Thyroid Hormones(12 13

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  • 1. DR. UMA K. Thyroid Hormones & Drugs BY DR.UMA KADAM M.B.B.S. MD ASSOCIATE PROFESSOR PHARMACOLOGY SKNMC
  • 2. A 29 YO female complains of restlessness and increasing anxiety. HR 135 bmp, PE: Tremors. Palpation on the neck reveals a 3cm nodule on her thyroid gland. Laboratory test are sent to confirm the diagnosis. In the meantime, with drug could be given to acutely reduce her physical symptoms?
    • Propylthiouracil.
    • Furosemide.
    • Prednisone.
    • Iodine.
    • Propanolol.
    DR. UMA K.
  • 3. Hormones and Your Health
    • What Is a Hormone?
    • Which Ones Especially Affect Women?
    • What Can Go Wrong?
    • Thyroid Disease - a “Hidden” Problem
    • for Women
    • Staying Healthy
    DR. UMA K.
  • 4. What Are Hormones?
    • Chemicals That Are Released
    • Into the Bloodstream
    • Regulators of Specific Body Functions
    DR. UMA K.
  • 5. Hormones of Special Interest to Women Thyroxine (T4) Thyronine (T3) Progesterone Estrogen
  • 6. DR. UMA K.
  • 7. Thyroid Disease The “Hidden” Health Problem DR. UMA K.
  • 8. Who do you know with thyroid disease? DR. UMA K.
  • 9. What Does Your Thyroid Gland Do for You?
    • Produces Three Hormones Called
      • Calcitonin, important in calcium homeostasis.
      • Thyroxine (T4)
      • Thyronine (T3), important in growth and metabolic function
    • Regulates Metabolism so Your Cells Function Properly
    • Affects Every Cell in the Body
    DR. UMA K.
  • 10. Thyroid Hormones
    • lodide is necessary for thyroid hormone synthesis.
    • Iodide is obtained from the diet and is absorbed from the gastrointestinal tract.
    • Once in the gland iodide is oxidized to an active iodine intermediate, which iodinates tyrosine residues of thyroglobulin.
    • An aerobic condensation of iodinated tyrosine molecules results in production of T3 and T4.
    DR. UMA K.
  • 11. Synthesis & release of thyroid hormones: DR. UMA K.
  • 12. Pharmacokinetics: Thyroid Hormones
    • 99% of T3 and T4 are bound to plasma proteins (TBG: thyroid-binding globulin).
    • They are excreted in the bile and urine.
    • T4 has a half-life of 6-7 days; T3 has a half-life of 1-2 days.
    • Some of the circulating T4 is deiodinated to T3, the more potent and rapidly acting form.
    DR. UMA K.
  • 13. DR. UMA K.
  • 14. Regulation of thyroid hormones: (Negative Feedback Loop) DR. UMA K.
  • 15. Thyroid Hormones
    • T4 and T3 are iodine-containing hormones that are analogs of tyrosine.
    • Regulated by TSH, which increases the Synthesis and secretion of these hormones.
    • TSH secretion is regulated by negative feed-back of the thyroid hormones; it is positively influenced by TRH from the hypothalamus.
    DR. UMA K.
  • 16. DR. UMA K. Thyroid hormones: Mechanism of action
  • 17. Thyroid Hormones: Mechanism of action
    • Activation of nuclear nonhistone protein receptors attached to DNA.
    • Binding leads to increased transcription of messenger RNA (mRNA).
    • Increasing the synthesis of specific proteins. (T3 x 10 potent).
    • Cell membranes receptors: increase amino acid and glucose uptake.
    • Inner mitochondrial membrane receptors: regulate energy metabolism.
    DR. UMA K.
  • 18. Thyroid Hormone Affects Many Organs and General Health DR. UMA K. Thyroid Uterus Heart Liver Kidney Brain Skin GI Tract Lungs Eyes
  • 19. Thyroid Hormones
    • Effects in most major systems, including normal growth and development.
