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ENDOCRINE GLANDS
ANTERIOR PITUITARY HORMONES
 Secrete hormones
ACTH
 Ductless GH
 Regulating system of the body (with the TSH
DRUGS FOR ENDOCRINE DISORDERS CNS) FSH
Jerico Isaiah Savellano Dumbrique, RPh
 Negative feedback/feedback inhibition LH
Line of thinking: Prolactin
HONOR and EXCELLENCE

Peripheral Target
Hypothala
Pituitary gland organ/res
mus
ponse

Adrenocorticotropic Hormone (ACTH) Adrenocorticotropic Hormone (ACTH) Steroid Hormones

  Corticotrophin releasing (CRH)  (I) diagnosis of adrenal insufficiency  CPPP nucleus
  Adrenal cortex  Sex steroids
 Estrogens
 Glucocorticoids (cortisol)
 Progestins
 Mineralocorticoids (aldosterone)  Androgens
 Effects  Corticosteroids*
 Glucocorticoids
 Gluconeogenesis – during stress
 Mineralocorticoids
 Sodium and water retention

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Corticosteroids Corticosteroids Corticosteroids

 A. Glucocorticoids  A. Glucocorticoids  A. Glucocorticoids

 Effects:  Uses:  Uses: (contd)

 1) Stimulate gluconeogenesis  1) Adrenal insufficiency (Addisonian  3) Anti-inflammatory – asthma, skin
crises) – weakness, hypotension,
 2) Catabolism of muscle, bone, skin, fat allergy
hyperpigmented
 3) Anti-inflammatory  2) congenital adrenal hyperplasia  4) immunosuppressant – auto-immune
 Inhibit phospholipase (PL)  Inc. androgen
diseases (SLE, RA), organ transplantation
 4) Immunosuppressive  Precocious puberty, Hermaphroditism
 Inhibit WBC function  Dec. gluco-/mineralocorticoid

Corticosteroids Corticosteroids Corticosteroids

 Produ ced8in the a drenal cortex (Solu-  A. Glucocorticoids  B. Mineralocorticoids
Short-acting – 12 •Hydrocortisone  S/E:
 A. Glu cocorticoidsCortef) 1. Cushing’s syndrome – moon face/buffalo  Natural
Intermediate hump
 Natural18 – 36 •Prednisone  Aldosterone
•Prednisolone 2. Adrenal suppression*
 Cort isol  Synthetic
•Methylprednisolone 3. Osteoporosis
 Synt hetic (Medrol) 4. Stunted growth (children)  Fludrocortisone, desoxycorticosterone
•Triamcinolone (Kenacort) 5. Psych: euphoria, depression
Long-acting 24 – 72 •Betamethasone 6. Peptic ulcer
 Effect: sodium and water retention
(Celestone, Betnelan) 7. Infection
•Dexamethasone 8. Edema, weight gain  Use: Adrenal insufficiency
(Decilone) 9. HPN, hyperglycemia  S/E: hypertension

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Growth Hormone (GH)
  Growth hormone releasing (GHRH)
 Effects:
 GROWTH – Bones & Muscles
Thyroid Stimulating Hormone (TSH)
 (I) Assessment of thyroid function
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Growth Hormone (GH) Thyroid Stimulating Hormone (TSH)
 GH/somatropin (Genheal, Humatrope,   Thyrotropin releasing (TRH)
Norditropin, Scitropin)   Thyroid
 Triiodothyronine (T3)
 (I) Dwarfism  Thyroxine (T4)
 Effects:
 Increase metabolic rate
 Growth in children
Thyroid Physiology Hypothyroidism
 Organification  Congenital hypothyroidism
 Tyrosine residues of thyroglobulin are  Cretinism
iodinated in the thyroid gland  MIT or
 Sx: Physical and mental retardation
DIT
 Coupling
 T4 = DIT + DIT; T3 = DIT + MIT  Dx: Newborn screening
 Peripheral Conversion  Tx: Thyroxine
 T4  T3 in tissues, liver, kidneys
 T3 >> T4 (10 times)
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Hypothyroidism Hypothyroidism Hypothyroidism

