PHARMACOLOGY | OPT 2207-3

2nd Sem | BSPT 2-3

OUTLINE INTERMEDIATE LOBE Small intermediate lobe

I. Introduction to Endocrine Pharmacology that may secrete
A. Primary Endocrine Glands and Their melanocyte
Hormones stimulating hormone but
B. Endocrine Physiology and MSH does not have any
Pharmacology apparent physiologic or
C. Clinical Use of Endocrine Drugs pharmacologic
significance in humans.
II. Adrenocorticosteroids
A. Steroid Synthesis POSTERIOR LOBE Secretes two hormones
B. Glucocorticoids (neurohypophysis) -ADH (Antidiuretic
C. Clinical Use of Glucocorticoids hormone) and oxytocin-;
D. Adverse Effects of Glucocorticoids cell bodies in the
E. Drugs that inhibit Adrenocortical paraventricular nuclei
Hormone Biosynthesis manufacture oxytocin
F. Mineralocorticoids and supraoptic nuclei
G. Special Concerns of Adrenal Steroid contain cell bodies that
Use in Rehabilitation Patients synthesize ADH.
III. Androgens
A. Source and Regulation of Androgen
Synthesis
B. Physiological Effects of Androgen
C. Pharmacologic Use of Androgen
D. Adverse Effects of Clinical Androgen
Use
E. Antiandrogens
F. Androgen Abuse
G. Effects of Androgen on Athletic
Performance
H. Adverse Effect of Androgen Abuse

THYROID GLAND
● Located in the anterior neck region
INTRODUCTION TO ENDOCRINE PHARMACOLOGY
approximately at the level of the 5th cervical
to 1st thoracic vertebrae.
PRIMARY ENDOCRINE GLANDS AND THEIR HORMONES ● Consists of bilateral lobes that lie on either
side of the trachea and connected by the
isthmus.
HYPOTHALAMUS AND PITUITARY GLAND ● Secretes T4 and T3
● Synthesis is controlled by the hypothalamic
PITUITARY GLAND pituitary system via TRH.
● Play a crucial role in helping maintain and
● A small, pea shaped structure regulate body heat (thermogenesis).
● Located within the sella turcica at the base ● “If nagpaswallow kay pt sumasabay ito kaya
of the brain nalalaman if may goiter, nakikita na enlarged”
● Lies inferior to the hypothalamus and
attached to the hypothalamus by the PARATHYROID GLAND
infundibulum
● Small, egg shaped structures embedded in
the posterior surface of the thyroid gland.
THREE LOBES ● Usually four with a glands located on each
half of the thyroid gland.
ANTERIOR LOBE Secretes 6 important
● PTH increases the concentration of calcium
(adenohypophysis) peptide hormones.
in the blood stream by mobilizing calcium
from storage sites in bone.

