ADVERSE EFFECTS

Mechanism of Action of insulin:

Tyrosine- kinase linked receptors

Insulin

β α α β

tyrosine kinase ATP

domain Tyr
P
IRS-1
↑Glucose transporters (GLUT) ADP Tyr P
Change in enzyme activity IRS-1
Gene expression
 Levothyroxine (L-T4) Liothyronine (T3)

Stable and low cost Stable but higher cost

Long t 1/2 (7days) Shorter t 1/2 (24h)

Given once daily Multiple daily doses

Less risk of cardiotoxicity Greater risk of cardiotoxicity

 T H Y R O I D
THERAPY:
1- Replacement therapy in
hypothyroidism Oral:
REMOVED
(levothyroxine) T3 and T4 are Deiodinase
Partly in bile &
absorbed better Enzyme
2-TSH suppression therapy Partly in urine
on empty
in thyroid cancer and convert T4 to T3
stomach
nontoxic goiter depending on the
Replacement during Pregnancy tissues (40% is
converted to the
A higher dose of L-T4 often is reverse inactive
required in hypothyroid “rT3”)
Interactions
pregnant (typically 25– 40%
over basal as early Food, antacids, Ca
development of the fetal brain products, iron
depends on maternal thyroxine). decrease absorption of
T4 but not T3
Enzyme inducers
increase metabolism
Myxedema Coma of thyroid hormones
Management (as it is metabolized
by P450)

Hydrocortisone i.v. is
Intravenous T3 can also be
A loading dose of used but may be more also needed, if the
levothyroxine patient has
cardiotoxic and more difficult
intravenously associated adrenal or
to monitor.
pituitary
insufficiency.

T H I O A M I D E

Takes long Time to ORALLY 1-Allergy, most

appear due to: commonly
Inhibit thyroid hormone Well Immunologica
papular rash and
a-The long T1/2 of synthesis by:- Absorbed GIT upset l reactions: In pregnancy:
thyroxine. e.g. vasculitis,
1-Inhibition of oxidation of 2- lymphadenop ●Both propylthiouracil and
b- The large store iodide to iodine. athy, a lupus- methimazole cross the
Agranulocytosis
of the hormones in : the most like reaction, placenta equally, and either
2-Inhibition of iodination of
the gland tyrosine (organification of serious but rare arthralgia, & may be used safely.
iodine). and reversible polyserositis
●Methimazole is usually
3-Inhibition of coupling of 3-Abnormal skin
avoided in the first trimester
iodotyrosines to T4 and T3 pigmentation
→ propylthiouracil is
preferred due to methimazole-
4- Inhibit conversion of T4
associated embryopathy, →
to T3 in the periphery
then methimazole is used for
(Propylthiouracil)
the remainder of the pregnancy
Methimazole is the
due to the concern for
ACTIVE FORM of
propylthiouracil-associated
Carbimazole
liver failure in pregnancy.
Hyperthyroidism:
1-Hepatotoxicity:
1-As principal therapy. Hepatitis (PTU) &
cholestatic jaundice
2-As adjuvant to I131 to
control the disease while (methimazole)
waiting its effect. 2-Hair Loss
3-To control the disorder
in preparation for surgical
treatment. Mech.of
Kinetics
action
4-Thyroid storm (PTU inhibits
Uses S/E
conversion of T4 to T3
 I O D I D E S A L T

