Drugs Affecting Endocrine Sys W23 TN ST 2nd update.txt PDF

Drugs Affecting the Endocrine System Course Instructor: Tarek Nasr 1 Drugs Affecting the Endocrine System Diabetes Mellitus Hypothyroidism/Hyperthyroidism Adrenal gland disorders 2 Intro Homeostasis  Nervous system and endocrine system Nervous system  Neurotransmitters  short dist...

Drugs Affecting the Endocrine System Course Instructor: Tarek Nasr 1 Drugs Affecting the Endocrine System Diabetes Mellitus Hypothyroidism/Hyperthyroidism Adrenal gland disorders 2 Intro Homeostasis  Nervous system and endocrine system Nervous system  Neurotransmitters  short distances (synapses)  rapid effect Endocrine system  Hormones  long distances (all parts of the body)  slow and last long Endocrine system  Hypothalamus, pituitary gland, pineal gland, thyroid, parathyroid, thymus, pancreas, adrenal glands, testes, ovaries) 3 Management of DM 4 Insulin – Mechanism Kaul, K., Tarr, J., Ahmad, S., Kohner, E., & Chibber, R. (2013). Introduction to Diabetes Mellitus. Advances In Experimental Medicine And Biology, 1-11. http://dx.doi.org/10.1007/978-1-4614-5441-0_1 5 Insulin – Physiological Effects Insulin is a hormone essential for regulation of carbohydrates, fat, and protein metabolism Insulin, along with glucagon, is released by the pancreas in response to the rise and fall of blood glucose, amino acid, and gut-derived hormone (incretin) levels 6 Diabetes Mellitus (DM) DM is a chronic metabolic disorder characterized by hyperglycemia due to defective insulin secretion, defective insulin action (resistance) or both.  Absolute OR Relative lack of insulin +/- resistance to its action Symptoms: acute metabolic symptoms such as polyuria, polydipsia, weight loss. Sometimes, asymptomatic with incidental discovery through routine lab screening Complications: involve small blood vessels (microvascular) and large blood vessels (macrovascular) of multiple organs/systems, depression, constipation, vaginal infection, ED, and amputations? (poor wound healing  infections) Microvascular - neuropathy, nephropathy, or retinopathy Macrovascular - hypertension, angina, and myocardial infarction 7 Diabetes Mellitus Symptoms Asymptomatic: incidental discovery through routine lab test Non-specific symptoms: such as fatigue, blurred vision, slow healing of wounds Acute metabolic symptoms: such as polyuria, polydipsia, polyphagia, weight loss. 8 Diabetes Mellitus Symptoms 9 Diabetes Mellitus Types Type 1 diabetes mellitus (T1DM) or IDDM Type 2 diabetes mellitus (T2DM) or NIDDM Gestational diabetes mellitus (GDM) Secondary diabetes 10 Diabetes Mellitus Types Type 1 diabetes mellitus (T1DM) or IDDM (autoimmune, 5–10%) Autoimmune ß-cell destruction  Absolute insulin deficiency Acute metabolic symptoms (polyurea, polydipsia, polyphagia) of relatively short duration in a child, adolescent or young adult Equally among males and females, but more in whites than in non-whites. Type 2 diabetes mellitus (T2DM) or NIDDM (insulin resistance & relative deficiency, genetic, common, 90% of DM) o Risk factors: age, obesity, lack of physical activity, diabetes family history, smoking, certain diseases and prior GDM. Non-modifiable & modifiable? 