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 PHARMACOLOGY | OPT 2207-3
2nd Sem | BSPT 2-3
● Primary factor regulating PTH release is the
level of calcium in the bloodstream.
● Appear to act as calcium sensors that
monitor circulating calcium levels.
PANCREAS
● Located behind the stomach in the lower left
area of the abdomen.
● Unique because it serves both endocrine and
exocrine function.
● Exocrine aspect involves digestive enzymes
that are excreted into the duodenum while as
an endocrine gland secretes two hormones
-insulin and glucagon- by the islets of
Langerhans (alpha and beta cells).
ADRENAL GLAND
● Located at the superior poles of each kidney.
● Composed of an outer cortex and inner
medulla.
● ADRENAL CORTEX - synthesizes and secretes
glucocorticoids and mineralocorticoids.
● GLUCOCORTICOIDS are involved in the
regulation of glucose metabolism and have
significant anti-inflammatory and
immunosuppressive properties.
o Controlled by the hypothalamic
pituitary system.
● CRH FROM HYPOTHALAMUS - stimulates
ACTH from the anterior pituitary which in
turn stimulates synthesis of glucocorticoids.
● MINERALOCORTICOIDS are involved in
controlling electrolyte and fluid levels –
specifically aldosterone.
o Mineralocorticoid release is
regulated by fluid and electrolyte
levels in the body and also the
renin-Angiostensin System.
● ALDOSTERONE - sodium reabsorption thus
facilitating reabsorption of water and also
inhibits reabsorption of potassium thus
increasing potassium excretion.
● ADRENAL MEDULLA - synthesizes and
secretes epinephrine and norepinephrine.
GONADS
Reproductive organs are the primary source of
steroid hormones which influence various aspects of
sexual and reproduction function.
Release of male and female sex steroids is controlled
by hormones from the hypothalamus and anterior
pituitary.
ENDOCRINE PHYSIOLOGY AND PHARMACOLOGY
HORMONE CHEMISTRY
● 2 primary categories according to their basic
chemical structure.
o STEROID HORMONES - derived from
lipids such as cholesterol e.g.
androgens, estrogens, progesterone
glucocorticoids, mineralocorticoid.
▪ “Which is why females on the
heavy side usually have a
problem sa menstrual cycle d/t
higher levels of cholesterol; this
will in turn convert and result to
higher levels of estrogen and
progesterone which will affect
the monthly cycle because of the
high level of hormones.”
o PEPTIDE HORMONES - consist of
amino acids linked together in a
specific sequence e.g. hypothalamic
releasing factors and pituitary
hormones, thyroid hormones are
manufactured from amino acid
tyrosine, epinephrine and
norepinephrine are synthesized from
either phenylalanine or tyrosine.
SYNTHESIS AND RELEASE OF HORMONES
● Synthesized within the cells of their
respective endocrine glands.
● Most hormones are synthesized and
packaged in storage granules within the
gland.
● When gland is stimulated, the storage
granule fuses with the cell membrane and
the hormone is released by exocytosis except
thyroid and steroid hormones which are not
stored but are synthesized on demand when
an appropriate stimulus is present.
● Hormone synthesis and release are initiated
by extrinsic (pain, temperature, light, smell)
and intrinsic factors (include various
humoral and neural factors).
FEEDBACK CONTROL MECHANISMS IN ENDOCRINE FUNCTION
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2nd Sem | BSPT 2-3
II.
Show how the hormones are controlled; this is through the
negative feedback control in the hypothalmic pituitary
endocrine pathways.
If may tissue na need ng hormone, it will tell you
hypothalamus or pituitary to release the needed hormones
tapos if okay na yung levels, magsesend ng signal na okay
na doon, maiinhibit na.
III.
EXCITATORY AND INHIBITORY EFFECTS are indicated by
either stimulating or inhibiting the release of the
hormones from your pituitary or hypothalamus.
HORMONE TRANSPORT
● Usually carried from their site or origin to the
target cell via the systemic circulation.
● During transport in the bloodstream, certain
hormones such as steroids are bound to
specific plasma proteins.
● Protein carriers appear to help prolong the
half-life of the hormone and prevent
premature degradation e.g. testes produce
androgen-binding protein which helps
transport and concentrate testosterone
within the seminiferous tubules of the testes.
HORMONE EFFECTS ON TARGET CELLS
● Most hormones affect their target cell by
interacting with a specific receptor.
● Primary locations of receptors:
I. SURFACE MEMBRANE RECEPTORS:
● Located on the outer surface of the plasma
membrane. Surface receptors tend to
recognize the peptide hormones and some
amino acid derivatives (e.g. Pituitary
hormones, catecholamines).
● When stimulated by a peptide-like hormone,
the receptor initiates some change in the
enzymatic machinery located within the cell
which results in the production of some
intracellular chemical 2nd messenger –
cAMP.
● E.g. ACTH is a polypeptide that binds to
surface receptor on adrenal cortex; the
surface receptor stimulates the
adenylate-cyclase enzyme to increase the
production of cAMP (acts as second
messenger).
CYTOSOLIC HORMONE RECEPTORS:
● The steroid hormones typically bind to
protein receptors which are located directly
within the cytosol.
● The hormone and receptor form a large
activated steroid – receptor complex that
travels to the cell’s nucleus where it binds to
specific genes located within the DNA
sequence.
● E.g. Anabolic Steroids increase muscle size
by facilitating the production of more
contractile proteins.
NUCLEAR HORMONE RECEPTORS:
● Located directly on the chromatin within the
cell nucleus are specific for the thyroid
hormones.
CLINICAL USE OF ENDOCRINE DRUGS
REPLACEMENT THERAPY
● Can be used for menopausal pts. (moody
feeling) and are obliged to receive hormonal
replacement therapy.
DIAGNOSIS OF ENDOCRINE DISORDERS
● Physicians may administer hormones or
their antagonists to determine the presence
of excess endocrine function or endocrine
hypofunction.
● E.g. Hormone administration to increase or
decrease pituitary secretion to determine if
pituitary function is normal.
TREATMENT OF EXCESSIVE ENDOCRINE FUNCTION
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2nd Sem | BSPT 2-3