    • Increased basal metabolic rate and activation of oxygen consumption.
    • Thermogenic effect (increased heat production).
    • Increased plasma glucose and free fatty acids, reduction in plasma cholesterol and triglycerides.
    • Increased HR, maturation of the CNS.
    DR. UMA K.
  • 20. When the Thyroid Doesn’t Work DR. UMA K.
    • Hyperthyroidism
    • Too Much Thyroid Hormone
    • Metabolism Speeds Up
    • Hypothyroidism
    • Too Little Thyroid Hormone
    • Metabolism Slows Down
  • 21. Thyroid Disease Affects Many Body Systems and Overall Health DR. UMA K.
    • Thyroid Disease Can Have Widespread Effects
    Thyroid
    • Increased LDL Cholesterol
    • Elevated Triglycerides
    Liver
    • Constipation
    • Decreased GI Activity
    Intestines
    • Decreased Fertility
    • Menstrual Abnormalities
    • May Harm Development of Infant
    Reproductive System
    • Depression
    • Decreased Concentration
    • General Lack of Interest
    Brain
    • Decreased Heart Rate
    • Increased/Decreased Blood Pressure
    • Decreased Cardiac Output
    Heart
    • Decreased Function
    • Fluid Retention and Edema
    Kidneys
  • 22. Thyroid drugs DR. UMA K.
  • 23. Thyroid Drugs
    • Replacement therapy.
    • Treatment for hypothyroidism.
    • Suppress TSH secretion.
    • Levo isomers are more potent in increasing basal metabolic rate.
    • Once absorbed, their pharmacokinetic and dynamic properties are identical to endogenous thyroid hormones.
    DR. UMA K.
  • 24. Thyroid Drugs
    • Adverse reactions :
    • Hyperthyroidism (or symptoms of hyperthyroidism).
    • Cardiovascular toxicity (tachyarrhythmias, angina, and infarction)
    • CNS stimulation, insomnia.
    DR. UMA K.
  • 25. Hypothyroidism: The Hidden Health Problem Affects Up to 25 Million People But Approximately 12 Million Are Undiagnosed
  • 26. Hypothyroidism Affects Multiple Body Systems Central Nervous System Female Reproductive System Cardiovascular System Hypothyroidism Can Cause Serious Harm to Your Health
  • 27. Signs and Symptoms of Hypothyroidism DR. UMA K. Tiredness Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair or Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Cold Intolerance Elevated Cholesterol Muscle Weakness or Cramps Constipation Infertility Menstrual Irregularities/ Heavy Period Slower Heartbeat Difficulty Swallowing Persistent Dry or Sore Throat Hoarseness/ Deepening of Voice Swelling (Goiter) Puffy Eyes
  • 28. Common Signs and Symptoms of Hypothyroidism
    • Tiredness
    • Loss of Interest and/or Pleasure
    • Forgetfulness
    • Dry, Coarse Hair
    • Loss of Lateral Eyebrow Hair
    • Puffy Face and Eyes
    • Goiter
    • Slow Heartbeat
    • Dry Skin
    • Cold Intolerance
    • Weight Gain
    • Heavy Menstrual Periods
    • Constipation
    • Brittle Nails
    DR. UMA K. May Include:
  • 29. Hypothyroidism: The “Hidden” Disease Cardiovascular: Slow Heartbeat Elevated Cholesterol Aging: Dry, Scaly Skin Sparse or Coarse Hair Gynecological: Irregular Menstruation Infertility Gastrointestinal: Constipation Weight Gain Muscular: Muscle Weakness Stiffness Ear, Nose & Throat: Hoarse Voice Psychiatric: Impaired Concentration Depression Lethargy, Fatigue Blood: Anemia
  • 30. How to Remember the Signs and Symptoms of Hypothyroidism
    • S leepiness, Fatigue, Lethargy
    • L oss of Memory, Trouble Concentrating
    • U nusually Dry, Coarse Skin
    • G oiter (Enlarged Thyroid)
    • G radual Personality Change, Depression
    • I ncrease in Weight, Bloating or Puffiness (Edema)
    • S ensitivity to Cold
    • H air Loss, Sparseness of Hair
    DR. UMA K.
