Thyroid Drugs2[1]

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  • Thyroid Drugs2[1]

    1. 1. Thyroid Drugs
    2. 2. FUNCTIONS OF THE ENDOCRINE SYSTEM <ul><li>Maintenance and regulation of vital functions </li></ul><ul><li>Response to stress and injury </li></ul><ul><li>Growth and development </li></ul><ul><li>Energy metabolism </li></ul><ul><li>Reproduction </li></ul><ul><li>Fluid, electrolyte, and acid-base balance </li></ul>
    3. 3. THYROID GLAND <ul><li>Located in the anterior part of the neck </li></ul><ul><li>Controls the rate of body metabolism and growth </li></ul><ul><li>Produces thyroxine (T 4 ), triiodothyronine (T 3 ), and thyrocalcitonin </li></ul>
    4. 4. Thyroid & Parathyroid Gland
    5. 5. PARATHYROID GLAND <ul><li>Located near the thyroid </li></ul><ul><li>Controls calcium and phosphorus metabolism </li></ul><ul><li>Produces parathyroid hormone (PTH) </li></ul>
    6. 6. Thyroid Gland <ul><li>Follicular cells produce 2 thryroid hormones </li></ul><ul><ul><li>Thyroxine = tetraiodothyronine = T 4 </li></ul></ul><ul><ul><li>Triiodothyronine = T 3 </li></ul></ul><ul><li>Thyroid hormones regulate: </li></ul><ul><ul><ul><li>Oxygen use and basal metabolic rate </li></ul></ul></ul><ul><ul><ul><li>Cellular metabolism </li></ul></ul></ul><ul><ul><ul><li>Growth & development </li></ul></ul></ul><ul><li>Parafollicular cells (C-cells) produce hormone </li></ul><ul><ul><li>Calcitonin </li></ul></ul><ul><ul><ul><li>Helps regulate calcium homeostatsis </li></ul></ul></ul>
    7. 7. Clinical Presentations Bradycardia Habitual abortion / sterility Impotence Anorexia Heat intolerance Diaphoresis Increased appetite Incidental Goiter Unexplained weight gain Constipation Myxedema Memory loss / impairment Tremor Muscle weakness & fatigue Dyspnea Dependant edema Impaired mentation (confusion) Later Depression & loss of concentration Dry skin (Pruritis) Cold intolerance Myalgias Somnolence & fatigue Menorrhagia Goiter Nervousness / Irritability Palpitations (tachycardia) Unexplained weight loss Diarrhea Sleep disturbances (insomnia) Vision changes (exopthalmos) Amenorrhea / oligomenorrhia Initial HYPOTHYROID HYPERTHYROID TYPE of S/S
    8. 8. Thyroid Drugs <ul><li>Generic Thyroid Drug Names </li></ul><ul><li>Levothyroxine /L- thyroxine | Liothyronine | Liotrix | Methimazole | Propylthiouracil / PTU | Natural Thyroid | Thyrotropin alfa </li></ul><ul><li>Thyroid Drugs Brand Names Armour Thyroid | Cytomel | Levothroid | Levoxyl | Naturethroid | Synthroid | Tapazole | Thyrogen | Thyrolar | Unithroid | Westhroid </li></ul>
    9. 9. Levothyroxine <ul><li>Brand names in the U.S : Synthroid , Levothroid , Levoxyl , Unithroid Brand names in Canada : Synthroid , Eltroxin, and PMS-Levothyroxine Brand names outside U.S .: Euthyrox, Thyroxine, Berlthyrox, Droxine, Eferox, Elthyrone, Eltroxin, Eutirox, Letrox, Levaxin, Levotirox, Levothyrox, Levotiroxina, Oroxine, T4KP, Thevier, Throxinique, Thyradin, Thyradin S, Thyrax, Thyrax Duotab, Thyrex, Thyro-4, Thyrosit, Thyroxin, Thyroxin-Natrium, Tiroidine </li></ul><ul><li>Description </li></ul><ul><li>Levothyroxine is the generic name for the synthetic form of thyroxine, a thyroid hormone replacement drug. </li></ul>