● Excessive endocrine function is often treated

pharmacologically.
● Hormone antagonists can be used for
prolonged periods to counteract the effects
of excessive hormone production.

EXPLOITATION OF BENEFICIAL HORMONE EFFECTS

● Hormones and their synthetic analogs are
often administered to exaggerate the
beneficial effects of their endogenous
counterparts.
● E.g. Use of corticoids to treat inflammation.
o Doses of glucocorticoids that are
much higher than the physiological
levels produced by the body can be
very effective in decreasing
inflammation in a variety of clinical
conditions.

USE OF HORMONES TO ALTER NORMAL ENDOCRINE FUNCTION

● Administration of exogenous hormones can
often affect the normal release of hormones.
o This fact can be exploited in certain
situations to cause a desired change
in normal endocrine function. ● With cholesterol, it can produce 4 hormones:
● E.g. Oral contraceptives containing estrogen 1. Aldosterone
and progesterone inhibit ovulation by 2. Cortisol
inhibiting the release of LH and FSH from the 3. Testosterone
anterior pituitary. 4. Estradiol
● Cholesterol can also go through 3 different
USE OF HORMONES IN NON-ENDOCRINE DISEASE
pathways:
● Certain forms of cancer respond to treatment 1. Mineralcorticoid Pathway
with glucocorticoids. 2. Glucocorticoid Pathway
● Drugs that block the cardiac beta-1 receptors 3. Sex Hormone Pathway
may help control angina and hypertension by
preventing excessive stimulation from MINERALOCORTICOI GLUCOCORTICOID SEX HORMONE
adrenal medulla hormones.
D PATHWAY PATHWAY
ADRENOCORTICOSTEROIDS PATHWAY

