Endocrine drugs

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Endocrine drugs

  1. 1. Endocrine Drugs, Hormones andEndocrine Drugs, Hormones and Related CompoundsRelated Compounds
  2. 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. 3. Endocrine SystemEndocrine System
  4. 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. 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. 6. Nervous SystemNervous System
  7. 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. 8. Endocrine vs NervousEndocrine vs Nervous NOTE: there is close interrelationship between the endocrine and nervous systems
  9. 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. 10. HormonesHormones
  11. 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. 12. Endocrine DrugsEndocrine Drugs
  13. 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. 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. 15. Hypothalamic & PituitaryHypothalamic & Pituitary HormonesHormones
  16. 16. HypothalamusHypothalamus - master endocrine organ - secretes releasing/inhibiting hormones
  17. 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. 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. 19. Growth HormoneGrowth Hormone
  20. 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. 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. 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. 23. DwarfismDwarfism
  24. 24. SomatremSomatrem - a therapeutically equivalent drug of GH - contains an extra terminal methionyl group
  25. 25. Growth Hormone InhibitingGrowth Hormone Inhibiting HormoneHormone
  26. 26. Growth Hormone InhibitingGrowth Hormone Inhibiting Hormone (GHIH)Hormone (GHIH) - aka: Somatostatin - inhibits Growth Hormone - Indications: Pituitary Gigantism (pre-pubertal) Acromegaly (post-pubertal)
  27. 27. Pituitary GigantismPituitary Gigantism
  28. 28. AcromegalyAcromegaly macrognathia (large jaw) wide-spaced teeth macroglossia thickened lips broad nose enlarged joints cardiomegaly organomegaly
  29. 29. OctreotideOctreotide - synthetic octapeptide analog of somatostatin - 45x more potent than GHIH
  30. 30. Adrenocorticotropic HormoneAdrenocorticotropic Hormone
  31. 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. 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. 33. Addison’s DiseaseAddison’s Disease • hyposecretion of adrenocorticosteroids • characterized by: – anorexia – dehydration – weakness and lethargy – hyperpigmentation (bronze-colored skin)
  34. 34. Cushing’s SyndromeCushing’s Syndrome • hypersecretion of adrenocorticosteroids • characterized by: – moon face – buffalo hump – pendulous abdomen – hypertension
  35. 35. Cushing's SyndromeCushing's Syndrome
  36. 36. CosyntropinCosyntropin - synthetic human ACTH - more preferred since animal ACTH can cause allergic reactions
  37. 37. Thyrotropin StimulatingThyrotropin Stimulating HormoneHormone
  38. 38. 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)
  39. 39. 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
  40. 40. HypothyroidismHypothyroidism - inability of the thyroid gland to supply sufficient thyroid hormone to the body - manifestations: Cretinism (infant-state) Myxedema (adult-state)
  41. 41. CretinismCretinism - infant-state hypothyroidism - characterized by physical and mental retardation
  42. 42. MyxedemaMyxedema - adult-state hypothyroidism - characterized by: • bradycardia • weakness and lethargy • dry skin and hair • coldness • goiter
  43. 43. HyperthyroidismHyperthyroidism - overabundance of thyroid hormone in the body - thyrotoxicosis - Forms: Graves’ Disease - most common Plummer’s Disease - less common - with cardiac abnormalities
  44. 44. Graves' DiseaseGraves' Disease
  45. 45. GonadotropinsGonadotropins
  46. 46. 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
  47. 47. 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
  48. 48. Non-Pituitary GonadotropinsNon-Pituitary Gonadotropins 1. Menotropins 2. Urofollitropin 3. Human Chorionic Gonadotropin
  49. 49. Non-Pituitary GonadotropinsNon-Pituitary Gonadotropins - Indications: women: to induce ovulation & pregnancy men: to induce spermatogenesis - Adverse effects: ovarian enlargement multiple births gynecomastia in men
  50. 50. 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
  51. 51. UrofollitropinUrofollitropin - Metrodin® - obtained from the urine of post- menopausal women - high in FSH-like activity
  52. 52. Human Chorionic GonadotropinHuman Chorionic Gonadotropin - aka: hCG, Follutein® - a placental hormone - LH agonist effect -obtained from the urine of pregnant women
  53. 53. Hormones of the PosteriorHormones of the Posterior Pituitary GlandPituitary Gland
  54. 54. Hormones of the PosteriorHormones of the Posterior Pituitary GlandPituitary Gland 1. Oxytocin 2. Vasopressin
  55. 55. 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
  56. 56. OxytocinOxytocin
  57. 57. 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
  58. 58. 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
  59. 59. DesmopressinDesmopressin - modified analog of vasopressin - more preferred for DI and nocturnal enuresis because it is largely free of pressor effects and is longer-acting
  60. 60. Steroid HormonesSteroid Hormones
  61. 61. Steroid HormonesSteroid Hormones - contain the steroid nucleus, CPPP cyclopentanoperhydrophenanthrene
  62. 62. Steroid HormonesSteroid Hormones • Carbon 3 & Carbon 17 • -OH (sterol) • =O (sterone)