- Iodine is converted Iodism: 1-Thyroidectomy (gland

in liver into iodide Distributed (dose-dependet, Decrease size & size & vascularity).
which is selectively chronic adverse
extracellular vascularity of Allergic reactions: (Preparation for surgery)
taken up and effects)
concentrated by hyperplastic
-Angioedema, rash, 2-Thyroid crisis (storm)
thyroid gland. thyroid gland
(inhibit hormone release).
drug fever and
1-Inhibition of ulceration of mucous 3-To Prevent where goiter
iodide -Metallic taste, painful salivary glands, membranes is endemic . (Added to
organification excess salivation, running eyes & salt, water and bread).
ORALLY nose, sore throat, cough and diarrhea.
2-Inhibition of
the response Well
of thyroid Excreted in milk
Absorbe
gland to TSH Emits Beta rays (cytotoxic)
d C.I. in Lactation
which destroy the gland
3-Inhibition of tissue. RADI O ACTIVE Action appears after 1-2 months
proteolysis of and becomes maximal in another 2
months (Slow onset).
thyroglobulin Lugol,s
Potassiu Rapidly
→  Release iodine uses
m iodide absorbed
of T3&T4 (KI) ORAL THYROID + R
1-Hyperthyroidism in adults over 45 years
2-Hyperthyroidism in patients not fit for
● (5% iodine Concentrated surgery
+ 10% KI in by thyroid 4-Thyroid cancer.
●↑effect starts in 1-2
water). gland 3-Recurrence after medical or surgical
days and is maximum in Age:
treatment
10 - 14 days, then benefit
C.I. in Crosses placenta S/E
declines even with
Young age C.I. in pregnancy THYROID + R
continuous
1-Hypothyroidism (The chief toxic effect).
administration Mech.of
Kinetics 2-Thyroid storm (Release of thyroid
(compensatory ↑ in action
hormone).
TSH). Uses S/E
3-Require Repeated doses
 PARATHYROID HORMONE

Mechanism of action

Stimulate
Adenylate Cyclase
enzyme

In BONE & KIDNEY

INCREASE C-AMP

Increases Ca++ level in

TERIPARATIDE
the blood but reduces
serum phosphate

Recombinant Administered
segment of human once-daily by Net effect of
parathyroid subcutaneous stimulating new bone
hormone injection formation leading to
increased bone
mineral density

Uses:

Treatment of osteoporosis
 VITAMIN D ACTIONS

THE MAIN SITE OF ACTION is

(G.I.T)
D2 D3
(Ergosterol) (Cholecalciferol)

Increases BOTH
calcium & phosphate
absorption
From plant origin Synthesized in the skin from From animal
7- dehydrocholesterol by sources
exposure to ultraviolet rays

Activation: by hydroxylation in liver & kidney

VITAMIN D PREPARATIONS ON BONE

Calcitriol Alfacalcidol Calcium level Calcium level

(1, 25-dihydroxycholecalcifrol) (One-alpha =1α-hydroxycholecalcifrol) is normal is low

It acts on osteoblasts It acts on osteoclasts → increases

(bone hardening). bone resorption → increases Ca++
ACTIVE Requires hepatic level in blood
It is synthesized and
activation to produce used for secondary
Calcitriol as the active hyperparathyroidism
metabolite due to renal failure.
ON KIDNEY
(WEAK ACTION)

↑↑ calcium & phosphate

reabsorption from kidney
 VIT D USES CALCITONIN USES

SYSTEMIC TOPICAL

Hypercalcemia & osteoporosis and Paget’s

Hypocalcemia Psoriasis disease
Given by SC
injection or
nasal spray

In renal
disease to decrease
cellular Relief of pain associated with osteoporotic fracture.
Vit D proliferation Therefore, calcitonin may be beneficial in patients
deficiency (1, 24-OH vit D3). who have recently suffered a vertebral fracture.

Rickets
Osteomalacia

CALCITONIN DRUGS USED IN TREATMENT OF

OSTEOPOROSIS

Polypeptide hormone produced and secreted by parafollicular

cells of the thyroid gland in response to high calcium Anabolic
Anti-Resorptive Monoclonal
agents agents antibodies
against RANKLE
receptors

TERIPARATIDE
DENOSUMAB
Decrease BOTH
calcium & phosphate

Hormonal Replacement Bisphosphonates Calcitonin

Therapy

Chronic Glucocorticoids
Post Menpausal
Osteoporosis Hyperparathyroidism
SERMS
Thyrotoxicosis
Post Menopausal women
Estrogen→ Enhance Avoid breast &
breast cancer uterine cancer → HIGH RISK FOR OSTEOPOROSIS
 Other agents affecting
Ca homeostasis

Bisphosphonates Estrogens Glucocorticoids Thiazides Fluoride

Inhibit bone Prevent ↓Ca absorption

resorption resorbing effect and ↑ bone
and increase of P.T.H. in early resorption
bone density menopause

↓renal Ca
Alendronate, excretion.
Risedronate
Supplement with Ca → is known to ↓ frequency
Used in of fracture.
Osteoporosis However, EXCESS fluride may ↑ fracture risk