 Myxedema  Causes  Levothyroxine (T4) (Synthroid, Eltroxin,

 Hypothyroidism in adults  1) Hashimoto’s disease – autoimmune Euthyrox)
 Sx: Decreased metabolic rate  disease  DOC for hypothyroidism
lethargy, weakness, bradycardia, weight  2) Iodine deficiency  Less potent but longer duration of
gain, edema  3) Drugs, radiation exposure, goitrogens action (6-7 days vs 1-2 days for T3)

 Dx: Low T4, high TSH  S/E: tachycardia, palpitation, tremors

 Tx: Thyroxine  Nervousness, insomnia, weight loss

Hypothyroidism Hyperthyroidism Hyperthyroidism

 Other preparations  Increased metabolic rate  Dx: High T4, low TSH
 1) Thyroid USP (dessicated thyroid) Weight loss Increased appetite
Heat intolerance Sweating
 Pork/beef thyroid gland; allergen  Tx (definitive): Radioactive Iodine,
Tachycardia Palpitations thyroidectomy
 2) Thyroglobulin = 2.5:1 of T4:T3
Tremors
 Hog  Others: Thioureas/Thionamides, KI,
 3) Liothyronine = synthetic T3  Graves’ disease (autoimmune) – most Propranolol
 More S/E, expensive common form
 4) Liotrix = synthetic 4:1 of T4:T3
 Expensive

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Hyperthyroidism
 1) Radioactive Iodine (I-131)
 Oral liquid DF
 M: Destroys some thyroid cells
 Advantages: non-invasive, high cure
rate
 CI: Pregnancy
 S/E: Hypothyroidism
Hyperthyroidism
 3) Thioureas/Thionamides/Thiourylenes
 S/E: rash, arthralgia, agranulocytosis
(fever, malaise, oropharyngeal infection)
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Hyperthyroidism Hyperthyroidism
 2) Thyroidectomy (total/subtotal)  3) Thioureas/Thionamides/Thiourylenes
 Propylthiouracil
 S/E: hypothyroidism, hoarseness  Methimazole (Tapazole)
 Carbimazole (Neo-Mercazole)
 MOA: block organification, and coupling
of thyroglobulin (by inh. Iodoperoxidase)
 (PTU) – prevent peripheral conversion
Hyperthyroidism Hyperthyroidism
 4) Iodides  5) Propranolol
 Lugol’s solution (6.3 mg I/drop)
 Sat’d solution/SSKI (38 mg I/drop)  Also inhibits T4  T3 conversion
(minimal)
 MOA: decrease synthesis and release of  To reduce palpitations, tachycardia,
thyroid hormones tremors
 Ind: Thyroid storm
 Fever, tachycardia, restless, tremors
 Preparation for thyroidectomy
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Follicle Stimulating Hormone (FSH) Follicle Stimulating Hormone (FSH) Luteinizing Hormone (LH)
  Gonadotrophin releasing (GRH)  FSH/Follitropin (Gonal-F, Puregon)   Gonadotrophin releasing (GRH)
  Ovary   Ovary
 Estrogen  (I) Tx/Dx of infertility  Progesterone
 Effect: Endometrium
 Effects:
 Growth of endometrium   Testis
 Secondary sex characteristics – breast,  Testosterone
hips  Effect: Secondary sex characteristics in
males

Luteinizing Hormone (LH) Non-pituitary Gonadotropins Steroid Hormones

 (I) Treatment of infertility  Menotropin  CPPP nucleus
 Human Menopausal Gonadotropin  Sex steroids*
 Estrogens
 FSH, LH
 Progestins
 Androgens
 Urofollitropin  Corticosteroids
 Glucocorticoids
 FSH
 Mineralocorticoids

 Human Chorionic Gonadotropin

 LH

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Estrogens & relateddrugs Estrogens & relateddrugs Estrogens & relateddrugs

