Endocrine drugs
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    Endocrine drugs Endocrine drugs Presentation Transcript

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