Bisphosphonates

If Patient unable
ORAL INTRAVENOUS
to tolerate Oral

Alendronate Risedronate Zoledronic

Ibandronate
Acid

Once Once
daily Once / 3 Once / Year
daily
or monthes
or
weekly weekly
or
monthly

FOOD significantly INTERFER with ABSORPTION

OF oral Bisphosphonates
 Denosumab Gonadotropin releasing hormone

Monoclonal antibody that targets Receptor Activator of Nuclear Factor Pulsatile secretion from the
Kappa-B Ligand (RANKL)→ Block Osteoclast Activation hypothalamus

Essential for the release of the gonadotropins follicle-stimulating

hormone (FSH) and luteinizing hormone (LH) from the anterior
pituitary.

If

Continuous
administration

Inhibits gonadotropin release through down-regulation of

the GnRH receptors on the pituitary

Denosumab uses GnRH Analogues

►Approved for Treatment of POST MENOPAUSAL

OSTEOPOROSIS in women AT HIGH RISK OF FRACTURE Leuprolide Nafarelin

►VERY EXPENSIVE → Should be reserved for women

INTOLERENT OR UNRESPONSIVE to other osteoporosis agents They are given I.V., S.C. or
nasal spray
Administered via
S.C. INJECTION / 6 MONTHES

Denosumab Side effects Given continuously → to inhibit gonadotropins

release →reduced production of androgens and
estrogens → thus these agents are used in:
INCREASE risk of

Cancer Uterine Precocious

Infections 2ry Malignancies Hypocalcemia Dermatological Endometriosis
prostate fibroids puberty
Reactions
 Growth hormone-inhibiting hormone Clinically Important Anterior Pituitary Hormones
(Somatostatin)
Growth hormone
(GH)
Somatostatin is secreted in the hypothalamus, D-cells of
pancreas and in the gut.
Preparation

Binds to receptors in the pituitary that suppress GH

and thyroid-stimulating hormone release.
Somatotropin
recombinant human growth hormone

Increases growth via stimulates Use:

It also inhibits the release of insulin, glucagon,
stimulating the protein ● Promotes growth in
production of synthesis and Pituitary dwarfism (GH
and gastrin
somatomedins lipolysis deficiency), as
replacement therapy prior
to epiphyseal closure

Octreotide Gonadotropins

►Synthetic analog of somatostatin. ❶ Include FSH, LH which are glycoproteins.

►Its half-life is longer than that of the natural compound, and depot ❷The regulation of gonadal steroid hormones depends on these agents.
formulations are available, allowing for administration once every 4
weeks.
Preparations

USED IN
Human menopausal gonadotropin Human chorionic gonadotropin
B A D (hMG) (hCG)

has FSH & has LH

LH activity activity
Bleeding esophageal
Diarrhea and ►Given by injection (IM or SC)
varices Acromegaly
flushing ►Used in the treatment of infertility
associated with ►HMG injection over a period of 5 to 12 days causes
carcinoid tumors. ovarian follicular growth and maturation, and with
(IV infusion of octreotide)
subsequent injection of HCG, ovulation occurs
 Prolactin Desmopressin
(intranasal, IV infusion, oral)
Cause
Hyperprolactinemia,
which is associated
with galactorrhea ❶ Stimulates milk production
and hypogonadism
(amenorrhea- An analog of vasopressin and is preferred for
❷ Its secretion is inhibited by
galactorrhea the treatment of diabetes insipidus and
syndrome). dopamine acting at D2 receptors.
nocturnal enuresis as it:

Drugs that increase the Drugs that decrease the

secretion of prolactin secretion of prolactin
Has minimal activity at the Is longer acting than
V1 receptor → largely free vasopressin
D2 receptor of vasopressor effects
Dopamine Dopamine agonists
receptors release
antagonists inhibitors
Cabergoline
and
metoclopramide & reserpine, α-methyl Bromocriptine
antipsychotics such dopa
as risperidone

Clinically Important Posterior Pituitary Hormone Oxytocin

Antidiuretic hormone (ADH) = Vasopressin

(SC / IM / IV)

Stimulates the contraction of pregnant uterus

Has both antidiuretic and vasopressor effects and is reflexly released from pituitary following
suckling to contract myo-epithelium of breast.

