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ANDRADE, Ma. Triza D.

3E-Pharmacy
Pharmaceutical Chemistry II
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SEX HORMONES
Ovarian Hormones
NATURAL ESTROGENIC HORMONES
AND DERIVATIVE
Estradiol
Conjugated Estrogen
Estrone
Ethinyl estradiol


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Ethinyl Estradiol
Estrogen, Ethinyl, Ethinylestradiol, Synthetic estrogen,
Estrogen in the pill, Mestranol, EE, Envoid
A semisynthetic alkylated estradiol with a 17-alpha-ethinyl
substitution.
is a synthetic form of estrogen and is mainly used in various
hormonal contraceptives -- usually in combination with a
progestin.
It has high estrogenic potency when administered orally and is
often used as the estrogenic component in oral contraceptives.
Marketed mostly in combination with other compounds.
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tetracyclo[8.7.0.0,.0,]heptadeca-
2(7),3,5-triene-5,14-diol,
(1S,10R,11S,14R,15S)-14-ethynyl-15-
methyl-,
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tetracyclo[8.7.0.0,.0,]heptadeca
-2(7),3,5-triene-5,14-diol,
(1S,10R,11S,14R,15S)-14-ethynyl-15-
methyl-,
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tetracyclo[8.7.0.0
,7
.0
,
] heptadeca

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tetracyclo[8.7.0.0
,7
.0
,
] heptadeca
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tetracyclo[8.7.0.0
,7
.0
,
] heptadeca-
2(7),3,5-triene-5,14-diol,
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tetracyclo[8.7.0.0,.0,]heptadeca-2(7),3,5-
triene-5,14-diol, (1S,10R,11S,14R,15S)-14-
ethynyl-15-methyl-,
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STRUCTURE
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Mechanism of Action

Diffuse into their target cells and interact with
a protein receptor. Target cells include the
female reproductive tract, the mammary
gland, the hypothalamus, and the pituitary.
Estrogens increase the hepatic synthesis of
sex hormone binding globulin (SHBG),
thyroid-binding globulin (TBG), and other
serum proteins and suppress follicle-
stimulating hormone (FSH) from the anterior
pituitary.
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EE is prepared from estrone in one step by
ethinylation with ethyne, sodium and sodium
amide
SYNTHESIS
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INDICATION:
Moderate to severe vasomotor symptoms
associated with the menopause
Female hypogonadism
Prostatic carcinoma in the palliative therapy
of advanced disease
Breast cancer
Oral contraceptive
Emergency contraceptive
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The lower ethinyl estradiol amounts now available
in hormonal contraception enable women to obtain
both the contraceptive and non-contraceptive
benefits of birth control without as many of the
unpleasant side effects.
Ethinyl estradiol can assist in regulating your
period or help manage painful periods.
Because it helps to suppress ovulation, this
synthetic estrogen has also been found to lower
your risk of ovarian cancer, and due to
estrogens ability to block bone resorption, ethinyl
estradiol may help to increase bone mineral
density.
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CONTRAINDICATION
should not be used in women over 35 years
old who smoke due to the increased risk of
serious cardiovascular side effects.
Known or suspected carcinoma of the
breast, except in selected patients being
treated for metastatic disease.
Known or suspected estrogen dependent
neoplasia.
Known or suspected pregnancy.


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Active thrombophlebitis or
thromboembolic disease.
Undiagnosed abnormal genital bleeding.
A past history of thrombophlebitis,
thrombosis or thromboembolic disease
associated with the previous use of estrogen
containing compounds.

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ADVERSE EFFECT
Water and sodium retention, which may result in
edema, Weight gain, breast tenderness, and
breast enlargement. Changes in libido and
withdrawal vaginal bleeding are also reported.
Liver function impairment, jaundice and gallstones
may occur.
Headache, depression, dizziness, glucose
intolerance, and sensitivity to contact lenses are
described.
Large doses may produce hypercalcemia when
used in the treatment of metastatic carcinoma.
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Nausea, vomiting and diarrhea are common.
Dermatological effects include chloasma,
melasma, rashes and urticaria.
Erythema multiforme and erythema nodosum
occur.
Hypertension and thromboembolic disease
are reported.

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Brand Names w/ combination
Diane-35 Cyproterone Acetate + Ethinyl Estradiol
Althea Cyproterone Acetate + Ethinyl Estradiol
Yaz Drospirenone + Ethinyl Estradiol
Cyclen Ethinyl Estradiol + Norgestimate
Demulen Ethinyl Estradiol + Ethynodiol Diacetate
Desogen Ethinyl Estradiol + desogestrel

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ANTIDEPRESSANTS Tricylic
depressants
Dibenzocycloheptadiene
Amitryptylline

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AMITRYPTILINE
HYDROCHLORIDE
dibenzocycloheptene-derivative tricyclic antidepressant (TCA).
. In non-depressed individuals, amitriptyline does not affect
mood or arousal, but may cause sedation.
In depressed individuals, amitriptyline exerts a positive effect
on mood. TCAs are potent inhibitors of serotonin and
norepinephrine reuptake.
Tertiary amine TCAs, such as amitriptyline, are more potent
inhibitors of serotonin
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Dimethyl amine, {3-[(2Z)-
tricyclo[9.4.0.0
3,8
]pentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene]propyl}-, Hydrochloride

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Dimethyl amine

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Dimethyl amine, {3-[(2Z)-
tricyclo[9.4.0.0
3,8
]pentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene]propyl}-,

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{3-[(2Z)-
tricyclo[9.4.0.0
3,8
]pentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene]
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tricyclo[9.4.0.0
3,8
]pentadeca

