Syllabus

Hormones :
- Steroidal
hormones
- Amino acid hormones
NSAID & Opium analgesics
Vitamins
Antiaging

 " Chemical Carriers of Information

in the body
and they reflect the effect of CNS on the whole
function of the body through the hypothalamus "
A substance capable of causing the DNA of a
specific cell to produce one or more specific type
of protein by synthesis, which will lead to the
action of this protein.
Chemical messengers that course through bloodstream
and enter tissues where they turn on switches to the
genetic machinery that regulate every thing from
reproduction to emotions, general health and well being.

Classification of
Hormones
According to their chemical structure, hormones are
classified into the following classes:
1) Amino acid based hormones:

The building units are Amino Acid, they are either

a) Single Amino Acid hormone:
e.g. T3 & T4 of thyroid gland
b) Poly amino acid hormones:
Which include oxytocin, vasopressin, ACTH, LPH,
GH, HCG, calcitonin, insulin and hypothalamic
hormones.

Steroidal hormones:) 2

Which comprise sex hormones and adrenocortical

.hormones

Steroidal Hormones

Sex Hormones
Male Hormones

Adrenocorticoid Hormones

Female Hormones

Glucocorticoids

Miniraloorticoids

STEROID CHEMISTRY
12
13

11
1
2

10

D
8

14

22

18
12

16
19

15

1
2

5
4

21

17

Cyclopentanoperhydrophenanthrene

10

11
9

14

16

15

5
4

D
8

23

17

13

24

20

Side-chains on steroid scaffold

27
25
26

Steroid Hormone Action

The steroid hormones act on target cells by binding with

high affinity to intracellular receptors, resulting in the
formation of steroid-recepcomplexes that regulate gene
expression and protein biosynthesis

Then binding of the nuclear steroid-receptor complexes to DNA and interaction with
various nuclear transcriptional factors initiate the transcription of the gene to produce
messenger ribonucleic cid (mRNA).The elevated mRNA levels result in increased
protein synthesis in the endoplasmic reticulum. These proteins include enzymes,
receptors, and secreted factors that subsequently result in the steroid Hormonal
response regulating cell function, growth, differentiation .

SEX HORMONES ) I(

Sex steroids, also known as gonadal steroids, are

steroid hormones which interact with vertebrate androgen
or estrogen receptors. Natural sex steroids are made by
the gonads (ovaries or testes), by adrenal glands, or by
conversion from other sex steroids in other tissues such as
.liver or fat
-Sex steroids play important roles inducing the body
changes known as primary sex characteristics and
secondary sex characteristics.

I.1) Female sex hormones

They are steroidal hormones produced normally in ovaries, placenta
and in lower amount in adrenal cortex and as traces in testes.
They are grouped in two categories Estrogens and Progestins.
Functions:

(1) Development of female reproductive system.

(2) Control of menstrual cycle and pregnancy.
(3) Responsible for secondary sex characters

A) Estrogens
They responsible for primary and secondary sex characters in
female, they present in high level in females and low level in
males. The major natural human estrogens are estradiol,
estrone and estriol.

OH

O
estradiol deyhdrogenase

HO

HO

estradiol

estrone

16a-hydroxylase

16a-hydroxylase
O

OH
OH

HO

OH
estradiol deyhdrogenase
HO

estratriol

16a-hydroxyestrone

They characterized by having (1) aromatic ring (A)

phenolic OH at C3) 2
(
estratri-ene nucleus) 3
(
Estradiol
The most potent endogenous estrogen, exhibiting high affinity for
estrogen receptor and potency when administered parentally.
However its duration is short when administrated orally due to rapid
degradation by intestinal flora and rapid inactivation in the liver.

 To overcome this problem

the -face of 17-OH should be protected by using bulky group.
That is due to the attack occurring from face of 17-OH, where the
-face is hindered by angular methyl at C-18.

i) Orally active estrogens

introduction of an ethinyl group at 17 -position or methylation of
the 3 -OH also afford long acting and orally used estrogens e.g.

advantage of alkylation 3-OH group

on-steroidal synthetic estroge

These are synthetic compounds having the same estrogenic activity as the
natural steroidal estrogens. They are mainly used orally. According to
their structure, they classified into the following

Stilbene derivatives) 1
Diethylstilbesterol(DES).