V1 V2
Syntocinon
Found in liver, vascular Found in the
smooth muscle Kidney
A synthetic derivative
VASOCONSTRICTION USED IN :
Increase water permeability
and reabsorption in the collecting
tubules.
used in the management of: Control of
Induction of labor Impaired milk
•Cardiac arrest postpartum
in uterine inertia ejection
•In controlling bleeding due to The major use is to treat hemorrhage
(I.V) (nasal spray)
esophageal varices diabetes insipidus. (I.M)
 GLUCOCORTICOIDS
Hydrocortisone or Cortisol

Pharmacokinetics

D M E
A

Distribution Metabolism Excretion

Absorption

A. Distributed all over the body In liver: Conjugation with glucuronic acid &
Well absorbed orally
B. Bound to plasma proteins mainly to Inactive Cortisone → Active (Cortisol) sulfuric acid → Excreted in urine
Corticosteroids-Binding-Globulin
(CBG = Transcortin) & albumin.

Mechanism Of Action

Genomic NON-Genomic

● Cortisol is a Steroid i.e. Lipid soluble → Gains intracellular access by passive diffusion → Binds to cytoplasmic e.g. cortisol can stimulate membrane
glucocorticoids receptor (GR- & GR-) → Activation → Receptor-Hormone complex translocates into the nucleus. receptors in Hippocampus

● Receptor-Hormone complex attaches to glucocorticoid response elements and act as a transcription factor to express or
repress genes depending on the tissue.

a) Gene Expression→ DNA transcription → mRNA → Protein synthesis e.g. Lipocortin-I (Annexin-1) & catabolic enzymes.

b) Gene Repression→ Inhibition of protein synthesis (Catabolic) → decreases cyclooxygenase II (COX-II), Nitric Oxide
Synthase (NOS), inflammatory mediators & immunoglobulins (Antibodies).

G L U C O C O R T I C O I D S

Psychological
disturbances ♦Decreases lymphocytes →
Gastric Lymphopenea
INCREASE Increases
Increases ♦Decreases eosinophils → Suppresses
Cataract & increase CNS erythropoiesis & circulating
number of Eosinopenea release of
increases release of P.M.N.L. by
in intraocular platelets & corticotropin
RBCs from bone marrow ↓ their
pressure (IOP) Coagulability releasing hormone
↑HCl migration Delays Wound
●In Cushing’s disease (C.R.H.) from
&↓mucin → Euphoria & from the Healing: Catabolic
(Hypercortisolemia) hypothalamus &
worsen Depression circulation effect on
Cataract & increases →Polycythemia. Delays healing Suppresses
peptic ulcer →Psychological fibroblasts &
intra-ocular of wounds release of A.C.T.H.
disturbances ●In Addison’s disease connective tissue
pressure → (Hypocortisolemia) →
from Anterior
Glaucoma Anemia. pituitary → So if
DECREASE Sudden stop →
Hypernatremia → Hypervolemia → Addison’s Crisis
Uricosuric ♦EDEMA & HF Thromboembolic
effect: ♦HTN ↑ C.O.P. & ↑ blood pressure
manifestations
Increases uric ♦HYPOKALEMIA
(worsen digitalis Hyperglycemia & increase Decrease
acid excretion. toxcicty) STRESS &
Glycogen in liver Long-term treatment:
SHOCK
Decrease Decrease Vitamin D ►Abrupt withdrawal
Worsens Diabetes ↑ Sympatho-adrenal discharge
Inflammation →Decreases Ca2+ after long use → Acute
Peptic mellitus due to their
absorption from G.I.T Addisonian Crisis
ulceration. Anti-Insulin effect
C.N.S. stimulation →Sense of well- → Hypocalcemia
►Moon face & Buffalo
being & adaptive effect to stress. hump
Osteoporosis
& ►Full picture of the
Hypocalcemia Iatrogenic Cushing’s
disease
Synthesis of a Lipocortin-1 = Annexin-1→ Inhibition Repress genes of COX-II, Decreases Decreases
Decreases Stabilization Short-term treatment:
of Phospholipase A2 enzyme → Inhibits release of inducible NOS (nitric oxide formation of capillary
migration of of lysosomal
Arachidonic acid → ↓PGs (prostaglandins), LTs synthase), adhesion other permeability → ►Usually, there are no
leukocytes to membrane →
(leukotrienes) & P.A.F. (platelet activating factor) molecules & complement inflammatory ↓ Inflammatory serious adverse
site of ↓ Cell death.
components mediators & edema & joint effects when
cytokines inflammation
effusion. glucocorticoids are
used for short periods
►Retardation of growth in children. Sublaxation (<2 weeks)
of joints
►Teratogenicity→C.I. in pregnancy ►Insomnia,
Decreases antibody formation after
behavioral changes
Decrease Allergy repeated
(as hypomania), and
& Immunity intra-
acute peptic ulcers are
articular
Inhibition of Antigen / Antibody reaction. occasionally observed
Contraindication injections
even after only a few
Mask manifestations of
days of treatment.
bacterial & viral infections
‫نفس ال‬ Stabilization of mast cell → suppressing degranulation
with sense of well-being Immunosuppressant → ↑ ►Acute pancreatitis is
despite the seriousness of → ↓Release of allergic mediators
Susceptibility to infection, flare up a rare but serious
infection Side effects acute adverse effect of
present infection & reactivation of
latent T.B. lesion high-dose
Decreases tissue response to allergic mediators glucocorticoids
 USES

