1. Endocrine Drugs, Hormones andEndocrine Drugs, Hormones and
Related CompoundsRelated Compounds

2. OverviewOverview
Endocrine System
- composed of hormone-releasing organs such
as the:
hypothalamus thymus
pituitary gland pancreas
thyroid gland gonads
parathyroid -ovaries
adrenal glands -testes
pineal gland

3. Endocrine SystemEndocrine System

4. Endocrine SystemEndocrine System
- is controlled by the hypothalamus and
the pituitary gland
- along with the Nervous System, it
coordinates and directs body function
- maintains homeostasis by releasing
chemicals called hormones

5. Endocrine vs NervousEndocrine vs Nervous
- the nervous system communicates
locally by electrical impulses and
neurotransmitters directed through
neurons to other neurons or to specific
target organs such as muscle or glands
- nerve impulses generally act within
milliseconds

6. Nervous SystemNervous System

7. Endocrine vs NervousEndocrine vs Nervous
- the endocrine system releases
hormones into the blood stream
- the hormones are then carried by the
blood stream into target cells
throughout the body
- hormones have broader range of
response times (they act from seconds
to days or longer)

8. Endocrine vs NervousEndocrine vs Nervous
NOTE: there is close interrelationship
between the endocrine and nervous
systems

9. Endocrine SystemEndocrine System
Processes controlled by the endocrine
System:
1. growth & development
2. reproduction
3. body defenses
4. water, electrolyte and nutrient
balance
5. regulation of cellular metabolism
and energy balance

10. HormonesHormones

11. HormonesHormones
- Greek word, “to arouse”
- chemical substances secreted by the
cells into the extracellular fluids that
stimulate or regulate the metabolic
activity of other cells in the body.
- Gen. MOA: binding of the hormone to
the target cell or organ elicits response.

12. Endocrine DrugsEndocrine Drugs

13. Endocrine DrugsEndocrine Drugs
- Hormones are pharmacologically
classified as drugs
- can be natural (from animals), semi-
synthetic or synthetic compounds
- Indications:
a. replacement therapy
b. treatment for certain disorders
c. diagnostic purposes

14. Endocrine DrugsEndocrine Drugs
I. Hypothalamic & Pituitary Hormones
II. Steroid Hormones
A. Gonadal Hormones
1. Estrogens
2. Progestins
3. Androgens
B. Hormones of the Adrenal Cortex
1. Adrenocorticosteroids
2. Adrenal Androgens
III. Thyroid Hormones and Drugs for Thyroid
Disorders
IV. Anti-diabetic Agents

15. Hypothalamic & PituitaryHypothalamic & Pituitary
HormonesHormones

16. HypothalamusHypothalamus
- master endocrine organ
- secretes releasing/inhibiting hormones

17. Pituitary GlandPituitary Gland
- weighs 600 mg and rests in the sella
turcica under a layer of dura mater in
the brain
-composed of 2 lobes:
a. anterior lobe
b. posterior lobe

18. Hypothalamic & Pituitary HormonesHypothalamic & Pituitary Hormones
Hypothalamic Hormone Pituitary
Hormone
Target Organ Target Organ
Hormone
1. Growth Hormone –
Releasing Hormone
(GHRH)
aka: Sermorelin
Growth Hormone (GH)
aka: Somatotropin
Liver Somatomedins
2. Growth Hormone –
Inhibiting Hormone (GHIH)
aka: Somatostatin
Inhibits Growth Hormone
3. Corticotropin – Releasing
Hormone (CRH)
Adrenocorticotropic
Hormone (ACTH)
aka: Corticotropin
Adrenal Cortex Glucocorticoids
Mineralocorticoids
Adrenal Androgens
4. Thyrotropin – Releasing
Hormone (TRH)
Thyroid – Stimulating
Hormone (TSH)
aka: Thyrotropin
Thyroid Gland T3 (Triiodothyronine)
T4 (Thyroxine)
5. Gonadotropin – Releasing
Hormone (GnRH) or
Luteinizing Hormone –
Releasing Hormone
(LHRH)
Gonadotropins
a. Follicle Stimulating
Hormone (FSH)
b. Luteinizing Hormone
(LH)
Ovaries (Females)
Testes (Males)
Estrogen (by FSH)
Progesterone (by LH
in females)
Testosterone (by LH
in males)
6. Prolactin – Releasing
Hormone (PRH)
Prolactin Breasts
7. Prolactin – Inhibiting
Hormone (PIH)
Inhibits Prolactin
8. Oxytocin Stored in the Posterior
Pituitary Gland
9. Vasopressin Stored in the Posterior
Pituitary Gland

