PhChem Report

8/11/2019 PhChem Report

1/55

+

ANDRADE, Ma. Triza D.3E-Pharmacy

Pharmaceutical Chemistry II


2/55

+SEX HORMONES

Ovarian Hormones NATURAL ESTROGENIC HORMONES

AND DERIVATIVE

Estradiol Conjugated Estrogen Estrone

Ethinyl estradiol


3/55

+Ethinyl Estradiol

Estrogen, Ethinyl, Ethinylestradiol, Synthetic estrogen,Estrogen in the pill, Mestranol, EE, Envoid

A semisynthetic alkylated estradiol with a 17-alpha-ethinylsubstitution.

is a synthetic form of estrogen and is mainly used in varioushormonal contraceptives -- usually in combination with aprogestin.

It has high estrogenic potency when administered orally and isoften used as the estrogenic component in oral contraceptives.

Marketed mostly in combination with other compounds.


4/55

+

tetracyclo[8.7.0.0, .0, ]heptadeca-

2(7),3,5-triene-5,14-diol,(1S,10R,11S,14R,15S)-14-ethynyl-15-methyl-,


5/55

+

tetracyclo[8.7.0.0, .0, ]heptadeca

-2(7),3,5-triene-5,14-diol ,(1S,10R,11S,14R,15S)-14-ethynyl-15-methyl-,


6/55


7/55

+tetracyclo[8.7.0.0 ,7 .0 , ] heptadeca


8/55

+tetracyclo[8.7.0.0 ,7 .0 , ] heptadeca-

2(7),3,5-triene-5,14-diol,


9/55

+


10/55

+ tetracyclo[8.7.0.0, .0, ]heptadeca-2(7),3,5-triene-5,14-diol , (1S,10R,11S,14R,15S)-14-

ethynyl-15-methyl-,


11/55

+


12/55


13/55

+Mechanism of Action

Diffuse into their target cells and interact witha protein receptor. Target cells include the

female reproductive tract, the mammarygland, the hypothalamus, and the pituitary.Estrogens increase the hepatic synthesis ofsex hormone binding globulin (SHBG),

thyroid-binding globulin (TBG), and otherserum proteins and suppress follicle-stimulating hormone (FSH) from the anteriorpituitary.


14/55


15/55

+INDICATION:

Moderate to severe vasomotor symptomsassociated with the menopause

Female hypogonadism

Prostatic carcinoma in the palliative therapyof advanced disease

Breast cancer

Oral contraceptive

Emergency contraceptive


16/55

+ The lower ethinyl estradiol amounts now availablein hormonal contraception enable women to obtain

both the contraceptive and non-contraceptivebenefits of birth control without as many of theunpleasant side effects.

Ethinyl estradiol can assist in regulating yourperiod or help manage painful periods .Because it helps to suppress ovulation, thissynthetic estrogen has also been found to loweryour risk of ovarian cancer , and due to

estrogens ability to block bone resorption, ethinylestradiol may help to increase bone mineraldensity .


17/55

+CONTRAINDICATION

should not be used in women over 35 yearsold who smoke due to the increased risk ofserious cardiovascular side effects.

Known or suspected carcinoma of thebreast , except in selected patients beingtreated for metastatic disease.

Known or suspected estrogen dependentneoplasia .

Known or suspected pregnancy.


18/55

+

Active thrombophlebitis orthromboembolic disease.

Undiagnosed abnormal genital bleeding.

A past history of thrombophlebitis,thrombosis or thromboembolic diseaseassociated with the previous use of estrogencontaining compounds.


19/55

+ ADVERSE EFFECT

Water and sodium retention, which may result inedema, Weight gain, breast tenderness, andbreast enlargement . Changes in libido andwithdrawal vaginal bleeding are also reported.

Liver function impairment, jaundice and gallstonesmay occur.

Headache, depression, dizziness, glucoseintolerance, and sensitivity to contact lenses aredescribed.

Large doses may produce hypercalcemia when

used in the treatment of metastatic carcinoma.


20/55

+

Nausea, vomiting and diarrhea are common.

Dermatological effects include chloasma,melasma, rashes and urticaria.

Erythema multiforme and erythema nodosumoccur.

Hypertension and thromboembolic diseaseare reported.


21/55

+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


22/55

+ ANTIDEPRESSANTS Tricylicdepressants

Dibenzocycloheptadiene

Amitryptylline


23/55

+ AMITRYPTILINEHYDROCHLORIDE

dibenzocycloheptene-derivative tricyclic antidepressant (TCA).

. In non-depressed individuals, amitriptyline does not affectmood or arousal, but may cause sedation.

In depressed individuals, amitriptyline exerts a positive effecton mood. TCAs are potent inhibitors of serotonin andnorepinephrine reuptake.