STEROID SYNTHESIS Progesterone → 17 - Androstenedi

or ↓ Hydroxyprogeste one ↓
rone → or ↓

11-Deoxycortico 11 - Deoxycortisol Testosterone

sterone ↓ ↓ ↓

Corticosterone Cortisol Estradiol

↓

Aldosterone

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2nd Sem | BSPT 2-3
GLUCOCORTICOIDS
MECHANISMS OF ACTION
● Steroids alter protein synthesis in responsive
cells through a direct effect on the cell’s
nucleus.
● Alter the transcription of specific DNA genes
which results in subsequent changes in RNA
synthesis and the translation of RNA into
cellular proteins.
PHYSIOLOGIC EFFECTS
● It exerts effects on glucose, protein, and lipid
metabolism.
● Primary effect is to maintain blood glucose
and liver glycogen levels to enable a supply of
this energy substrate to be readily available
for increased activity.
ANTI-INFLAMMATORY EFFECTS
● Regardless of cause of inflammation,
glucocorticoids attenuate the heat, erythema,
swelling and tenderness of the affected area.
● Mechanisms of Action:
1. INHIBITION OF EICOSANOID BIOSYNTHESIS
● Inhibit production of prostaglandins and
leukotrienes by promoting synthesis of
lipocortins which inhibit the phospholipase
A2 enzyme (responsible for liberating
phospholipids from cell membranes to be
transformed).
2. INHIBITION OF CELLULAR COMPONENTS OF
THE INFLAMMATORY REACTION
● Inhibit release of chemicals (chemotactic
factors) that attract the leukocytes and
macrophages to the site of inflammation.
● Limit the ability of macrophages to
phagocytize and destroy invading
microorganisms in inflamed tissues.
● Inhibit the ability of various inflammatory
cells to synthesize and release inflammatory
mediators (PAF, TNF, interlukin 1)
OTHER INFLAMMATORY MECHANISMS
● Stabilize lysosomal membranes making
them less fragile and susceptible to rupture.
● Decrease vascular permeability by directly
causing vasoconstriction or by suppressing
release of histamine, kinins and other
chemicals that cause increased vascular
permeability.
IMMUNOSUPPRESSION
● Inhibit hypersensitivity reactions especially
delayed or cell-mediated allergic reactions.
● Suppress the ability of the leukocytes and
macrophages to synthesize or respond to
certain chemical mediators such as
interleukins and interferons.
OTHER EFFECTS
A. AFFECT RENAL FUNCTION
o By enhancing sodium and water
reabsorption and by impairing the
ability of the kidneys to excrete a
water load.
B. ALTER CNS FUNCTION
o Producing changes in behavior and
mood.
o Insomnia, euphoria, depression.
C. ALTER THE FORMED ELEMENTS IN THE
BLOOD
o By facilitating an increase in
erythrocytes, neutrophils, and
platelets while decreasing the
number of lymphocytes, eosinophils,
monocytes, and basophils.
D. ASSOCIATED WITH EFFECTS OF PEPTIC
ULCER
o Suppressing local immune response
against Helicobacter pylori.
E. EFFECTS ON DEVELOPMENT OF FETAL
LUNGS
o Production of pulmonary surfactants
F. CATABOLIC AND ANTI-ANABOLIC EFFECTS
o Lymphoid, connective tissue muscle,
peripheral fat and skin.
G. ANTAGONIZE EFFECT
o Vitamin D on calcium absorption.
CLINICAL USE OF GLUCOCORTICOIDS
1. Replacement therapy
2. Corticoids are administered systemically to
help restore normal function in conditions of
adrenal cortical hypofunction.
a. ADDISON'S DISEASE
● Chronic adrenocortical insufficiency
characterized by weakness, fatigue, weight
loss, hypotension, hyperpigmentation, and
inability to maintain blood glucose during
fasting.
b. CONGENITAL ADRENAL HYPERPLASIA
o Characterized by specific defects in
the synthesis of cortisol and most
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2nd Sem | BSPT 2-3
common defect is P450c21 (21 β
hydroxylase activity).
c. CUSHING SYNDROME
o Result from bilateral adrenal
hyperplasia secondary to an ACTH
secreting pituitary adenoma and
treated with surgical removal of
tumor.
d. PRIMARY ALDOSTERONISM
o Results from the excessive
production of aldosterone by an
adrenal adenoma or from a
malignant tumor.
EVALUATION OF ENDOCRINE DYSFUNCTION
A. Dexamethasone Suppression Test
● It is used for diagnosis of Cushing's
Syndrome.
B. Stimulation of Lung Maturation in the Fetus
● Lung maturation in the fetus is regulated by
the fetal secretion of cortisol.
● Treatment of the mother with large doses of
