'It is more blessed to give than to receive.

Sex Hormones
I-Androgens:
Natural: Testosterone and Androsterone (ineffective orally due to
extensive hepatic metabolism).
Synthetic: Testosterone propionate (SC, IM, SL)-'
Methyl testosterone (SL) .
• Indications:
K . l-Replacement therapy in male hypogonadism.
,_\ 2-In females: Premenopausal cancer breast-
Post-menopausal syndrome (used with estrogen) .
• Adverse effects:
I-Cholestatic hepatitis and jaundice.
2-Increased sexual activity.
3-Salt and water retention.
,,' 4-Precocious puberty and premature closure of epiphyses in children.
5-Masculinization (virilization) in females: deepening of voice, acne, and
hirsutism .
• Contraindications: Cancer prostate.

Anabolid steroids:
.Examples: Nandrolone - Methandrostenolone .
• Indications:
I-Aplastic anemia (bone marrow depression).
2-Acute renal failure.
3-0steoporosis.
4-General wasting .
• Adverse effects:
I-Precocious puberty in children.
2-Virilization in females (deepening of voice, hirsutism, and acne).
3-Testicular atrophy in adult males.

Anti-Androgens:
I-Flutamide and Cyproterone: competitive antagonists on androgen
receptors. Used in: cancer prostate-hirsutism-male hypersexuality-
cyproterone is also used as "male contraceptive" (see later).
2-Finasteride: inhibits 5-a reductase and thus inhibits conversion of
testosterone into more active dihydrotestosterone in prostate and other
tissues as hair follicles, but not in skeletal muscles (skeletal muscles do
not require activation of testosterone).
WhiteKnightLove

Used in benign prostatic hyperplasia (BPH).

1
 Freely you have received; freely give.

3-Ketoconazole: Antifungal and also inhibits synthesis of androgens and

cortisol.
4-Spironolactone: K+-sparing diuretic-aldosterone antagonist.
5-Cimetidine: Hj-antagonist.

• Male contracepti'.1es:
l-Gossypol: destroys seminiferous epithelium and decreases sperm count.
The main adverse effect is hypokalemia (may cause transient paralysis).
2-Testosterone in large doses.
3-Cyproterone (anti-androgen) + Levonorgestrel (progestogen).

II-Progestogens:
Therapeutic uses:
l-Contraception; either alone (e.g. minipill) or combined with estrogen.
2-Dysmenorrhea and premenstrual tension.
3-Endomeiriosis and endometrial carcinoma.
4;...
Threatenbd and habitual abortion.
5-Induction of artificial menstrual cycles in amenorrhea.
Preparations:
A-Natural: ineffective orally due to rapid hepatic metabolism, e.g.
Progesterone (IM oily solution or IM pellet implantation) and
Hydroxyprogesterone caproate (IM / week).
B-Synthetic: effective orally, e.g. Medroxyprogesterone (also given IM
depot / 3 months) and Norethisterone.
Adverse effects:
I-Sodium and water retention (edema).
2- Weak androgenic effect of some preparations derived from testosterone
. leading to virilization (acne vulgaris, hirsutism, and deepening of voice).
3-Psychic depression.
4-Elevation oftriglycerides and LDL-cholesterolleading to
atherosclerosis.

A nti-Progesterones:
l-Mifepristone: .
• Blocks progesterone receptors (progesterone antagonist) and in large
doses it blocks also glucocorticoid (cortisol) receptors .
• Uses:
l-Termination of early pregnancy given with PG analog as misoprostol,
as it sensitizes the uterus to prostaglandins. .
2-Post-coital contraceptive as it inhibits implantation.
WhiteKnightLove

2
'It is more blessed to give than to receive.

2-Danazol:
.Anti-gonadotrophIns: inhibits release of gonadotrophin releasing
hormones (GnRH) from hypothalamus ~ inhibition of release of
gonadotrophins (FSH and LH) from anterior pituitary -+ inhibition of
synthesis of estrogen and other steroids in the ovaries.
This leads to reduced ovarian function and endometrial atrophy .
• Binds to progesterone, androgen, and glucocorticoid (cortisol) receptors .
• It inhibits the mid-cycle surge of FSH and LH.
Uses: Endometriosis - Menorrhagia -Fibrocystic disease of breast -
Gynecomastia.
Adverse effects:
I-Virilization in females: Deepening of voice, decrease breast size, and
changes in libido
2-Edema and weight gain due to salt and water retention.
3-Hot flushes and headache.
4-Hepatic impairment.
5...GIT disturbances .

