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Microsoft powerpoint - 132 ritchie thyroid 6 25 12.pptx

• 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 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 • 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 related to hypothyroidism and hyperthyroidism. REGULATION OF THYROID GLAND Protein* binding + 0.03% free T4 Protein* binding + 0.3% free T3 Negative feedback * Thyroid hormone Binding: Transthyretin 15% -stored in thyroglobulin: 15:1 -secreted in blood: 10:1 Increased production due to any reason Leads to an increase in T3 Causes of Hypothyroidism:
Primary Hypothyroidism
Drugs That Cause Hypothyroidism Thyroid dysgenesisIodine deficiency • Cause Immune dysregulation-Interferon-alfa, Iatrogenic including radioiodine • Suppression of TSH-dopamine Hashimoto's thyroiditisReidel'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 antiseptics, Betadine douches Overt Primary 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 • 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 – 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 Subclinical Hypothyroidism • Prevalence of 3-8% • Prevalence increases with age, higher in • Medical texts and review articles are almost 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 (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. Alternative Medicine Review, Vol 9 (2); 157-179 Dong, BJ and et al. 1997, Bioequivalence of generic and brand-name levothyroxine Medications to Treat Hypothyroidism Levothyroxine (T4) • 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) Conditions That Will Increase Levoxyl Food Interactions Requirements (need to increase dose) • Drugs that may bind and decrease absorption of Levothyroxine from GI tract: • Oral Contraceptives-Estrogen therapy• Acute Porphyria -cotton seed meal • Chemotherapy: specifically 5 FU, Tamoxifen • Heroin/Methadone therapy • Clofibrate Therapy -caffeine (decreases 27-36%) • Dialysis Therapy• GI tract Altering Surgery (decreased absorption) Conditions That Increase T4 Drugs That Decrease T4 Absorption Absorption (Need to Lower Dose) (Need to Increase Dose) • Severe Liver Disease • Cation Exchange Resins: Kayexalate • Ferrous Sulfate • Severe hypoproteinemia • Androgen or corticosteroid therapy • Sucralfate• Antidepressants (Zoloft) • Familial hyper or hypo throxine binding • Furosamide (>80 mg/day) • Nicotinic acid therapy • Anti-inflammatory Drugs • Anti-seizure medications: Carbamazepine, Phenytoin, • Loss of Weight Phenobarbital, Rifampin • Glucocorticoids, androgens 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, 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 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 significant p = .02. Levothyroxine taken at HS -Total doses more than 300 mcg/day may be due to malabsorption or lack of compliance significantly improved thyroid hormone levels.
Bolk N et al. 2010.Effects of evening vs morning levothyroxine intake: a randomized double –blind crossover trial. Arch Intern Med. 170 (22): 1996-2003 Administration of Synthroid • 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 Infants with Congenital Dosing Guidelines • -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.
– 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 McDougall IR, Maclin. J Fam Pract. 1995 Sept; 41(3): 238-40/PMID- 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 • 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 • Overtreatment can have adverse cardiac effects: • Adrenal Insufficiency: should be treated with tachycardia, atrial fibrillation, precipitate replacement glucocorticoids prior to initation of Levoxyl. Failure to do so may precipitate an • Concommittent use with sympathomimetics may precipitate coronary insufficiency Adverse Reactions-Primarily Due to Adverse Reactions • General: fatigue, fever, sweating, increased • Dermatology: hair loss, flushing • Reproductive: impaired fertility, menstrual • CNS: headache, hyperactivity, anxiety, irritability, • Pseudotumor cerebri and slipped capital • Musculo-skeletal: tremors, weakness femoral epiphysis in children • Cardiovascular-heart palpitations, tachycardia, • Overtreatment in infants: craniosynostosis and heart failure, cardiac arrest, MI premature closure of epiphyses with • Respiratory-dyspnea compromised adult height • GI: diarrhea, vomiting, elevated liver enzymes • Seizures - rare Stevens-Johnson Syndrome related to • Case report 2009 per Cholongitas, etal- • Levothyroid contains Lactose and corn starch• Euthyrox contains corn starch, lactose, gelatin, – Stevens Johnson Syndrome in an adult related to magnesium stearate, croscarmellose over suppression of Levothyroxine • L-Thyroxin Henning contains corn starch, cellulose, silicon dioxide, ricinus oil, sodium thiosulfate • L-Thyroxin drops (Henning) contains propylene glycol, glycerol, sodium thiosulfate • Synthroid contains tartrazine (yellow dye) and • Synthroid/Levothyroxine 50 mcg tablet (white) contains no dyes. Cholongitas, etal. Dermatology Online Journal 15 (11): 16.2009 • Listen to your patients • Thyrolar/Liotrix• Combo pill of T3 and T4 • Ask how they feel on their thyroid replacement • Ratio of T4:T3 = 4:1 (not 15:1) (how tired are they? Quality of life?) • T3 still not slow release: actions maximum in 4-6 • Offer options if they don't feel well • Cost $22.50/Month • "High Riders" effect • Panicker, etal (2009)-gene in 16%United • Let Your Patients Be Active Participants in Their Kingdom-inability to convert T4 to T3-beneficial • Few small studies showing benefit • 1999 NEJM study 33 patients • Know what your patients are reading! • Benefit: mood & cognitive function Secure.medicalletter.org/TG-issue-84: PMID-2950057 (2010):Panicker, etal. J Clin Endocrinol Metab 2009; 94: 1623. • Derived from porcine thyroid glands • Used to lessen hypothyroid symptoms after thyroid cancer surgery prior to I131 scan • Combination of thyroxine, LT3 and iodine.