    10. 10. Hypothyroidism: Causes <ul><li>Primary (most common) </li></ul><ul><ul><li>Hashimoto’s thyroiditis - autoimmune </li></ul></ul><ul><li>Treatment-related (2 nd most common) </li></ul><ul><ul><li>Radioactive iodine Tx or surgery for hyperthyoidism </li></ul></ul><ul><li>Iodine deficiency </li></ul><ul><ul><li>Endemic goiter </li></ul></ul><ul><ul><li>Endemic cretinism: most common cause of congenital hypothyroidism in deficient areas </li></ul></ul><ul><ul><li>Major cause of mental deficiency worldwide </li></ul></ul><ul><li>Rare inherited enzyme deficiencies </li></ul><ul><li>Secondary </li></ul><ul><ul><li>Failure of H-P axis d/t deficient TRH or TSH secretion </li></ul></ul>
    11. 11. Hypothyroidism: Classified by the organ of origin <ul><li>Primary hypothyroidism ( thyroid gland ) The most common forms include Hashimoto's thyroiditis (an autoimmune disease) and radioiodine therapy for hyperthyroidism . </li></ul><ul><li>Secondary hypothyroidism ( pituitary gland ) Occurs if the pituitary gland does not create enough thyroid stimulating hormone (TSH) to induce the thyroid gland to create a sufficient quantity of thyroxine . </li></ul><ul><li>Although not every case of secondary hypothyroidism has a clear-cut cause, it is usually caused when the pituitary is damaged by a tumor, radiation, or surgery so that it is no longer able to instruct the thyroid to make enough hormone </li></ul><ul><li>Tertiary hypothyroidism , also called hypothalamic-pituitary-axis hypothyroidism ( hypothalamus ) Results when the hypothalamus fails to instruct the pituitary to produce sufficient TSH. </li></ul>
    12. 12. Thyroid Supplements Thyrogen Thyrotropin Dx Tool for Thyroid Ca Tapazole Methimazole Various generic Propylthiouracil (PTU) Thyroid Suppressants Thyrolar, Euthroid Liotrix (T 4 : T 3 = 4:1) Cytomel, Triostat Liothyronine (synthetic T 3 ) Synthroid, Levothroid, Levo-T Levothyroxin sodium (synthetic T 4 ) Thyroid Supplements TRADE GENERIC CLASS
    13. 13. Thyroid Hormones: Indications <ul><li>Primary, secondary or tertiary hypothyroidism </li></ul><ul><li>Replacement therapy </li></ul><ul><li>Pituitary TSH suppression </li></ul><ul><ul><li>Euthyroid goiters </li></ul></ul><ul><ul><li>Nodular thyroid </li></ul></ul><ul><ul><li>Thyroid cancer </li></ul></ul><ul><li>NOT recommended as treatment for </li></ul><ul><ul><li>Transient thyroiditis </li></ul></ul><ul><ul><li>Obesity (unlabelled use – neither safe nor effective) </li></ul></ul><ul><ul><li>Fertility </li></ul></ul>
    14. 14. Thyroid Hormones: Action <ul><li>Increased: </li></ul><ul><ul><li>Basal metabolic rate </li></ul></ul><ul><ul><li>Oxygen consumption </li></ul></ul><ul><ul><li>Respiratory rate </li></ul></ul><ul><ul><li>Body temperature </li></ul></ul><ul><ul><li>Cardiac output </li></ul></ul><ul><ul><li>Heart rate </li></ul></ul><ul><ul><li>Blood volume </li></ul></ul><ul><ul><li>Rate of fat, protein, and CHO metabolism </li></ul></ul><ul><ul><li>Enzyme system activity </li></ul></ul><ul><ul><li>Growth & maturation </li></ul></ul><ul><ul><li>CNS development in children </li></ul></ul>
    15. 15. Myxedema