-DES can be viewed as steroidal nucleus but rings B and C were opened
and ring D become six member (trans ,/ -diethyle-4,4/-stilbene-diol) or
3,4 bis(p-hydroxyphenyl) hex-3-ene
-Trans form is 10 times more potent than cis form due to its similarity to
estradiol

SAR of Estrogens
distance between 3-OH and the hydrated
17B-OH are critical for the receptor

aromatic ring A and the phenolic OH group

are essential for the estrogenic activity

OH

R
C

Esterification of 3-OH or 17B-OH groups

increase duration and activity

Insertion of 17a-ethinyl moiety produced

orally activeand metabolic resistant
estrogen e.g. ethinylestradiol

HO

insertion of unsaturation in ring B

reduce the estrogenic effect

the intact D ring is not essential but the distance

between the hydrated 17B-OH and -C3-OH (12.1A) in
addition to the molecule distance (8.55A) are essential.

Therapeutic Uses:
-As a component of combination oral contraceptive and as
a hormone replacement therapy in postmenopausal women.
- Useful in preventing osteoporosis
-lower the incidence of heart attack in women over 60 years and
prevent vagainitis.

side effects:
The major side effects are cancer, thromoembolic disease, metabolic changes for carbohydrate and lipid, hypertension, nausea, migraine
.and change in mood

* Estrogen Antagonist
Antiestrogen can be classified into:
1) Estrogen antagonists-impeded estrogens
2) Triphenylethylene antagonists
3) Aromatase inhibitors

2) Triphenylethylene antagonists:
Mode of Action
They exhibit a strong and persistent binding to the estrogenic
receptor, producing antiestrogenic-receptorand complexes that
are either unable to translocate into the nucleus of target cells
or, if translocated, do not bind properly to the acceptor site of
the chromatin to produce an estrogenic response (competitive
estrogenic antagonists).
Clomiphene citrate (Clomid).
Cl

-Has both estrogenic and antiestrogenic properties

(partial agonist).
induce ovulation for the treatment of infertility -

O
N

CH3

CH3

-The Z isomer displays estrogenic activity and the E isomer has antiestrogenic activity but their mixture was found to have synergistic activity

Tamoxifen (Nolvadex)
-Tamoxifen is an estrogen agonist-antagonist
(partial agonist)
used as an antiestrogen in the treatment of. estrogen-dependent breast cancer
-orally administered as Z isomer which rapid
undergoes N-demethylation to its major metabolite
N-demethyltamoxifen or converted to its minor
metabolite, 4-hydroxytamoxifen which is the
active metabolite of Tamoxifen.

O
N
H3C

CH3

OH

O
N
H3C

CH3

3) Aromatase inhibitors
a) Steroidal aromatase inhibitors
These agents inhibit aromatase enzyme which responsible for
conversion of androgens to estrogens by aromatization of
ring A
O
O

O
O

S
OH

O
OH

O
OH
-4-hydroxyandrostenedione
( Formestane).

NH2
7a-P-aminophenylthioandrost-4-ene-3,17dione

-Testolactone

Therapeutic uses
Antiestrogens are used to
-Treat infertility in women.
Clomiphen stimulate ovulation by opposing the negative
feedback of endogenous estrogens resulting in increased
secretion of gonadotropins e.g. LH and FSH.
-In men, clomiphene stimulates gonadotropin release and
thus enhances spermatogenesis.
- Antiesrogens have been also used in the treatment of

breast cancer.