Tertiary amine TCAs, such as amitriptyline, are more potentinhibitors of serotonin


24/55


25/55

+Dimethyl amine


26/55

+


27/55

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


28/55

+


29/55

+

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


30/55

+tricyclo[9.4.0.0 3,8 ]pentadeca


31/55

+

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


32/55

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


33/55

+Z


34/55

+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


35/55

+


36/55

+

SYNTHESIS:

the hydrogenation of an aminopropylidene derivative of a5H-dibenzo-[a,d]-cycloheptene to produce the correspondingaminopropylidene derivatives of a 5 H-dibenzo-[a,d]-l0,1l-

dihydrocycloheptene.


37/55

+Mechanism of Action

inhibition of neurotransmitter uptake (neuronal uptake ofnorepinerphrine and serotonin into presynaptic nerveterminals).


38/55

+INDICATION

In the pharmacologic management of depressive illness

may be used in the depressed phase of bipolar affectivedisorder or in melancholic or psychotic depression.

widely used as an atypical analgesic in the management ofseveral conditions including fibromyalgia and variousneuropathies

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 inpalliative care


39/55

+Typical patient who may takeAmitriptyline

patient suffering from a Major Depressive Episode

Depressed mood and/or loss of interest or pleasure (irritability)

Or any one of these:


40/55

+ ADVERSE EFFECT

A nt ich ol inergic effects : Blocking of acetylcholine receptorsleads to blurred vision, dry mouth, urinary retention,constipation, and aggravation of glaucoma and epilepsy.

Cardiov ascular : Cardiac over stimulation which can be life-

threatening in case of an overdose.

Orthos ta tic hypotens ion : Due to blockade of -adrenergicreceptors which also leads to reflex tachycardia.

Sedation : Especially prominent during the first weeks oftreatment.


41/55

+ Endocr ine : weight gain, increased or decreased libido,impotence. In isolated cases: gynecomastia in the male, breastenlargement and galactorrhea in the female.

Hem atologic : agranulocytosis, eosinophilia, leukopenia, andthrombocytopenia may occur as an idiosyncratic response.

Hypersensi t iv i ty : Occasionally: skin rash, photosensitization(avoid excessive exposure to sunlight).

Gastroin tes t inal : Occasionally: nausea, vomiting, anorexia

Withdrawal : If prolonged treatment is terminated suddenly,withdrawal symptoms may occur. These may include sleepdisturbances, gastrointestinal discomfort, anxiety, anddepression. These usually occur within 1 to 3 days oftermination and are mild and self-limiting.


42/55

+WARNING

An ticho l inergic Effects : Because of its strong anticholinergicproperties, amitriptyline must be used with caution in patientswith urinary retention, benign prostatic hypertrophy, angle-closure glaucoma or increased intraocular pressure.

Cardiovascular : Orthostatic hypotension, arrhythmias andconduction abnormalities have occurred during therapy withamitriptyline. Caution is advised if tricyclic antidepressants areused in patients with pre-existing cardiovascular disease.

Sedation : Patients should be warned of the potential dangerof operating machinery or driving a motor vehicle if thisoccurs.

Suic ide : The potential for attempted suicide must always beconsidered in depressed patients.


43/55

+One should avoid these while takingthe medication

Do not drink alcohol. It can cause dangerous side effects whentaken together with amitriptyline. This medication may impairyour thinking or reactions. Be careful if you drive or do anythingthat requires you to be alert. Avoid exposure to sunlight ortanning beds. Amitriptyline can make you sunburn more easily.Wear protective clothing and use sunscreen (SPF 30 or higher)when you are outdoors.


44/55


45/55

+THIOTEPA

(ThioTEPA) is a cancer chemotherapeutic member of thealkylating 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 andbladder cancer. It is also used as conditioning for Bone marrowtransplantation.

Its main toxicity is myelosuppression


46/55

+

Triaziridine, 1,1',1 '-phosphorothioyl


47/55

+ Aziridine


48/55

+thioyl


49/55


50/55

+Synthesis


51/55

+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 anunstable ethylenimmonium ion, which alkylates or binds withmany intracellular molecular structures, including nucleic acids.Its cytotoxic action is primarily due to cross-linking of strands ofDNA and RNA, as well as inhibition of protein synthesis.


52/55

+INDICATION:

Superficial papillary carcinoma of the urinary bladder.Intracavitary effusion due to neoplasm of serosal cavities.

Bladder, kidney, and other urologic cancers


53/55

+CONTRAINDACATIONS

Renal, hepatic, or bone marrow dysfunction;


54/55

+Warnings/Precautions:

Bone marrow suppression; monitor blood and platelets weeklyduring and for at least 3 weeks after therapy. Discontinue ifWBC 3000/mm3 or platelets 150,000/mm3. Monitor renaland hepatic function. Use effective contraception if patient orpartner is of childbearing potential. Elderly. Pregnancy (Cat.D).Nursing mothers: not recommended.


55/55

+ Adverse Reactions:

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

Documents

PhChem Report