EstrogensEstrogens

Natural Estrogens:Natural Estrogens:

Female Sex HormonesFemale Sex Hormones(Estrogens and Progestins)(Estrogens and Progestins)

Sex HormonesSex Hormones

HO

OH

OH

HO

O

HO

OH

17-estradiol Estrone Estriol

Structure Activity Relation Structure Activity Relation ShipsShips

AromaticAromatic ring with C-3-OH is ring with C-3-OH is essential for essential for activityactivity.. Steroidal Steroidal structures is structures is not essential for not essential for activityactivity.. Alkylation of the aromaticAlkylation of the aromatic ring ring decreasedecrease the activity.the activity. Unsaturation of ring B decreases the Unsaturation of ring B decreases the activity.activity. 1717αα- and 16 position when modified - and 16 position when modified enhance the activity.enhance the activity.

HO

OH

OH

HO

O

HO

OH

17-estradiol Estrone Estriol

Physiological EffectsPhysiological Effects Development of the female sexual organs.Development of the female sexual organs. Development of the female secondary sex Development of the female secondary sex

characters.characters. Control of the menstrual cycle.Control of the menstrual cycle.

UsesUses Birth control pills.Birth control pills. Failure of ovarian development.Failure of ovarian development. Menstrual disturbances.Menstrual disturbances. Postmenopausal osteoporosis.Postmenopausal osteoporosis. Prostate cancer.Prostate cancer.

Side EffectsSide Effects Nausea, vomiting and diarrhea.Nausea, vomiting and diarrhea. Sodium and water retention.Sodium and water retention. Inhibition of ovulation in large doses.Inhibition of ovulation in large doses.

Steroidal Estrogenic DrugsSteroidal Estrogenic Drugs

Estradiol:Estradiol: Most active natural estrogen.Most active natural estrogen. Very short duration of action. Very short duration of action. Mainly used for local effect on the uterus.Mainly used for local effect on the uterus.

Ethinyl estradiol:Ethinyl estradiol: 15- 20 more potent than estradiol orally.15- 20 more potent than estradiol orally.

HO

OHC CH

HO

OH

17-estradiol Ethinyl estradiol(Stertoidal Semisynthetic estrogen)

Nonsteroidal EstrogensNonsteroidal Estrogens

Diethylstilbestrol:Diethylstilbestrol: The The transtrans form is the active one. form is the active one.

Advantages:Advantages: As active as Estradiol.As active as Estradiol. Longer duration of action.Longer duration of action. Orally activeOrally active Cheap.Cheap.

Disadvantages:Disadvantages: Increase the risk of uterine cancer.Increase the risk of uterine cancer.

Uses:Uses: Treatment of prostate cancer.Treatment of prostate cancer.

OH

HO

ProgestinsProgestins

Progesterone in the major natural Progesterone in the major natural progestin.progestin.

Secretion:Secretion: By the ovary mainly the corpus By the ovary mainly the corpus luteum during the second half of the menstrual luteum during the second half of the menstrual cycle.cycle.

Physiological Effects:Physiological Effects: Development of the endometrium.Development of the endometrium. Development of the mammary gland during Development of the mammary gland during

pregnancy.pregnancy.

Structure Activity Relation-Structure Activity Relation-ships:ships:

Steroidal nucleus essential Steroidal nucleus essential for activity.for activity.

Removal of the 19 CHRemoval of the 19 CH33 increase activity.increase activity.

Unsaturation of ring B or Unsaturation of ring B or C increase the activity.C increase the activity.

Have some androgenic Have some androgenic activity.activity.

Removal of the keto Removal of the keto function remove function remove androgenic activity.androgenic activity.

O

O

Progestrogenic DrugsProgestrogenic Drugs

Lynestrenol:Lynestrenol: Semisynthetic progestin with pure Semisynthetic progestin with pure

progestrogenic activity.progestrogenic activity.

O

O

Progesterone(Natural)

OH

Lynesrenol(Synthetic)

C CH

Uses:Uses: Contraceptive pills.Contraceptive pills. Uterine bleeding.Uterine bleeding. Prevention of abortion.Prevention of abortion. Amenorrhea, dysmenorrhea, Amenorrhea, dysmenorrhea,

endometriosis.endometriosis. Renal and breast carcinoma.Renal and breast carcinoma.