Supplementary & Suppressive therapy

→ Use pharmacological doses of drugs with powerful gluco- and minimal or no mineralo-corticoid activity → Many adverse effects

EYE CNS CVS GIT Uro-genital BLOOD JOINT SKIN

Respiratory

ALLERGY Encephalitis, ►Rheumatic

bronchial ►Hemolytic &
cerebral edema &↑ carditis ►Inflammatory Nephritis & ►Suppress
asthma aplastic anemia,
Intra-cranial bowel syndrome nephritic ►Rheumatic, hypertrophic
►Shock thrombocytopenia
pressure e.g. ulcerative syndrome Rheumatoid, Gouty scars &
colitis ►Treat lymphoma & & Osteoarthritis keloid
leukemia formation
►Chronic active ►Collagen disease:
hepatitis ►Suppress tissue & Polyarthritis & ►ALLERGY
organ rejection systemic lupus
►Hypervitaminosis D erythematosis
& Hypercalcemia

Replacement Therapy in Adreno-Cortical Insufficiency (Addison’s disease)

→ Use physiological doses → Almost NO adverse effects:
a- Primary Addison’s → Replace BOTH Gluco- & Mineralo-corticoid activities.
b- Secondary Addison’s ( ACTH) → Replace ONLY Glucocorticoid activity

Acute Addisonian Chronic Addison’s

Crisis Disease

Cortisol 100 mg I.V. Saline (0.9 % NaCl) +

followed by I.V. Glucose 5% + Blood Mineralo.: Gluco.:
-DOCA (S.L., I.M., S.C. pellet implantation) or -Cortisone Acetate 25 – 37.5 mg/day
infusion / 6 hours transfusion +
Fludrocortisone acetate Orally + Generous salt & sugar diet.
Vasopressors.
(0.1-0.3 mg /day orally, most conventient).

Precautions During Long Term Glucocorticoid

Gradual Test for Routine X-ray Add Weight Measure Avoid in Increase dose Diet should
withdrawal glucose in spine anabolics estimation blood Digitalis in stress be Rich in
urine pressure toxicity Proteins,
K+& Ca2+ &
Low in NaCl

Preparations Of Commonly Used Corticosteroids

Preparations with primarily glucocorticoid activity Preparations with primarily mineralocorticoid activity

Fludrocortisone
Short acting Intermediate acting Long acting In pregnancy

Prednisone Dexamethasone The only glucocorticoid that has no effect

on the fetus in pregnancy is
Hydrocortisone Cortisone
(cortisol) Mineralocorticoid activity is less Mineralocorticoid activity is Prednisone→ It is a prodrug that is not
with Prednisone (prodrug) absent with dexamethasone. converted to the active compound,
prednisolone, in the fetal liver.