19. Growth HormoneGrowth Hormone

20. Growth Hormone (GH)Growth Hormone (GH)
- aka: Somatotropin, Asellacrin®
- a large polypeptide: about 191 amino
acids (MW: 21,500)
- released by the anterior pituitary in
response to GHRH (Sermorelin)
produced by the hypothalamus
- produced synthetically by recombinant
DNA technology

21. Growth Hormone (GH)Growth Hormone (GH)
- animal source is ineffective in humans
- induces the release of somatomedins in
the liver
- promotion of cell proliferation and bone
growth at open epiphyses
- boosts cartilage synthesis

22. Growth Hormone (GH)Growth Hormone (GH)
Indications:
- for long term treatment in growth
hormone deficiency in children
(Dwarfism)
- for non-GH deficient short children (can
grow up to 2 cm per year)

23. DwarfismDwarfism

24. SomatremSomatrem
- a therapeutically equivalent drug of GH
- contains an extra terminal methionyl
group

25. Growth Hormone InhibitingGrowth Hormone Inhibiting
HormoneHormone

26. Growth Hormone InhibitingGrowth Hormone Inhibiting
Hormone (GHIH)Hormone (GHIH)
- aka: Somatostatin
- inhibits Growth Hormone
- Indications:
Pituitary Gigantism (pre-pubertal)
Acromegaly (post-pubertal)

27. Pituitary GigantismPituitary Gigantism

28. AcromegalyAcromegaly
macrognathia (large jaw)
wide-spaced teeth
macroglossia
thickened lips
broad nose
enlarged joints
cardiomegaly
organomegaly

29. OctreotideOctreotide
- synthetic octapeptide analog of
somatostatin
- 45x more potent than GHIH

30. Adrenocorticotropic HormoneAdrenocorticotropic Hormone

31. Adrenocorticotropic Hormone (ACTH)Adrenocorticotropic Hormone (ACTH)
- aka: Corticotropin, Acthar®
- single-chain polypeptide containing 39
amino acids
- precursor: pro-opiomelanocortin
- released by the anterior pituitary in
response to CRH produced by the
hypothalamus

32. Adrenocorticotropic Hormone (ACTH)Adrenocorticotropic Hormone (ACTH)
- stimulates the adrenal cortex to produce
adrenocorticosteroids & androgens
- is used primarily for the diagnosis and
differentiation of primary & secondary
adrenal insufficiency
- Primary: Addison’s Disease associated
with adrenal atrophy
- Secondary: caused by inadequate
secretion of ACTH by the pituitary

33. Addison’s DiseaseAddison’s Disease
• hyposecretion of adrenocorticosteroids
• characterized by:
– anorexia
– dehydration
– weakness and lethargy
– hyperpigmentation (bronze-colored skin)

35. Cushing’s SyndromeCushing’s Syndrome
• hypersecretion of adrenocorticosteroids
• characterized by:
– moon face
– buffalo hump
– pendulous abdomen
– hypertension

36. Cushing's SyndromeCushing's Syndrome

37. CosyntropinCosyntropin
- synthetic human ACTH
- more preferred since animal ACTH can
cause allergic reactions

38. Thyrotropin StimulatingThyrotropin Stimulating
HormoneHormone

39. Thyrotropin Stimulating Hormone (TSH)Thyrotropin Stimulating Hormone (TSH)
- aka: Thyrotropin
- released by the anterior pituitary in
response to TRH (aka: Protirelin)
produced by the hypothalamus
- stimulates the thyroid to produce T3 and
T4
- T3: triiodothyronine (most active)
- T4: thyroxine
(converted to T3 in the body)

40. Thyrotropin Stimulating Hormone (TSH)Thyrotropin Stimulating Hormone (TSH)
- the thyroid hormones T3 and T4 are
essential for the normal growth and
maturation of the body
- Conditions:
hypothyroidism
hyperthyroidism