  63. 63. Gonadal / Sex HormonesGonadal / Sex Hormones
  64. 64. 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
  65. 65. Gonadal / Sex HormonesGonadal / Sex Hormones
  66. 66. EstrogensEstrogens
  67. 67. EstrogensEstrogens - basic nucleus: estrane Estradiol
  68. 68. EstrogensEstrogens - Effects: 1. normal female maturation and development 2. inhibit bone resorption 3. increase HDL, decrease LDL 4. decrease platelet adhesiveness
  69. 69. EstrogensEstrogens - Indications: contraception postmenopausal hormone therapy primary hypogonadism osteoporosis
  70. 70. 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
  71. 71. PremarinPremarin
  72. 72. Synthetic Steroidal EstrogensSynthetic Steroidal Estrogens Ethinyl estradiol Mestranol Quinestrol
  73. 73. 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
  74. 74. 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
  75. 75. Estrogen Related DrugsEstrogen Related Drugs Aromatase Inhibitors Selective Estrogen Receptor Modulators
  76. 76. 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
  77. 77. SERMsSERMs - Selective Estrogen Receptor Modulators - reduce bone resorption and decrease bone turnover - used for the prevention of osteoporosis - Raloxifene
  78. 78. ProgestinsProgestins
  79. 79. ProgestinsProgestins - basic nucleus: pregnane
  80. 80. 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
  81. 81. ProgestinsProgestins - Indications: contraception for menstrual disorders -dysfunctional uterine bleeding -dysmenorrhea endometriosis
  82. 82. 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
  83. 83. Synthetic ProgestinsSynthetic Progestins - more stable to first-pass metabolism, allowing for lower doses when administered orally - medroxyprogesterone hydroxyprogesterone megestrol norethindrone norgestrel
  84. 84. 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
  85. 85. Oral & ImplantableOral & Implantable ContraceptivesContraceptives
  86. 86. Major ClassesMajor Classes 1. Combination Pills 2. Progestin Only Contraceptives 3. Postcoital Contraceptives
  87. 87. 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
  88. 88. Combination PillsCombination Pills - progestin: prevents implantation in the endometrium and makes the cervical mucus impenetrable to the sperm norethynodrel norethindrone norgestrel
  89. 89. 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
  90. 90. Progestin Only ContraceptivesProgestin Only Contraceptives c. intramuscular - given every 3 months 150 mg of medroxyprogesterone acetate (Depo-Provera®)
  91. 91. Progestin Only ContraceptivesProgestin Only Contraceptives d. intrauterine device (IUD) - for yearly insertion; Progestasert®
  92. 92. 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
  93. 93. AndrogensAndrogens
  94. 94. AndrogensAndrogens - basic nucleus: androstane Testosterone
  95. 95. AndrogensAndrogens - group of steroids that have anabolic and/or masculinizing effects in both males and females
  96. 96. 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
  97. 97. Synthetic AndrogensSynthetic Androgens Methyltestosterone Danazol Stanozolol Nandrolone
  98. 98. 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)
  99. 99. Unapproved UseUnapproved Use Used to increase lean body mass, muscle strength and aggressiveness in athletes and body builders (Nandrolone & Stanozolol)
  100. 100. AntiandrogensAntiandrogens - inhibit the action of androgens by interfering with androgen synthesis or by blocking their receptors a. Finasteride - used in Benign Prostatic Hypertrophy (BPH)
  101. 101. AntiandrogensAntiandrogens b. Flutamide - for prostatic carcinoma c. Cyproterone acetate - for hirsutism in females
  102. 102. Hormones of the AdrenalHormones of the Adrenal CortexCortex
  103. 103. Hormones of the Adrenal CortexHormones of the Adrenal Cortex 1. Adrenocorticosteroids a. Mineralocorticoids b. Glucocorticoids 2. Adrenal Androgens
  104. 104. Adrenal CortexAdrenal Cortex 3 Zones: 1. Zona glomerulosa - produces mineralocorticoids 2. Zona fasciculata - produces glucocorticoids 3. Zona reticularis - produces adrenal androgens
  105. 105. Adrenal CortexAdrenal Cortex Zona glomerulosa Zona fasciculata Zona reticularis Kidney
  106. 106. MineralocorticoidsMineralocorticoids - possess sodium-retaining and potassium-secreting effects - essential for fluid and electrolyte balance - endogenous: aldosterone desoxycorticosterone - synthetic: fludrocortisone
  107. 107. 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
  108. 108. 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
  109. 109. GlucocorticoidsGlucocorticoids Therapeutic Uses: Allergy Inflammation of joints and bones Skin diseases Organ transplant immunosuppression Pulmonary Diseases: Bronchial Asthma COPD
  110. 110. GlucocorticoidsGlucocorticoids Adverse effects: Cushing’s syndrome Adrenal suppression osteoporosis PUD impaired wound healing increased susceptibility to infection hyperglycemia/DM cataract
  111. 111. Addison’s DiseaseAddison’s Disease • hyposecretion of adrenocorticosteroids • characterized by: – anorexia – dehydration – weakness and lethargy – hyperpigmentation (bronze-colored skin)
  112. 112. Cushing’s SyndromeCushing’s Syndrome • hypersecretion of adrenocorticosteroids • characterized by: – moon face – buffalo hump – pendulous abdomen – hypertension
  113. 113. Cushing's SyndromeCushing's Syndrome
  114. 114. Thyroid Hormones andThyroid Hormones and Drugs for Thyroid DisordersDrugs for Thyroid Disorders
  115. 115. Thyroid GlandThyroid Gland