C) Progestins

are secreted by the corpus luteum of the overy during the menstrual cycle
of the non-pregnant females and during early pregnancy. They are
secreted also by placenta during the first weeks of pregnancy. Small
amounts of progestins are secreted from testes and adrenals
-The most abundant natural progestin is progesterone.

a) Natural progestins
Progesterone is the only active natural progestin.
It secreted just before ovulation.
O

Progesterone
Pregn-4-ene 3,20-dione

Pharmacological Action

control many functions such as normal menstrual bleeding, release

the ovum, preparation of uterine endometrium to receive fertilized
ovum, suppression of ovulation during pregnancy, maintenance of
pregnancy via depression of uterine contractility and development o
the alveolar system of the breast. Progesterone increase basal insulin
level and in turn enhances carbohydrate metabolism. It also enhances
fat deposition

17-Ethinyl-19-nortestosterone derivatives
OH

O
Testosterone

OH
C

Ethisterone
-15 times orally active as progesterone.
-few androgenic side effects.
-It used in treatment of menstrual dysfunction.

H3C

Norgestrel () or levonorgestrel (-)

methyl group at C18 provide more
protection for ring D.

OH
C

CH

CH

II.2) Androgens

Testosterone
a)Androgenic action
Controls the development and maintenance of the primary
and secondary sex characteristics of the male.

b)Anabolic action
Causes nitrogen retention by increasing the rate of protein
synthesis while decreasing the rate of protein catabolism.
maturation and mineralization of skeleton.
OH

Metabolism of testosterone
-5-position of testosterone is attacked by reductase
enzyme. If the attack takes place from the -face
by 5-reductase enzyme, it will give
5 Dihydrotestosterone (5DHT)

OH

If the reductase enzyme attacks take place from the -face, it will give
. Dihydrotestosterone (5DHT) which is inactive metabolite 5
Testosterone also, can be converted to estradiol by aromatase enzyme.
Mechanism of action
Binding of dihydrotestosterone to its receptor
dimerization
binding to a specific DNA
gene expression,
stimulation of new mRNA
protein biosynthesis.

 Classification of androgens according to the

androgenic / anabolic ratio
A) High androgenic / anabolic ratio
OR

1) Testosterone
Testosterone is orally inactive because
of rapid first pass metabolism to
. inactive 17-ketosteroid

(5) 17-Methyltestosterone

O
Testosterone propionate
Testosterone enanthanate
Testosterone cypionate

R= CH3CH2CO
R=CH3(CH2)5CO
R=
CH CH CO

pro-drugs

increased duration of action when given orally

b) Anabolic steroids
1) 19-norandrogens
2) 17-Methyltestosterone derivatives
3) 17-Testosterone acetate derivatives
1) 19-norandrogens
Removal of the 19-CH3 group of the androgen results in reduction of its
androgenic properties but retention of its anabolic, tissue-building proper.
OR

O
Nandrolone
R= H
Nandrolone decanoate
R= CH3(CH2)8CO
Nandrolone phenopropionate R=C6H5(CH2)3CO

OH
C2H5

OH
C2H5

O
Norethandrolone

Ethylestrenol

- Nandrolone
anabolic/ androgenic ratio is 4/1.
-Norethandrolone has oral and parentral anabolic activity without
androgenic and progestational side effects.

2) 17-Methyltestosterone derivatives
Oxandrolone
-2-oxasteroid analog of 17-methyltestosterone
which contains a lactone in the A ring
it has three times the anabolic activity of. 17-methyltestosterone

OH
CH3
O
O

Stanazolol

OH
CH3

another heterocyclic compound used for its

anabolic effects and contain pyrazole ring.
HN
N

ORAL CONTRACEPTIVES
COMBINATION TABLETS
The combinations of estrogens and progestins were very effective
as ovulation inhibitors.

SEQUENTIAL TABLETS
In sequential contraceptive treatment, an only
estrogen containing tablet is
.taken daily from 5th day to 22nd day of the menstrual cycle

PROGESTIN TABLETS
Higher doses of progestin are reported to produce suppression of
ovulation while it has been found that the amount contained in the
minipill do not suppress ovulation in all women

-They are synthesized in the cortex of the adrenal gland and

secreted under the influence of hypothalamo-pituitary peptides
The hypoth.
- Can be

CTR
classified

ACTH
into

glucocorticoids

and

mineralocorticoids.
Pathogenic condition
Addisons disease
-Hypoadrenalism
-weakness, anaemia, low Bp
Hyper-pigmentation of the skin
Mental depression.
-Caused by destruction of the cortex by T.B or atrophy, ACTH

Cushings disease (Hyperadrenalism)

-Caused by (1) adrenal cortex tumors
(2) Increased production of ACTH
due to pituitary carcinoma.
-Characterized by :
Hypertension , excessive retention of water
(odema).