    16. 16. Pharmacokinetics: Supplements Biliary / Renal 99% T3: 3-5 days T4: 1-3 wk T3: 2-3 days T4: 6-7 days T3: 24-72 hr T4: 1-3 wk T3: 12-36 hr T4: ? Variable in GI but T3 > T4 Liotrix Biliary / Renal 99% PO: 3-5 days 2-3 days PO: 24-72 hr PO: 12-36 hr Complete in GI (95% in 4 hr) Liothyro-nine Biliary 99% (T4>T3) PO: 1-3 wk IV: ? 6-7 days PO: 1-3 wk IV: 24 hr PO: ? IV: 6-8 hr Variable in GI (50-80%) Levothy-roxine METABOLISM PROTEIN- BINDING DURA TION ½-LIFE PEAK ONSET ABSOR-PTION DRUG
    17. 17. Thyroid Hormones: Tx Principles <ul><li>Critical decisions with initial dose & dose changes </li></ul><ul><li>Individualized treatment </li></ul><ul><li>Careful laboratory monitoring for management </li></ul><ul><li>Start at low dose and  Q 4-6 wks until nL TSH </li></ul><ul><ul><li>Initial T4: 25-75 mcg </li></ul></ul><ul><ul><li>Maintenance T4: 75-150 mcg </li></ul></ul><ul><li>Single dose before breakfast </li></ul><ul><li>T4 </li></ul><ul><ul><li>Treatment of choice </li></ul></ul><ul><ul><li>Slow onset & cumulative effects </li></ul></ul><ul><li>T3 </li></ul><ul><ul><li>Rapid onset & dissipation </li></ul></ul><ul><ul><li>May be preferable for rapid correction of hypothyroidism </li></ul></ul>
    18. 18. Thyroid Hormones & Geriatrics <ul><li>Hypothyroidism common </li></ul><ul><li>May exacerbate CV disease </li></ul><ul><li>At risk for angina with initiation of thyroid hormone </li></ul><ul><ul><li>Start low and gradually increase dosage </li></ul></ul><ul><li>Absorption may be increased with aging </li></ul><ul><ul><li>Dosage adjustments may be required </li></ul></ul>
    19. 19. Thyroid Hormones & Pediatrics <ul><li>Critical for normal growth & development, esp. CNS </li></ul><ul><ul><li>Undiagnosed  Cretinism </li></ul></ul><ul><li>Screening for at-risk neonates (T4 & TSH) </li></ul><ul><li>Require higher doses to meet metabolic demands for growth & development in first 3 years of life </li></ul>
    20. 20. Thyroid Hormones: Contraindications <ul><li>Untreated thyrotoxicosis </li></ul><ul><li>Uncorrected adrenal insufficiency  will precipitate crisis </li></ul><ul><li>Hypersensitivity </li></ul>
    21. 21. Thyroid Hormones: Cautions <ul><li>Aggravation of known cardiac disease </li></ul><ul><li>Manifestation of occult cardiac disease </li></ul><ul><ul><li>Start with low dose & administer cautiously in high-risk patients </li></ul></ul><ul><li>Aggravation of diabetes mellitus & diabetes insipidus </li></ul>
    22. 22. Thyroid Hormones: Adverse Effects Weight loss Heat intolerance Weight loss Heat intolerance Weight loss Heat intolerance Metabolic Diarrhea, Abdominal cramps, N / V Diarrhea, Abdominal cramps, N / V Diarrhea, Abdominal cramps, N / V GI Irregular menses Hyperglycemia Hypocholesterolemia Irregular menses Hyperglycemia Hypocholesterolemia Irregular menses Endocrine Diaphoresis Alopecia (children) Diaphoresis Diaphoresis, Alopecia (children) Derm Irritability, Nervousness, Insomnia Nervousness, Headache, Insomnia Irritability, Nervousness, Insomnia CNS Tachycardia, Arrhythmias, Angina Angina, Arrhythmias, Palpitations Tachycardia, Arrhythmias, Angina CV LIOTRIX LEVOTHYROXINE LIOTHYRONINE SYSTEM