Equal glucocorticoid (anti-inflammatory) & mineralocorticoid (salt-retaining)

activities, cortisone is a prodrug → systemic administered → activated
 Adreno-statics

a- It causes a reduction in the synthesis of all

hormonally active steroids. Because it inhibits
conversion of Cholesterol →Pregnenolone (First step in
A.C.T.H. Dependent steroidogenesis). Aminoglutethimide A.C.T.H. Independent
Cushing’s b- It can be used with metyrapone or ketoconazole to Cushing’s
reduce steroid secretion in patients with Cushing’s
syndrome due to adrenocortical cancer who do not
respond to mitotane.

Pasireotide Cabergoline Cyproheptadine

A somatostatin analogue →↓ ACTH ● long-acting dopamine D2 receptor agonist ● Antihistamine (H1-blocker) + Anti-
and growth hormone secretion and ↓ used primarily to treat hyperprolactinemia.
serotonin.
the circulating levels of cortisol in ● Cabergoline also inhibits ACTH secretion
from corticotroph tumors (off-label use).
● Suppresses release of A.C.T.H
patients with ACTH-producing
● Bromocriptine can also be used
pituitary tumors and is also used in
the treatment of acromegaly.

- Cushing’s disease +
Aminoglutethimide.
Ketoconazole Metyrapone Mitotane
USES - Test the function of
(Mitopirone)
anterior pituitary to
●Anti-fungal. secrete A.C.T.H a- Destruction of adrenocortical cells.
●Inhibits adrenal steroid hormone
synthesis when used in larger Inhibits 11-B-Hydroxylase enzyme selectively b- Useful in Cushing’s disease &
doses →↓ Synthesis of BOTH Aldosterone & Cortisol →↑ ACTH Inoperable adrenocortical carcinoma.
●Useful in Cushing’s disease

Mineralocorticoids
Aldosterone

1-Steroid hormone synthesized and secreted from Zona glomerulosa.

2-Very powerful mineralocorticoid & very weak glucocorticoid activity.

Control Of Release of Aldosterone:

a) Renin-Angiotensin System activation by hypovolemia & hyponatremia.

b) Hyperkalemia.

Escape Phenomenon: Prolonged hypervolemia → Sensitivity of distal convoluted tubules (D.C.T.) to the effect of Aldosterone → No Na+& Water retention BUT
still K+ excretion.

**Aldosterone is rarely used clinically. But its antagonist (Spironolactone) is useful as K+-Retaining diuretic especially in cases of hyper-aldosteronism.

Mineralocorticoid preparations

Des-Oxy-Corticosterone Fludrocortisone Acetate

(D.O.C.) (9- Fluoro-Hydrocortisone)

1-Pure mineralocorticoid with NO glucocorticoids activity.

2-1/100 activity of aldosterone. 1-Synthetic mineralocorticoid.
3-Used to replace mineralocorticoid activity in Addison’s disease. 2-Mineralocorticoid (125 X Cortisol) & Glucocorticoid (10 X Cortisol)
4-NOT effective orally due to extensive hepatic first pass metabolism activities.
3-Useful orally to replace mineralocorticoid activity in Addison’s disease.
Preparations:
●Desoxycorticosterone Acetate (D.O.C.A.):
- Sublingual - I.M. - Subcutaneous Pellet Implantation

●Desoxycorticosterone Trimethyl Acetate

 Estrogen

Routes of Administration

ORAL TRANASDERMAL TOPICAL

PATCH

Natural and Topically in the

synthetic estrogens vagina as pessaries
Most estrogens are
are well absorbed or creams
absorbed from skin
and mucous
membrane

PREPARATIONS

Natural Semisynthetic Synthetic

(Steroidal synthetic)

Estradiol
Diethylstilbestrol
Ethinyl estradiol Mestranol
undergo first- pass
metabolism →when
taken orally have low Highly potent, taken orally rapidly oxidized to ethinyl estradiol. Non-steroidal, Effective
bioavailability. because ethinyl group orally
Fat soluble, stored in adipose tissue:
protects from inactivation by long duration.
the liver.