11 T2DM Risk Factors 12 Diabetes Mellitus Types Gestational diabetes mellitus (GDM) first onset or recognition of glucose intolerance during pregnancy in 2nd or 3rd trimester Possibly due to pregnancy hormones or by lack of insulin Symptoms disappear after delivery; 20%-50% increased risk for T2DM within 5-10 years. Secondary diabetes: o Diseases: pancreatitis, hormones hypersecretion (e.g., growth hormone, thyroid hormone, cortisol, adrenaline) o Drugs: corticosteroids, thiazide or loop diuretics, OCS, β blockers, 2nd gen antipsychotics (e.g., olanzapine, quetiapine, risperidone), immunosuppressive agents (e.g., tacrolimus) 13 Diabetes Mellitus Genetic Age Sedentary life Obesity Pancreas produce more insulin Insulin resistance Normal blood glucose Impaired glucose tolerance (pre-diabetes) NIDDM β cells failure Ramlo-Halsted BA, Edelman SV. The natural history of type 2 diabetes. Implications for clinical practice. Prim Care 1999;26:771-89. 14 Genetic Glucotoxicity High FFA level Diabetes Mellitus Diagnosis Random plasma glucose ≥11.1 mmol/L Random = any time of day regardless of interval since last meal Fasting plasma glucose (FPG) ≥7 mmol/L Fasting = no caloric intake for ≥8 h 2-Hour OGTT (Oral glucose tolerance test) ≥11.1 mmol/L A test done 2 hours after a 75 g oral glucose load HbA1c ≥6.5% (in adults) Gives info of blood glucose level over a 2 to 3-month period Prediabetes: FPG 6.1 – 6.9 mmol/L OR 2-hour OGTT: 7.8 – 11 mmol/L 15 Diabetes Mellitus – Non-Pharm Non-pharmacological measures: Education Diet Exercise Blood glucose monitoring Periodic Reassessment - Ongoing monitoring of other organ systems Mansell K, Arnason T. Diabetes Mellitus. In: Compendium of Therapeutic Choices. 7th ed. Ottawa: Canadian Pharmacists Association; 2014:369-410. 16 Diabetes Mellitus – Non-Pharm Education: Patient Self-Management Education Diet: Nutritional management (dietician, foods with low glycemic index, CHO intake & insulin dosing linked, CHO count  ↓ wt. & improve BG) Exercise: Reduces mortality, better BG control, enhance insulin sensitivity,↓ BP, ↓ wt., and ↓ lipids. Aerobic exercise totaling ≥150 minutes per week is recommended Blood glucose monitoring: Self-monitoring of blood glucose (SMBG) Flash glucose monitoring (FGM) Continuous glucose monitoring (CGM) HbA1c q 6 months (q 3 months if target values not met) Periodic Reassessment: BP measurements, HbA1c, foot and eye examination, cardiovascular, and albumin in urine Mansell K, Arnason T. Diabetes Mellitus. In: Compendium of Therapeutic Choices. 7th ed. Ottawa: Canadian Pharmacists Association; 2014:369-410. 17 Diabetes Mellitus – Non-Pharm Patient Self-Management Education Basic understanding of diabetes Role of diet, exercise and medications How & When to self-monitor blood glucose & interpret results Management of sick days Recognition and treatment of hypoglycemia Care of the feet Awareness of heart-health & importance of risk-factor control, including body weight and smoking cessation Awareness of appropriate follow-up to other organs (e.g., eyes, kidneys) that may be affected by diabetes 18 Diabetes Mellitus – Non-Pharm Diet: Nutritional management (dietician, foods with low glycemic index, CHO intake & insulin dosing linked, CHO count  ↓ wt. & improve BG) The GI (glycemic Index) is a scale out of 100. Ranks carbohydrate-containing food or drink by how much it raises your blood sugar levels after eating or drinking. Low GI (55 or less) e.g., whole-grain bread, parboiled rice, fruits such as apple, banana, pear Medium GI (56-69) e.g., white or whole-wheat pita/roti bread, basmati rice, fruits such as ripe banana, cherries, grapes High GI (70 or more) e.g., white, whole-wheat bread or nan, fruits such as banana (brown, overripe), watermelon Read Glycemic Index Food Guide PDF (SLATE) Source: https://www.diabetes.ca/en-CA/managing-my-diabetes/tools---resources/the-glycemic-index-(gi) 19 Diabetes Mellitus – Non-Pharm Blood glucose monitoring: 1) Allows recognition of hypoglycemia 2) Provides immediate feedback about effects of meds Self-monitoring of blood glucose (SMBG) - Conventional blood glucose test strips + Glucometers (e.g., One Touch®) Flash glucose monitoring (FGM) e.g., FreeStyle Libre Continuous glucose monitoring (CGM) e.g., FreeStyle Libre2 / Dexcom G6 SMBG involves capillary blood glucose testing via a finger prick FGM and CGM measure glucose in interstitial fluid via an attached sensor/device that is replaced every 10 or 14 days. SMBG, FGM and CGM are particularly important in patients using insulin. Min 3 testing/day for those on basal-bolus insulin HbA1c q 6 months (q 3 months if target values not met) Mansell K, Arnason T. Diabetes Mellitus. In: Compendium of Therapeutic Choices. 7th ed. Ottawa: Canadian Pharmacists Association; 2014:369-410. 20 Treatment of Diabetes Mellitus Classes of Hypoglycemic Drugs Injectable Insulin preparations Incretin mimetics (injection) Oral Biguanides Sulfonylurea DPP-4 inhibitors SGLT2 Inhibitors Meglitinides Thiazolidinediones (TDZ) α- glucosidase inhibitors Incretin mimetic (oral) 21 Injectable Drugs for DM 22 Insulin type Trade names Rapid-acting Insulin Analogue (clear) (RAIAs) (bolus insulin) Insulin Lispro: Humalog®, Admelog® and Humalog U200® Insulin Aspart: NovoRapid®, Trurapia® and Fiasp® Insulin Glulisine: Apidra® Adv.: Flexible dosing, good for irregular eater, better postprandial control, Humalog U200 allows smaller volume Fast-acting - Fiasp® Regular or Short-acting insulin Insulin Zinc (Humulin-R®) and Insulin human (Novolin® ge (clear) Toronto) 20–30 minutes before meals or short (bolus insulin) Insulin (Entuzity U500) Intermediate-acting (cloudy) (basal insulin) Insulin NPH: Humulin® N, Novolin® ge NPH Inject regardless of meals Long-acting Analogue (basal insulin) (clear) (LAIAs) (basal insulin) Insulin glargine: Lantus®, Basaglar®, and Toujeo® 300 U/mL Insulin detemir: Levemir® Ultra long-acting Analogue (clear) (basal insulin) Insulin Degludec: (Tresiba®). Duration is 42 hours with NO PEAK. Available in U100 and U200 (200 U/mL is non-standard strength – caution) Premixed (cloudy) (basalbolus insulin) Many (rapid or regular + intermediate): e.g., Humalog 30/70 23 24 Insulin may be administered by syringe, pen or continuous subcutaneous insulin infusion (CSII or insulin pump) Insulin – Notes Storage Production Forms Route of administration Devices 25 Insulin – Notes Aids in metabolism of carbohydrates, fats, and proteins Used to treat all types of diabetes T1DM: Is the only drug administered T2DM: May be added to oral drugs or replace oral drugs Originally from animal sources (pig and cow). Now, produced using recombinant DNA technology from bacteria or yeast to match human insulin (insulin analogues). In Canada, pork insulin NPH (Hypurin NPH) can only be obtained through the Special Access program from UK. 26 Insulin – Notes Insulin is a protein so it cannot be taken orally (digestion in the stomach acid) Administered SC. Regular insulin may also be administered IV Dosage delivery systems: Vials, cartridges, prefilled disposable pens, pump LAIAs and ultra long-acting analogues: (insulin detemir, glargine and degludec) appear to produce more predictable effects than intermediate-acting human insulin (NPH) and are associated with fewer episodes of hypoglycemia, particularly nocturnal hypoglycemia (i.e., lower risk for nighttime hypoglycemia when compared with NPH insulin) 27 Insulin – Dose Timing Rapid-acting: Inject 10-15 minutes before, during, or up to 20 minutes after starting meal Fiasp® is faster acting insulin - Inject 2 minutes before, during, or 20 minutes after meals. Regular or Short-acting: inject 30 minutes before meals NPH: Inject routinely regardless of the meal (QD