  116. 116. 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
  117. 117. Thyroid HormonesThyroid Hormones - the thyroid hormones T3 and T4 are essential for the normal growth and maturation of the body
  118. 118. 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
  119. 119. 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
  120. 120. HypothyroidismHypothyroidism - inability of the thyroid gland to supply sufficient thyroid hormone to the body - manifestations: Cretinism (infant-state) Myxedema (adult-state)
  121. 121. CretinismCretinism - infant-state hypothyroidism - characterized by physical and mental retardation
  122. 122. MyxedemaMyxedema - adult-state hypothyroidism - characterized by: • bradycardia • weakness and lethargy • dry skin and hair • coldness • goiter
  123. 123. 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
  124. 124. HyperthyroidismHyperthyroidism - overabundance of thyroid hormone in the body - thyrotoxicosis - Forms: Graves’ Disease - most common Plummer’s Disease - less common - with cardiac abnormalities
  125. 125. Graves' DiseaseGraves' Disease
  126. 126. Antithyroid DrugsAntithyroid Drugs 1. Thioamides 2. Inorganic Anions/Anionic Inhibitors 3. Iodides 4. Radiocontrast dyes 5. Beta-blocker 6. Dexamethasone 7. Radioactive Iodine
  127. 127. ThioamidesThioamides - MOA: inhibit iodine organification and coupling - examples: Propylthiouracil (PTU) Methimazole Carbimazole - S/E: pruritic maculopapular rash agranulocytosis
  128. 128. 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
  129. 129. 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
  130. 130. Radiocontrast DyesRadiocontrast Dyes - MOA: inhibit peripheral conversion of T4 to T3; also inhibit proteolysis - examples: Ipodate Iopanoic acid
  131. 131. Beta-blockerBeta-blocker - MOA: symptomatic relief of the sympathetic manifestations of hyperthyroidism; may also inhibit peripheral conversion of T4 to T3 - Propranolol
  132. 132. DexamethasoneDexamethasone - MOA: inhibits peripheral conversion of T4 to T3
  133. 133. 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
  134. 134. Anti-diabetic AgentsAnti-diabetic Agents
  135. 135. PancreasPancreas - is a mixed gland - Exocrine portion -releases pancrealipase & chymotrypsin - Endocrine portion -1million islets of Langerhan -have at least 4 hormone-producing cells
  136. 136. 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)
  137. 137. 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
  138. 138. Types of DMTypes of DM Type 1 Type 2 Gestational DM Secondary DM
  139. 139. 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
  140. 140. 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
  141. 141. Gestational DMGestational DM - defined as any degree of glucose intolerance that has its onset during pregnancy
  142. 142. 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
  143. 143. 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
  144. 144. 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
  145. 145. 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
  146. 146. 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
  147. 147. 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
  148. 148. Oral Hypoglycemic DrugsOral Hypoglycemic Drugs • Insulin secretagogues • Biguanides • Alpha-glucosidase inhibitors • Thiazolidinedione derivatives
  149. 149. Insulin SecretagoguesInsulin Secretagogues • Sulfonylureas • Meglitinides
  150. 150. SulfonylureasSulfonylureas MOA: - stimulate pancreatic release of insulin - inhibit pancreatic release of glucagons - increase insulin receptor binding - decrease hepatic extraction of insulin
  151. 151. SulfonylureasSulfonylureas Ist Generation Chlorpropamide Acetohexamide Tolbutamide Tolazamide 2nd Generation Glibenclamide Glipizide Gliclazide Glimepiride
  152. 152. SulfonylureasSulfonylureas Side-effects: hypoglycemia blood dyscrasias disulfiram-like reactions with 1st Gen and glipizide weight gain
  153. 153. MeglitinidesMeglitinides - MOA: increase pancreatic insulin secretion - short duration of action: 1 to 3 hours - examples: Repaglinide Nateglinide - S/E: hypoglycemia weight gain
  154. 154. 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
  155. 155. 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
  156. 156. 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
  157. 157. Let’s see how muchLet’s see how much you can recall… :)you can recall… :)
  158. 158. 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
  159. 159. 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
  160. 160. 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
  161. 161. 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
  162. 162. Question 5:Question 5: All of the following are steroidal hormones except: A. testosterone B. levothyroxine C. cortisone D. dexamethasone E. estradiol B
  163. 163. 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
  164. 164. 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
  165. 165. 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
  166. 166. 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
  167. 167. Question 10:Question 10: Which of the following is a sulfonylurea? A. metformin B. repaglinide C. acarbose D. rosiglitazone E. glibenclamide E
  168. 168. ““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
  169. 169. Thank You for Listening!Thank You for Listening!

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