Bicalutamide
• Effective orally for the treatment of metastatic
prostatic cancer.
49
.