glucocorticoid reduces the incidence of
respiratory distress syndrome in infants
delivered prematurely.
C. Intramuscular Betamethasone
NONENDOCRINE D/O TREATED C GLUCOCORTICOIDS
● INFECTIONS - acute respiratory distress
syndrome, sepsis, systemic
inflammatory syndrome.
● INFLAMMATORY CONDITIONS OF BONES
AND JOINTS - arthritis, bursitis,
tenosynovitis
● ORGAN TRANSPLANTS - prevention and
treatment of rejection
● RENAL DISORDERS - Nephrotic
Syndrome
● THYROID DISEASES - Malignant
exopthalmos, subacute thyroiditis
SPECIFIC AGENTS
● Betamethasone (Celestone)
● Betamethasone Sodium Phosphate
● Cortisone (Cortone Acetate)
● Dexamethasone (Decadrone, Decilone)
● Dexamethasone Acetate (Decadrone LA)
● Dexamethasone Sodium Phosphate
(Decadrone Phosphate, Adrecort)
● Hydrocortisone (Cortef)
● Hydrocortisone Acetate
● Hydrocortisone Cypionate (Cortef)
● Hydrocortisone Sidium Phosphate
(Hydrocortone, Solu-Cortef)
● Methylprednisolone (Medrol)
● Methyprednisolone Acetate (Depomedrol)
● Methyprednisolone Sodium Succinate
(Solu-Medrol)
● Prednisolone (Prelone, Prednecort)
● Prednisolone Sodium Phosphate
(Optipred)
● Prednisone (Meticorten, Orasone 10 or 20)
● Triamcinolone
● Triamcinolone Acetonide (Kanosole,
Kenacort A)
● Triamcinolone Diacetate
ADVERSE EFFECTS OF GLUCOCORTICOIDS
1. ADRENOCORTICAL SUPPRESSION
● It can be a serious problem when
glucocorticoid therapy is terminated.
● Abrupt withdrawal can be
life-threatening in patients.
● Glucocorticoids must be withdrawn
slowly by tapering the dose.
2. DRUG-INDUCED CUSHING SYNDROME
● Symptoms associated with Cushing
Syndrome:
o Roundness and puffiness in the
face.
o Fat deposition and obesity in the
trunk region.
o Muscle wasting in the
extremities.
o Hypertension
o Osteoporosis
o Increased body hair (hirsutism)
o Glucose intolerance
3. BREAKDOWN OF SUPPORTING TISSUES
● Glucocorticoids appear to weaken these
supporting tissues by
i. Inhibiting the genes responsible for
production of collagen and other
tissue components.
ii. Increasing the expression of
substances that promote breakdown
of bone, ligaments, tendon, muscle,
skin.
DRUGS THAT INHIBIT ADRENOCORTICAL
HORMONE BIOSYNTHESIS
Metyrapone (Metopirone)
● Selective inhibitor of steroid synthesis.
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2nd Sem | BSPT 2-3
● Inhibits 11 hydroxylation, interfering with
cortisol and corticosterone synthesis.
● Commonly used in tests of adrenal
function and pituitary function.
● Withdrawn from the market in the USA.
Aminoglutethimide (Cytadren)
● Blocks the conversion of cholesterol to
pregnenolone and causes a reduction in the
synthesis of all hormonally active steroids.
● Used in conjunction with dexamethasone or
hydrocortisone to reduce or eliminate
estrogen production in patients with
carcinoma of the breast but use has been
replaced by tamoxifen.
TAMOXIFEN
● Antiestrogen; for carcinoma/breast ca
● Used in conjunction with metyrapone or
ketoconazole to reduce steroid secretion in
patients with Cushing’s syndrome d/t
adrenocortical cancer who do not respond to
mitotane.
● Shown to enhance the metabolism of
dexamethasone.
Ketoconazole
● An antifungal imidazole derivative which is a
potent and rather nonselective inhibitor of
gonadal steroid synthesis.
● Inhibits the cholesterol side chain cleavage.
● Used for the treatment of patient with
Cushing’s syndrome d/t several causes.
● Dosages of 200 - 1200 mg/d
● SIDE EFFECT: Has some hepatotoxicity
MINERALOCORTICOIDS
ALDOSTERONE
● Is the principal mineralocorticoid involved in
maintaining fluid and electrolyte balance in
the body.
● Works on the kidneys to increase sodium and
water reabsorption and potassium excretion.
REGULATION OF MINERALOCORTICOID SECRETION
● Primary stimulus for aldosterone release is
increased levels of Angiotensin II.
o Renin-Angiotensin System (RAS) on
antihypertensive drugs.
● Regulated by increased plasma potassium
levels, thus, causing increased potassium
excretion.
● ACTH may also play a role in aldosterone
release.
MECHANISM OF ACTION AND PHYSIOLOGIC EFFECTS
● Aldosterone exerts its effects on the kidneys
by binding specific receptors in epithelial
cells that line the distal tubule of the
nephron.
● Aldosterone binds to receptors → activated
hormone receptor complex → travels to the
