Update on Thyroid Medications Objectives Objectives Disclosures
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8/17/2012 Objectives • 1. Identify specific actions, side effects, drug interactions, and specifics in patient education Update On Thyroid Medications in drugs to treat hypothyroidism. • 2.Identify specific actions, side effects, drug interactions, and specifics in patient education By in drugs utilized to treat hyperthyroidism. Debbie Ritchie, RN FNP, GNP, BC • 3. Identify new updates in treatment of September 7, 2012 hyperthyroidism per AACE 1 2 Objectives Disclosures • 4. Analyze case study presentations and • I have no real or perceived conflicts of interest participate in open discussions as to decision that relate to this presentation or any off label making related to drugs utilized in treatment use. related to hypothyroidism and hyperthyroidism. 3 4 REGULATION OF THYROID GLAND Thyroid Function hypothalamus T4 Protein* binding + 0.03% free T4 TRH 80% (peripheral) Thyrotropin-releasing hormone T3 20% Protein* binding + 0.3% free T3 Negative feedback * Thyroid hormone Binding: pituitary TBG 75% TSH Ratio of T4:T3 Transthyretin 15% -stored in thyroglobulin: 15:1 Albumin 10% T3 and T4 Thyroid-stimulating hormone -secreted in blood: 10:1 Increased production due to any reason Leads to an increase in T3 1 8/17/2012 Causes of Hypothyroidism : Primary Hypothyroidism Drugs That Cause Hypothyroidism Congenital: Thyroid dysgenesis Iodine deficiency • Cause Immune dysregulation-Interferon-alfa, Acquired Iatrogenic including radioiodine Interleukin-2 and surgery Suppression of TSH-dopamine Hashimoto’s thyroiditis • Reidel’s thyroiditis • Destructive thyroiditis-Sunitinub Infiltrative diseases (amyloidosis) • Inhibition of thyroid hormone synthesis or Central Hypothyroidism release: iodine containing drugs including Pituitary lesions ( secondary hypothyroidism) radiographic agents, expectorants (Combid, Hypothalamic lesions( tertiary Organidin), kelp tablets, SSKI, topical hypothyroidism) antiseptics, Betadine douches 8 Overt Primary Hypothyroidism Subclinical Hypothyroidism • Prevalence is 3.8-4.6 % : higher in women (4/1000) • Defined as being present when TSH is above the than per men (0.6/1000) upper limit of reference range (but less than • Most common cause-autoimmune thyroiditis 10mU/L) and free T4 levels are in normal range • Cause may be Iodine deficiency in underdeveloped and the patient is asymptomatic countries • 2 causes are transient: subacute thyroiditis; • Recommendations for treatment postpartum thyroiditis(75-85% will correct) – f/u closely with repeat TSH in 6 months (AACE • Current debate to lower TSH goal levels to .4 – 2.5 guidelines, 2002). No consensus on management (versus 4.2mC/L) – Treat if more than 10mU/L (some studies) • Diagnosis must be made chemically: symptoms in only – Treat with Levothyroxine if symptomatic, positive TPO 2-24%. TSH above 4.2 mC/L currently, low free T4, low antibodies T3. 9 10 Subclinical Hypothyroidism Hypothyroidism • Prevalence of 3-8% • Prevalence increases with age, higher in • Medical texts and review articles are almost women unanimous in recommending Levothyroxine (T4) as the only appropriate treatment for • Growing evidence that SCH is associated with hypothyroidism (Gaby, A., Alternative lipid abnormalities, increasing cardiovascular Medicine Review,Vol 9, No. 2, 2004) risk. Controversy over who if normal tsh levels • Generic and Brand Name are bioequivalent by need to be lowered from 4.2 mU/L to 2.5 current Food and Drug Administration criteria mU/L (JAMA, 1997; 277: 1205-1213) ISRN Endocrinol. 2011: 810251. Pubmed. Ertugrul, et al. Gaby A. 2004, Sub-laboratory Hypothyroidism and the Empirical Use of Armour Thyroid. 11 Alternative Medicine Review, Vol 9 (2); 157-179 12 Dong, BJ and et al. 1997, Bioequivalence of generic and brand -name levothyroxine 2 8/17/2012 Medications to Treat Hypothyroidism Levothyroxine (T4) • Names: • Synthetically made; Cost around $4.80/Month Synthroid, Tsynthroid, Levoxyl, Levotabs, Levo- • 50 mcg white pill no dye (hypoallergenic) T, Unithroid, Evotrox, L-thyroxine • No T3 (but 80% of T3 comes from T4 conversion) All patients made euthyroid biochemically • Used in hypothyroidism and pituitary TSH • • Most (but not all) patients feel normal suppression (hashimoto’s, euthryoid goiters, • Metabolized by liver, excreted by kidney: 80% absorbed well-differentiated thyroid cancer) by small intestine; • Half life is 7 days • Has synthetic Levothyroxine T4 sodiums • Average replacement dose is 1.7 mcg/kg per day in identical to that produced by human thyroid. adults (dose is higher in children and infants) 13 Conditions That Will Increase Levoxyl Food Interactions Requirements (need to increase dose) • Drugs that may bind and decrease absorption of • Pregnancy Levothyroxine from