    23. 23. Thyroid Hormones: Drug Interactions <ul><li>Oral anticoagulants </li></ul><ul><ul><li> effect r/t vitamin K metabolism </li></ul></ul><ul><li>Cholestyramine (Questran) & colestipol (Colestid) </li></ul><ul><ul><li> absorption of thyroxine </li></ul></ul><ul><li>Androgens & estrogens </li></ul><ul><ul><li> protein-binding &  effectiveness of medication </li></ul></ul><ul><li>Insulin & oral hypoglycemics </li></ul><ul><ul><li>Become less effective & dosage adjustments may be needed to maintain BG levels </li></ul></ul><ul><li>B-blockers & digitalis </li></ul><ul><ul><li>Less effective as hypothyroidism improves </li></ul></ul>
    24. 24. Thyroid Hormones: Overdosage <ul><li>Toxicity: </li></ul><ul><ul><li>S/S of hyperthyroidism; may mimic thyrotoxicosis (hyperthyroidism, Graves' disease) </li></ul></ul><ul><li>Decrease or temporarily D/C Tx for 5-7 days, then resume at lower dose </li></ul>
    25. 25. Thyroid Hormones: Monitoring Therapy <ul><li>Measure TSH in 4-6 weeks </li></ul><ul><li>4-6 weeks for full therapeutic effectiveness </li></ul><ul><li>Monitor TSH monthly until normal & stable </li></ul><ul><li>Annual evaluation once maintenance therapy achieved </li></ul><ul><li>Evaluate levels if s/s of over/under-dosage </li></ul><ul><li>Maintain children < 3 on upper level of T4 therapeutic range and normal TSH </li></ul><ul><ul><li>Laboratory assessment: < 1 Year: Q 1-2 months Age 1-3: Q 2-3 months > 3 Years: Q 3-12 months </li></ul></ul>
    26. 26. Thyroid Hormones: Monitoring Therapy cont’d <ul><li>Response NOT immediate. Sx improvement in 2 wks. </li></ul><ul><li>Lifelong Tx – importance of compliance </li></ul><ul><li>Do NOT alter or abruptly stop dose </li></ul><ul><li>Do NOT alter brand </li></ul><ul><ul><li>Great variability in bioequivalence b/w manufacturers </li></ul></ul><ul><li>Take at same time every day </li></ul><ul><ul><li>Before breakfast on an empty stomach to  absorption </li></ul></ul><ul><ul><li>Later  difficulty falling asleep </li></ul></ul><ul><li>Report s/s of over/under-dosage </li></ul>
    27. 27. Hyperthyroidism: Causes <ul><li>Graves’ disease (diffuse toxic goiter) </li></ul><ul><ul><li>Autoimmune </li></ul></ul><ul><li>Toxic nodular goiter </li></ul><ul><ul><li>Hyperfunctioning multinodular goiter </li></ul></ul><ul><li>Thyroiditis </li></ul><ul><ul><li>Transient hyperthyroidism </li></ul></ul><ul><li>Iodine-induced hyperthyroidism </li></ul><ul><ul><li>Iatrogenic </li></ul></ul>
    28. 28. Thyroid Suppressants: Indications <ul><li>Hyperthyroidism </li></ul><ul><ul><li>Long-term use for disease remission </li></ul></ul><ul><ul><li>If surgery contraindicated </li></ul></ul><ul><ul><li>Prior to surgery (subtotal thyroidectomy) or radiation (radioactive iodine) </li></ul></ul><ul><li>Unlabelled use for PTU </li></ul><ul><ul><li>Alcoholic liver disease to  hypermetabolic state </li></ul></ul><ul><li>Control of thyroid overproduction </li></ul><ul><ul><li>~ ½  permanent remission; ~ ½  become hypothyroid </li></ul></ul><ul><ul><li>Sx improvement in 1-2 weeks; euthyroid in 4-8 weeks </li></ul></ul><ul><ul><li>Should be euthyroid prior to surgery </li></ul></ul>