  • 31. DR. UMA K. Hypothyroidism After Before
  • 32. Levothyroxine
    • Synthetic levo isomer of T4.
    • PO and IV available.
    • Preferred drug for hypothyroidism.
    • Better standardization and stability and long duration.
    • Long half-life of T4.
    • Facilitates maintenance of a steady physiologic replacement.
    DR. UMA K.
  • 33. Liothyronine
    • Synthetic L-T3.
    • More difficult to monitor than T4.
    • More expensive.
    • Shorter duration of action.
    • Treatment of choice for Myxedema coma.
    DR. UMA K.
  • 34. Liotrix
    • Combination of Levothyroxine and Liothyronine.
    • Ratio of 4:1.
    • No advantage over Levothyroxine.
    DR. UMA K.
  • 35. Antithyroid Drugs DR. UMA K.
  • 36. Antithyroid Drugs
    • Inhibit the formation of thyroid hormones.
    • Used in the treatment of hyperthyroidism.
    DR. UMA K.
  • 37. DR. UMA K. Signs and Symptoms Of Hyperthyroidism Bulging Eyes/Unblinking Stare Menstrual Irregularities or Light Period Excessive Vomiting in Pregnancy First-Trimester Miscarriage Family History of Thyroid Disease or Diabetes Nervousness Irritability Difficulty Sleeping Swelling (Goiter) Frequent Bowel Movements Warm, Moist Palms Hoarseness or Deepening of Voice Difficulty Swallowing Rapid or Irregular Heartbeat Infertility Weight Loss Heat Intolerance Increased Sweating Persistent Sore or Dry Throat
  • 38. Common Signs and Symptoms of Hyperthyroidism
    • Nervousness
    • Irritability
    • Difficulty Sleeping
    • Bulging Eyes
    • Unblinking Stare
    • Goiter
    • Rapid Heartbeat
    • Increased Sweating
    • Heat Intolerance
    • Unexplained Weight Loss
    • Scant Menstrual Periods
    • Frequent Bowel Movements
    • Warm, Moist Palms
    • Fine Tremor of Fingers
    DR. UMA K. May Include:
  • 39. DR. UMA K. Hyperthyroidism Before After
  • 40. If You Have Hyperthyroidism, You’re in Good Company DR. UMA K. Barbara Bush 1984 Pre-treatment Barbara Bush 1991 Post-treatment
  • 41. lodide
    • Small amounts of iodine (75-100 ng/day) are required for hormone synthesis.
    • But high concentrations (+ 50 mg/day) produce autoinhibition.
    • lodide blocks the uptake of iodide, inhibiting synthesis and release of thyroid hormones.
    • Diminishes vascularity of the gland.
    DR. UMA K.
  • 42. lodide
    • Used only preoperatively to shrink the gland. (prior to surgical removal of the gland).
    • Treatment of thyroid storm.
    • It is given as Lugol's solution (iodine and potassium iodide).
    • Effects are visible within 24 hours. It is no longer used in long-term therapy.
    DR. UMA K.
  • 43. lodide
    • Adverse reactions:
    • Hypersensitivity reaction .
    • Drug fevers, metallic taste, bleeding disorders.
    • Gastric irritation.
    • Long-term use can lead to sudden disinhibition of hormone synthesis, producing acute hyperthyroidism.
    DR. UMA K.
  • 44. Thioamides
    • Propyithiouracil (PTU), methimazole.
    • Inhibit the peroxidase enzymes catalyzing the oxidation of iodide, thus reducing the synthesis of thyroid hormones.
    • PTU also inhibits the peripheral deiodination of T4 to T3.