• 3-Progesterone Receptor Modulators:

• Example: Asoprinsil .
• Mechanism of action: partial agonist-antagonist on progesterone
receptors .
• Uses: Fibroids-Endometriosis-Abnormal uterine bleeding .
• Adverse effects: mild androgenic actions.

WhiteKnightLove

3
 Freely you have received; freely give.

111- Estrogens:
*Mechanism of action:
.Estrogens stimulate specific intracellular nuclear estrogen receptors
(known as ER) leading to "change" in DNA transcription into mRNA .
• There are 2 subtypesof Ek:
l-ERx which stimulates transcription in tissues.
2-E~ which inhibits transcription in tissues.
*Actions:
I-Development and maintenance of2ry sex characters infemales.
2-Responsible for the proliferation of endometrium (proliferative phase),
and stimulation of endometrial secretion (secretory phase together with
progesterone ).
3-Salt and water retention.
4-Mild anabolic action compared to androgens.
5-1 LDL and i HDL (anti-atherogenic).
6-,Stimulates hepatic synthesis of prothrombin (factor II), factors VII, IX,
andX.
7-Stimulates calcium deposition in bones (antagonizes parathormone-
induced bone resorption) .
. *Indications:
I-Replacement therapy in primary hypogonadism.
'- 2-Honnonal Replacement Therapy (HRT) in postmenopausal syndrome
(climacteric syndrome) to prevent and treat osteoporosis, hot flushes,
atrophic or senile vaginitis, and hyperlipidemia causing atherosclerosis
and ischemic heart diseases.
3-Dysmenorrhea (with progestins to suppress ovulation).
4-Endometriosis.
5-OraI Contraception.
6-Suppression of lactation (bromocriptine is safer).
7-Functional uterine bleeding.
8-Postmenopausal cancer breast (some cases).
9-Acne vulgaris and Hirsutism.
1O-Cancer prostate.

N.B.: Treatment of dysmenorrhea:

I-Oral contraceptives. .
2-NSAIDs (avoid aspirin as it may increase bleeding).
3-~z-agonists as ritodrine.
4-CCBs as nifedipine.
WhiteKnightLove

4
'It is more blessed to give than to receive.

*Preparations:
A-Natural estrogens:
eInclude: Estradiol. (main estrogen secreted by the ovaries and the most
potent natural estrogen)- Estrone- Estriol.
eTheyare "steroids". '. . .
e They have low oral bioavailability due to marked first pass hepatic
metabolism. Estradiol monobenzoate is given IM: 2-3 times / week, and
Estradiol valerate is given IM once / 3-4 weeks .
. • Premarin is a sulphate-conjugated estrogen which is effective orally.
B-Semisynthetic estrogens:
.eInclude: Ethinyl estradiol- Mestranol (converted into ethinyl estradiol).
e Potent.
eEffective orally.
eFat soluble and stored in adipose tissues so they have long duration.
C-Synthetic:
e Include: Diethylstilbosterol.
e Non-Steroidal.
eEffective orally.
N.B.: estrogens may be also given as vaginal pessaries or creams (but
may be systemically absorbed), and also as trans dermal patches as they
are well absorbed from the skin.

*Adverse effects:
I-GIT: Nausea mainly and less commonly vomiting, abdominal pains,
diarrhea or.constipation.
2-CVS: Salt and water retention leading to edema, weight gain (may be
. also due to !the anabolic effect), hypertension, and heart failure.
3-Blood:
eThromboembolism and antagonizes the action of oral anticoagulants as
warfarin due to increase in hepatic synthesis of coagulation factors II
(prothrombin), VII, IX, and X.
This may cause deep venous thrombosis (DVT) leading to pulmonary
embolism, acute myocardial infarctions and cerebrovascular strokes.
The risk of thromboembolism is higher in females over 35 years and in
smoker females.
e Increase TBG and CBG, and elevate sedimentation rate.
eHyperglycemia and impaired glucose tolerance.
4-CNS: . .
e Headache and increased frequency of migraine.
e Depression.
5-Breast:
eBreast tenderness (mastalgia).
WhiteKnightLove

ePremenopausal breast carcinoma (estrogen-dependent tumors).