41. HypothyroidismHypothyroidism
- inability of the thyroid gland to supply
sufficient thyroid hormone to the body
- manifestations:
Cretinism (infant-state)
Myxedema (adult-state)

42. CretinismCretinism
- infant-state hypothyroidism
- characterized by physical and mental
retardation

43. MyxedemaMyxedema
- adult-state hypothyroidism
- characterized by:
• bradycardia
• weakness and lethargy
• dry skin and hair
• coldness
• goiter

45. HyperthyroidismHyperthyroidism
- overabundance of thyroid hormone in
the body
- thyrotoxicosis
- Forms:
Graves’ Disease - most common
Plummer’s Disease - less common
- with cardiac abnormalities

47. Graves' DiseaseGraves' Disease

48. GonadotropinsGonadotropins

49. GonadotropinsGonadotropins
- include:
Follicle-Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
- released by the anterior pituitary gland
in response to GnRH / LHRH
- stimulates the gonads (ovaries & testes)
to produce sex hormones
- Females: FSH → estrogen
LH → progesterone
- Males: LH → testosterone

50. GonadotropinsGonadotropins
NOTE: Pituitary gonadotropins (FSH, LH)
are not available for therapeutic use,
however, there are non-pituitary
gonadotropins that have FSH-like or
LH-like activity and are the ones used
therapeutically

51. Non-Pituitary GonadotropinsNon-Pituitary Gonadotropins
1. Menotropins
2. Urofollitropin
3. Human Chorionic Gonadotropin

52. Non-Pituitary GonadotropinsNon-Pituitary Gonadotropins
- Indications:
women: to induce ovulation &
pregnancy
men: to induce spermatogenesis
- Adverse effects:
ovarian enlargement
multiple births
gynecomastia in men

53. MenotropinMenotropin
- aka:
Human Menopausal Gonadotropin
(hMG)
Pergonal®
- obtained from the urine of post-
menopausal women
- partially broken down into FSH and LH
in the body

54. UrofollitropinUrofollitropin
- Metrodin®
- obtained from the urine of post-
menopausal women
- high in FSH-like activity

55. Human Chorionic GonadotropinHuman Chorionic Gonadotropin
- aka: hCG, Follutein®
- a placental hormone
- LH agonist effect
-obtained from the urine of pregnant
women

56. Hormones of the PosteriorHormones of the Posterior
Pituitary GlandPituitary Gland

57. Hormones of the PosteriorHormones of the Posterior
Pituitary GlandPituitary Gland
1. Oxytocin
2. Vasopressin

58. OxytocinOxytocin
- stimulates uterine contraction and plays an
important role in the induction of labor
- also promotes breast milk ejection
- Indications:
to induce contraction during labor
to control postpartum bleeding
- Contraindications:
abnormal fetal presentation
fetal distress
premature births

59. OxytocinOxytocin

60. VasopressinVasopressin
- aka: Antidiuretic Hormone (ADH)
- has both antidiuretic and vasopressor
activity
-acts by binding to its receptor in the
kidneys promoting the reabsorption of
water in the collecting tubules
-Indications:
Diabetes Insipidus
Postoperative Abdominal Distention

61. Diabetes Insipidus (DI)Diabetes Insipidus (DI)
- a disorder due to the deficiency or lack
of response to Antidiuretic Hormone
(ADH)
- 2 Types:
a. Central DI - deficiency in ADH
b. Nephrogenic DI - sufficient ADH
but body does not respond
to the hormone

62. DesmopressinDesmopressin
- modified analog of vasopressin
- more preferred for DI and nocturnal
enuresis because it is largely free of
pressor effects and is longer-acting

63. Steroid HormonesSteroid Hormones

64. Steroid HormonesSteroid Hormones
- contain the steroid nucleus, CPPP
cyclopentanoperhydrophenanthrene

65. Steroid HormonesSteroid Hormones
• Carbon 3 & Carbon 17
• -OH (sterol)
• =O (sterone)

66. Gonadal / Sex HormonesGonadal / Sex Hormones

67. Steroid HormonesSteroid Hormones
A. Gonadal / Sex Hormones
1. Estrogens
2. Progestins
3. Androgens
B. Hormones of the Adrenal Cortex
1. Adrenocoticosteroids
a. Glucocorticoids
b. Mineralocorticoids
2. Adrenal Androgens