 Basic: Estrane, 2-OH Steroidal Non-steroidal  Indications:
Natural Synthetic  1) Oral contraceptives (in combination
Estradiol Ethinyl Diethylstilbestr with contraceptives)  dec. FSH  no
Estrone estradiol ol ovulation
Estriol Mestranol  2) Post-menopause HRT
Quinestrol  Hot flushes, osteoporosis, vaginitis
 3) Hypogonadism
 Functions: Endometrium growth,  4) Acne
development of reproductive organs,  5) Prostate cancer
secondary sex characteristics  6) Osteoporosis

Estrogens & relateddrugs Estrogens & relateddrugs Estrogens & relateddrugs

 S/E  ESTROGEN ANTAGONIST (ANTI-  ESTROGEN ANTAGONIST (ANTI-
 Nausea, vomiting ESTROGENS) ESTROGENS)
 HPN, stroke, MI  Tamoxifen (Nolvadex),
 Uterine/Breast CA  Toremifene  Clomiphene (Clomid)
 Hepatic adenoma  Adjuvant in breast CA
 S/E:  Pituitary gland – no negative feedback 
 hot flashes, vaginal bleeding, inc. FSH, LH  ovulation
endometrial CA  Ind: Infertility
 stroke, PE, DVT  S/E: Multiple births

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Estrogens & relateddrugs Estrogens & relateddrugs Progestins & related drugs
 AROMATASE INHIBITORS  SELECTIVE ESTROGEN RECEPTOR  Basic: Pregnane
 Prevent conversion of androgens  MODULATORS (SERMs)
estrogens
 Raloxifene (Evista)
 (Bone) Estrogen agonist
 Anastrozole (Arimidex)
 (Breast & uterus) antagonist
 Letrozole (Femara)
 Dec. bone resorption & turnover
 Ind: Breast CA  Ind: Osteoporosis  Function: endometrial growth 
 S/E: hot flushes, VTE implantation

Progestins & related drugs Progestins & related drugs Progestins & related drugs
NATURAL SYNTHETIC  Uses:  PROGESTIN ANTAGONIST
Progesterone Medroxyprogesterone  1) Contraception*
(Provera)  2) Dysfunctional uterine bleeding,  Mifepristone
Hydroxyprogesterone dysmenorrhea  Abortifacient
Megestrol  3) Endometriosis
Norethindrone
Norgestrel
 S/E: Irregular menses, spotting/bleeding
 Weight gain

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OCPs OCPs OCPs

 B. Progestin only
 A. Combination (21/28 day packs)  1) Mini pill  C) Postcoital Contraceptives
Estrogen Progestin  350 μg norethindrone  Morning after pills – high dose estrogen
Suppress ovulation Prevent implantation  75 μg norgestrel  72 hours after coitus
 2) Progestin implant - subdermal  Then 2x for 5 days
Ethinyl estradiol Norgestrel  216 mg Norgestrel (Norplant)
Mestranol Norethindrone  3) IM
 150 mg medroxyprogesterone acetate  Ethinyl estradiol
Norethynodrel
(Depo-Provera)  Diethylstilbestrol
 4) IUD  Conjugated estrogen
 Progestasert – prevent implantation
 Estrone
 Copper – kill sperm

OCPs Androgens & related substances Androgens & relatedsubstances

Monophasic Biphasic Triphasic  Basic: Androstane Natural Synthetic
Constant 1 component 1 or both Testosterone (main) Mesterolone (Proviron)
Changed once component (Andriol)
Changed twice dihydrotestosterone oxandrolone
Dehydroepiandroste- nandrolol
rone
androstenedione Stanazolol
Danazol

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Androgens & related substances
 Effects
 Anabolic: Increase muscle mass
 Androgenic: secondary sex characteristics
 Uses:
 1) Hypogonadism
 2) Infertility, Impotence, decreased libido
 3) Severe trauma/debilitating cond.
 4) Osteoporosis
 5) Performance enhancer*
 6) Endometriosis (sp. Danazol)
Androgens & related substances
 S/E:
 (Men) shrinkage of testicles, dec. sperm
count, baldness
 HPN, stroke, MI
 Psychological changes
 (Women) Masculinization – amenorrhea,
clitoral enlargement, hirsutism
 acne
Androgens & related substances
 ANDROGEN ANTAGONIST
 Finasteride (Propecia, Proscar)
 M: inhibit 5α-reductase (testosterone 
dihydrotestosterone)
 I: Benign prostatic hyperplasia, Alopecia