or BID) Long and Ultra Long-acting: Inject routinely regardless of the meal once daily (HS) Premixed: inject with meals depending on the bolus ingredient 28 Insulin – Storage Most products: opened vials, cartridges, and pens: Discard opened packs after 4 weeks Levemir® / Toujeo®: Discard opened packs after 6 weeks Tresiba®: Discard opened packs after 8 weeks 29 30 Insulin – Adverse Reactions Hypoglycemia: Weight gain Localized fat hypertrophy (lipohypertrophy) Allergic reaction Immune-mediated production of insulin antibodies Lasbury, M. (2013). As Many Exceptions As Rules: The Skinny On Fat. iologicalexceptions.blogspot.ca. Retrieved 10 September 2016, from http://biologicalexceptions.blogspot.ca/2013/12/the-skinny-on-fat.html 31 Hypoglycemia Most common AE esp. with patients aiming for a tight blood sugar control Major concern: unaware, asymptomatic, occurs at night, masked by drugs Risk factors/Reasons: Missing a meal/ Eating later than usual/ Eating less than usual High dose of antidiabetic drug or Drug-Drug interactions ↑ activity Stress Long time diabetes Food insecurity/ being on welfare Neuropathy Inability to identify: Dementia, children and young adults Low health literacy Clayton D, Woo V, Yale J.F. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Hypoglycemia. Can J Diabetes 2013;37(suppl 1):S69-S71 32 Hypoglycemia Frequent hypoglycemic events may lead to reduced autonomic symptoms (hypoglycemia unawareness) Symptoms: Mild to moderate hypoglycemia: sweating, tremors, tachycardia, hunger, nausea and fatigue. Severe hypoglycemia: confusion, altered behavior, difficulty speaking, and disorientation  Seizures & coma Three Criteria: Patient develops symptoms BG < 4 mmol/L (if on insulin secretagogue tabs or insulin) Responds to oral glucose Considered severe if BG < 2.8, unconscious, and/or need others to assist in administering glucose 33 Hypoglycemia Signs and symptoms Hoskins, M. (2013). The Big Hypo Chill: National Diabetes Month 2013 DSMA. Healthline. Retrieved 10 September 2016, from http://www.healthline.com/diabetesmine/the-big-diabetes-chill-strikes-first-diabetes-month-2013-dsma#2 34 Hypoglycemia Clayton D, Woo V, Yale J.F. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Hypoglycemia. Can J Diabetes 2013;37(suppl 1):S69-S71 35 Hypoglycemia - Management Mild-moderate hypoglycemia: 15 g of oral sugar (6 life savers, 3 glucose tabs/candies or teaspoonful table sugar, ½ cup fruit juice, ½ cup regular soda pop, 15 mL honey, or syrup. NO Chocolate / NO Sugar gel  raise blood glucose approx. 2 mmol/L within 20 minutes. Severe hypoglycemia: If conscious: 20 g oral sugar should be used, preferably as glucose tablets or equivalent. Glucose gel not preferred? Must be swallowed + very slow response If unconscious/cannot eat/no response to oral sugar/ seizures  Glucagon GLUCAGEN HYPOKIT / BAQSIMI Once conscious, patients should consume a fast-acting sugar followed by food ASAP Hospitalized  IV dextrose or glucagon Clayton D, Woo V, Yale J.F. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Hypoglycemia. Can J Diabetes 2013;37(suppl 1):S69-S71 36 Hypoglycemia - Management If unconscious/cannot eat/no response to oral sugar/ seizures  Glucagon GLUCAGEN HYPOKIT / BAQSIMI (nasal) 37 https://www.baqsimi.com/how-to-use-baqsimi Insulin – Role of P. Tech. Appropriate storage Identify the concerning pattern of use/monitoring Patient education 38 Incretin Mimetics 39 What are the Incretin Hormones? ONLY for T2DM (responsible for 50 – 70% of postprandial insulin release) Pratley, R. (2008). T2DM: Glucagon-like Peptide-1 Analogs and Dipeptidyl Peptidase-4 Inhibitors. Medscape. Retrieved 