68. Gonadal / Sex HormonesGonadal / Sex Hormones

69. EstrogensEstrogens

70. EstrogensEstrogens
- basic nucleus: estrane
Estradiol

71. EstrogensEstrogens
- Effects:
1. normal female maturation and
development
2. inhibit bone resorption
3. increase HDL, decrease LDL
4. decrease platelet adhesiveness

72. EstrogensEstrogens
- Indications:
contraception
postmenopausal hormone therapy
primary hypogonadism
osteoporosis

73. Natural Steroidal EstrogensNatural Steroidal Estrogens
Estradiol - most potent estrogen
produced by women
Estrone, Estriol - have about one tenth
the potency of estradiol
* Premarin - a preparation of conjugated
estrogens (sulfate esters of estrone &
equilin)
- obtained from pregnant mare’s urine

74. PremarinPremarin

75. Synthetic Steroidal EstrogensSynthetic Steroidal Estrogens
Ethinyl estradiol
Mestranol
Quinestrol

76. Synthetic Nonsteroidal EstrogensSynthetic Nonsteroidal Estrogens
Diethylstilbestrol - possible cause of a
rare, clear cell cervical or vaginal
adenocarcinoma among daughters of
women who took the drug during early
pregnancy

77. Estrogen Antagonists /Estrogen Antagonists /
AntiestrogensAntiestrogens
Clomiphene - fertility drug; it induces
ovulation by negative feedback
mechanism
Tamoxifen & Toremifene - palliative
treatment of advanced breast cancer in
postmenopausal women

78. Estrogen Related DrugsEstrogen Related Drugs
Aromatase Inhibitors
Selective Estrogen Receptor Modulators

79. Aromatase InhibitorsAromatase Inhibitors
- are potent and selective non-steroidal
inhibitors of aromatase, an enzyme
reponsible for the conversion of
androgens to estrogens
- used to treat advanced breast cancer
- Anastrozole, Letrozole

80. SERMsSERMs
- Selective Estrogen Receptor Modulators
- reduce bone resorption and decrease
bone turnover
- used for the prevention of osteoporosis
- Raloxifene

81. ProgestinsProgestins

82. ProgestinsProgestins
- basic nucleus: pregnane

83. ProgestinsProgestins
- Effects:
1. endometrial changes
2. alveolobular development of
secretory apparatus in breasts
3. hepatic glycogenesis &ketogenesis
4. increase lipoprotein lipase activity
and fat deposition

84. ProgestinsProgestins
- Indications:
contraception
for menstrual disorders
-dysfunctional uterine bleeding
-dysmenorrhea
endometriosis

85. Natural ProgestinNatural Progestin
Progesterone
- endogenous progestin produced in
response to luteinizing hormone (LH)
- also synthesized by the adrenal cortex
- in females, it promotes the development
of a secretory endometrium that can
accommodate implantation of a newly
forming embryo

86. Synthetic ProgestinsSynthetic Progestins
- more stable to first-pass metabolism,
allowing for lower doses when
administered orally
- medroxyprogesterone
hydroxyprogesterone
megestrol
norethindrone
norgestrel

87. Progestin Antagonist /Progestin Antagonist /
AntiprogestinAntiprogestin
Mifepristone
- aka: RU 486
- progestin antagonist with partial
agonist activity
- can cause abortion of the fetus due to
the interference with progesterone and
the decline in hCG

88. Oral & ImplantableOral & Implantable
ContraceptivesContraceptives

89. Major ClassesMajor Classes
1. Combination Pills
2. Progestin Only Contraceptives
3. Postcoital Contraceptives

90. Combination PillsCombination Pills
- contain both estrogen and progestin
- provided as 21 day or 28 day-packs
- most common type of oral contraceptives
- estrogen: suppresses ovulation
ethinyl estradiol - most common
mestranol

91. Combination PillsCombination Pills
- progestin: prevents implantation in the
endometrium and makes the cervical
mucus impenetrable to the sperm
norethynodrel
norethindrone
norgestrel