Side Effects:Side Effects:

Nausea, vomiting, irregular bleeding, Nausea, vomiting, irregular bleeding, edema, weight gain.edema, weight gain.

Female Oral ContraceptiveFemale Oral Contraceptive

Sequential Preparations:Sequential Preparations: Estrogens for 16 days then Estrogen and Estrogens for 16 days then Estrogen and

Progesterone for 5- 6 days.Progesterone for 5- 6 days. 98- 99% successful.98- 99% successful.

Combination Preparation:Combination Preparation: Estrogens and Progesterone from the Estrogens and Progesterone from the

beginning to the end in small doses.beginning to the end in small doses. 99- 100% successful.99- 100% successful.

Mechanism:Mechanism: The above two types inhibit both FSH The above two types inhibit both FSH

and LH so prevent ovulation.and LH so prevent ovulation.

Female Oral Contraceptive (Cont.)Female Oral Contraceptive (Cont.)

Minipills:Minipills: Small doses of Progesterone from the Small doses of Progesterone from the

beginning to the end.beginning to the end. 97- 98% successful.97- 98% successful.

Mechanism:Mechanism: Alter the structure of the Alter the structure of the Endometrium.Endometrium.

Increase consistency of the cervical Increase consistency of the cervical mucus.mucus.

Male Sex HormonesMale Sex Hormones(Androgens)(Androgens)

Natural Androgens:Natural Androgens:

O

OH

Testosterone(Natural)

O

OH

Dihydrotestosterone(Natural)

H

Physiological EffectsPhysiological Effects Development of the male sexual organs Development of the male sexual organs

and male secondary sex characters.and male secondary sex characters. Anabolic effect.Anabolic effect.

UsesUses Replacement therapy in cases of Replacement therapy in cases of

hypogonadism.hypogonadism. Anabolic effect.Anabolic effect.

Side EffectsSide Effects Sodium and water retention leads to Sodium and water retention leads to

edema.edema. Masculinization of women.Masculinization of women. Hepatic dysfunction.Hepatic dysfunction.

Structure Activity Relation-Structure Activity Relation-ships:ships:

Steroidal nucleus essential for activity.Steroidal nucleus essential for activity. The C-3 and C-17 oxygenation increase the The C-3 and C-17 oxygenation increase the

activity.activity. Oxidation of C-17 to Oxidation of C-17 to carbonyl eliminatescarbonyl eliminates

activity.activity. C-17 C-17 esters prolongedesters prolonged the activity. the activity. Trans A/B ring junction is essential for Trans A/B ring junction is essential for

activity.activity. 17 17 -substitutions render compounds orally -substitutions render compounds orally

active.active.

O

OH

Androgenic DrugsAndrogenic Drugs

17 17 -methyltestosterone:-methyltestosterone: Orally active.Orally active. Prolonged action.Prolonged action. Androgenic and anabolic effects.Androgenic and anabolic effects.

Synthetic Anabolic Steroids:Synthetic Anabolic Steroids:NorethandroloneNorethandrolone

Orally active.Orally active. Anabolic effects.Anabolic effects. C-10 CHC-10 CH33 group removed to group removed to eliminate androgenic effect.eliminate androgenic effect.

O

OH

17-Methyltestosterone(Semisythetic)

CH3

O

OH

Norethandrolone(Sythetic-Pure anabolic)

C2H5

Adrenal cortex secretes:

- Mineralocorticoids (mainly aldosterone) - Glucocorticoids (mainly cortisol)

Adrenal medulla secretes: -Epinephrine and lesser amounts of

norepinephrine.

Adrenal Gland

Secretion:Secretion: Adrenal cortex of the adrenal gland.Adrenal cortex of the adrenal gland.

Regulation:Regulation: Stimulation:Stimulation: ACTH. ACTH. Inhibition:Inhibition: Feed back Mechanism. Feed back Mechanism.