5
 Freely you have received; freely give.

-Suppression of lactation.
6-Genital system:
eAmenorrhea may occur for a variable time after cessation and may be
rarely permanent. .
eFailure of withdrawal bleeding (misinterpreted as pregnancy).
e Fibroids and endometrial carcinoma (corrected by adding progestins).
- Excessive vaginal secretions. .
- Vaginal carcinoma in females whose mothers received estrogen
(diethylstilbestrol) as post-coital pills.
-Decreased libido (corrected by adding progestins).
7-Liver and gall bladder: Cholestatic hepatitis and jaundice, gall stones,
cholangitis, .and cholecystitis.
8-Skin: Chloasma (localized skin darkness).
9-Feminiza,ion in males (e.g. reversible gynecomastia) with cancer
prostate treated by estrogen.

*Contraindications:
l-Hypertension, ischemic heart disease, and heart failure.
2-Thromboembolic diseases and history of thromboembolism, and
. .
vancose vems.
3-Diabetes mellitus.
, 4-Migraine.
5-Depression .
6-Fibroids and endometrial carcinoma (estrogen-dependent).
7-Pre-menopausal breast carcinoma (may be estrogen-dependent).
S-Undiagnosed vaginal bleeding (which may be due to endometrial
carcinoma which is estrogen-dependent).
9-Liver and gall bladder diseases.
lO-Women over 35 years.

*Drug interactions:
A-Pharmacokinetic interactions:
l-Hl\.1E inducers as rifampicin, phenytoin, carbamazepine, and
phenobarbitone increases clearance of estrogens (contraceptives) and
cause failure of therapy (i.e. conception).
2-Hl\.1Einhibitors as cimetidine decrease clearance of estrogens and may
increase adverse effects.
3-Estrogens have mild HME inhibitory action and may reduce clearance
of other drugs as digitoxin and aminophylline.
4-Mineral oils as paraffm oil (lubricant purgative used in treatment 'of
chronic constipation) reduce absorption of estrogen and other steroids.
WhiteKnightLove

6
'It is more blessed to give than to receive.

B-Pharmacodynamic interactions:
l-Estrogens antagonize the action of:
• Anticoagulants .
. • Diuretics.
e Antihypertensives .
• Antidiabetics.
2-Tobacco smoking and antifibrinolytics (aminocaproic acid and
tranexamic acid) increase the incidence of thromboembolism in females
receiving estrogen.

N.B.: Drugs that decrease the effect of estrogen (as contraceptive) may
lead to pregnancy or break-through bleeding, they include:
I-HME inducers.
2-Mineral oils as paraffin oil.

Anti-Estrogens:
A':..SelectiveEstrogen Receptor Modulators (SERMs):
eThey act as estrogen agonists by stimulation of ERa in bone, lipids,
endometrium, and coagulation factors ~ stimulation of transcription.
e They act as estrogen antagonists by stimulation of E~ in breast and
anterior pituitary ~ inhibition of transcription.
eExamples include:
Clomiphen: agonist on E~ in anterior pituitary ~ prevention of
negative feed-back inhibition onFSH and LH ~ increase in FSH and LH
~ induction of ovulation.
Adverse effects: multiple ovulations and multiple pregnancies-hot
flushes-headache-visual disturbances-constipation-reversible hair loss.
Tamoxifen~and Raloxifen: used mainly in treatment of osteoporosis
(agonists or ERa in bones) and estrogen-dependent premenopausal breast
carcinoma (agonists on E~ in breast).
B-Estrogen Synthesis Inhibitors:
I-Danazol: see before.
2-Gonadotrophin releasing hormones (~ .
Continous administration of GnRH leads to desensitization of the anterior
pituitary and inhibition of gonadotrophin (FSH and LH) release and
finally inhibition of estrogen synthesis by the ovaries. .
3-Aromatase inhibitors (AIs): inhibit synthesis of estrogen from androgen
by inhibition of aromatase enzyme. . .
Used in cancer breast resistant to tamoxifen. There are 2 types of AIs:
a-Steroidal = Irreversible inhibitors = Suicide inhibitors.
Example: Exemestane.
b- Non-steroidal= Reversible. Examples: Nastrazole and Letrazole.
WhiteKnightLove