Androgens & related substances Androgens & related substances Prolactin (PRL)
 ANDROGEN ANTAGONIST  ANDROGEN ANTAGONIST   Prolactin releasing (PRH)

 Flutamide (Fugerel),  Cyproterone acetate (Cyprostat)  Effect:

 bicalutamide,  Milk production
 nilutamide  I: Hirsutism in females

 M: Androgen receptor blocker

 I: Prostate cancer

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Prolactin (PRL) Vasopressin/Anti-diuretic Hormone(ADH)

POSTERIOR PITUITARY
 Bromocriptine (Parlodel)  Effect: WATER REABSORPTION in kidney
ADH/Vasopressin
tubules @ COLLECTING TUBULES
Oxytocin
 M: Dopamine agonist  (-) prolactin
release  (Minirin) SC/nasal spray
 Ind: Hyperprolactinemia  Desmopressin
 Amenorrhea
 Galactorrhea
 Impotence
 I: Treatment of Diabetes Insipidus

Oxytocin Insulin
OTHER HORMONES
 Effect: Milk ejection, uterine contraction  A chain (21 aa) + B chain (30 aa)
Diabetes Mellitus & Insulin
 Proinsulin (86 a.a.) = Insulin + C-peptide
Calcium homeostasis
 BN: Pitocin, Syntocinon  Beta cells of pancreas

 I: Labor Induction  Effects

 Prevention of post-partum hemorrhage  Promotes glucose entry to cells
 Glycogenesis: Liver, muscle
 C/I: Fetal distress, abnormal presentation  Protein synthesis
 Fat storage

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Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus

Type 1 DM Type 2 DM  Diagnosis  Monitoring
Insulin dependent (IDDM) Non-insulin dependent
(NIDDM)  Symptoms of diabetes mellitus + RBG  Hemoglobin A1c goal: < 7%
Juvenile-onset Adult-onset >=200 mg per dL (11.1 mmol per L);
No insulin Normal or increased
insulin levels  Complications
Autoimmune- B cell Insulin resistance  FBG >=126 mg per dL (7.0 mmol per L)  Macrovascular: CHD, stroke, peripheral
destruction vascular disease
Normal weight obese
genetic genetic, environment  OGTT (75 g) 2hr postload glucose  Microvascular: nephropathy,
ketoacidosis Hyperosmolar coma >=200 mg per dL (11.1 mmol per L) neuropathy, retinopathy
Insulin Diet, exercise,
Oral antidiabetics, insulin

Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus

 INSULIN (SC, IV [regular])  INSULIN  INSULIN
 A. Short-acting
 Source:  1) Regular (insulin injection/crystalline zinc  B. Intermediate Acting
 Bovine or porcine  allergy insulin) (Humulin R, Actrapid)  1) NPH (Humulin N, Insulatard)
 Can be mixed, IV; slow onset, given 30
 Recombinant DNA  no allergy  Insulin + protamine (no excess)
minutes prior to meals
 2) Semilente (prompt insulin zinc  2) Lente (insulin zinc suspension)
suspension) (Monotard)
 Type 1 DM: 0.5-0.6 units/kg/day
 3) Lispro (Humalog) - shortest onset and
 Type 2 DM: 0.7-2.5 units/kg/day duration  70% ultralente + 30% semilente
 4) Aspart
 5) Glulisine

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Diabetes Mellitus Diabetes Mellitus