Steroidal HormonesSteroidal Hormones(Adrenocorticosteroids, (Adrenocorticosteroids,

Adrenocorticoids, Corticosteroids, Adrenocorticoids, Corticosteroids, Corticoids)Corticoids)

Classification of Classification of corticosteroidscorticosteroids

Corticosteroids

GlucocorticoidsRegulate carbohydrates, lipids

and proteins metabolisme.g. Hydrocortisone

MineralocorticoisControl electrolytes and water

balancee.g. Aldosterone.

O

O

OH

HO

HO

A B

C D

Structure-Activity Relationship

Essential for activity

1

2

3

4

5

9

10

19

18

11 13

14

16

17

1, 2 Double bond improve carbohydrate metabolism to Na+ retention

-CH3 increaseglucocorticoid activity

6

-CH3 in Cortisol increase all activities

-CH3 in Prednisolone increase antiinflammatory activity&Decrease Na+ retaining activity

9-Fluoro increase all activitiesF Br Cl

Essential for antiinflammatory activity& carbohydrate regulatory activity

12

-F increase all activities if no OH at C-17-F with 16dihydroxy--inactive compounds

CH3 or OH eleminate Na+ retention activity

Essential for activity

Essential for antiinflammatory activity

Ether & esters

increase antiinflammat

ory & glucocorticoid

activities

21

Halogen & halomethylene greatly increase Topical antiinflammatory activity

Physiological Functions and Physiological Functions and Pharmacological EffectsPharmacological Effects

of corticosteroids : of corticosteroids : Carbohydrates and Proteins Metabolism:Carbohydrates and Proteins Metabolism:

Stimulate glucose formation in the brain.Stimulate glucose formation in the brain. Decrease peripheral utilization of glucose.Decrease peripheral utilization of glucose. Promote storage of glucose in the liver.Promote storage of glucose in the liver. Promote gluconeogenesis.Promote gluconeogenesis.

Lipids Metabolism:Lipids Metabolism: Redistribution of body fat (Buffalo hump, Redistribution of body fat (Buffalo hump,

Moon face).Moon face). Enhance lipolyses of Triglycerides.Enhance lipolyses of Triglycerides.

Electrolyte and Water balance:Electrolyte and Water balance: Enhance reabsorption of sodium and water Enhance reabsorption of sodium and water

into plasma.into plasma. Increase urinary excretion of potassium.Increase urinary excretion of potassium.

Blood Picture:Blood Picture: Increase hemoglobin and Red blood cells.Increase hemoglobin and Red blood cells. Decrease white blood cells.Decrease white blood cells.

Anti-inflammatory effects:Anti-inflammatory effects: Suppress inflammations regardless to their Suppress inflammations regardless to their

cause.cause.

Immunosuppressive Effects:Immunosuppressive Effects: Decrease immunity as a result of decrease the Decrease immunity as a result of decrease the

WBC’s.WBC’s.

Disease States (abnormalities of adrenal cortex function):Disease States (abnormalities of adrenal cortex function):

Addison’s disease:Addison’s disease: Rare syndrome 1/100,000 due to Rare syndrome 1/100,000 due to Hypoadrenalism.Hypoadrenalism.

Causes:Causes: Atrophy of adrenal gland.Atrophy of adrenal gland. Tuberculoses (result of infectious diseaseTuberculoses (result of infectious disease)).. Low level of ACTH.Low level of ACTH.

Symptoms:Symptoms: Weakness, fatigue, depression and irritability.Weakness, fatigue, depression and irritability. Anemia and low blood pressure.Anemia and low blood pressure. Loss of sodium and dehydration.Loss of sodium and dehydration. Low blood sugar.Low blood sugar. Excess pigmentation on skin.Excess pigmentation on skin. Nausea and vomiting.Nausea and vomiting.

Cushing’s disease:Cushing’s disease:

Rare syndrome 2- 5/Million due to Rare syndrome 2- 5/Million due to Hyperadrenalism.Hyperadrenalism.

Causes:Causes: Tumor of the Adrenal Cortex.Tumor of the Adrenal Cortex. Tumor of the Pituitary gland.Tumor of the Pituitary gland.

Symptoms:Symptoms: Alteration of fat distribution.Alteration of fat distribution. Hypertension.Hypertension. Osteoporosis.Osteoporosis. Growth retardation.Growth retardation. Decrease Immunity.Decrease Immunity.