7
 Freely you have received; freely give.

Contraceptives

Methods of contraception:
l-Hormonal contraceptives: either orally or parenterally.
2-Intrauterine device (rtID).
3.;.Mechanical contraceptives (male condom and vaginal diaphragm).
4-Chemicalcontr,aceptives (spermicides).
5-Physiological methods (safe period).
6-Sterilizatipn in females or males.

i; Hormonal Contraceptives:
They are administered either: orally, IM, s.c.implantation, or by intra-
uterine device (IUD) which releases progesterone inside the uterus.

ORAL CONTRACEPTIVES:
These drugs are given orally to prevent conception (pregnancy).
They include the following methods:

A-Combined Method:
Pills contain combination of estrogen (ethinyl estradiol) and progestin
(norethindrone, levonorgestrel, or desogestrel which is less androgenic).
They are started at the 5th day of the menstrual cycle and used
continuously for 21 days then stopped for 7 days to allow menstruation
which is mainly due to progesterone withdrawal.
They are subdivided into:
I-Monophasic pills:
Pills contain fixed amount of estrogen and progesterone (1 type of pills).
2-Biphasic pills:
There are 2 types of pills containing the same dose of estrogen, but
different doses of progestins.
3-Triphasic pills (e.g. Triovlar®):
There are 3 types of pills given at 3 phases:
First Phase: Pills containing 30 ug, ethinyl estradiol + 50 J.lg:L-
norgestrel given from 5th day of menstruation for 6 days.
Second Phase: Pills containing 40 ug, ethinyl estradiol + 75}lg. L-.
norgestrel given for 5 days (both doses of estrogen and progesterone are
raised).
Third Phase: Pills containing 30 ug.ethinyl estradiol + 125 jig.
L-norgestrel given for 10 days (the dose of estrogen is reduced but the
dose of progesterone is further raised).
WhiteKnightLove

8
'It is more blessed to give than to receive.

Advantages of Triphasic method:

I-Most effective oral method.
2-Lower amounts.of hormones are used.
3~Similar to the natural menstrual cycle.
4":Less adverse effects, than other oral contraceptive methods:
Less breakthrough bleeding and spotting and less thromboembolism.

*Mechanism of action' of Combined method:

I-Inhibition ofFSH release by estrogen and inhibition of ovarian follicle
development ..
2-Inhibition ofLH release by progestins mainly and accordingly
inhibition of ovulation.
3-Increase the viscosity of cervical mucus which prevents sperm
penetration = • the cervical mucus is inhospitable to sperms (by
progestins mainly).
4-Induce endometrial changes which interfere with implantation (by both
estrogen and progestins).
5-Interfere with coordinated contraction of the uterus, cervix, and
Fallopian tubes which interferes with fertilization and implantation (by
both estrogen and progestins).
;

l
B- Progestin onlv contraceptives:
Mechanism of action:
l-Inhibition ofLH release mainly and accordingly inhibition of ovulation
( • inhibition of ovulation is inconsistent).
2-Increase the viscosity of cervical mucus which prevents sperm
.penetration ~ • the cervical mucus is inhospitable to sperms.
3-Induce endometrial changes which interfere with implantation.
4-Interfere with coordinated contraction of the uterus, cervix, and
Fallopian tubes which interferes with fertilization and implantation.

Progestin only contraceptives include:

I-MinipilL-
Pills containing small doseof progestogen only (norethindrone or
L-norgestrel) are given orally continuously without stop .
. Disadvantages:
I-"Break-through bleeding" and "spotting" is common.
2-Irregular menstrual cycles. . ..
3-Less effective than combined method • Missing a dose -t conception.
WhiteKnightLove

9
 Freely you have received; freely give.

2- Depot therapy Oong actinz):

Medroxyprogesterone 150 mg. is given IM every 3 months, used in
lactating females as it does not suppress lactation.
Disadvantages:
,.1-Irregular menstruation.
2-Infertility may persist for many months after stoppage.

