- •Contents
- •1. Pharmacokinetics
- •3. Practice Questions
- •2. Antiarrhythmic Drugs
- •3. Antihypertensive Drugs
- •3. Anticonvulsants
- •5. Opioid Analgesics
- •8. Drugs of Abuse
- •1. Antibacterial Agents
- •4. Antiprotozoal Agents
- •1. Histamine and Antihistamines
- •3. Drugs Acting on Serotonergic Systems
- •1. Drugs Used in Diabetes
- •2. Steroid Hormones
- •6. Endocrine Drug List
- •1. Anticancer Drugs
- •1. Immunopharmacology
- •1. Toxicology
- •2. Toxicology Practice Questions
- •Index
Steroid Hormones |
2 |
ADRENAL STEROIDS
•Nonendocrine uses: For use in inflammatory disorders (and accompany ing adverse effects), see Section VI, Drugs for Inflammatory and Related Disorders.
•Endocrine uses of glucocorticoids (e.g., prednisone, dexamethasone) and the mineralocorticoid (fludrocortisone) include:
Addison disease--replacement therapy
Adrenal insufficiency states (infection, shock, trauma)--supplementation
-Premature delivery to prevent respiratory distress syndrome- supplementation
-Adrenal hyperplasia--feedback inhibition ofACTH
•Adrenal steroid antagonists:
-Spironolactone
-Blocks aldosterone and androgen receptors (see Section III, Cardiac and Renal Pharmacology)
•Mifepristone:
-Blocks glucocorticoid and progestin receptors
•Synthesis inhibitors:
Metyrapone (blocks II-hydroxylation)
- Ketoconazole
ESTROGENS
•Pharmacology: Estradiol is the major natural estrogen. Rationale for synthet ics is to i oral bioavailability, i half-life, and i feedback inhibition of FSH and LH.
•Drugs:
-Conjugated equine estrogens (Premarin)-natural
-Ethinyl estradiol and mestranol-steroidal
-Diethylstilbestrol (DES)-nonsteroidal
•Clinical uses:
-Female hypogonadism
-Hormone replacement therapy (HRT) in menopause --7j,bone resorption (J, PTH)
-Contraception-feedback j, of gonadotropins
-Dysmenorrhea
-Uterine bleeding
-Acne
-Prostate cancer (palliative)
MEDICAL 275
Chapter 2 • Steroid Hormones
Table Vlll-2-1. Comparison ofTamoxifen and Raloxifene in Various Tissues |
· |
|||
Drug |
Bone |
Breast |
Endometrium |
|
Tamoxifen |
Agonist |
Antagonist |
Agonist |
|
Raloxifene |
Agonist |
Antagonist |
Antagonist |
|
PROGESTIN
•Pharmacology: Progesterone is the major natural progestin. Rationale for synthetics is i oral bioavailability and i feedback inhibition of gonadotro pins, especially luteinizing hormone (LH).
•Drugs:
-Medroxyprogesterone
-Norethindrone·
Desogestrel is asyntheticprogestindevoidofandrogenicand antiestrogenic activities, common to other derivatives
•Clinical uses:
- Contraception (oral with estrogens)-depot contraception (medroxypro gesterone IM every 3 months)
Hormone replacementtherapy (HRT)-with estrogens to j, endometrial cancer
•Side effects:
-j, HDL and i LDL
-Glucose intolerance
-Breakthrough bleeding
-Androgenic (hirsutism and acne)
-Antiestrogenic (block lipid changes)
-Weight gain
-Depression
•Antagonist: mifepristone-abortifacient (use with prostaglandins [PGs])
ORAL CONTRACEPTIVES
•Pharmacology:
-Combinations of estrogens (ethinyl estradiol, mestranol) with progestins
(norgestrel, norethindrone) in varied dose, with mono-, bi-, and triphasic variants
-Suppress gonadotropins, especially rnidcycle LH surge
•Side effects:
-Side effects are those of estrogens and progestins, as seen previously
•Interactions: j, contraceptive effectiveness when usedwith antimicrobials and enzyme inducers
•Benefits:
-j, risk of endometrial and ovarian cancer
j, dysmenorrhea - j, endometriosis
MEDICAL 277
Chapter 2 • Steroid Hormones
Chapter Summary
Adrenal Steroids
•The nonendocrine uses in inflammatory disorders were discussed in the previous chapter.
•The glucocorticoids are used to treat Addison disease and adrenal insufficiency states, as a supplement in infantile respiratory distress syndrome, and in adrenal hyperplasia.
Estrogens
•Synthetic estrogens are used to increase the oral bioavailability and half-life relative to that obtained with estradiol and to induce feedback inhibition of FSH and LH.
•The uses and adverse affects of estrogens are listed.
•The clinical uses of anastrozole (decreases estrogen synthesis), danazol
(decreases ovarian steroid synthesis), clomiphene (decreases feedback inhibition), and the selective estrogen-receptor modulators tamoxifen and raloxifene are considered.