nucleus to initiate transcription of
messenger RNA units → specific membrane
related proteins → help open sodium pores
on the cell membrane → sodium leave the
tubule and enter the epithelial cell by passive
diffusion → sodium is actively transported
out of the cell and absorbed into the
bloodstream.
THERAPEUTIC USE OF MINERALOCORTICOID DRUGS
ALDOSTERONE AGONISTS
● Frequently administered as replacement
therapy in pt. c chronic adrenocortical
insufficiency (Addison’s dse), following
adrenalectomy or other forms of adrenal
cortex hypofunction.
FLUDOCORTICONE
● Primary aldosterone like agents used in
replacement therapy.
● Most widely used
● Potent steroid c both glucocorticoid and
mineralocorticoid activity.
● Doses of 0.1 mg 2 x- 7x weekly orally
● Used in the treatment of adrenocortical
insufficiency assoc. c mineralocorticoid
deficiency.
ADVERSE EFFECTS
● Hypertension
● Peripheral edema
● Weight gain
● Hypokalemia
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2nd Sem | BSPT 2-3
MINERALOCORTICOID ANTAGONISTS
SPIRONOLACTONE (ALDACTONE)
● Competitive antagonist of aldosterone
receptor.
● Binds to the receptor but does not activate it.
● Used primarily as a diuretic in treating
hypertension.
● Classified as potassium sparing diuretic
because it helps increase sodium and water
excretion with increasing the excretion of
potassium.
● Also used to help diagnose
hyperaldosteronism.
EPLERENONE
● Another aldosterone antagonist approved for
the treatment of hypertension.
● More selective than spironolactone and no
reported effects on androgen receptors.
DROSPIRENONE
A progestin in an oral contraceptive also antagonizes
the effects of aldosterone.
SPECIAL CONCERNS OF ADRENAL STEROID USE IN REHABILITATION
PATIENTS
● The primary aspect of glucocorticoid
administration that should concern
therapists is the catabolic effect of these
hormones on supporting tissues.
● Remember, that there’s always a catabolic
effect if patient is always on steroids.
● Be careful in doing your treatments, for
example, the treatment used is massage. If
too much pressure on the bony area, expect
that it can be fragile or it can trigger fracture
or can tear muscle.
● Therapists may help attenuate some of the
catabolic effects of these drugs.
● Strengthening activities help maintain
muscle mass and prevent severe wasting of
the musculotendinous unit.
● Various strengthening and weight bearing
activities may also reduce bone loss to some
extent.
● Therapists must use caution to avoid
injuring structures that are weakened by
glucocorticoid use
● The load placed on the musculoskeletal
system must be sufficient to evoke a
therapeutic response but not excessive so
that musculoskeletal structures are
damaged.
● Therapists should routinely monitor blood
pressure in patients taking either type of
agent.
ANDROGENS
SOURCE AND REGULATION OF ANDROGEN SYNTHESIS
Testosterone
● Synthesized by Leydig’s cells located in the
interstitial space between the seminiferous
tubules.
● Production is regulated by pituitary
gonadotrophins (LH & FSH).
● Produced constantly
Luteinizing Hormone (LH)
● Binds to receptors on the surface of Leydig’s
cells and directly stimulates production.
Follicle Stimulating Hormone (FSH)
● Increase Leydig’s cells differentiation and
function.
● Increases the number of LH binding sites on
Leydig’s cells acts on the Sertoli cells to
stimulate production of ABP which enables
testosterone to reach target tissues within
the seminiferous tubules and help transport
testosterone to the epididymis.
Growth Hormone & Prolactin
● May also increase the effects of LH on
testosterone synthesis.
● Release of LH & FSH is regulated by
Gonadotropin Releasing Hormone (GnRH)
from the hypothalamus thru the negative
feedback system.
PHYSIOLOGICAL EFFECTS OF ANDROGEN
Development of male characteristics
● Testosterone influence on sexual
differentiation begins in utero.
● At puberty, a complex series of hormonal
events stimulates the testes to begin to
synthesize significant amounts of
testosterone.
● Androgens enter the target cell → bind to a
cytoplasmic receptor → activated steroid
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receptor complex travels to the nucleus and ANEMIA