Conns syndrome
Inability of the adrenal cortex to carry out 17-hydroxylation in
the biosynthesis of hormones, resulted in increase production of
mineralocorticoids on the expense of glucocorticoids which cause
-hypernatremia, polyuria, alkalosis and hypertension

Glucocorticoids
Medicinal uses
-Has phospholipase A2 inhibitory activity
Inhibite synthesis of
Both PG& leukotriens, so used as Anti inflammatory and
Anti asthmatics
-To prevent rejection of transplanted organs due to Anti immune
Properties.
- Replacement therapy.
-Most important natural glucocorticoids are cortisone and
Hydrocortison (cortisol), which are biochemically interconvertible
HO
HO

HO
O

OH

Hydrocortisone

Cortisone

O
OH

Glucocorticoids with enhanced anti-inflammatory

-Corticoids

Cortisone
Cortisole
HO

Prednisone

Prednisolone
HO

HO

OH

O
OH

Prednisone

Prednisolone

Triamcinolone (kenacort)

HO

-9-Fluoro-11, 16,17, 21 tetrahydroxy

Pregna-1,4-diene-3,20-dione

OH
OH
OH

F
O

This drug combines the structural features of both -Corticoids and

9-Fluoro corticoid
16 OH decrease the mineralocorticoid activity and causes sod.
Excretion
used in the form I.M inj. In treatment of dermatosis- more safe.

Mineralocorticoids
11-Deoxycorticosteron acetate (DOCA)
O

-21-Hydroxy-4-pregnene-3,20-dione acetate
-Shows 40 times the salt retention activity of
.Hydrocortisone and has zero anti-inflam
*It used for treatment of Addisons disease

O
OCCH3

Aldosterone

11,21-Dihydroxy-18-aldo-4-pregnen-3,20-dione
HOH2C

HOH2C
OH

CH=O

CH3

CH3
H

CH-OH

(Aldol form)

(Hemiacetal form)
Active form
Aldosterone is known as anti-diuretic hormone secreted by adrenal
cortex. It has 300 times the mineralocortical activity of hydrocort.
and only 0.2 times its anti-inflam. activity

SAR of corticosteroids
(1) 11-keto gp in cortisone must reduced
invivo to OH gp (Hdrocortisone) to be active.

HO

HO

O
(2) 9-Fluro:
a) prevent metabolic oxidation of 11 -OH to C=O
b) Increase activity (glucocorticoid) by its inductive effect, by
increase dissociation of 11 -OH so, increase formation of H-B to
biological receptor.

(3) OH gp in position 11,17 reduces the Na retention activity so,

mineralocorticoids have no OH at this position.
.9-Fluro > 9-Cl > 9-Br in retention of sod) 4(
Insertion of 16- OH gp decrease sod. Retention by a) opposite) 5(
.The effect of 9-Fluro b) increase sod. excretion

OH

Thyroid Functions & Thyroid

Drugs

Therapeutic Agents used for treatment of

Hyperthyroidism (Anti-thyroid Drugs)

1) Iodide
Mode of Action
Inhibition of the release of thyroid hormone by
decreases the vascularity of the enlarged thyroid
gland and also lowers the elevated BMR.
2) Methimazole, Propylthiouracil, and Related compounds
Thionamides are the most important class of antithyroid
compounds in clinical practice used in nondestructive therapy of
hyperthyroidism. These agents are potent inhibitors of thyroid
peroxides
enzyme (TPO) responsible for iodination of tyrosine residues of
thyroglobulin & the coupling of iodotyrosine residues to form
iodothyronines.

Thank you