THE DRUG THERAPY OF

ENDOCRINE DISORDERS

INDWIANI ASTUTI
DEPT. OF PHARMACOLOGY & TOXICOLOGY,
FAC. OF MEDICINE
GADJAH MADA UNIVERSITY
 INTRODUCTION
 The endocrine system affects height, weight,
metabolism, growth, sexual development,
menstruation, hair and bone growth, fertility,
pregnancy, and breast milk production, as well as
some aspects of personality and behavior.
 the two adrenal glands, located on the top of each kidney;
 the pancreas, found in the abdominal cavity behind the
stomach;
 the parathyroid and thyroid, located at the base of the neck;
 the pituitary, located at the base of the brain; and
 the ovaries and testes, the female and male sex glands
 Pharmacological intervention in the treatment
of endocrine malfunction or disease state
generally takes one of three approaches:
1. Replacement or supplementation of the natural
hormone
2. Use of the hormone to obtain a specific response
3. Use of drugs to modify the concentration or
action of a specific hormone
 Hypothalamic-Pituitary Hormones

Therapeutic Overview
 Hypothalamic Hormones:
GnRH: Replacement therapy (central
amenorrhea, idiopathic hypogonadotropic
hypogonadism)
GNRH analogs: prostate cancer, Idiopathic
precocious puberty, Endometriosis,
Contraception
GHRH: Short stature
 Dopamin Agonists (Bromocriptine):
Physiological hyperprolactenemia
Pathological hyperprolactenemia
Acromegaly
Parkinson’s disease
 Somatostatin & analogs
Carcinoid tumor
VIP secreting tumor
 Pituitary Hormones
 LH & FSH
Infertility in women
Infertility
In men with hypogonadotropic
hypergonadism
 GH
Short stature
 AVP
Diabetes Insipidus
 Clinical Problems

 Hypothalamic Hormones & Analogs

 GnRH
Adverse reactions infrequent
Occasional nausea, headache, abdominal
discomfort
Anaphylaxis (rare) with IV use
Localized problems at injection site
 GHRH
Facial flushing
Antibodies with repeated use
 Bromocriptine
Nausea, orthostatic hypotension initially
Confusion, hallucination in Parkinson’s disease
Erythromelalgia, dyskinesia worsening
Discontinue during pregnancy
 Somatostatin analogs
Hyperglycemia, loose stools, gallstones
Pituitary Hormones & Analogs
 LH & FSH
Multiple pregnancy
Gynecomastia in men
Occasional febrile reactions
 GH
Antibodies
Misuse in Athletes,
constitutional delay of growth
 AVP
Nausea, vertigo, headache
Anaphylaxis
Angina, myocardial infarction
Water intoxication
 Drug interaction

 Bromocriptine:
Phenothiazine or butyraphones, prevents
dopamine agonist action
 Vasopressin analogs:
Carbamazepine, chlorpropamide, clofibrate,
urea, fludrocortisone, tricyclic antidepressant,
 potentiate action
Demeclocycline, norepinephrine, lithium,
heparin, alcohol  inhibit action
 Estrogens, Progestins, & Oral
Contraceptives
Therapeutic Overview
 Fertility control
Combination oral contraception (estrogen,
progestin)
Progestin-only contraception
Postcoital contraception (estrogens, progestins)
Contragestation (antiprogestins)
 Hormone Replacement Therapy
Menopause (estrogen, progestin (?))
Osteoporosis (estrogen, progestin (?))
Ovarian failure (estrogen, progestin)
Dysfunctional uterine bleeding (estrogen,
progestin)
Luteal phase dysfunction (estrogen)
 Ovulation Induction
Infertility (Clomiphene citrate)
 Cancer Chemotherapy
Breast cancer (estrogens, progestins,
antiestrogens, steroidogenesis inhibitors)
Endometrial cancer (progestins, antiestrogens
(?))
Prostate cancer (estrogens)
 Others
Endometriosis (danazol, progestins,
gonadotrophin releasing hormone)
Diagnostic (progestins)
Clinical Problems

 Estrogens:  Progestins
 GI disturbance  GI disturbance
 Menstrual disorders
 Menstrual disorders
 Breast discomfort
 Adverse changes in
 Thromboembolic disorders
lipoprotein levels
 Hypertention
 Abnormal glucose
 Endometrial cancer
intolerance
 Decreased lactation
 Drug interaction
 Drug interaction
 Adverse effect on fetus
 Adverse effect on fetus
(diethylstilbestrol)
 Clommiphene Citrate
 GI disturbance  Aminoglutethimide
 Vasomotor symptoms  GI disturbances
 Ovarian enlargement  CNS disturbances
 Visual disorders  Danazol
 Multiple gestation  Androgenic effect in
 Tamoxifen women
 GI disturbance  Antiestrogen-like effects
 Menstrual disorders  Adverse changes in
 Vasomotor Symptoms lipoprotein
concentration
 Mifeprestone (RU 486)
 Adverse effect on the
 Menstrual disturbance
fetus
(rare)
 Androgens & Antiandrogens

Therapeutic Overview
 Androgens:
Primary testicular insufficiency
Hypogonadotrophic hypoganadism
Constitutional delay of growth & adolescence
Osteoporosis, anemia
Testosterone derivatives used for replacement
therapy
 Antiandrogens & Antagonists:
Virilization in women
Precocious puberty in boys
Male contraceptive
Drugs used to decrease androgen synthesis or
block androgen action
Clinical Problems

