1. Chapter 22:Drugs & Endocrine Disorers Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

2. Chapter 22 Outline ▫Pituitary Gland ▫Thyroid hormones ▫Female sex hormones ▫Male sex hormones ▫Other agents that affect sex hormone systems

3. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Pituitary Gland

4. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Pituitary Hormones “Master gland” 2 lobes that release many different hormones ▫See next slide

5. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. “Master gland” 2 lobes that release many different hormones

6. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

7. Thyroid Hormones

8. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones Thyroid gland hormone secretion ▫Hypothalamus secretes TRH ↓ ▫Travels to ant pituitary ↓ ▫Ant pituitary secrete TSH ↓ ▫TSH binds to thyroid receptors ↓ ▫Stimulates production T 4 (cont’d next slide)

9. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

10. Thyroid Hormones T 4 Thyroxine (levothyroxine) released ↓ Travels to target tissue ↓ T 4 converted to T 3 (Triiodothyronine) ↓ T 3 enters cell & binds to receptors ▫87% T 3 derived from T 4 & 13% synthesized from thyroid gland ▫Iodine required for T 4 synthesis (get from dietary salt) ▫T 3 greater biological activity than T 4  T 3 half-life = 1 day  T 4 half-life = 7 days  Blood tests for thyroid dysfunctions = measure T 4 & TSH levels

11. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones Thyroid hormones are 99% plasma-PRO bound  Protect hormones from being metabolized along their path to target organs

12. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones HYPOthyroidism (lack of T 3 or T 4 ) ▫Etiology (book correction/clarification p.246)  Tx with radioactive iodine  Hashimoto’s disease (autoimmune thyroiditis)  Cretinism (congenital hypothyroidism)  Tumor  Drugs-induced: oral sulfonylureas (diabetes), lithium

13. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones HYPOthyroidism (lack of T 3 or T 4 ) ▫Symptoms in adults: myxedema (book correction)  Slurred speech, depression, bradycardia, weight gain, low body temperature ▫Sensitive to opioids & sedatives ▫No dental special accommodations needed Drug Tx HypothyroidismNOTATIONS L-thyroxine(Levoxyl, Synthyroid, Levothroid) L-triodothyronine(Cytomel)Cardiac side effects Liotrix(Thyrolar) Thyroid USP(Armour)Allergic rxns

14. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones HYPERthyroidism  Etiology 1.Graves disease: autoimmune disease where body develops antibodies against its own thyroid 2.Plummer’s disease: enlargement of thyroid gland Book correction p.247: Hashimoto’s disease NOT an etiology of HYPER, is of HYPO!!!

15. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones HYPERthyroidism Dental Implications ▫Pain threshold: ↑ sensitivity to pain  May need larger doses of local anes or sedation ▫Epi should be used in cardiac dose (NBQ)  Cardiovascular effects  Black-box warning that those drugs may exacerbate an underlying cardiovascular condition  No epi considerations for HYPOthyroidic

16. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Thyroid Hormones Drug Tx Hyperthyroidism USES/NOTATIONS Propylthiouracil(PTU)Short-term tx Graves Agranulocytosis side effect Methimazole(Tapazole)Short-term tx Graves Agranulocytosis side effect Radioactive iodineWill result in permanent hypothyroidism Iodine (Lugol’s solution, Potassium iodide SSKI) Tx thyroid storm Lugol’s: OTC in USA in 2007 Beta-blockers (propranolol, nadolol) Not approved in USA for tx hyperthyroidism (book correction p.247) CCB (diliazem, verapamil)Block effects of thyroid hormone, do not affect underlying disease CorticosteroidsThyroid storm

17. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Don’t need to know Antithyroid Agents p.247

18. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones

19. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones 2 major female sex hormones 1.Estrogens 2.Progesterone ▫Both are secreted primarily by the ovaries ▫Levels vary daily  Dependent on hormones LH, FSH secreted from pituitary gland

20. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones Estrogens ▫Available naturally or synthetically ▫Female body produced 3 natural estrogens 1.Estradiol 2.Estrone 3.Estriol ▫ ↑ HDL & triglyceride levels ▫ ↓ LDL ▫Drugs available as:  Oral  Vaginal tablet  Vaginal cream  Skin cream (transdermal)

21. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones Estrogen Uses 1.Estrogen replacement therapy: estrogen only drugs for menopause (drugs on next slide) 2.Birth control (in combo w/progestins) 3.Osteoporosis 4.Skin issues (acne) 5.Infertility: clomiphene(Clomid) 6.Breast cancer ▫Nonsteroidal estrogens diethylstilbesterol(DES) ▫Anti-estrogens (prevent estradiol actions)

22. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones Estrogen Hormone Replacement Conjugated estrogens(Premarin) Estradiol micronized(Estrace) Estradiol transdermal Ethinly estradiol(Estinyl) Estradiol cypionate(Depo-Estradiol) Quinesterol(Estrovis)

23. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones Estrogens ▫ Adverse Effects  Risk for blood clots in smokers  Risk for Stroke (esp in smokers)  Possible increase risk for breast cancer in long-term use (rsrch controversial)  ABX can reduce effectiveness

24. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones Progestins ▫ 2 main groups 1.Progesterone 2.Testosterone ▫ Uses 1.Birth control: ↓ ovulation 2.Menstrual disorders 3.Endometriosis 4.HRT (hormone replacement therapy): progesterone + estrogen therapy for menopause (drugs next slide)

25. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. HRT: Estrogen + Progesterone Activella Combipatch Estratest FemHRT Ortho-Prefest Prephase Prempro Active Chemicals: 1.Progesterone (Dydrogestrone, hydroxyprogestrone, medroxyprogesterone) 2.Testosterone (Norethindrone, Norethynodrel) 3.Estrogen derivatives

26. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Female Sex Hormones Oral Contraceptives ▫Estrogen + Progestin (drugs on next slide)  Suppress FSH = Inhibit ovulation  Used to tx endometriosis  Mono/Bi/Tri-Phasic ▫Progestin Only  Useful for women who smoke, when estrogen is contraindicated, older women Progestogens Progestrone Norethindrone(Aygestin) Medroxyprogesterone(Depo-Provera) Minipill

27. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Oral Contraceptives Estrogen + Progestin Demulen Ortho Evra Ortho Novum Ovcon Yasmin Yaz Zovia Lo/Ovral Loestrin Levora Norinyl Seasonale Allow a menstrual cycle once every 3 months Nuva Ring Only one on list w/out progestin (2 estrogens) Lunelle Injection in-office 1x/mo

28. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. DH considerations (your text & Mosby’s) 1.GI 2.HBP 3.Gingivitis 4.ABX - 5.Your text lists dry socket – per Mosby’s this was a risk factor with older drugs but not so much with newer formulations Box 22-3, p.250 – don’t worry about other risks listed, just be familiar with this list

29. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Male Sex Hormones

30. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Male Sex Hormones Male sex hormones are steroids referred to as Androgens (testosterone) ▫Uses  Hypogonadism in men  Breast cancer in women ▫Most drugs given parentally ▫Anabolic steroids (testosterone-like compounds)  Can be abused (muscle gaining)  Alleviate post-menopausal osteoporosis  Weight gain after surgery

31. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Male Sex Hormones Androgens Fluoxymesterone(Halostestin) Methyltestosterone(Android) Testestrone(Androderm) Anabolic Steroids Nandrolone decanoate(Deca-Durabolin) Only drugs need to know are listed above, not need to know Table 22-4 (you are welcome! Haha!)

32. Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved. Other agents that affect sex hormone systems TREATMENT OF INFERTILITY Clomiphene(Clomid, Serophene) Leuprolide(Lupron) TREATMENT BREAT CANCER/DISEASE These like to show up on boards! Tamoxifen(Nolvadex) Danazol(Danocrine) Aromatase Inhibitor class