10 September 2016, from http://www.medscape.com/viewarticle/578051_3 40 Incretin Mimetics (injections) Mechanism: GLP-1 receptor agonist Indication: Add-on to metformin, SU and/or BASAL insulin Drug in Canada: Ozempic® (semaglutide), Trulicity® (dulaglutide), Byetta® (exenatide), Victoza® (liraglutide), and Adlyxine® (lixisenatide) 41 Incretin Mimetics (SC injections) Mechanism: GLP-1 receptor agonist Indication: Add-on to metformin, SU and/or BASAL insulin Drugs in Canada: Ozempic® (semaglutide), Trulicity® (dulaglutide), Victoza® (liraglutide), Byetta® (exenatide), and Adlyxine® (lixisenatide) Dosing: SC injection Ozempic® (semaglutide), 0.25mg/0.5mg pen and 1 mg pen: once weekly – Starting dose 0.25mg. Taper up to 0.5mg or 1 mg for glycemic control. Why? Trulicity® (dulaglutide), single-use prefilled pen 0.75 mg, 1.5 mg, 3mg and 4.5mg once weekly – Starting dose 0.75 mg may increase to 1.5 mg or 3mg once weekly for more glycemic control 42 Incretin Mimetics (SC injections) Victoza® (liraglutide), 6 mg/mL Initial: 0.6 mg once daily for at least one week. Increase to 1.2–1.8 mg once daily SC Byetta® (exenatide): 5 mcg BID SC increased to 10 mcg BID SC after 1 month if required Adlyxine® (lixisenatide): Initial: 0.01 mg once daily SC for 14 days, then increase to 0.02 mg once daily SC 43 Incretin Mimetics (oral) Mechanism: GLP-1 receptor agonist Indication: Add-on to metformin, SU and/or BASAL insulin Drug in Canada: semaglutide (Rybelsus®) is the first oral glucagonlike peptide 1 (GLP-1) receptor agonist 3 mg, 7 mg and 14 mg tablets Starting dose of RYBELSUS® is 3 mg qd for 30 days, then increased to a maintenance dose of 7 mg qd. If additional glycemic control is needed after at least 30 days on the 7 mg dose, the dose can be increased to a maintenance dose of 14 mg qd Why tapering up? 44 Incretin Mimetics Adverse Effects: Nausea and vomiting (most common), hypoglycemia, weight loss (sometimes too fast), arrhythmia, pancreatitis May reduce rate of absorption of some oral medications - Why? Contraindication: in pregnancy and those with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Storage - injections: fridge. Once opened, room temp for 4 weeks EXCEPT dulaglutide for 2 weeks and 8 weeks for semaglutide Storage – Reyblsus: Room temp. 45 Oral Antidiabetic Agents 46 Oral Anti-diabetic Agents Biguanide metformin (Glucphage®, Glumetza®) Sulfonylureas gliclazide (Diamicron®, Diamicron MR®) glimepiride (Amaryl®), glyburide (Diabeta®) Meglitinides repaglinide (Gluconorm®) Glitazones pioglitazone (Actos®), rosiglitazone (Avandia®) α-glucosidase inhibitor acarbose (Glucobay®) DPP-4 Inhibitors saxagliptin (Onglyza®), sitagliptin (Januvia®), linagliptin (Trajenta®), alogliptin (Nesina®) SGLT2 inhibitors canagliflozin (invokana®), dapagliflozin (Forxiga®), and empagliflozin (Jardiance®) Combinations Komboglyze®, Invokamet®, and Janumet® 47 Metformin Mechanisms of action: ↑ sensitivity of liver, muscle, and fat cells to insulin and ↓ hepatic glucose production. First line agent in NIDDM Preferred agent to be used with insulin Dose: 500mg to max. of 2g/day divided BID – QID Glumetza ER® is dosed once daily (no other adv.) No hypoglycemia ↓ body wt. Non-diabetic benefits??? 