92. Progestin Only ContraceptivesProgestin Only Contraceptives
- less effective than combination pills
- dosage forms/ delivery systems:
a. “mini-pill” - low dose progestins
350 µg norethindrone or
75 µg norgestrel
b. progestin implants - subdermal implant
of 216 mg of norgestrel (Norplant®)
effective for 5 years

93. Progestin Only ContraceptivesProgestin Only Contraceptives
c. intramuscular - given every 3 months
150 mg of medroxyprogesterone
acetate (Depo-Provera®)

94. Progestin Only ContraceptivesProgestin Only Contraceptives
d. intrauterine device (IUD) - for yearly
insertion; Progestasert®

95. Postcoital ContraceptivesPostcoital Contraceptives
- called, “morning-after pills”
- high dose estrogen administered within
72 hours after coitus and continued 2x
for 5 days
- ethinyl estradiol
diethylstilbestrol
conjugated estrogens
estrone

96. AndrogensAndrogens

97. AndrogensAndrogens
- basic nucleus: androstane
Testosterone

98. AndrogensAndrogens
- group of steroids that have anabolic
and/or masculinizing effects in both
males and females

99. Endogenous AndrogenEndogenous Androgen
Testosterone
- primary natural endogenous androgen
- synthesized by Leydig cells in the testes
of males and in smaller amounts by the
cells in the ovary of females, and in the
adrenal gland
-produced in response to LH

100. Synthetic AndrogensSynthetic Androgens
Methyltestosterone
Danazol
Stanozolol
Nandrolone

101. Therapeutic UsesTherapeutic Uses
1. Androgenic Effects
- in hypogonadism in males
2. Anabolic Effects
- in senile osteoporosis, severe burns,
speedy recovery from surgery or from
chronic debilitating diseases
3. Endometriosis (Danazol)

102. Unapproved UseUnapproved Use
Used to increase lean body mass, muscle
strength and aggressiveness in athletes
and body builders (Nandrolone &
Stanozolol)

103. AntiandrogensAntiandrogens
- inhibit the action of androgens by
interfering with androgen synthesis or
by blocking their receptors
a. Finasteride - used in Benign Prostatic
Hypertrophy (BPH)

104. AntiandrogensAntiandrogens
b. Flutamide - for prostatic carcinoma
c. Cyproterone acetate - for hirsutism in
females

105. Hormones of the AdrenalHormones of the Adrenal
CortexCortex

106. Hormones of the Adrenal CortexHormones of the Adrenal Cortex
1. Adrenocorticosteroids
a. Mineralocorticoids
b. Glucocorticoids
2. Adrenal Androgens

107. Adrenal CortexAdrenal Cortex
3 Zones:
1. Zona glomerulosa
- produces mineralocorticoids
2. Zona fasciculata
- produces glucocorticoids
3. Zona reticularis
- produces adrenal androgens

108. Adrenal CortexAdrenal Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
Kidney

109. MineralocorticoidsMineralocorticoids
- possess sodium-retaining and
potassium-secreting effects
- essential for fluid and electrolyte
balance
- endogenous: aldosterone
desoxycorticosterone
- synthetic: fludrocortisone

110. GlucocorticoidsGlucocorticoids
- Endogenous: Cortisol
Cortisone
Corticosterone
Hydrocortisone
- essential for the metabolism of
carbohydrates, fats and proteins
- they enhance response of the vascular
and bronchial smooth muscles to
catecholamines

111. GlucocorticoidsGlucocorticoids
Other Preparations:
Prednisone Betamethasone
Methylprednisolone Dexamethasone
Triamcinolone
- anti-inflammatory, anti-allergy and
immunosuppressant effects
- inhibit cell growth and division
- catabolic effects on protein and bones

112. GlucocorticoidsGlucocorticoids
Therapeutic Uses:
Allergy
Inflammation of joints and bones
Skin diseases
Organ transplant immunosuppression
Pulmonary Diseases: Bronchial Asthma
COPD

113. GlucocorticoidsGlucocorticoids
Adverse effects:
Cushing’s syndrome
Adrenal suppression
osteoporosis
PUD
impaired wound healing
increased susceptibility to infection
hyperglycemia/DM
cataract

114. Addison’s DiseaseAddison’s Disease
• hyposecretion of adrenocorticosteroids
• characterized by:
– anorexia
– dehydration
– weakness and lethargy
– hyperpigmentation (bronze-colored skin)