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{3-[(2Z)-
tricyclo[9.4.0.0
3,8
]pentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene]
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Dimethyl amine, {3-[(2Z)-
tricyclo[9.4.0.0
3,8
]pentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene]propyl}-,

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Z
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Dimethyl amine, {3-[(2Z)-
tricyclo[9.4.0.0
3,8
]pentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene]propyl}-, Hydrochloride


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SYNTHESIS:



the hydrogenation of an aminopropylidene derivative of a
5H-dibenzo-[a,d]-cycloheptene to produce the corresponding
aminopropylidene derivatives of a 5 H-dibenzo-[a,d]-l0,1l-
dihydrocycloheptene.
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Mechanism of Action
inhibition of neurotransmitter uptake (neuronal uptake of
norepinerphrine and serotonin into presynaptic nerve
terminals).
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INDICATION
In the pharmacologic management of depressive illness
may be used in the depressed phase of bipolar affective
disorder or in melancholic or psychotic depression.
widely used as an atypical analgesic in the management of
several conditions including fibromyalgia and various
neuropathies
Amitriptyline can be also used in anxiety disorders, back pain,
chronic fatigue syndrome, headache in adults and children,
herpes zoster, Irritable bowel syndrome and pain control in
palliative care
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Typical patient who may take
Amitriptyline
patient suffering from a Major Depressive Episode
Depressed mood and/or loss of interest or pleasure (irritability)
Or any one of these:


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ADVERSE EFFECT
Anticholinergic effects: Blocking of acetylcholine receptors
leads to blurred vision, dry mouth, urinary retention,
constipation, and aggravation of glaucoma and epilepsy.
Cardiovascular: Cardiac over stimulation which can be life-
threatening in case of an overdose.
Orthostatic hypotension: Due to blockade of -adrenergic
receptors which also leads to reflex tachycardia.
Sedation: Especially prominent during the first weeks of
treatment.
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Endocrine: weight gain, increased or decreased libido,
impotence. In isolated cases: gynecomastia in the male, breast
enlargement and galactorrhea in the female.
Hematologic: agranulocytosis, eosinophilia, leukopenia, and
thrombocytopenia may occur as an idiosyncratic response.
Hypersensitivity: Occasionally: skin rash, photosensitization
(avoid excessive exposure to sunlight).
Gastrointestinal: Occasionally: nausea, vomiting, anorexia
Withdrawal: If prolonged treatment is terminated suddenly,
withdrawal symptoms may occur. These may include sleep
disturbances, gastrointestinal discomfort, anxiety, and
depression. These usually occur within 1 to 3 days of
termination and are mild and self-limiting.

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WARNING
Anticholinergic Effects : Because of its strong anticholinergic
properties, amitriptyline must be used with caution in patients
with urinary retention, benign prostatic hypertrophy, angle-
closure glaucoma or increased intraocular pressure.
Cardiovascular : Orthostatic hypotension, arrhythmias and
conduction abnormalities have occurred during therapy with
amitriptyline. Caution is advised if tricyclic antidepressants are
used in patients with pre-existing cardiovascular disease.
Sedation : Patients should be warned of the potential danger
of operating machinery or driving a motor vehicle if this
occurs.
Suicide : The potential for attempted suicide must always be
considered in depressed patients.

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One should avoid these while taking
the medication
Do not drink alcohol. It can cause dangerous side effects when
taken together with amitriptyline. This medication may impair
your thinking or reactions. Be careful if you drive or do anything
that requires you to be alert. Avoid exposure to sunlight or
tanning beds. Amitriptyline can make you sunburn more easily.
Wear protective clothing and use sunscreen (SPF 30 or higher)
when you are outdoors.
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ANTINEOPLASTIC AGENTS
Alkylating agents
ETHYLAMINES
Thiotepa
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THIOTEPA
(ThioTEPA) is a cancer chemotherapeutic member of the
alkylating agent group, now in use for over 50 years.
It is a stable derivative of N,N,N- triethylenephosphoramide
(TEPA).
It is mostly used to treat breast cancer, ovarian cancer and
bladder cancer. It is also used as conditioning for Bone marrow
transplantation.
Its main toxicity is myelosuppression
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Triaziridine, 1,1',1'-phosphorothioyl

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Aziridine
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thioyl
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Synthesis
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MECHANISMS OF ACTION
Thiotepa is an alkylating agent of the nitrogen mustard type.
Thiotepa is a trifunctional alkylating agent, and is cell cycle
phase nonspecific. Activity occurs as a result of formation of an
unstable ethylenimmonium ion, which alkylates or binds with
many intracellular molecular structures, including nucleic acids.
Its cytotoxic action is primarily due to cross-linking of strands of
DNA and RNA, as well as inhibition of protein synthesis.
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INDICATION:
Superficial papillary carcinoma of the urinary bladder.
Intracavitary effusion due to neoplasm of serosal cavities.
Bladder, kidney, and other urologic cancers
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CONTRAINDACATIONS
Renal, hepatic, or bone marrow dysfunction;
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Warnings/Precautions:
Bone marrow suppression; monitor blood and platelets weekly
during and for at least 3 weeks after therapy. Discontinue if
WBC 3000/mm3 or platelets 150,000/mm3. Monitor renal
and hepatic function. Use effective contraception if patient or
partner is of childbearing potential. Elderly. Pregnancy (Cat.D).
Nursing mothers: not recommended.


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Adverse Reactions:
Myelosuppression, fatigue, febrile or allergic reactions, inj site
reactions, urinary retention, dysuria, GI disturbances, anorexia,
alopecia, dizziness, headache, drowsiness, blurred vision,
amenorrhea, interferes with spermatogenesis. Intravesical
administration: rare: chemical or hemorrhagic cystitis.