binds to specific chromatin units (DNA gene
segments) → increases protein synthesis →
cause change in cellular function.
SEXUAL CHARACTERISTICS/DIFFERENTIATION:
● Increased body hair, increased skeletal
muscle, voice change and maturation of the
external genitalia.
Role in Spermatogenesis
● Testosterone then enters the tubules to
directly stimulate the production of sperm
through an effect on protein synthesis within
the tubule cells.
● Potent stimulators of erythropoietin
synthesis from kidneys and other tissues.
● Used in certain types of anemia caused by
renal failure or in congenital conditions (e.g.
aplastic anemia, hypoplastic anemia,
myelofibrotic anemia, sickle cell anemia,
hemolytic anemia).
● Recombinant erythropoietin has largely
replaced androgens for this purpose.
OSTEOPOROSIS
● Used alone or in conjunction with estrogen.
● Bisphosphonates have largely replaced
androgen use.

GYNECOLOGIC DISORDERS
PHARMACOLOGICAL USE OF ANDROGEN ● Used to reduce breast engorgement during
REPLACEMENT THERAPY postpartum period usually in conjunction
with estrogens.
● Administered when endogenous productions
o Danazol - weak androgen used in
like orchiectomy, testicular failure
treatment of endometriosis.
(cryptorchidism, orchitis) and problems in
● Given in combination with estrogen for
the endocrine regulation of testosterone
replacement theory in postmenopausal
production such as lack of LH production.
period to eliminate endometrial bleeding
CATABOLIC STATES that may occur when only estrogens are used.
● Also enhance libido.
● Administered for their anabolic properties in
conditions in which there is substantial AGING
muscle catabolism and protein loss (e.g.
● Preliminary studies of androgen replacement
chronic infections, severe trauma, and
in aging males with low androgen levels
recovery from extensive surgery,
show an increase in lean body mass and
controversial prolonged immobilization, and
hematocrit and decrease in bone marrow.
in patients with debilitating diseases).
● Longer studies will be required to assess
● Used in conjunction with dietary measures
usefulness.
and exercise.

DELAYED PUBERTY

● Administered on a limited basis to accelerate

the normal onset of puberty.
● Treatment is difficult to control even with
frequent x-ray examinations since the action
of hormones on epiphyseal centers may
continue for many months after the therapy
is discontinued.

BREAST CANCER

● Used to treat a limited number of

hormone-sensitive tumors such as certain
cases of breast cancer in women and
typically combined with other antineoplastic
treatments. ADVERSE EFFECT OF CLINICAL ANDROGEN USE
● Related to dose and duration of androgen use