    • Delay in onset (until preformed hormones have been metabolized).
    DR. UMA K.
  • 45. Thioamides
    • Used for control of hyperthyroidism until surgery.
    • Suppression of thyroid hormone synthesis until the effect of radioactive iodide begins.
    • Long-term therapy of mild-to-moderate hyperthyroidism.
    • The drugs are given PO.
    DR. UMA K.
  • 46. Thioamides
    • Adverse reactions.
    • Mild maculopapular rash, joint pain, headache, nausea, and loss of hair.
    • Rare: agranulocytosis.
    • Crosses the placenta and enter breast milk, which can lead to hypothyroidism in the fetus and nursing infant.
    • Pregnancy ?
    DR. UMA K.
  • 47. Radioactive iodine ( 131 I)
    • PO or IV.
    • Rapidly taken, then is incorporated into thyroglobulin.
    • Leads to partial or total destruction of the gland by emission of beta particles.
    • Damage to surrounding tissue is minimal.
    DR. UMA K.
  • 48. Radioactive iodine ( 131 I)
    • Used in the treatment of hyperthyroidism.
    • Side effects and toxicity.
    • Major: hypothyroidism .
    • Should be avoided during pregnancy.
    DR. UMA K.
  • 49.  -Blockers
    • Excess thyroid hormones, upregulation of  -adrenergic receptors.
    • Tachycardia, tremors, anxiety.
    • Inhibits peripheral conversion of T4 to T3.
    DR. UMA K.
  • 50. Propranolol
    • Adjuncts in the treatment of hyperthyroidism.
    • Reduce the symptoms of the disease (e.g., tachycardia. anxiety) until the antithyroid drugs can take effect.
    • Propranolol also inhibits the peripheral conversion of T4 to T3 via 5' deiodinase.
    DR. UMA K.
  • 51. Myxedema
    • Both hypo or hyperthyroidism.
    • Myxedema w/hypothyroidism
    • Apathy, listlessness, edema accumulates in skin and other tissues.
    • Broadening of facial features.
    DR. UMA K.
  • 52. Myxedema
    • Myxedema w/hyperthyroidism.
    • Localized areas of hyperpigmentation.
    • Usually in feet and lower legs.
    DR. UMA K.
  • 53. Interactions w/receptors
    • Amiodarone:
    • Structurally resembles thyroid hormones.
    • May cause hypo or hyperthyroidism.
    • Lithium
    • L-Dopa
    • Estrogens
    DR. UMA K.
  • 54. A 29 YO female complains of restlessness and increasing anxiety. HR 135 bmp, PE: Tremors. Palpation on the neck reveals a 3cm nodule on her thyroid gland. Laboratory test are sent to confirm the diagnosis. In the meantime, with drug could be given to acutely reduce her physical symptoms?
    • Propylthiouracil.
    • Furosemide.
    • Prednisone.
    • Iodine.
    • Propanolol.
    DR. UMA K.
  • 55. TSH Testing Thyroid “ Sends Telegram” Pituitary T3 & T4 TSH
  • 56. Why Test Women Over 40?
    • Early Detection
    • Early Treatment
    • Prevention of:
      • Organ Damage
      • Unpleasant Symptoms
      • Other Negative Health Consequences
    DR. UMA K.
  • 57. Treating Thyroid Disorders
    • Radioiodine Therapy
    • Stop Thyroid Hormone Production
      • Anti-thyroid Drugs Often Helpful
      • Replacement Therapy Often Needed
    • Surgery Maybe Necessary
    • Monitoring Tailored to Individual Patient Status and Needs
    DR. UMA K. Hyperthyroidism
  • 58. Treating Thyroid Disorders
    • Daily Oral Medication to Replace Missing Hormone
    • Individualized Dosing Adjustment to Find the Right Dose for Each Patient
    • Annual Monitoring
    DR. UMA K. Hypothyroidism
  • 59. DR. UMA K. Thank you Thank you