Progestin
•Synthetic progestins are used to increase oral bioavailability and half-life relative to progesterone and to induce feedback inhibition of gonadotropins, especially LH.
•The progestin-like drugs, their use in contraception and in hormonal replacement therapy, and their adverse effects are considered.
•Mifepristone is an antagonist used with PG as an abortifacient.
•The pharmacology of oral contraceptives and their adverse effects, drug interactions, and benefits are pointed out.
Androgens
•Clinically useful androgen analogs include methyltestosterone and 17-alkyl derivatives. Their clinical and illicit uses and side effects are presented.
•Clinically useful drug antagonists are flutamide (an androgen-receptor blocker used to treat prostate cancer), leuprolide (a GnRH analog used to treat prostate cancer), and finasteride (a 5-a-reductase inhibitor used to treat benign prostatic hyperplasia and male pattern baldness).
MEDICAL 279
Section VIII • Endocrine Pharmacology
•Thioamides: propylthiouracil and methimazole
-Use: uncomplicated hyperthyroid conditions; slow in onset
-High-dose propylthiouracil inhibits 5' deiodinase
-Common maculopapular rash
-Both drugs cross the placental barrier, but propylthiouracil is safer in pregnancybecause it is extensivelyprotein bound
•Iodide
-Potassium iodide plus iodine (Lugol's solution) possible use in thyrotoxi cosis: used preoperatively -+t gland size, fragility, and vascularity
-No long-term use because thyroid gland "escapes" from effects after 10 to 14 days
Chapter Summary
•The steps in thyroid hormone synthesis and the antithyroid agents' effects upon them are summarized in Table Vlll-3-1. The clinical uses and their potential complications are presented in greater detail for the thioamides (propylthiouracil and methimazole) and iodine.
282 MEDICAL
Drugs Related to Hypothalamic |
4 |
|
|
and Pituitary Hormones |
|
Table Vlll-4-1. Drugs Related to Hypothalamic and Pituitary Hormones
Hormone |
Pharmacologic Agent |
Clinical Uses |
|
GH |
Somatrem or somatropin |
Pituitary dwarfism, osteoporosis |
|
Somatostatin |
Octreotide |
Acromegaly, carcinoid and secretory |
|
|
|
GI tumors |
|
ACTH |
Cosyntropin |
Infantile spasms |
|
GnRH |
Leuprolide, nafarelin |
Endometriosis, prostate carcinoma |
|
|
|
(repository form) |
|
FSH and LH |
Urofollitropin (FSH), |
Hypogonadal states |
|
|
placental HCG (LH), |
|
|
|
menotropins (FSH and LH) |
|
|
PIH (DA) |
Bromocriptine |
Hyperprolactinemia |
|
Oxytocin |
Oxytocin |
Labor induction |
|
Vasopressin |
Desmopressin |
• |
Neurogenic (pituitary) diabetes |
|
(V2 selective) |
|
insipidus |
|
|
• |
Hemophilia A (t factorVIII from liver) |
|
|
• von Willebrand disease (tvW factor |
|
|
|
|
from endothelium) |
|
|
• |
Primary nocturnal enuresis |
Definitionofabbreviations: ACTH, adrenocorticotropin hormone; DA, dopamine; FSH, follicle-stimulating hormone; GH, growth hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; PIH, prolactin-inhibiting hormone.
ChapterSummary
•The clinical uses of drugs used to treat functions associated with hypothalamic or pituitary hormones are summarized in Table Vlll-4-1.
MEDICAL 283
Drugs Used for Bone and |
5 |
|
|
Mineral Disorders |
|
BISPHOSPHONATES
•Mechanisms: stabilize hydroxyapatite bone structure and also induce osteoblasts to secrete inhibitors of osteoclasts -+1. bone resorption .i. progression of osteoporosis
•Clinical uses:
-Established use in Paget disease
Efficacy in postmenopausal osteoporosis depends on individual drug, but alendronate is effective and with HRT causes I bone min eral density (BMD).
-Alendronate is drug ofchoice forglucocorticoid-induced osteoporosis
•Side effects:
-Etidronate and pamidronate bone mineralization defects
Gastrointestinal distress, including esophageal ulcers (alendronate)
TERIPARATIDE
•Mechanism: recombinant DNA PTH analog
•Clinical use: once dailyto stimulate osteoblasts and new bone formation
•Continuous infusion would stimulate osteoclast activity
•Used for less than 2 years; may I risk ofosteosarcoma
Chapter Summary
•The bisphosphonates decrease bone resorption and slow the progress of osteoporosis. Alendronate is effective fortreatment of postmenopausal and steroid-induced osteoporosis. The principal potential side effects are gastrointestinal distress and esophageal ulcers.
MEDICAL 285