116. Cushing’s SyndromeCushing’s Syndrome
• hypersecretion of adrenocorticosteroids
• characterized by:
– moon face
– buffalo hump
– pendulous abdomen
– hypertension

117. Cushing's SyndromeCushing's Syndrome

119. Thyroid Hormones andThyroid Hormones and
Drugs for Thyroid DisordersDrugs for Thyroid Disorders

120. Thyroid GlandThyroid Gland

121. Thyroid Hormone SynthesisThyroid Hormone Synthesis
1. Iodide uptake
2. Peroxidation of iodide to iodine
3. Organification of iodine
4. Coupling reaction: DIT + DIT → T4
MIT + DIT → T3
5. Proteolysis
6. Peripheral conversion of T4 to T3

122. Thyroid HormonesThyroid Hormones
- the thyroid hormones T3 and T4 are
essential for the normal growth and
maturation of the body

123. T4T4
- thyroxine
- converted to T3 by the action of the
enzyme deiodinase
- 99.98% protein bound to thyroxine-
binding globulin
- 0.02% is in free form
- half-life: 7 days

124. T3T3
- triiodothyronine
- most active form
- 3-4x more potent than T4
- responsible for most of the effects of the
thyroid hormones
- has 10-fold greater affinity for the receptors
- 99.8 % protein bound
- 0.2% is in free form
- half-life: 1.5 days

125. HypothyroidismHypothyroidism
- inability of the thyroid gland to supply
sufficient thyroid hormone to the body
- manifestations:
Cretinism (infant-state)
Myxedema (adult-state)

126. CretinismCretinism
- infant-state hypothyroidism
- characterized by physical and mental
retardation

127. MyxedemaMyxedema
- adult-state hypothyroidism
- characterized by:
• bradycardia
• weakness and lethargy
• dry skin and hair
• coldness
• goiter

128. Thyroid Hormone PreparationsThyroid Hormone Preparations
Preparation T4:T3 ratio
Thyroid, USP
Beef 4:1
Pork 2-3:1
Thyroglobulin 2:1
Levothyroxine Pure T4
Levothyronine Pure T3
Liotrix 4:1

129. HyperthyroidismHyperthyroidism
- overabundance of thyroid hormone in
the body
- thyrotoxicosis
- Forms:
Graves’ Disease - most common
Plummer’s Disease - less common
- with cardiac abnormalities

130. Graves' DiseaseGraves' Disease

131. Antithyroid DrugsAntithyroid Drugs
1. Thioamides
2. Inorganic Anions/Anionic Inhibitors
3. Iodides
4. Radiocontrast dyes
5. Beta-blocker
6. Dexamethasone
7. Radioactive Iodine

132. ThioamidesThioamides
- MOA: inhibit iodine organification and
coupling
- examples:
Propylthiouracil (PTU)
Methimazole
Carbimazole
- S/E:
pruritic maculopapular rash
agranulocytosis

133. Inorganic AnionsInorganic Anions
- aka: Anionic Inhibitors
- MOA: interfere with the uptake of iodine
and cause the discharge of intra-
thyroidal iodine
- examples:
Potassium perchlorate
Potassium thiocyanate
- S/E:
aplastic anemia, nephrotic syndrome

134. IodidesIodides
- MOA: inhibit organification and hormone
release
- they decrease the size and vascularity
of goiter
- examples:
KISS - Potassium iodide saturated
solution
Lugol’s solution - strong iodine
solution

135. Radiocontrast DyesRadiocontrast Dyes
- MOA: inhibit peripheral conversion of T4
to T3; also inhibit proteolysis
- examples:
Ipodate
Iopanoic acid

136. Beta-blockerBeta-blocker
- MOA: symptomatic relief of the
sympathetic manifestations of
hyperthyroidism; may also inhibit
peripheral conversion of T4 to T3
- Propranolol

137. DexamethasoneDexamethasone
- MOA: inhibits peripheral conversion of
T4 to T3

138. Radioactive iodineRadioactive iodine
- 131
I
- MOA: destruction of thyroid cells by
emission of high-energy beta radiation
- can offer cure
- Contraindicated to pregnant women or
women who will become pregnant