48 Metformin Who should not take it: Type I DM, patients with kidney/ liver dysfunction, and history of lactic acidosis Adverse reaction: GI (most bothersome N/V, diarrhea, metallic taste, flatulence). Start low, go slow/Take with food Rare but serious ADR: Lactic acidosis Auxiliary label??? Precaution in women with polycystic ovary 49 Sulfonylurea Mechanisms of action: insulin secretagogue  ↑ both prandial and basal insulin release. Who should not take SU: Patients allergic to sulfa, Type 1 DM, liver/kidney impairment and thyroid impairment Generally, should be taken with food. Synergistic effect with metformin If used as 1st agent, they can worsen glycemic control Gliclazide MR: used once daily. Take with food and require regular food intake Treatment failure is common Sulfonylureas gliclazide (Diamicron®, Diamicron MR®) glimepiride (Amaryl®), glyburide (Diabeta®) 50 Sulfonylurea Adverse reactions: o Weight gain (all patients) o Hypoglycemia o Photosensitivity o GI (nausea, vomiting, taste alteration and teeth discoloration, abdominal pain, diarrhea) o Skin: urticaria and eruption (D/C if persists) Drug Interactions: o Alcohol?? o With enzyme inducers and inhibitors 51 Meglitinides Mechanisms of action: insulin secretagogue. Increases only postprandial insulin release. Take only with meals (within 15 minutes) Missing meal? Flexibility Take 1 month for full effect May cause hypoglycemia but less than SU Adverse reactions: N/V, diarrhea, visual disturbance, hepatic abnormality 52 Thiazolidinediones (Glitazones) Mechanisms of action: ↑ sensitivity of target tissue to insulin and ↓ hepatic glucose production Prevent diabetes in high-risk patients +/- food Delayed onset 6 – 12 wks Not approved for use with insulin because of ↑ edema Not recommended in patients with CHF No hypoglycemia Glitazones pioglitazone (Actos®), rosiglitazone (Avandia®) 53 Thiazolidinediones (Glitazones) Adverse effects: Edema Weight gain ↓ BMD – Recommendation? Rosiglitazone: ↑ risk of MI (Patient must sign a consent) Macular edema Pioglitazone ↑ the risk of bladder cancer Resume ovulation in females with PCOS 54 Acarbose Mechanisms of action: Inhibits alpha glucosidase enzymes  slow CHO digestion after meals  ↓ postprandial glucose. Take with first bite of the meal No hypoglycemia (What if hypoglycemia develops?) No weight gain Reduce the progression of diabetes Start low and go slow Adverse reaction: No systemic toxicity GI: most bothersome. flatulence, diarrhea, nausea, vomiting Hepatitis and jaundice 55 Gliptins (DPP-4 inhibitors) Dipeptidyl peptidase-4 inhibitors = DPP-4 inhibitors Dipeptidyl peptidase-4 inhibitor. (2016). Wikipedia. Retrieved 12 September 2016, from https://en.wikipedia.org/wiki/Dipeptidyl_peptidase-4_inhibitor 56 Gliptins (DPP-4 inhibitors) Used alone or in combination with metformin All of them used once daily +/- food Do not cause hypoglycemia Weight neutral Adverse reactions: Generally well tolerated, but may cause: UTI, URTI, nasopharyngitis Anemia, hepatitis and headache DPP-4 Inhibitors saxagliptin (Onglyza®), sitagliptin (Januvia®), linagliptin (Trajenta®), alogliptin (Nesina®) 57 SGLT2 Inhibitors Sodium-glucose co-transporter 2 inhibitor Chao, E. & Henry, R. (2010). SGLT2 inhibition — a novel strategy for diabetes treatment. Nature Reviews Drug Discovery, 9(7), 551-559. http://dx.doi.org/10.1038/nrd3180 58 SGLT2 Inhibitors Used as only drug (if cannot take metformin) or as add on Effect needs good kidney function They should not be used with diuretics Usually given once daily with the 1st meal SGLT2 inhibitors canagliflozin (invokana®), dapagliflozin (Forxiga®), and empagliflozin (Jardiance®) 59 SGLT2 Inhibitors Adverse Reactions CVS: hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration. ↑the risk of stroke and MI in the 1st 30 days of treatment Electrolytes: ↑ K+, P+3, Mg+2, and ↓ Ca+2 ↑ LDL Weight loss UTI and vaginal infection ↑ urination (frequency and volume) 60 Treatment of Thyroid Disorders 72 Thyroid gland Regulation of metabolism and calcium homeostasis Tetraiodothyronine (T4 or thyroxine) / Triiodothyronine (T3) Affect almost all body cells. Iodine is important for synthesis Levels controlled by negative feedback loop  TRH  TSH T3 is about 4 X more potent than T4 T4 is converted to T3 by deiodination. Calcitonin  calcium homeostasis controls Ca+2 levels by increasing bone formation by osteoblasts and inhibiting bone breakdown by osteoclasts (lowers blood calcium level) 73 Treatment of Thyroid Disorders Synthesis of the thyroid hormone Brown, R. (1999). Synthesis and Secretion of Thyroid Hormones. Arbl.cvmbs.colostate.edu. Retrieved 13 September 2016, from http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/synthesis.html Iodine is selectively taken up by thyroid gland in the process of synthesizing T4 & T3 Thyroid gland dysfunctions Hypothyroidism Hyperthyroidism http://www.vivo.colostate.edu/hbooks/pathphys/endocrine /thyroid/synthesis.html 74 Thyroid gland Overactivity or underactivity of the thyroid gland Hyperthyroidism or hypothyroidism Thyroid disease is 8 X more in women than men Diagnosis: TSH levels / Free T4 (FT4) Low TSH level  Hyperthyroidism. Why? High TSH level  Hypothyroidism. Why? Low FT4  ?? High Ft4  ?? Diagnosis: Thyroid antibody test  Autoimmune thyroid disease Diagnosis: Radioactive iodine uptake (RAIU) test low dose radioactive iodine (131I)  High? Low? 75 Thyroid Hormones Regulate metabolism/metabolic rate: Intolerance to cold or heat weight loss or weight gain Slow down/speed up heart rate Raise/lower body temperature Slow down/speed up GI movement 76 HYPOthyroidism Underactivity of the thyroid gland Causes: Hashimoto thyroiditis (autoimmune, most common cause) Medications for (e.g., lithium, amiodarone) Surgical removal of thyroid Iodine deficiency (rare in NA) Pituitary or hypothalamus disorder Symptoms Myxedema coma (emergency): severe hypothyroidism  hypotension & ↓ consciousness level TTT: levothyroxine IV + steroids IV 77 HYPOthyroidism Thyroid replacement therapy Levothyroxine (T4): Synthroid®, Eltroxin® Liothyronine (T3): Cytomel® - more potent Desiccated thyroid 78 HYPOthyroidism Levothyroxine Replacement therapy with levothyroxine (L-T4)  TTT of choice T4 analogue - Mimics endogenous thyroxin – tablets color-coded Two brand names in Canada Eltroxin® and Synthroid® Do not change brands if possible Preferably administered on empty stomach (food delays absorption) before breakfast Monitor the response by checking TSH Higher dose in pregnancy Can be abused for?? 79 HYPOthyroidism Levothyroxine Adverse reactions Symptoms of hyperthyroidism?? May exacerbate angina Long term use may cause OP in PM women Drug interactions Absorption ↓ by iron, calcium, and cholestyramine (separate intake by 6 hours) High protein binding, can affect many drugs (warfarin) May affect response to anti-diabetic agents Cold remedies?? 80 HYPERthyroidism Excess production of thyroid hormone Thyrotoxicosis = excessive thyroid hormone and its effects Causes: Graves disease (autoimmune) Nodules Cancer Others 81 HYPERthyroidism Non-pharm: Surgery Anti-thyroid drugs Thioamides: 2 agents available in Canada - ↓ production of thyroid hormones Methimazole (MMI) (Tapazole®) Propylthiouracil (PTU) (Propyl-Thyracil®) 131 Radioactive iodine I Iodine preparation: Oral Lugol’s solution 100 mg/mL Beta blockers 82 HYPERthyroidism Thioamides Mechanism of action: inhibit thyroid peroxidase  inhibit the synthesis of T4 and T3 Blocks the conversion of T4 to T3 in periphery. Sulfa sensitivity Adverse reactions: Hypothyroidism symptoms??? Patient must stop treatment if develop rash, fever, or sore throat (may indicate a rare but potentially fatal agranulocytosis (