GI tract: • Hepatitis -soybean formula • Oral Contraceptives-Estrogen therapy • Acute Porphyria -cotton seed meal • Chemotherapy: specifically 5 FU, Tamoxifen -walnuts • Heroin/Methadone therapy -dietary fiber • Clofibrate Therapy -caffeine (decreases 27-36%) • Dialysis Therapy -vitamins • GI tract Altering Surgery (decreased absorption) 15 16 Conditions That Increase T4 Drugs That Decrease T4 Absorption Absorption (Need to Lower Dose) (Need to Increase Dose) • Nephrosis • Calcium • Severe Liver Disease • Cation Exchange Resins: Kayexalate • Acromegaly • Ferrous Sulfate • Severe hypoproteinemia • Orlistat • Androgen or corticosteroid therapy • Sucralfate • Antidepressants (Zoloft) • Familial hyper or hypo throxine binding • Furosamide (>80 mg/day) globulinemias. • Heparin • Nicotinic acid therapy • Anti-inflammatory Drugs • Elderly • Anti-seizure medications: Carbamazepine, Phenytoin, • Loss of Weight Phenobarbital, Rifampin • Glucocorticoids, androgens 17 18 3 8/17/2012 Drugs that Levothyroxine Alters Administration of Synthroid • Coumadin-will decrease effectiveness of • Rules of Thumb: • Diabetic Medications-will decrease effectiveness -take 4 hours from Vitamins, Ferrous Sulfate, of Carafate, Antacids, Colestid, Questran • Digoxin-will decrease effectiveness of -take 2 hours from food, caffeine • Antidepressants-will increase receptor sensitivity -check tsh, free T4 level on a changed dose in 6-8 weeks leading to CNS stimulation (seizures) -know your drug interactions: know what goal level of TSH you are aiming for. • Katamines-can cause HTN, tachycardia -take on empty stomach: only with water • Beta blockers-may block their affects -may need to alter days/time if on dialysis, multiple meds. • Theophylline-may block the receptor site -MOST IMPORTANT-TAKE DAILY • Lithium 19 20 Literature Administration of Synthroid • Study by Bolk, etal 2010: pilot study showed that • Half life is 7 days: 4-6 weeks for therapeutic effect Levothyroxine intake at bedtime significantly • Dosing is critical decreased thryotropin levels and increased free thyroxine and total T3 levels. -infants-start at 10-15 mcg/kg/day -if at risk of cardiac problems-start at 25 mcg / day and increase by • Number: 90. Take medication in the morning x 3 25 mcg every 4-6 weeks months: switched to HS x 3 months. -children with severe hypothyroidism or chronic conditions: start at 25 mcg /day and increase 25 mcg/day every 2-4 weeks • Findings: decrease in TSH level of 1.25, increase -Elderly-start at 1.0 mcg/kg/day: monitor closely. Change dose every in total T3 and free T4 levels of .07. Both 4-6 weeks -Total doses more than 300 mcg/day may be due to malabsorption significant p = .02. Levothyroxine taken at HS or lack of compliance significantly improved thyroid hormone levels. Bolk N et al. 2010.Effects of evening vs morning levothyroxine intake: a randomized 21 22 double –blind crossover trial. Arch Intern Med. 170 (22): 1996-2003 nih.gov/pubmedhealth/PMH0000685 Administration of Synthroid Infant/Child • for infants/children-crush tablets and suspend in • Check TSH and free T4 at 2 weeks, 4 weeks water-use immediately: do not store as a suspension after initiating : then every 1-2 months for the • Dosing guidelines: first year, every 2-3 months age 1-3, then – 0-3 months-10-15 mcg/kg/day every 3-12 months until growth complete – 3-6 months-8-10 mcg/kg/day – 6-12 months-6-8 mcg/kg/day – 1-5 years-5-6 mcg/kg/day – 6-12 years-4-5 mcg/kg/day – >12 but puberty incomplete: 2-3 mcg/kg/day – Puberty complete-1.7 mcg/kg/day 23 24 http://secure.medicalletter.org/TG-issue-84 : 4 8/17/2012 Infants with Congenital Dosing Guidelines Hypothyroidism • -Pregnancy: requires increased requirements • Beware of anomalies: pulmonary stenosis, – Check levels every trimester and again 6-8 weeks postpartum. Keep TSH close to 1 – 1.5. atrial defects – No known increased risk of congenital anomalies • Maintain total or free T4 in upper half of but hypothyroidism in pregnancy complications normal: TSH may not normalize due to include spontaneous abortion, pre-eclampsia, resetting of pituitary thyroid feedback stillbirth and premature delivery – Thyroid hormones cross the placental barrier, but threshold as a result of in utero may not be adequate to prevent in utero hypothyroidism hypothyroidism 25 McDougall IR, Maclin. J Fam Pract. 1995 Sept; 41(3): 238-40/PMID- 26 19636287: ATA guidelines, 2011 Patients with Heart Disease Patients with Endocrine Disorders • Can increase risk of occult cardiac disease so • Hypothalmic/pituitary hormone deficiences: initiate at lower doses : 25 mcg every 4 weeks: other hormone deficiences need to be treated check TSH at 4-6 weeks as well • If symptoms develop, lower or withhold dose for • DM: may require increased dosage of diabetic 1 week and then start back at lower dose slowly meds • Overtreatment