3-Subcutaneous implants: .
L-norgestrel is given as SC implant which lasts about 5 years
(6 capsules are placed SC in upper arm). .
Advantages:
I-Effective.
2-Cheaper than oral contraceptives.
3-Does not depend on patient's compliance.
4-Reversible by surgical removal of the implants.
Disadvantages:
l-Irregular menstruation.
2-Headache.

4-Intra-Uterine Device (1. UD.): .

Releases low amounts of progestin locally, changed yearly.

C-Post-Coital Pills (EmergencyPills =Morning after = Rape pills):

Types:
.l-Estrogen only (diethylstilbestrol) is given within 72 hours after coitus
(sexual intercourse) and for 5 consecutive days. .
2-Estrogen+ progestogen given twice (every 12 hours) within 72 hours
after intercourse.
3-MifepristQne + Misoprostol once (see before).
" *Mechanism of action:
I-Alter the motility of Fallopian tubes.
2-Induce endometrial changes making it unsuitable for implantation.
3-Withdrawal of large doses of estrogen leads to bleeding ..
Disadvantages:
. Nausea and vomiting is very frequent and leads to loss of pills.

*Adverse effects of Oral Contraceptives:

See page 23 +:
lu-Break-through bleeding or spotting Clueto using progestin only or
small doses of combination pills.
II-Hirsutism, and acne due to progestins having androgenic effects.
12-Vaginal infections and bacteruria.
WhiteKnightLove

10
'It is more blessed to give than to receive.

13- • Progestogen is thought to increase the risk of atherosclerosis due to

increase in triglycerides and cholesterol, leading to cerebrovascular and
myocardial infarctions .
.*Contraindications:
See page 24.
*Drug interactions: .
See page 24 +:
Progestogens antagonize the action of anti-hyperlipidemic drugs.

Drugs used to induce ovulation:

l-Clomiphen (SERM).
2-Bromocriptine (in anovulation due to hyperprolactinemia).
3-Gonadotrophins (Human Menopausal Gonadotrophins =HMG having
FSH and LH activity, followed by Human Chorionic
Gonadotrophins=HCG having LH activity only).
4- .• Metformin: useful in polycystic ovarian syndrome to restore regular
menstrual cycles and to induce ovulation (the main use of metformin is in .
treatment of type II diabetes especially in obese patients);
5- • Aromatase inhibitors as Lestrazole: inhibits aromatase enzyme -*
inhibition of estrogen synthesis from androgens --+ no negative feedback
of estrogen -* i GnRH from hypothalamus --+ iFSH from pituitary-»
, induction of ovulation. Better given with small doses of FSH.

WhiteKnightLove

11
 Freely you have received; freely give.

Pituitary Hormones
Anterior Pituitary Hormones
.l-Growth Hormone (GH) =Somatotropin: polypeptide -synthesized
by recombinant DNA technology-used in treatment of dwarfism
(replacement therapy, given before closure of epiphyses).
2-Gonadotrophins= FSH and LH: used to induce ovulation. They
are prepared as human menopausal gonadotrophins (HMG contains both
FSH and LH) and human chorionic gonadotrophins (HCG contains LH).
3-Prolactin: inhibited by the action of hypothalamic dopamine on D2-
receptors (dopamine = PIP). Dragonists as bromocriptine are used in
treatment ofhyperprolactinemia and to suppress lactation. D2-antagonists
as chlorpromazine and metoclopramide, and drugs reducing dopamine
level in CNS as u- methyldopa and reserpine cause hyperprolactinemia .