• Is a T3 substitute • Assess with TSh only on these patients • Dosage 10-25 mcg/day • 95 % is absorbed in 4 hours: cost $3.00/mth • Half-life is 1.5 days: begins acting in 2-4 hours • Dose 15-180 mg/day. 100 mcg T4=60mg Armour • Not recommended for replacement therapy • Similar drug interactions to Levothyroxine • Systematic review of literature 2005 (Archive): no benefit to symptoms to use combined with • Radio of T3:T4 is 1: 4.22 • L4 is preferred for replacement therapy • One new study looked at giving 3x daily Wiersinga, W.European Society of Endocrinology.October, Escobar-Morreale J, et al. 2005. Treatment of Hypothryoidism with combinations of 36Levothyroxine plus Liothyronine. Archive 90 (8); 4946-4961.
• Results from excessive amounts of thyroid Grave's disease ( 80%) Thyrotoxicosis factitiaToxic multinodular goiter • -Prevalence of 1.2%: most common causes Toxic adenomaThyroiditis Hyperemesis gravidarumStruma ovarii • Toxic multinodular goiter• Toxic adenoma• Graves' Disease Drugs That Cause Hyperthyroidism • Stimulation of thyroid hormone synthesis: • An autoimmune disease with a male to female iodine, amiodarone ratio of about 3.5:1. • specific manifestations include – ophthalmopathy • Immunedysregulation-Interferon-alfa, – pretibial myxedema Interleukin-2, Denileukin diftitox, Ipilimumab, • TSH is suppressed, Free T4 is elevated and specific Thyroid antibodies are elevated Uptodate per literature review of Drug Interactions with Thyroid ATA/AACE Guidelines-May, 2011 Thionamide drugs• propylthiouracil and methimazole• inhibit thyroid hormone synthesis• Side effects include agranulocytosis • Recommendations: and hepatic dysfunction – Beta-adrenergic blockage should be given in elderly pts with thyrotoxicosis and to other thyrotoxic patients with resting heart rates in excess of 90 bpm or coexistent Metoprolol, Propanolol cardiovascular disease Radioiodine Therapy – Beta –adrenergic blockade should be considered in all • Most commonly used treatment in the USA patients with symptomatic thyrotoxicosis.
• May lead to hypothyroidism – In patients who are not candidates (bronchospastic • "Radiation thyroiditis" is uncommon asthma): may give calcium channel blockers (Verapamil • May exacerbate Grave's opthalmopathy – Patients with Graves Disease who have free T4 levels more than 2-3 x normal and worsening s/s: should be treated • Reserved for patients who refuse other options • Have nodules suspicious for cancer with beta blockade PRIOR to radioactive iodine therapy AACE Guidelines, 2011 Beta Blockers / Hyperthyroidism Beta Blockers for Hyperthyroidism • Decrease symptoms of increased adrenergic -dose of 10-40 mg tid/qid tone (tremors , palpitations, sweating) -preferred agent if pregnant • Indications for use: palpitations, tachycardia -may block T4 to T3 at high doses • Inpatients-Use Propanolol tid or qid – Dose of 25-100 mg qd or bid– Increased compliance • Outpatients-Use Atenolol or Metoprolol: more beta-1 selective with longer duration of action – -40-160 mg qd • May require 2x usual dose to control – Least experience with to date symptoms: taper off as hyperthyroidism – Use only with IV pump 50 -100 ug/kg/min in thyroid storm in intensive care Hyperthyroidism Management Guidelines, Endocr Pract.2011; 17 (No 3) Methimazole-Adverse Side Effects • Indications: hyperthyroidism • Chance of side effects is 5%.