 Masculinization in women
 Growth disturbance in children
 Fetal masculinization in pregnancy
 Jaundice
 Edema
 Acne
 Hypertention
 Weight gain
 Glucocorticoids & Mineralocorticoids

Therapeutic Overview
 Glucocorticoids:
Replacement therapy in adrenal insufficiencies
Antiinflammatory & immunosuppressive action
Myeloproliferative diseases
Drugs used:
 Hydrocortisone, cortisone, prednisone,prednisolone,
fludrocortisone, methylprednisolone, betamethasone,
triamcinolone, ddexamethasone
 Mineralocorticoid
Hypoalderosteronism
Drug used: fludrocortisone
 Steroid synthesis inhibitors
Adrenocortical Hyperfunction
Drugs used: metyrapone, ketoconazole
 Effects of Glucocorticoids
 Metabolic
 Increased glycogenolysis & gluconeogenesis
 Increased Protein catabolism & decreased protein
synthesis
 decreased Osteoclast formation & activity
 Antiinflammatory
 Local & systemic effects including:
 Decreased production of prostaglandins, cytokines &
interleukins
 Decreased proliferation & migration of lymphocytes &
macrophages
 Other:
 Decreased calcium absorption from gastrointestinal
tract
 Decreased thyroid-stimulating hormone secretion
Clinical Problems

 Side effects caused mainly by high

(pharmacological as compared to
physiological) concentrations & for long
times
 Most common side effects:
Development of cushingoid habitus (trunkal
obesity, moon faces, buffalo hump), salt
retention & hypertention (iatrogenic Cushing”s
Syndrome)
 Suppression of the immun system (rendering
the patient vulnerable to common &
opportunistic infections)
 Osteoporosis (rendering the patient vulnerable
to fractures)
 Peptic ulcers (resulting in gastric
hemorrhagies or intestinal perforation)
 Suppression in growth in children
 Behavioral problems
 Prolonged suppression of the hypothalamic-
pituitary-adrenal axis after drug
discontinuation
 Thyroid & Antithyroid Drugs

Therapeutic Overview
 Hypothyroidism:
 Exogenous thyroxine (T4) or triiodothyronine (T3)
 Hyperthyroidism:
 Surgery
 Radioactive iodine
 Drugs:
 Thioureylenes (Propylthiuracil, carbimazole, methimazole)
 Beta adrenergic receptor blockers
 Corticosteroids
 iodides
 Clinical Problems

 Iodide
Angioedema, hemorrhage, sore teeth & gums,
salivation, induction in goiter & myxedema
 Thioureylene:
Agranulocytosis, granulocytopenia, skin rash
 Thyroid Preparations:
Drug interaction with warfarin, bound (T3, T4)
by cholestyramine in GI tract
 Diabetes Mellitus
 Treatment : For both types of diabetes, the
goal of treatment is to keep blood sugar
normal or as near to normal as possible.
Treatment also consists in preventing the
condition from affecting the eyes, kidneys,
heart, or nerves, and decreasing the
incidence of infection. A combination of
diet, exercise, and medication is usually
prescribed.
 There are two major types of diabetes mellitus:
 • Type 1—Insulin-dependent diabetes mellitus
(IDDM). Former names of this type of diabetes
mellitus include juvenile diabetes
 Type 2—Noninsulin-dependent diabetes mellitus
(NIDDM). Former names of this type of diabetes
mellitus include maturity-onset diabetes,
 Insulin & Oral Hypoglycemic Agents

Therapeutic Overview
 IDDM:
 Insulin
 Diet
 Exercise
 NIDDM:
 Oral hypoglycemic agents (sulfonylurea)
 Insulin
 Diet
 Weight reduction
 Exercise
 Clinical Problems

 Insulin:  Sulfonylurea:
 Hypoglycemia  Hypoglycemia
 Local or systemic  GI disturbances
allergy reactions  Hematological
 Visual disturbances disturbances
 Peripheral edema  Flushing especially with
concurrent alcohol
ingestion
 Contraindicated with
hepatic or renal
insufficiency
 Drug interactions
 Calcium-Regulating Hormones & Other
Agents Affecting Bone
 Therapeutic Overview
 Vitamin D & Its metabolites:
 Rickets
 Osteomalacia
 Hypocalcemia
 Hypoparathyroidism (10x large doses)
 Vitamin D-resistant rickets
 EDTA, Furosemide, Ethacrynic acid, & etc.
 Hypercalcemia
 Calcium, Estrogen, Calcitonin
 Osteoporosis
 Parathyroid hormone
Diagnostic agents for
pseudohypoparathyroidism
 Calcitonin
Paget’s disease of bone
Osteoporosis
Hypercalcemia of pregnancy
Clinical Problems

 Vitamin D & metabolites  Diphosphonates

 Hypercalcemia
 Benzothiazides can
increase hazards of
 Fluoride
hypercalcemia
 Parathyroid hormone
 Hypercalcemia (unlikely
with diagnostic use)
 Calcitonin
 Local hypersensitivity
 “Escape” loss of
effectiviness
 Osteomalacia
 Bone pain
 GI side effects including
nausea
 Musculoskeletal pain
 Joint swelling
 Mottled teeth enamel
 Dose related bone
fracture possibility