    29. 29. Thyroid Suppressants: Action <ul><li>Reduce absorption of iodine  decreased hormone synthesis </li></ul><ul><li>Do NOT inhibit stored or circulating levels of T 3 or T 4 </li></ul><ul><li>Do NOT affect oral or parenteral thyroid supplements </li></ul><ul><li>Normal synthesis resumes rapidly with cessation of Tx </li></ul><ul><li>PTU: </li></ul><ul><ul><li>Inhibits conversion of T 4 to T 3 </li></ul></ul><ul><li>Methimazole: </li></ul><ul><ul><li>Longer acting  less frequent dosing </li></ul></ul>
    30. 30. Pharmacokinetics: Suppressants Hepatic Hepatic METABOLISM Renal 80% Weeks 1-2 hr 6-10 wk 10-21 days Rapid Good in GI Propyl- thiouracil Renal Min Weeks 5-6 hr 4-10 wk 1 wk Rapid Good in GI Methima-zole (Tapazol) EXCRETION PROTEIN - BINDING DURA- TION ½-LIFE PEAK ONSET ABSORPTION DRUG
    31. 31. Thyroid Suppressants: Tx Principles <ul><li>Dose titrated to achieve max response with min dose </li></ul><ul><li>Tx maintained 12-24 months </li></ul><ul><li>Once euthyroid x 6-12 months, dosage reduced to determine remission </li></ul><ul><li>If remission  D/C Tx </li></ul><ul><li>Consultation at initiation of Tx & remission determination </li></ul><ul><li>B-blockers (propranolol) for s/s of hyperthyroidism r/t sensitization of SNS) </li></ul>
    32. 32. Thyroid Suppressants: Geriatric & Pediatric Considerations <ul><li>Geriatric </li></ul><ul><ul><li>Hypothyroidism more common than hyper </li></ul></ul><ul><ul><li>May have atypical presentation - often atrial fibrillation is presenting symptom </li></ul></ul><ul><li>Pediatric </li></ul><ul><ul><li>PTU hepatotoxicity  D/C if s/s of liver dysfunction </li></ul></ul><ul><li>Pregnancy & Lactation </li></ul><ul><ul><li>Category D ( There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks ). </li></ul></ul><ul><ul><li>Can cross placenta & induce goiter or cretinism </li></ul></ul><ul><ul><li>Should NOT be given while breastfeeding </li></ul></ul><ul><ul><li>PTU drug of choice if needed - followed by endocrinologist </li></ul></ul>
    33. 33. Thyroid Suppressants: Contraindications & Cautions <ul><li>Contraindications </li></ul><ul><ul><li>Hypersensitivity </li></ul></ul><ul><li>Cautions </li></ul><ul><ul><li>AGRANULOCYTOSIS !!! </li></ul></ul><ul><ul><li>Also:leukopenia, thrombocytopenia, & aplastic anemia </li></ul></ul><ul><ul><li>Monitor bone marrow function </li></ul></ul><ul><ul><li>D/C if: agranulocytosis, aplastic anemia, hepatitis, fever, exfoliative dermatitis </li></ul></ul><ul><ul><li>Use with caution in: age > 40, other agranulocytosis-precipitating medications </li></ul></ul><ul><ul><li>Carcinogenesis in laboratory animals Tx > 1 year </li></ul></ul>
    34. 34. Thyroid Suppressants: Adverse Effects Arthralgia Arthralgia Musculoskeletal Agranulocytosis Aplastic anemia Leukopenia Thrombocytopenia Hypoprothrombinemia Agranulocytosis Aplastic anemia Leukopenia Thrombocytopenia Hypoprothrombinemia Hematologic N/V, Hepatitis (maybe FATAL!) Diarrhea, Diminished taste N/V, Hepatitis (maybe FATAL!) GI Rash, Urticaria, Skin Discoloration Rash, Urticaria, Pruritis Derm Headache, Drowsiness, Vertigo Paresthesia, Headache, Vertigo CNS PTU METHIMAZOLE (Tapazole) SYSTEM
    35. 35. Thyroid Suppressants: Overdosage <ul><li>S/S: nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritis, edema, pancytopenia, & agranulocytosis </li></ul><ul><li>Rare: exfoliative dermatitis, hepatitis, neuropathies, CNS stimulation or depression </li></ul><ul><li>Monitor: </li></ul><ul><ul><li>Airway & VS (may require resuscitation) </li></ul></ul><ul><ul><li>CBC, ABGs, lytes, bone marrow, PT, LFTs </li></ul></ul>