Conn’s syndrom:Conn’s syndrom:

Causes:Causes: Conn's syndrome is a disease of the adrenal Conn's syndrome is a disease of the adrenal

glands involving excess production of glands involving excess production of aldosterone (hyperaldosteronism).aldosterone (hyperaldosteronism).

Symptoms:Symptoms: Hypertension.Hypertension. Alkalosis.Alkalosis. Polyuria.Polyuria. Edema.Edema.

Adrenocorticoid DrugsAdrenocorticoid Drugs

Systemic CorticosteroidsSystemic Corticosteroids::* * They can be administered by IV, IM, oral, topical or by They can be administered by IV, IM, oral, topical or by inhalation.inhalation.

* They can be short, intermediate or long-acting. * They can be short, intermediate or long-acting.

Cortisone and Cortisone acetate:Cortisone and Cortisone acetate: Can be given orally or by IM injection.Can be given orally or by IM injection. Acetate has longer duration of action.Acetate has longer duration of action. Drug of choice in replacement therapyDrug of choice in replacement therapy..

Cortisone acetate

O

O

OH

HO

O

O

O

OH

HO

HO

Cortisone CortisolHydrocortisone

Fludrocortisone:Fludrocortisone: 99-fluorocortisone. -fluorocortisone. 10 times more active than cortisone as 10 times more active than cortisone as

antiinflammatory.antiinflammatory. 300- 800 times more active as mineralocorticoids.300- 800 times more active as mineralocorticoids.

Prednisone and Prednisolone:Prednisone and Prednisolone: They are They are ΔΔ1 1 corticoids. corticoids. 3, 4 times more active than cortisone and 3, 4 times more active than cortisone and

hydrocortisone.hydrocortisone.

O

O

OH

HO

O

O

O

OH

HO

HO

Prednisone Prednisolone

Dexamethasone:Dexamethasone: 99-fluoro, 16-fluoro, 16-methylprednisolone.-methylprednisolone. 5- 7 times more active than prednisolone.5- 7 times more active than prednisolone.

Betamethasone:Betamethasone: 99-fluoro, 16-fluoro, 16-methylprednisolone.-methylprednisolone. Slightly more active than Dexamethasone.Slightly more active than Dexamethasone.

O

O

OH

HO

Dexamethasone

F

CH3

O

O

OH

HO

Betamethasone

F

CH3

HOHO

Clinical usesClinical uses

Hypoadrenalism.Hypoadrenalism. Rumatic diseases.Rumatic diseases. Renal diseases.Renal diseases. Collagen diseases.Collagen diseases. Ocular diseases.Ocular diseases. Skin diseases.Skin diseases. GIT inflammation.GIT inflammation. Liver diseases.Liver diseases.

Side effectsSide effects

Due to Prolonged use:Due to Prolonged use: Fluid and electrolyte disturbances, edema Fluid and electrolyte disturbances, edema

and hypertension.and hypertension. Hyperglycemia and glucosuria.Hyperglycemia and glucosuria. Peptic ulcer.Peptic ulcer. Increase susceptibility to infections.Increase susceptibility to infections. Growth arrestGrowth arrest OsteoporosesOsteoporoses

Withdrawal Symptoms:Withdrawal Symptoms: Rapid withdrawal after prolonged use leads Rapid withdrawal after prolonged use leads

to sever hypoadrenalism.to sever hypoadrenalism.

The posterior lobe is the source of 2 hormones:The posterior lobe is the source of 2 hormones: Vasopressin (ADH)Vasopressin (ADH) Oxytocin (OT)Oxytocin (OT)

Hormones of posterior lobe of Hormones of posterior lobe of Pituitary glandPituitary gland

Antidiuretic Hormone (ADH) Antidiuretic Hormone (ADH) Function:- ADH is to conserve body water by reducing the loss of water

in urine.

- ADH binds to receptors on cells in the collecting ducts of the

kidney and promotes reabsorption of water back into the

circulation.