.Posterior Pituitary Hormones

J-Oxytocin: polypeptide- causes uterine contraction and contraction of
myoepithelial cells of breast.
Uses: l-induction of labor in uterine inertia. 2- control of post partum
hemorrhage. 3-milk ejection in breast engorgement.
Syntocinon is a synthetic drug.
Oxytocic Drugs = Uterine Stimulants:
I-Oxytocin and syntocinon.
2-PG analogs as misoprostol and dinaprostone.
3-Ergometrine and methylergometrine.
They are used in Fduction of labor and abortion, and to control
postpartum hem9rrhage. .
Tocolytic Drugs'T Uterine Relaxants:
I-NSAIDs. I
2-~ragonists as ritodrine.
3-CCBs as nifedlpine.
They are used in/dysmenorrheal-premature labor-threatened abortion-
contraction ring of the uterus.
2-A_nti-Diuretib Hormone (ADH) = Vasopressin:
Polypeptide- acts on specific V-receptors:
-Vj-receptors in smooth muscles --+ contraction (V:C. and may elev~te
ABP - spasmogenic on smooth muscles of GIT which may cause colics
and diarrhea).
-Vrreceptors in collecting tubules --+ facultative water reabsorption.
Indications:
WhiteKnightLove

12
'It is more blessed to give than to receive.

I-Replacement therapy in pituitary (central) type of diabetes insipidus

(given as nasal spray, but may cause nasal atrophy and nasal ulcers).
2-To stop bleeding in esophageal varices in patients with portal
hypertension (given by injection). '

N.B.: Types and treatment of diabetes insipidus: .

I-Pituitary type: treated by ADH~ carbamazepine- chlorpropamide-
metformin.
2-Nephrogenic type: caused by ADH antagonists as demeclocycline-
lithium-methoxyflurane, and treated by thiazides (amiloride is used in
treatment of lithium-induced nephrogenic diabetes insipidus).

HVDothalamic
- Hormones

i-Gonadotrophin releasing hormones (GnRH):

-Decapeptide given IV, SC, or as nasal spray.
-Continous administration cause's desensitization of the anterior pituitary
and inhibits release ofFSH and LH and inhibit estrogen synthesis (see
'anti-estrogens ).
- Pulsatile administration stimulates FSH and LH.
, -Synthetic analogs: Leuprilide and Nafarelin
-Uses:
l-Cancer prostate.
2-Fibroids.
3-Endometriosis:
4-Polycystic ovary.
5-Central precocious puberty.
6-Induction of ovulation (pulsatile administration).
7-Stimulation of spermatogenesis (pulsatile administration).

2-Somatostatin =GH inhibitory hormone:

_Peptide secreted also in gut and from Dscells of pancreas.
-Inhibits growth hormone, insulin, glucagon,HCl, and gut motility.
_Used in treatment of acromegaly.
Octreotide synthetic
.
analog used in treatment of acute bleeding from
'. .

esophageal varices.

3-Corticotropin Releasing Hormone (CRlfl.:.

4- Thyrotropin Releasing Hormone ffRHL

WhiteKnightLove

13
 Freely you have received; freely give.

Factors A.ffecting Calcium Homeostasis

-Serum calcium (Ca2+) is maintained at a normal range of9-l1 mg. % by
the action of parathyroid hormone (parathorm one), calcitonin, and
vitamin D mainly.
-Serum Ca2+ is found in 3 forms:
l-Free Ca2+ which is biologically active (blood coagulation-release' of
hormones and neurotransmitters-nerve excitability-skeletal muscle
contraction-cardiac contraction).
2-Plasma protein bound. 3-Bound to organic ions.
.Hormone Mechanism and Indications ROutes of.
'; Actions administration
l-Parathormone +Activation of G, I-Treatment of LM. (ineffective
(polypeptide): coupled membrane hypoparathyroidism causing orally).
.receptors and hypocalcemia and tetany.
increase c-AMP. 2-Intermittent use of small
2
+rserum'Ca + (and 'doses of Teriparatide
Mg2) ,and (recombinant human =rh
!phos~hate by: 'parathormone) stimulates
l-t'Ca + and bone growth and increases
phosphate absorption bone size in osteoporosis.
from GIT.
2-Stimultes bone
. 0fC a.2+
resorption
3-tRenal
reabsorption of Ca2+
and [phosphate
excretion in urine.
Z-Calcltonin +Activation of 1-Treatment of I.M., S.C., nasal
(polypeptide) : membrane receptors. hypercalcemia. spray (ineffective
2 orally).
+! Serum Ca + and , 2-Post-menauposal
phosphate by:. osteoporosis.
1-[Bone resorption. 3-Paget's disease of bone.
2-trenalreabsorption.
. 3- Vitamin D +As steroid l-Hypocalcemia and tetany . Oral and LM.
(steroid): . hormones. 2-Rickets and osteomalacia.
2
+t serum Ca + and 3-Post-menauposal
phosphate by: osteoporosis (+dietary Ca2+.
I:-tGIT absorption. 4-Synthetic analogs as l-a-
,2- Irenal reabsorption. hydroxy-vitamin D2 is used
3-Regulates bone . in hyperparathyroidism
resorption Iformation. 'secondary to renal failure.
WhiteKnightLove

14
'It is more blessed to give than to receive.