    36. 36. Thyroid Suppressants: Drug Interactions <ul><li>Oral anticoagulants </li></ul><ul><ul><li> effect r/t vitamin K metabolism </li></ul></ul><ul><li>Digoxin </li></ul><ul><ul><li>Levels may  with euthyroid </li></ul></ul><ul><li>I-131 </li></ul><ul><ul><li> thyroid uptake </li></ul></ul><ul><li>Amiodarone, iodine, potassium iodide, iodinated glycerol </li></ul><ul><ul><li>Decrease medication effectiveness </li></ul></ul>
    37. 37. Thyroid Suppressants: Monitoring Therapy <ul><li>Laboratory testing prior to initiating therapy & periodically until euthyroid (usu. 3-5 months) </li></ul><ul><ul><li>Serum T4 & T3 initially & after 2 weeks </li></ul></ul><ul><ul><li>Once euthryroid: elevated TSH  need lower dose </li></ul></ul><ul><li>Monitor WBC with differential </li></ul><ul><ul><li>Before initiating Tx & any s/s of infection </li></ul></ul><ul><li>Monitor PT </li></ul><ul><ul><li>Esp. before surgical procedures </li></ul></ul><ul><li>Monitor for hepatotoxicity </li></ul><ul><ul><li>LFTs: AST, ALT, alkaline phosphatase, LDH, bilirubin, PT </li></ul></ul><ul><li>Resolution of hypermetabolic state </li></ul><ul><ul><li> Pulse, BP, weight, nervousness/tremor </li></ul></ul><ul><li>Evaluate for: hepatitis, agranulocytosis, GI irritation </li></ul>
    38. 38. Thyroid Suppressants: Patient Education <ul><li>Require routine monitoring </li></ul><ul><li>Medication exactly as prescribed </li></ul><ul><ul><li>Regular schedule & evenly spaced </li></ul></ul><ul><li>Discuss other medications with provider before using </li></ul><ul><li>Avoid foods/substances containing iodine </li></ul><ul><li>Promptly notify provider of any s/s of illness </li></ul><ul><ul><li>Fever, sore throat, malaise, bleeding/bruising, headache, skin rash, lymph node enlargement </li></ul></ul><ul><li>Adequate rest & diet; avoid stress </li></ul>
    39. 39. Thyrotropin (Thyrogen) <ul><li>Indications </li></ul><ul><ul><li>Post-surgical evaluation for remnant thyroid tissue </li></ul></ul><ul><ul><li>Thyroid cancer recurrence or metastases </li></ul></ul><ul><ul><li>Used in conjunction w/ or w/o radioiodine imaging </li></ul></ul><ul><li>Mechanism of Action </li></ul><ul><ul><li>Enhances sensitivity of thyroglobulin testing </li></ul></ul><ul><ul><li>Avoids hypothyroid effects during radioimaging scans </li></ul></ul><ul><li>Adverse Effects </li></ul><ul><ul><li>Nausea, headache, mild hypersensitivity (rash/urticaria) </li></ul></ul>
    40. 40. Resources <ul><li>Avicenna </li></ul><ul><ul><li>www.avicenna.com </li></ul></ul><ul><li>Clinical Pharmacology </li></ul><ul><ul><li>www.cponline.gsm.com </li></ul></ul><ul><li>Drug database </li></ul><ul><ul><li>www.pharminfo.com/drugdb/db_mnu.html </li></ul></ul><ul><li>DoctorNet </li></ul><ul><ul><li>www.doctornet.com </li></ul></ul><ul><li>Health Finder </li></ul><ul><ul><li>www.healthfinder.org </li></ul></ul><ul><li>HealthGate </li></ul><ul><ul><li>www.healthgate.com </li></ul></ul>

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