 INSULIN  INSULIN
 C. Long-acting  S/E: hypoglycemia, weight gain
 1) Ultralente (extended insulin zinc  lipodystrophy
suspension)
 2) PZI  Treatment of hypoglycemia:
 Insulin-Zn-protamine (xss) complex  Glucose 10-15 g oral- for conscious
 3) Glargine (Lantus)  Dextrose IV for unconscious
 “peakless”, less nocturnal  Glucagon 1g IM for unsconscious, no IV
hypoglycemia than NPH access

Diabetes Mellitus (OHAs) Diabetes Mellitus (OHAs) Diabetes Mellitus (OHAs)

 A. Insulin Secretagogues/Releasers  A. Insulin Secretagogues/Releasers  A. Insulin Secretagogues/Releasers
 1) Sulfonylureas  1) Sulfonylureas  1) Sulfonylureas
 1st Generation  2nd generation- more potent  CI:
 Chlorpropamide (Diabinese)  Glibenclamide (Euglucon)  Pregnant, lactating
 Longest duration (60 hrs), disulfiram-like reaction
 Gliclazide (Diamicron)  Children
 Acetohexamide
 Glimepiride (Solosa)  Allergy to sulfa
 w/ diuretic and uricosuric activity

 Tolbutamide, Tolazamide  Glipizide (Minidiab)  Stressful conditions such as infection,

injury or surgery (use insulin)

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Diabetes Mellitus (OHAs)
 A. Insulin Secretagogues/Releasers
 1) Sulfonylureas
 S/E:
 hypoglycemia, hyponatremia
(chlorpropramide)
 disulfiram-like reaction,
 nausea, vomiting, headache, gastric
discomfort,
 rashes,
 anemia, agranulocytosis,
Diabetes Mellitus (OHAs)
 B. Insulin Sensitizers
 2) Thiazolidinediones
 Rosiglitazone (Avandia)
 Pioglitazone (Actos)
 Troglitazone
 Banned (hepatotoxicity)
 MOA:
 activate PPAR-γ enhance insulin
sensitivity in muscle, liver and fat tissues
Diabetes Mellitus (OHAs)
 B. Insulin Sensitizers
 1) Biguanides
 Metformin (Glucophage)
 Phenformin
 Banned (lactic acidosis)
 MOA:
 Enhances insulin sensitivity and glucose
uptake in liver and muscles
 Reduces TG and LDL, increases HDL
Diabetes Mellitus (OHAs)
 B. Insulin Sensitizers
 2) Thiazolidinediones
 S/E:
 Hepatotoxicity
 Fluid retention, weight gain
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Diabetes Mellitus (OHAs)
 B. Insulin Sensitizers
 1) Biguanides
 S/E:
 Stomach upset, diarrhea
 Metallic taste
 Lactic acidosis (in kidney/liver disease)
Diabetes Mellitus (OHAs)
 C. Decrease digestion of CHOs
 Alpha glucosidase inhibitors
 Acarbose (Glucobay, Gluconase)
 Voglibose (Basen)
 Miglitol (Glyset)
 MOA:
 Retards absorption of CHO by preventing
the breakdown of sucrose and complex
CHO in the intestines
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Diabetes Mellitus (OHAs) Calcium Homeostasis Calcium Homeostasis

 C. Decrease digestion of CHOs
 Alpha glucosidase inhibitors
 For post prandial hyperglycemia
 Take with first bite of meal
 S/E:
 Flatulence, bloating
 Diarrhea
 1) Parathyroid hormone- ↑ Ca, ↓ P  3) Vitamin D
 Bone reabsorption of Ca, P •7-dehydrocholesterol
 Intestine absorption of Ca, P Skin •cholecalciferol
 Kidney reabsorption of Ca
 Excretion of P
•25-dihydroxy
 Activates Vitamin D Liver
 2) Calcitonin- ↓ Ca, ↓ P •1,25 dihydroxy (CALCITRIOL)
 Decreases reabsorption of Ca and P Kidneys
from bones

Calcium Homeostasis
 3) Vitamin D
 Most toxic vitamin due to
hypercalcemia-
 S/E:
 groans (abdominal pain, renal stones)
 bones (weakness)
 moans (confusion, delirium)

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