• Rapidly absorbed by GI tract: half life of 5-13 hours: duration of action 40 hours • Agranulocytosis: s/s sore throat/fever: • Mechanism of Action: inhibits the addition of iodine to neutropenia. Perform cbc: treat with thyroglobulin by the enzyme thyroperoxidase, a necessary recombinant human granulocyte colony step in the synthesis of triiodothyronine (T3) and thyroxine(T4). Its acts at CXCL10. NOT PROTEIN BOUND: does not • Other side effects: inhibit T4 to T3.
• Dosage-starting doses 10-40 mg daily: maintenance dose is – Skin rash, itching (most common) 5-15 mg / day. Easy to dose 1x day – Upset stomach, vomiting, loss of taste • AACE Recommendation 13-should be used in every patient – Abnormal hair loss who chooses antithyroid drug therapy for Graves, except during first trimester of pregnancy when PTU is preferred. – Joint and muscle pain Methimazole-Side Effects ATA/AACE Recommendation 14: 15 • Abnormal sensations (tingling, prickling, burning, • 14-Patients should be informed to contact provider IMMEDIATELY and stop their medication • Joint and muscle pain – Pruritic rash -pharyngitis -dark urine – Abdominal pain • Aplasia cutis congenita (prenatal exposure) with • 15-Prior to initiating antithyroid drug therapy for choanal and esophageal atresia Graves, patients need to have: • Stevens-Johnson syndrome – Complete CBC with differential • Cholestatic Jaundice – Liver profile including bilirubin and transaminases ATA/AACE Recommendations 16, 17, Methimazole Drug Interactions • 16-obtain CBC with differential in all patients with • Increases the Effect of: pharyngitis and febrile illness on antithyroid – Beta Blockers • 17-obtain liver functions tests on patients with PTU who have rash, jauntice, dark urine, joint – Diabetes Medications pain, abdominal pain or bloating, anorexia, nausea, or fatigue • 19-if Methimazole is the primary therapy for Graves Disease, use for 12-18 months, then taper off or DC if TSh is normal. Patient Education • Methimazole is preferred over PTU : • Let the provider know if you plan pregnancy – Can be given 1x daily, efficacious at low doses, and or become pregnant on this medication major adverse reactions are rare (<5%) • Call for sore throat, tiredness, fever – Prospective trial in Japan (n=240) treatment with • Be aware of risk of Stevens-Johnson Syndrome Methimazole 30 mg/day more effective at normalizing FT4 levels than PTU 300 mg /day or • Do not take this medication if pregnant Methimazole 15mg/day) • Let your provider know if you are going to PMID-196362287: Nakamura, etal: J Clin Endocrinol Metab 2007; 92; PTU: Drug Interactions • Pharmacokinetics: • Anticoagulants-increases effects of – Absorbed by GI tract • Beta –Blockers-increases effects of – Eliminated by kidney (35%) • Digoxin-increases effects of – Acts by inhibiting synthesis of thyroid hormones • Theophylline-increases effects of – Comes in 50 mg tablets • Corticosteroids-decreases effects of Dosage: 300 mg/day in 3 equal doses every 8 hours Not Recommended for Children due to liver damage PTU Adverse Drug Reactions • Agranulocytosis-usually in 1st 3 months of • Class D in pregnant: positive evidence of fetal therapy. C/o sore throat, fever, GI problems. Decreased wbc along with thrombocytopenia which may lead to severe bleeding • Preferred over methimazole only in 1st • Severe liver failure, necrosis and death trimester and in woman who may become (documented in children). Can occur anytime during therapy pregnant (in 2nd and 3rd trimester- • Generally well-tolerated: 1/100 will have side Methimazole preferred) effects of joint aches, heartburn, N &V • Incidence of fetal goiter is 12% • ANCA-positive vasculitis syndrome including renal failure, periarteritis, drug fever Methimazole/PTU Patient Education Treatment with PTU or Methimazole • Do not double dose this drug if you forget it • Clinical resolution of thyrotoxicosis begins after 2 weeks of treatment: biochemical resolution between 4-8 weeks of treatment • Do not flush down toilet-dispose of per • Check FT4, total T3, and TSH at 4-6 week intervals until levels stabilize • Call immediately for GI symptoms or sore • TSH may remain suppressed for several months after FT4 levels have normalized.