Other Factors Affecting Calcium Homeos.tasis:

1-Bisphosphonates:
e Inhibit bone resorption and increase bone density .
• Used in: osteoporosis- Paget's disease - hypercalcemia associated with
malignancy.
eExamples: Alendronate, Risedronate, Pamidronate, Etidronate.

2-Estrogens and SERM as Raloxi(en: inhibit parathormone-induced bone

resorption in menopause, used it treatment and prophylaxis of
postmenopausal osteoporosis.

3-Thiazide diuretics: decrease Ca2+ excretion in urine and cause

hypercalcemia, used in hypocalcemia and idiopathichypercalciuria.

4-Loop diuretics: decrease blood Ca2+ and are used in hypercalcemia.

5':'Glucocorticoids: antagonize vitamin D and decrease Ca2+ absorption

from GIT leading to hypocalcemia, and are used in hypercalcemia.

6-Fluor.ide: given with Ca2+ to reduce the incidence of bone fractures.

Treatment of Osteoporosis:
Causes:
1- Post-menopausal syndrome.
2-Long treatment with glucocorticoids.
3 - Hyperparathyroidism.
4-Thyrotoxicosis.
5-Alcoholism.
Treatment:
A-General measures: Ca + and vitamin D.
B-Anti-Resorptive Agents:
l-Bisphosphonates, ,
2-Estrogen and SERMs as Raloxifen (better than estrogen to reduce the
risk of breast and endometrialcarcinoma).
3-Calcitonin.
4-Fluoride-sustained release.
C-Anabolic Agent: Teriparatide: recombinant parathormone given in
small pulse doses.
WhiteKnightLove

15
 Freely you have received; freely give.

Treatment ofHvvocalcemia:
. l-Ca2+ and vi1:am~ D.
2-ParathOln10ne.
3-Thiazides.

Treatment of Hypercalcemia.:
l-Biphosphonates.
2-Loop diuretics.
3-Calcitonin.
4-Glucocorticoids.
.i7:''
5-Ca2+-chelating agents as disodium edetate IV .
6-Phosphate.

Treatment of hypoparathyroidism:
Hypoparathyroidism is either idiopathic or following thyroidectomy.
It is characterized by low Ca2+ and high phosphate leading to tetany.
Treatment by:
l-Parathormone (resistance occurs).
2-Calcium gluconate slowly IV.
3-Vitamin D.
4-Dihydrotachysterol (AT 10) to elevate serum calcium.

WhiteKnightLove

16
'It is more blessed to give than to receive.

GLUCAGON

Chemistry:
Polypeptide composed of a single chain of 29 amino acids secreted from
A cells of pancreas. '
Pharmacokinetics:
I-Given parenterally: 1M or SC (never orally).
2-Metabolizeq in.liver, plasma, and kidney.
Pharmacodynamics:
Mechanism of action: stimulates specific membrane-bound G-protein
coupled receptors leading to activation of adenyl cyclase and increase in
intracellular c-AMP.
Pharmacological actions:
l-Hyperglycemia (anti-insulin).
2-Stimulation of release of insulin '(secondary to hyperglycemia),
catecholamines, and calcitonin. ..
3..;Cardiac stimulation: +ve inotropic and +ve chronotropic.
4-Smooth muscle fibers (e.g. GIT): relaxation.
Therapeutic uses: . .'.
l-Treatment of hypoglycemic coma (glucagon lmg. 1M or SC followed
by oral glucose).
2-To assess the secretory reserve of pancreatic B-cells (Glucagon test).
3- Treatment of cardiac depression due to overdose of ~-:blockers (~1
agonists as isoprenaline are ineffective).
4-To relax the intestine during bowel radiology.

WhiteKnightLove

17