cases model answer for Hormones final.pptxcases model answer for Hormones final.pptxcases model answer for Hormones final.pptxcases model answer for Hormones final.pptx

1. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
A.H is a 45 year old man, has been diagnosed with lung cancer 2 years ago, Recently he suffered from weakness, weight
loss and other symptoms of cachexia, He also suffered from chemotherapy-induced lower testicular function.
From Medicinal chemistry point of view examine the following agents then answer the following questions .
A)17α-Methyl
testosterone
D)Finasteride
B)Testosterone Cypionate C)Stanozolol
1. Select the most suitable drug(s) for this case, justify your selection
Male sex hormones
Case 1
Hormonal Drugs

2. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
This patient is suffering from:
1. Cachexia symptoms.
2. lower testicular function
So he needs a testosterone derivative that provides both anabolic and androgenic effects So
Drug A (17α-Methyl testosterone) (Orally)
and B (Testosterone Cypionate) (Long-acting IM depot preparation) are the DOC in this case.
While other drugs couldn’t be used due to:
Drug (C) Stanozolol
(It is a heterocyclic analogue
(pyrazole) of 17α-methyl DHT)
Due to removal of the 19-CH3 group
results in ↓ of the androgenic
properties and retention of its
anabolic properties.
And Due to the presence of pyrazole
ring it lacks androgenic effect that is
required for the patient. But only has
anabolic effects, so couldn’t be used
in this case
✓ It is effective orally
as anabolic agent in
females.
✓ Has Anabolic with
No androgenic
activity
Drug (D) Finasteride.
(Selective inhibitor of type II
5α-reductase enzyme
(responsible for the conversion
of testosterone to the more
potent DHT)
✓ It has no affinity for the AR
(Androgen receptors) and hence has
No androgenic effects (has no
hormonal effect). So, it's
contraindicted in this case.
✓ It is effective orally
in the treatment of :
A) Benign prostatic
hyperplasia.
B) Androgenic
alopecia.

3. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
2. Explain the role of the encircled groups in drugs (A & D)
3.Clarify the effect of removal of the encircled group in drug B.
The removal of the 19-CH3 group results in:
1. Reduction of the androgenic properties
2. Retention of its anabolic (tissue-building) properties.
Drug
(A)
17α-Methyl
group
✓ Makes the drug orally active and overcoming the rapid metabolism of testosterone
(The natural androgen-Testosterone- is inactive orally due to rapid hepatic oxidation
into the relatively inactive 17-ones).
Drug
(D)
4-azasteroid
17-amide
✓ Have no androgenic effects.
✓ Increase affinity to type II 5α-reductase enzyme.
✓ Effective orally.

4. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
S.A 45 year old hypertensive female
physician
suffered from weight loss, muscle weakness after long
period of hospitalization. Her prescribed her deep IM anabolic agent. But she wants
to shift to another oral medication. She
view
also complained of having excessive hairy skin.
From Medicinal chemistry point of examine the following agents then answer the
following questions.
C)Stanozolol
A)17α-methyltestosterone B)Fluoxymesterone
D)Nandrolone decanoate
R=COC9H20
E) Testosterone Cypionate
Case 2

5. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
1. Select the most suitable oral drug for this case, justify your selection.
This patient is Female suffering from:
I.
II.
Muscle wasting.
Having excessive hairy skin.
✓ So she needs anabolic derivatives that lack any androgenic effects, So Stanozolol is the drug of choice .
2. Select the drug responsible for the hairy skin side effects appearing on the patient, justify your selection.
The correct answer is: Drug (D) Nandrolone decanoate.
The reason(s):
✓ It is deep IM agent with minimal androgenic activity and increased anabolic activity to overcome her muscle
weakness.
So you have to select drug D not E
✓ Despite that negligible androgenic properties of Nandrolone it caused hairy skin side effect due to minimal
activation of androgenic receptors in that female.
✓ Drug E (Testosterone cypionate taken IM but has both androgenic and anabolic activity so contraindicated in this
case)

6. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
3. Select drug(s) contraindicated in this case, justify your selection.
Drug NO Generic name Cause of contraindication
Drug (A) 17α-
methyltestosterone.
Has both androgenic and anabolic activity in equal ratio.
✓ (C/I: Female)
Drug (B) Fluoxymesterone. 9α-fluoro increases:
✓ The anabolic activity 20 times
✓ The androgenic activity 10 times than parent drug
(17α- methyltestosterone)
(C/I: Female).
✓ Sodium and water retention (edema) (similar to glucocorticoids).
✓ (C/I: Hypertension)
Drug (E) Testosterone
Cypionate
Has both androgenic and anabolic activity in equal ratio
(C/I: Female)

7. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
G.C 56 year old man with
he
a history
was
of poor liver functions suffered from urinary retention and
enlarged
From
prostate diagnosed with
the
benign prostatic hyperplasia.
Medicinal chemistry point of view examine following agents then answer the
following questions.
B)Medroxy
progesterone acetate
D)Finasteride
A)Alfatradiol C)Flutamide
Case 3

8. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
1. Select the most suitable oral drug for this case, justify your selection
The correct answer is: Drug D (Finasteride)
The reason(s):
✓(Finasteride) (Drug D) decreases level of testosterone in prostate by in hibition of 5 α -Reductase enzyme (Which
is
responsible for testosterone activation) so it is the DOC for treatment of Benign prostatic hyperplasia.
✓While Alfatradiol (Drug A) is 5α-Reductase inhibitor, but it is used topically for the treatment of androgenic
alopecia (hair loss) in men and women.
✓Drug (B) is Medroxy progesterone acetate which is steroid hormone related to progesterone not related to our
case.
✓(Drug C) (Flutamide) is Nonsteroidal Antiandrogens block androgenic receotors which could be used in
malignant prostatic cancer not benign

9. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
2. Mention the effect of epimerization of the encircled group in drug A.

10. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
3. Clarify the possible metabolic pathways of drug C.
• Extensive 1st pass metabolism (Hydroxylation) give major more potent metabolite named 2-hydroxyflutamide by
CYP1A2.
• The reduction of the nitro group is catalyzed by NO synthases with the formation of either or both hepatotoxic
metabolites:
1. Nitro anion free radical.
2. Hydroxylamino derivative.

11. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
L.A 34 year old woman with low level of estrogen after uteroectomy, her physician prescribed her a long acting oral
hormonal replacement therapy.
From Medicinal chemistry point of view examine the following agents then answer the following questions
B)Quinesrtrol
A)Estradiol 3,17 propionate
D)Ethinyl estradiol
C)Fulvestrant
Female sex hormones
Case 1

12. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
1. Select the most suitable oral drug for this case, justify your selection
The correct answer is: Drug (B) Quinesrtrol
The reason(s):
✓ As its Long acting hormonal replacement that could be used
orally
✓ While other de riv a tives couldn’t be used du e to :
Drug(A) Estradiol 3,17 di-
propionate
Intermediate acting hormonal replacement.
Used parentally.
Drug(C) Fulvestrant It is a complete estrogen receptor antagonist with
no agonist effects so its contraindicated here.
It is used for treatment of breast cancer
Drug(D) Ethinyl estradiol Short acting hormonal replacement
Used Orally

13. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
2. Clarify the activation pathway of compound B.
3. Role of the encircled group in structure C upon its pharmacological activity is …
✓ The lipophilic moiety pentafluropentylsulfinylnonyl converts the compound into a competitive receptor
antagonist. It is used for treatment of breast cancer.

14. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
F.A 65 year old postmenopausal woman diagnosed with osteoporosis with medical history of uterine cancer. her
physician prescribed her oral medication to overcome her case
From Medicinal chemistry point of view examine the following agents then answer the following questions .
A)Diethylstilbestrol B)Tamoxifen C) Raloxifene D)Letrozole
1. Select the most suitable oral drug for this case, justify your selection
The correct answer is: Drug (C) Raloxifene
Case 2

15. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
The reason(s):
As it is Selective Estrogen Receptor Modulator (SERM)
I. Estrogen agonist effects on bone and lipid metabolism (To overcome her postmenopausal symptoms
(Osteoporosis)).
Estrogen antagonist effects on the breast and endometrium (safe in her uterine cancer).
II.
It is safe in cases with uterine and breast cancer.
While other drugs couldn’t be used due to:
Drug (A) Diethylstilbestrol
(DES)
Synthetic Non-
Steroidal Estrogen
(Hormonal Replacement therapy).
Increase risk of uterine cancer
Drug (B) Tamoxifen Selective Estrogen Receptor Modulators (SERMs)
Antagonist in breast tissue
but is agonist in bone and uterus
(increases risk of uterine cancer).
C/I in uterine cancer.
Not C/I in breast cancer.
Drug (D) Letrozole Non-Steroidal aromatase inhibitors.
They reversibly bind to the aromatase enzyme so inhibit its action
. Aromatase enzyme convert androgens to estrogens in peripheral
(extra-gonadal) tissues. so letrozole depletes the last amount of
estrogen that may present in her body so this will exacerbate her
postmenopausal symptoms.
It is used in treatment of breast cancer.

16. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
2.Mention the optimum configurational isomer of drug A to give estrogenic effect, justify your selection.
✓ A trans isomer, has 10-fold the estrogenic potency of its cis-isomer, largely because the trans isomer more closely
resembles estradiol.
✓ The distance between the two phenolic OH groups was the same as the 3- OH to 17β -OH distance in estradiol, so it
could fit the same receptor.

17. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
✓ Important positions in steroid nucleus ►►
✓ 5α-dihydrotestosteron [DHT] is more potent than Testosterone.
➢ Medical uses:
✓
✓
(Promoting male sex characteristics and sperm production).
(Muscle building and stimulating protein synthesis).
➢ What would happen if men used testosterone esters for their anabolic effect??
➢ Health risks involving the cardiovascular system include heart diseases occur.
➢ And effects to the reproductive system as sexual dysfunction, sterility, prostate enlargement.
Androgenic activity
Anabolic activity (
Important notes: Male sex hormones

18. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
➢ Route of
administration:
3.
4.
Long acting injectable products: Testosterone 17β-esters (The prodrug Testosterone Cypionate).
Orally active products: 17α-Methyltestosterone, Fluoxymesterone, Stanozolol.
17α-Methyltestosterone
(17α-Methyl group)
Fluoxymesterone (9α-halogen) Stanozolol
(Pyrazole ring)
✓ 17α-Methyl group
makes the drug orally
active and
overcoming the rapid
hepatic oxidation of
testosterone to the
relatively inactive 17-
ones).
✓ Anabolic and androgenic activity.
✓ Edema (similar to
glucocorticoids due to 9α-fluoro
a nd 11 α -
hydroxy).
✓ Anabolic with No
androgenic activity due to
removal of
the 19-CH3 group results in
↓of the androgenic properties
and retention of its anabolic
properties
✓And Due to the presence of
pyrazole ring it lacks
androgenic effect that is
required for the patient. But
only has anabolic effects, so
couldn’t be used in this case

19. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
1. Androgen receptor antagonists: (
2. 5α-reductase inhibitors:
) used in prostatic carcinoma.
✓
✓
Used topically for the treatment of Androgenic Alopecia (hair loss) in men and women.
: Used in Benign prostatic hyperplasia and Androgenic Alopecia.
Female sex hormones
➢ Medical
uses:
✓
✓
and Treatment of Estrogen Deficiency (Ovarian Failure or after Oophorectomy).
: Estrogen increases absorption of calcium and synthesis of vitamin D needed for Ca2+
absorption.
➢
✓ 17α-ethynyl (ethinyl) group increases oral bioavailability.
✓ Ex: Ethynyl estradiol, Mestranol, Quinestrol.
✓ A trans isomer, has 10-fold the estrogenic potency of its
cis-isomer, As the distance between the two phenolic OH groups was the same as the 3-OH to 17β -OH distance in
estradiol.
Diethylstilbestrol (DES): Synthetic Non-Steroidal Estrogen:
Orally active estrogens
Hormone Replacement Therapy
Treatment of osteoporosis: Estro
Alfatradiol
Finasteride
Flutamide
Androgen Antagonists

20. Medicinal Chemistry-2 (PD-422) Level four-2022 B Pharm Program (C.H. System)
❖ Pure Estrogen Antagonists. Ex.
❖ Selective Estrogen Receptor Modulators (SERMs, a drug that has tissue specific estrogenic agonist or antagonist
activity): Tamoxifen, Raloxifen.
❖
❖ Aromatase Inhibitors: Block the conversion of androgens to estrogens in peripheral (extra-gonadal) tissues.
➢ Non-Steroidal aromatase inhibitor
cancer.
First-line treatment of postmenopausal women with breast
(Letrozole)
Drug Tamoxifen Raloxifen
Agonist • Bone
• Uterus
• ttt of
osteoporosis.
• Increasing risk of
uterine cancer.
• Bone
• Lipid
metabolism
• ttt of osteoporosis.
Antagonist • Breast • ttt of breast
cancer.
• Breast
• Uterus
(endometrium)
• Safe in breast & uterine
cancer.
Fulvestrant
Estrogen Antagonists