Diabetis insipidus DI (Hyposecretion of ADH)

Sign & symptoms: polyuria (10-12 L/ day)

Treatment: Synthetic vasopressin injection (Pitressin)

This condition can arise from either of two situations: Hypothalamic diabetes insipidus: ■ Results from a deficiency in secretion of ADH from the posterior pituitary. ■ Causes of this disease include head trauma and infections or tumors involving the hypothalamus. Nephrogenic diabetes insipidus: ■ occurs when the kidney is unable to respond to ADH. ■ Most commonly, this results from some type of renal disease.

Function in female:

Oxytocin

-Stimulation of milk ejection

- Stimulation of uterine smooth muscle contraction.

A food supplement, also known as dietary supplement or nutritional supplement, is a preparation intended to provide nutrients that are missing or are not consumed in sufficient quantity in a person's diet.

Marketed as pills, tablets, capsules, liquids in measured doses.

Definition

Essential organic nutrients: Essential organic nutrients: that promote that promote energyenergy for living for living

organisms requiring them are: organisms requiring them are: - - Amino acidsAmino acids (the precursors of protein) (the precursors of protein) - - Fatty acidsFatty acids - - CarbohydratesCarbohydrates.. - - Purine and pyrimidine and their derivativesPurine and pyrimidine and their derivatives (precursors (precursors of nucleic acids).of nucleic acids). - - VitaminsVitamins. .

Essential inorganicEssential inorganic nutrientsnutrients that promote the that promote the growthgrowth and and

maintenance of living organisms such as:maintenance of living organisms such as: boron, calcium, iodine, iron, magnesium, boron, calcium, iodine, iron, magnesium, potassium, selenium and zincpotassium, selenium and zinc

All nutrients required for human life work interdependently All nutrients required for human life work interdependently in order to metabolize and facilitate optimal functioning. in order to metabolize and facilitate optimal functioning. E.g.: intake of calcium requires a complementary amount of E.g.: intake of calcium requires a complementary amount of

magnesium so the calcium will be absorbed properly. magnesium so the calcium will be absorbed properly. An excess of calcium may be responsible for a magnesium An excess of calcium may be responsible for a magnesium

deficiency. deficiency.

When You May Need a Dietary When You May Need a Dietary SupplementSupplement

You eat a very low-calorie diet You eat an all-plant diet (vegan) You are in a certain stage of the life cycle (e.g., a pregnant,

breastfeeding) Your doctor may prescribe a supplement for you if:

You have a disease, infection, or injury or recently had surgery

You have a nutritional deficiency You are taking medications that interfere with your body’s

use of specific nutrients

Dietary supplement would include: ■ Vitamins (e.g.: Vitamin B6, Niacin,Vitamin C) ■ Minerals (e.g.: Calcium and Iron)

■ Amino acid (e.g.: Tyrosine, Creatine, L-tryptophan, Phenylalanine)

■ Herbals

Pregnant women.Pregnant women. Infants. Infants. Children. Children. Adolescents. Adolescents. Elderly.Elderly. Individuals with inherited disorders of amino acid metabolism.Individuals with inherited disorders of amino acid metabolism. Individuals with certain diseases. Individuals with certain diseases.

E.g.: L-tryptophan L-tryptophan andand phenylalanine phenylalanine in dietary supplement in dietary supplement caused potential risks for:caused potential risks for:

Food and Drug Administration (FDA) advises caution with amino acid supplements.

Eosinophilia-myelgia syndrome (EMS) was associated with the ingestion of L-tryptophan in a dietary supplement. EMS is a systemic connective tissue disease characterized by: - Severe muscle pain - Increase in white blood cells - Certain skin and neuromuscular manifestations.

People with phenylketonuria (PKU), a rare genetic condition, when ingest too much phenylalanine, serious problems could occur, especially brain and mental problems in children.

Some of the fastest growing herbal categories include the following:

Herbals that increase circulation (Ginko biloba) Herbals used for calmative effect (Kava kava, Valerian, Chamomile) Herbals to lessen a cold flu symptoms and boost immunity (Echinacea, Goldenseal) Herbs for mild depression (St. John's Wort ). Herbs for inflammation (Curcuma domestica). Herbs for lowering cholesterol (Allium sativum). Herbs to treat hypertension (Valariana officinalis, Panax ginseng)

HerbsHerbs Combining herbals with medicines can result in an adverse reaction

where "double-dosing" can occur or a worsening of symptoms in those with a chronic medical condition.