Mechanism of Action

Genomic Non-genomic

More rapid actions

•Steroid hormones diffuse across the cell membrane
and bind with high affinity to specific nuclear-receptor
proteins.
•The activated steroid–receptor complex interacts with ♦Activation of an estrogen receptor in the membranes of
nuclear chromatin to initiate hormone-specific RNA hypothalamic cells has been shown to couple to a G
synthesis. protein, there by initiating a 2nd messenger cascade.
•This results in the synthesis of specific proteins that ♦Estrogen-mediated dilation of coronary arteries occurs
mediate a number of physiologic functions. by the increased formation and release of nitric oxide and
prostacyclin in endothelial cells.

Therapeutic uses

C P R

Replacement therapy:
Postmenopausal hormonal therapy (HT)
(estrogen & progestogen)

Contraception with 1ry hypogonadism

progestogens For menopausal symptoms” hot flushes & vaginal (ovarian failure).
atrophy”
:‫ شروط‬4
Premature menopause

intact uterus →add Doses of HT are less than that Lowest effective doses If only vaginal
progestogen →to in oral contraception: less for the shortest possible atrophy: use Surgical menopause
decrease risk of side effects time (for risk of side vaginal
endometrial carcinoma. effect) estrogen
 Adverse Effects & Contraindications

THE MOST COMMON is

Nausea and Breast tenderness

5 INCREASE’S :

INCREASE levels of INCREASE Weight gain INCREASE blood INCREASE Risk INCREASE Risk
factors II, VII, IX and X (edema) & Blood pressure sugar levels of breast endometrial
cancer. carcinoma

add
Thromboembolic events & Due to Salt & water progesterone to
myocardial infarction retention decrease risk

Contraindicated in Carcinomas of
endometrium, certain types of
Contraindicated in History of cancer breast, both are estrogen
thromboembolic disorders dependent.

Drug Interactions

Hepatic microsomal enzyme inducers as phenytoin and rifampicin increase

estrogens metabolism and decrease their effect as contraception

THE PROGESTINS

Progesterone is the natural progestational Hormone (Progestogens).

PREPARATIONS

Natural Synthetic progestin preparations

Rapidly Metabolized (IM injection) (effective orally)
Adverse Effects
►Weak androgenic
actions of some of the
progestogens derived
Hydroxy-progesterone from testosterone.
Progesterone Derivatives of progesterone Derivatives of nor-testosterone
caproate ►Edema (androgenic precursor)
►Psychic depression.
►Increase Cholesterol:
►oily IM. IM, weekly atherosclerosis
►Rapidly metabolized
Medroxy-progesterone
acetate
►May be implanted IM as Nor-ethindrone Nor-gestrel
pellets or microcrystals

orally, daily
IM/3 months orally, daily orally or SC
implantation

USES
MAIN USE
Amenorrhea A B C D&E

artificial cycle: estrogen for 25 days supplemented with BLEEDING Contraception (ORAL) DYSMENORRHEA
progesterone 15th to 25th day .Menstruation occurs on withdrawal (FUNCTIONAL UTERINE) Alone or with estrogen ENDOMETRIOSIS
 Selective Estrogen Receptor Modulators (SERMs) Estrogen Synthesis Inhibitors
Anti-Estrogens
Estrogen-related compounds that display selective agonism or antagonism for Aromatase Inhibitors (AIs)
estrogen receptors depending on the tissue type
Estrogen Receptor Modulators at
estrogen receptors. ►Decrease the production of estrogen

Used as Ovulation-inducing agent ►The aromatase reaction is responsible for the extra-adrenal
synthesis of estrogen from androstenedione, which takes place in
Tamoxifen Raloxifene Clomiphene
liver, fat, muscle, skin, and breast tissues, including breast
Citrate malignancies. Peripheral aromatization is an important source of
estrogen in postmenopausal women

USED IN: Adverse effects: No effect on endometrium

Adverse effects:
►Treatment of ►Hot flushes USED IN: Steroidal Ais Non-steroidal Ais
►Does not relieve Post-
metastatic Breast (exemestane) (letrezole)
►Increase risk of ►Effective for prevention & Menopausal hot flushes
Cancer Binds permanently to Bind reversibly to aromatase
endometrial cancer treatment of osteoporosis used in treatment of breast cancer &
►Increase risk of venous aromatase enzyme
►Adjuvant therapy ►Increase risk of DVT ►Reduction in risk of thromboembolism (high) (suicide inhibition) induction of ovulation.
after mastectomy or breast cancer - It is devoid from the androgenic side
& pulmonary embolism
radiation effect of steroidal AIs