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● Reversible and symptoms will diminish with
discontinued use.
● Vocal changes in females may persist even
after the drugs are withdrawn.
● Skeletal changes are irreversible.
IN WOMEN:
● Hirsutism
● Hoarseness or deepening of voice
● Changes in external genitalia (enlarged
clitoris)
● Irregular menstrual periods
● Acne
IN MEN:
● Bladder irritation
● Breast swelling and soreness
● Frequent or prolonged erections
● Acne
● Erythrocytosis
● With supraphysiologic doses, may cause
azoospermia and decrease in testicular size.
IN CHILDREN:
● Accelerated sexual maturation
● Impairment of normal bone development due
to premature closure of epiphyseal plates.
SERIOUS SIDE EFFECTS:
● Peliosis hepatica (blood filled cysts within
the liver).
● Cholestasis
● Hepatic failure
● Hepatic adenomas and carcinomas
● Hypertension due salt and water retaining
effects.
● Lower plasma HDL and increased LDL
● Psychologic dependence
BICALUTAMIDE
● Increased aggressiveness
● Psychotic symptoms
ANTIANDROGENS
Drugs that inhibit the synthesis or effects of
endogenous androgen production.
NILUTAMIDE
SPECIFIC AGENTS:
Finasteride (*Proscar)
● Inhibits conversion of testosterone to
dihydrotestosterone (accelerates growth and
development of prostate gland).
● Used in benign prostatic hypertrophy (dose 5
mg/d).
● Not approved for use in women and children
in USA.
● Used successfully in treatment of hirsutism
in women and early male pattern of baldness
in me (1mg/d).
Cyproterone Acetate (*Androcur)
● Inhibit action of androgens at the target
organ
● Marked progestational effect that
suppresses the feedback enhancement of LH
and FSH.
● Used as contraceptive pill in combination
with estrogen.
● Used in men to decrease excessiveness
sexual drive.
Flutamide (*Prostanon)
● Not a steroid but behaves like a competitive
antagonist at the androgen receptor.
● Used in treatment of prostatic carcinoma.
● Frequently causes gynecomastia and
occasionally mild reversible hepatic toxicity.
● Preliminary studies indicate that it is also
useful in management of excess androgen in
women.
Bicalutamide and Nilutamide (Casodex and
Nilandron)
● Potent orally active antiandrogens.
● Administered as single daily dose.
● Used in metastatic prostatic carcinomas.
● Is recommended for use in combination with
GnRH.
● Analog to reduce tumor flare (dosage is 150 -
200 mg/d).
● Is approved for use following surgical
castration (dose is 300 mg/d for 30 days
followed by 150 mg/d).
Spironolactone (*Aldactone)
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 PHARMACOLOGY | OPT 2207-3
2nd Sem | BSPT 2-3
● A competitive inhibitor of aldosterone also
competes with dihydrotestosterone for the
androgen receptors in target tissues.
● Used to treat hirsutism in women and
appears to be as effective as Finasteride,
Flutamide, or Cyproterone (50-200 mg/d).
GnRH agonists or Analogs
● Cause an increase in pituitary LH release
which stimulates testicular androgen
production with initial dose.
● Continued administration desensitizes
pituitary GnRH receptors thus decreasing LH
and testosterone production from pituitary
and testes, respectively.
● Used as stimulants in female and male
infertility and diagnosis of LH
responsiveness.
● Used to suppress gonadotropin production in
endometriosis, uterine leiomyomata, central
precocious puberty, controlled ovarian
hyperstimulation, advanced breast and
ovarian cancer and prostate cancer.
o Goserelin (*Zoladex)
o Leuprolide (Lupron, *Leuprolex)
o Histrelin
o Nafarelin
o Triptorelin (*Decapeptyl CR)
● “Medyo may kamahalan, an injection will cost you
around P7000-9000 and usually given for about 6
injections.”
ANDROGEN ABUSE
NATURE:
● Controversial
● Associated with athletes involved in strength
and power activities such as weight lifting,
bodybuilding, shot put.
● Several different androgens are often taken
in combined doses that is 10 to 40x greater
than the therapeutic dose.
● Self-administered in cycles that last between
7 and 14 weeks and dosage is progressively
increased during the cycle.
● To control abuse, randomized drug testing at
any point in training as well as at the time of
competition has been instituted.
EFFECTS OF ANDROGEN ON ATHLETIC PERFORMANCE
● Increased muscle strength with steroid use
as not been consistently reported in all
research studies.
● Appear to increase aggressiveness.
● Strength increments in athlete, may be
brought by the enhanced quality and
quantity of training rather than as direct
effect of anabolic steroids on muscle protein
synthesis.
ADVERSE EFFECTS OF ANDROGEN ABUSE
● Avascular necrosis of femoral head was
reported in a weight lifter.
Contributors
Colleen Guillang Merry Rose Payawal
Gerielle Cura Nizhel Ritual
Rose Marie Holasca Ruth Pacio
Jayrianne Cesar
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