Be careful when using Herbal Supplements:Be careful when using Herbal Supplements: Herbals can interact with drugs used for anesthesia (all herbals be Herbals can interact with drugs used for anesthesia (all herbals be

discontinued 2-3 weeks prior to a scheduled surgery).discontinued 2-3 weeks prior to a scheduled surgery). Stop all herbals if pregnant or breast-feeding.Stop all herbals if pregnant or breast-feeding. Many herbals can interact with the anticoagulant:Many herbals can interact with the anticoagulant: - Avoid taking supplements of garlic, - Avoid taking supplements of garlic, ginko bilobaginko biloba, ginger, , ginger, while taking the blood thinner Coumadinwhile taking the blood thinner Coumadin®® as these as these herbs can further prolong clotting times. herbs can further prolong clotting times. Don't give herbal remedies to children without first checking with Don't give herbal remedies to children without first checking with

the child's pediatrician. the child's pediatrician.

Many drugs interact with St. John's Wort, prompting the FDA to Many drugs interact with St. John's Wort, prompting the FDA to issue a health advisory: issue a health advisory:

St. John's Wort can cause some drugs to be eliminated from the body St. John's Wort can cause some drugs to be eliminated from the body too quickly, making them less effective such as oral contraceptives, too quickly, making them less effective such as oral contraceptives, anti-cancer agents, heart medications and drugs that fight HIV. anti-cancer agents, heart medications and drugs that fight HIV.

Don't take herbal products containing ephedra. Many deaths have been Don't take herbal products containing ephedra. Many deaths have been associated with its use.associated with its use.

Possible Side Effects of Possible Side Effects of Supplement UseSupplement Use

DehydrationDehydration Nervousness and DizzinessNervousness and Dizziness Changes in Blood Pressure and Heart RateChanges in Blood Pressure and Heart Rate Heart AttackHeart Attack Seizures Psychosis Death Interaction with medications

Supplements to AvoidSupplements to Avoid Steroids and Steroid-Enhancers

Linked to liver toxicity and increased risk of heart attack.

Kava Kava Linked to liver damage Banned in European countries and Canada

St Johns Wort Interferes with a huge number of medications

Dietary Supplements Dietary Supplements D/SD/S

Distinguished from Drugs:Distinguished from Drugs: Drug must undergo FDA approval after clinical studies to Drug must undergo FDA approval after clinical studies to

determine effectiveness and safety determine effectiveness and safety D/S = no pre-market testingD/S = no pre-market testing

DSHEA (Dietary Supplement Health Education Act) DSHEA defines a dietary supplement as any product that contains a vitamin,

mineral, herb, or amino acid and that is intended as a supplement to the normal diet.

DSHEA authorized to provide DSHEA authorized to provide accurate informationaccurate information to consumers and to consumers and the label must include:the label must include: NameName of each ingredient of each ingredient QuantityQuantity of each ingredient of each ingredient Total weightTotal weight of all ingredient if a blend of all ingredient if a blend Identity of Identity of part of plantpart of plant derived from derived from Term “Term “Dietary SupplementDietary Supplement””

Statements may be included on the label that give the manufacturers Statements may be included on the label that give the manufacturers description of the role of the D/Sdescription of the role of the D/S Not authorized by FDANot authorized by FDA

Food coloring is any substance that is added to food or drink

to change its color.

Purpose of food coloringOffsetting color loss due to light, air, extremes of temp., moisture, and storage conditions. - Enhancing naturally occurring colors. - Decorative purposes.

Natural food dyes• Caramel coloring (E150), made from caramelized sugar, used in cola products and also in cosmetics. Annatto (E160b), a reddish-orange dye made from the seed of the Achiote. • Turmeric (curcuminoids, E100) • Saffron (carotenoids, E160a) • Paprika (E160c)

• A great deal of research finds definite connections between

behavioral problems and hyperactivity in children.

• Other effects on health from food dyes are allergies, headache,

asthma, fatigue, nausea, concentration problems, agitation and

nervousness.

Side effects of coloring agents