139. Anti-diabetic AgentsAnti-diabetic Agents

140. PancreasPancreas
- is a mixed gland
- Exocrine portion
-releases pancrealipase &
chymotrypsin
- Endocrine portion
-1million islets of Langerhan
-have at least 4 hormone-producing
cells

141. Endocrine PancreasEndocrine Pancreas
Cell Type % islet Hormone
A (alpha) 20 glucagon
proglucagon
B (beta) 75 insulin
pro-insulin
D (delta) 3-5 somatostatin
F (PP cell) <2 pancreatic
polypeptide (PP)

142. Diabetes Mellitus (DM)Diabetes Mellitus (DM)
- diabetes = Greek “siphon”
mel = honey
- “something sweet is passing through or
siphoning from the body”
- a metabolic disorder in which glucose
levels in the blood are too high and
begins to spill in the urine because the
kidney tubule cells cannot reabsorb it
fast enough

143. Types of DMTypes of DM
Type 1
Type 2
Gestational DM
Secondary DM

144. Type 1Type 1
- insulin-dependent DM (IDDM)
- juvenile-onset DM
- ketosis-prone diabetes
- most common in children
- insulin secretion is destroyed
- dependent upon exogenous insulin to
sustain life

145. Type 2Type 2
- non-insulin-dependent DM (NIDDM)
- adult-onset DM
- not insulin dependent
- endogenous insulin levels may appear
normal or increased but beta-cell
dysfunction is manifested by a relative
insulin insufficiency

146. Gestational DMGestational DM
- defined as any degree of glucose
intolerance that has its onset during
pregnancy

147. Secondary DMSecondary DM
- broad term used to classify patients who
have unusual causes of DM due to
certain diseases of the pancreas,
endocrinopathies or drugs

148. 3 Cardinal Signs of DM3 Cardinal Signs of DM
1. Polyuria - excessive urination to flush
out the glucose and ketones
2. Polydipsia - excessive thirst resulting
from water loss
3. Polyphagia - excessive hunger due to
inability to use sugars and the loss of
fats and proteins from the body

149. InsulinInsulin
- is the storage and anabolic hormone of
the body
- produced by the Beta-cells of the
pancreas
- principal hormone required for proper
glucose use in normal metabolic
processes
- previously extracted from beef/pork
pancreas
- now is produced via recombinant DNA

150. Insulin - EffectsInsulin - Effects
1. It facilitates transport of glucose across
cell membrane
2. In the liver, it promotes glycogenesis
and gluconeogenesis
3. In the muscles, it increases amino acid
transport, protein synthesis and
glycogenesis
4. In adipose tissues, it increases
triglyceride storage

151. Insulin - IndicationsInsulin - Indications
• Diabetes Mellitus Type 1
• Diabetes Mellitus Type 2 that cannot be
controlled by diet, exercise and oral
hypoglycemic agents (OHAs)
• Ketoacidosis
• Diabetic coma

152. Insulin PreparationsInsulin Preparations
Activity in hoursPharmakokinetic
Type
Species Type
Peak Duration
Ultra rapid-acting
Insulin Lispro
Human
(Modified) 0.25 – 0.50 3 – 4
Rapid acting
Insulin injection, USP
(Regular, Crystalline)
Human, Pork 0.50 – 3 5 – 7
Intermediate acting
NPH Insulin
(Isophane)
Lente Insulin
(Insulin zinc susp)
Human, Pork
Human, Pork
8 – 12
8 – 12
18 – 24
18 – 24
Long acting
Ultralente Insulin
(Insulin zinc susp
extended)
Human 8 – 16 18 – 28
Ultra long acting
Insulin glargine Human
(Modified)
No peak > 24

153. Oral Hypoglycemic DrugsOral Hypoglycemic Drugs
• Insulin secretagogues
• Biguanides
• Alpha-glucosidase inhibitors
• Thiazolidinedione derivatives

154. Insulin SecretagoguesInsulin Secretagogues
• Sulfonylureas
• Meglitinides

155. SulfonylureasSulfonylureas
MOA:
- stimulate pancreatic release of insulin
- inhibit pancreatic release of glucagons
- increase insulin receptor binding
- decrease hepatic extraction of insulin