Mifepristone Danazol
Inhibits the activity of progesterone Anti-Progestogens (Anti - gonadotrophins) USED IN

endometriosis &
BINDS TO Combined with Inhibits fibrocystic disease
Interferes with USED as
of breast

The prostaglandin analog Postcoital The mid-cycle

The progesterone & proved surge of LH
misoprostol (administered contraceptive e.g. Steroid synthesis in the
Progesterone receptors with Glucocorticoid very effective in terminating and FSH, but
orally or intravaginally) to in rape. ovary
no progesterone activity receptors early pregnancy with no effect on Reduces ovarian function
induce uterine
(progesterone antagonist). contractions. basal level leading to atrophic changes in
the endometrium

Clomiphene Metformin
citrate
OVULATION-INDUCING AGENTS Adverse effects OF Anti-
►It lowers insulin, androgen and Progestogens
cholesterol levels 1) Androgenic: acne,
Aromatase ►It is useful in restoring regular hirsutism & Deepening
menstrual cycle and starting of voice
►Nonsteroidal compound used to induce Adverse-effects: Inhibitors.
ovulation (Letrezole) ovulation in about 50% of women 2) Weight gain
►Hot flushes, Headache, Visual with polycystic ovary syndrome
►It blocks ER in hypothalamus disturbances and reversible hair 3) Decrease breast size
→↓↓negative feedback effect of estrogen loss.
HMG 4) Libido changes
on GnRH →↑↑FSH → marked stimulation ►Ovarian enlargement Multiple ►The drug →↓estrogen synthesis
and enlargement of ovaries & increase Ovulation & multiple pregnancies. →↑GnRH release →↑ FSH release →
estrogen secretion & induction of induction of ovulation
►Constipation. ►It has FSH and LH activities
ovulation. ►Its use must be followed by
►Better to be given with small dose of FSH
HCG with LH activity only

Androgens

►Secreted from testes, adrenal cortex and ovaries

►Essential for spermatogenesis, secondary sex characters, increase protein synthesis
and increase libido in males and females

PREPARATIONS Contraindication
USES Adverse effects
cancer prostate

►Replacement therapy in male 1ry

Natural Synthetic hypogonadism due to deficiency of
androgens or 2ry hypogonadism due to
failure of pituitary

►Cholestatic ►Masculinization ►Precocious

jaundice (with in females puberty
Androsterone testosterone Testosterone Methyl testosterone)
(more active) ►Hirsutism ►Premature
propionate testosterone ►Undesirable closure of
►Salt retention
sexual activity epiphyseal plates
in children
Sublingual, I.M. or Sublingual
Ineffective orally S.C.
Rapidly metabolized in liver
Anabolic Steroids

Testosterone is metabolized by reductase enzyme

into active dihydrotestosterone
but
Nandrolone Methandrostenolone
Its action on skeletal muscles does not require the
active form
USED IN : Adverse effects

►Osteoporosis ►General wasting ►In children →Precocious puberty.

►Acute renal failure ►Aplastic anemia. ►In women →virilization (Acne, hirsutim, voice change)
 Anti-androgens

Finasteride 1.Flutamide
2.Cyproterone

MECHANISM OF USES
ACTION MECHANISM OF
ACTION USES

►Inhibits conversion of testosterone into di-hydro- It is given orally to Compete with testosterone for
testosterone by inhibiting 5α-reductase → blocks reduce benign prostatic ►Hypersexuality in males
receptors
action of androgen on tissues requiring hyperplasia (BPH). ►Hirsutism
dihydrotestosterone
►Cancer prostate
(prostate and hair follicles)

MECHANISM OF Spironolactone
ACTION

USES
►Competitive inhibitor of aldosterone
►Competes with di-hydro-testosterone for the
androgen receptors in target tissues.
►It also reduces 17α-hydroxylase activity→ ►Treatment of hirsutism in women and appears to
lowering plasma levels of testosterone and be as effective as finasteride, flutamide or
androstenedione cyproterone.