• Call immediately if you think you are pregnant • Persistent elevation of total T3 with normal • Always keep up away from children FT4 requires an increase in dose Treatment with Thionamides Iodine Treatment for Hyperthyroidism • Patients with Graves'-may achieve remission with 12- • Mechanism of Action: inhibit thyroid hormone 18 months of thionamide therapy alone, but only 1/3 release from gland achieve lasting remission • Recurrence rate of Graves is 50-60%-if recurs, • Highly useful in patients with severe radioactive iodine is the recommended tx.
thyrotoxicosis, thyroid storm • AACE guideline #20-Measurement of TRAb levels prior • Beneficial effects occur immediately so useful in to stopping antithyroid drug therapy is suggested- thyroid storm but may last only a few weeks normal levels indicate greater chance for remission (TSH receptor antibodies) • CONTRAINDICATED IN PREGNANCY • In toxic nodular hyperthyroidism-radioactive therapy or • Found to decrease blood flow in thyroid in surgery should be the first-line therapy (high studies (Erbil et al. 2007).
recurrence rate with thionamides) Erbil, Y et al. 2007. Effect of Lugol Solution on Thyroid Gland Blood Flow and Microvessel Density in the Patients with Graves Disease. Archieve 92 (6): 2182-2189.
Adverse Reactions Treatment With Iodines – Contains 38 mg Iodine per drop of solution • Iodism – metallic taste, sore throat, – Dose is 1-3 drops tid rhinorrhea, sore gums, diarrhea • Should NOT be used in pregnancy • Lugol's Solution • May make hyperthyroidism worse in nodular – Contains 6mg Iodine per drop of solution goiter-start only after thionamide has been – Dose: 5 drops tid given in these patients Radioactive Iodine (RAI-131) • Given as oral pill or liquid • Slow onset and long time until peak effect- biochemical euthyroid state may not occur • Releases beta particles, causing a slow until 2-6 months after therapy inflammatory process that destroys the • Majority of pts will become hypothyroid 4-12 thyroid over a period of weeks to months months after therapy • Radiation thyroiditis-occurs in first two weeks: Convenience, low cost, widely available, – Causes low anterior neck pain and release of pre- and high efficacy formed thyroid hormone from the gland-causing thyrotoxicosis • Some studies show a slight increase in thyroid cancer and thyroid cancer mortality in patients – Thionamides are treatment of choice: both drugs with nodule thyroid disease treated with RAI-131 cross placenta: risks involved (12%) vs Graves (Metso, etal) – PTU may be preferable due to Methimazole (can • A large study in England found small increase in cause asplasia cutis, choanal and esophageal cardiovascular mortality compared to general population (Franklyn, etal) • Some studies have recommended holding – Radioactive Iodine is Contraindicated thionamides for 5-7 days before RAI-131 (Walter, etal, 2007) PMID-19636287: Franklyn et al. Jama 2005. Metso, etalJ Clin Endocrinol • 85 yo male with TSH of 9.5, free T4 normal • 22 yo female presents with TSH of 5.4, free T4 • Meds: Digoxin, Nitroglycerin, Coumadin low, TPO antibodies elevated • PMH: CHF, atrial fibrillation • No symptoms of hypothyroidism: "maybe falling out of hair". • No symptoms of hypothyroidism • Meds: Prilosec, Multivitamins, BCP • Do you treat her with Levothyroxine? • Do You Treat Him With Levothyroxine? • What dose do you start her at? • When do you recheck her TSH? • One of your patients calls you and she just • 59 yo male with head/neck cancer presents found out she's pregnant! for 6 week f/u. Had CT scan with prior visit – TSH of 0.22: free T4 0.33 • What TSH goal do you want her? • When do you check her TSH? Do you start him on betablockers or methimazole? When do you recheck his TSH? • 22 yo female presents with heart palpitations • T4 (Levothyroxine) is the drug of choice alone • TSH is 0.005, free T4 8.2, T3 elevated to treat hypothyroidism and thyroid cancer • Methimazole is the drug of choice to treat hyperthyroidism: PTU is the drug of choice in • What test do you do first? women wanting to get pregnant and in first trimester.
• What test do you do second (by AACE • AACE guidelines of 2011 make • What drug do you start her on first to get her recommendations specific to treatment of hyperthyroidism under control? • 1. Identification of side effects, interactions, dosages with hypothyroidism drugs • 2. Identification of side effects, interactions, dosages with hyperthyroidism drugs • 3.Identification of new AACE guidelines in management of hyperthyroidism • 4. Participation in discussion of case studies specific to patients with these problems.

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