156. SulfonylureasSulfonylureas
Ist Generation
Chlorpropamide Acetohexamide
Tolbutamide Tolazamide
2nd Generation
Glibenclamide Glipizide
Gliclazide Glimepiride

157. SulfonylureasSulfonylureas
Side-effects:
hypoglycemia
blood dyscrasias
disulfiram-like reactions with 1st Gen
and glipizide
weight gain

158. MeglitinidesMeglitinides
- MOA: increase pancreatic insulin
secretion
- short duration of action: 1 to 3 hours
- examples: Repaglinide
Nateglinide
- S/E:
hypoglycemia
weight gain

159. BiguanidesBiguanides
- unknown MOA
- reduce blood glucose level even in the
absence of beta cell function
- proven as a useful initial therapy among
DM Type 2 patients, especially among
obese patients
- not associated with hypoglycemia
- ex. Metformin (most proven)
Phenformin ( no longer available)
- S/E: lactic acidosis, megaloblastic
anemia

160. Alpha-glucosidase inhibitorsAlpha-glucosidase inhibitors
- MOA: competitive inhibition of intestinal
alpha-glucosidase enzyme, preventing
digestion of dextrins and disaccharides
into absorbable monosaccharides
- examples: Acarbose
Voglibose
Miglitol
- S/E: flatulence, potential hepatotoxicity
of acarbose

161. Thiazolidinedione derivativesThiazolidinedione derivatives
- MOA: insulin sensitizers - increase
skeletal muscle sensitivity to insulin;
they also decrease hepatic
gluconeogenesis
- examples: Rosiglitazone
Pioglitazone
- S/E: Hepatic failure (reason for the
withdrawal of Troglitazone), edema and
mild anemia

162. Let’s see how muchLet’s see how much
you can recall… :)you can recall… :)

163. Question 1:Question 1:
Which of the following is generally true of
hormones?
A. Exocrine glands produce them.
B. They travel throughout the body in the
blood.
C. They affect only non-hormone
producing organs.
D. All steroid hormones produce very
similar physiologic effects in the body.
B

164. Question 2:Question 2:
All of the following substances are
endogenous tropic hormones secreted
by the pituitary gland EXCEPT:
A. Somatotropin
B. hCG
C. FSH
D. TSH
E. Corticotropin
B

165. Question 3:Question 3:
Which of the following is secreted by the
posterior pituitary gland?
A. Luteinizing Hormone
B. ACTH
C. Oxytocin
D. Thyrotropin
E. Growth Hormone
C

166. Question 4:Question 4:
ACTH or Adrenocorticotropic Hormone is
released by the anterior pituitary gland
in response to which hypothalamic
hormone?
A. GnRH
B. TRH
C. GHIH
D. CRH
E. PRH
D

167. Question 5:Question 5:
All of the following are steroidal hormones
except:
A. testosterone
B. levothyroxine
C. cortisone
D. dexamethasone
E. estradiol
B

168. Question 6:Question 6:
Which of the following insulins can be
administered IV?
A. Lente insulin
B. Isophane insulin
C. Protamine Zinc Insulin
D. Ultralente insulin
E. Regular insulin
E

169. Question 7:Question 7:
It is a fertility drug. It induces ovulation by
negative feedback mechanism.
A. Tamoxifen
B. Ethinyl estradiol
C. Clomiphene
D. Finasteride
E. Prednisone
C

170. Question 8:Question 8:
Which of the following is not properly
paired with its indication?
A. testosterone - hypergonadism
B. finasteride - BPH
C. cyproterone - hirsutism
D. PTU - hyperthyroidism
E. Tamoxifen - estrogen-dependent
breast cancer
A

171. Question 9:Question 9:
Which of the following drugs can be used
for rheumatoid disorders?
A. diethylstilbestrol
B. triiodothyronine
C. methimazole
D. betamethasone
E. metformin
D

172. Question 10:Question 10:
Which of the following is a sulfonylurea?
A. metformin
B. repaglinide
C. acarbose
D. rosiglitazone
E. glibenclamide
E

173. ““Success is to be measured not so much by theSuccess is to be measured not so much by the
position that one has reached in life, but by theposition that one has reached in life, but by the
obstacles which he has overcome.”obstacles which he has overcome.”
-- Booker T. WashingtonBooker T. Washington

174. Thank You for Listening!Thank You for Listening!