Levothyroxine / Triiodothyronine
- T4 analog (Thyroxine replacement) / T3 analog
- Binds to nuclear receptors
- Increased Protein synthesis and Metabolic rate
- Increased Beta-receptor Increased sensitivity to Catecholamines
- Tx: Hypothyroidism / Myxedema
- SE: Hyperthyroidism (Tachy, Heart failure, Sweating, Tremor, Arrhythmias, Diarrhea)
Methimazole, Propylthiouracil (PTU)
Inhibits Thyroid Peroxidase --> Blocking Synthesis
- Propylthiouracil (PTU) also inhibits Peripheral conversion of T4 --> T3 by blocking 5'-deiodinase
- PTU avoided as first line treatment
- PTU used during First Trimester in pregnancy (Teratogenic effects)
- Tx: Hyperthyroidism, 3 Ps of PTU
- SE: Rash, Urticaria, Fever, Nausea, Agranulocytosis, Thrombocytopenia, Acute Hepatic necrosis, Vasculitis, Hepatotoxicity (Propylthiouracil) Possible Teratogen (Methimazole)
Iodine and Radioiodine
- Inhibits Thyroid Hormone release
131I concentrated in the Thyroid gland and emits Beta and Gamma XRT
- Drug of choice for destroying Toxic Adenoma
- NEVER USE w/ Pregnant women
- Tx: Thyroid Storm and Before Thyroidectome (prevents Thyroid Storm), Hyperthyroidism, Adjunctive Tx for some Thyroid cancers
- SE: Dysgeusia (metalic taste), Excessive salvation, Diarrhea, Rash
- Stabilizes bony matrix
- Coats hydroxyapatite to prevent Osteoclasts from Resorbing bone
- Tx: Postmenopausal Osteoporosis, Paget disease
- SE: Heartburn, Erosive esophagitis, Stomach upset, Joint/Back pain, Osteonecrosis of the Jaw
- Lowers Serum Calcium
- Mild analgesic properties for Bone pain
- Intranasal / Subcutaneous
- Tx: Hypercalcemic states
- SE: Runny nose, and Nasal discomfort, Flushing
- Activated form of Vitamin D
- Increases Calcium absorption from Intestines
- Tx: Hypocalcemia, Vit. D replacement in Pts. w/ End-Stage Renal Disease
- SE: Vit. D. Intoxication: Hypercalcemia, Polyuria, Weakness, Headache, Somnolence, and Constipation
Rx for Hypothyroidism?
Rx for Hyperthyroidism?
2nd: PTU (Propylthiouracil)
Pregnancy: 1st Trimester = PTU, 2nd - 3rd = Methimazole
Rx for Thyroid Storm?
131I or Radioiodine
Rx for Postmenopausal Osteoporosis?
Rx for Paget Disease to reduce bone turnover?
Rx for Hypercalcemic states?
- Intoxication w/ Vit. D
- Alkali (Mikl-alkali syndrome)
- Paget Disease
Rx for Hypocalcemia?
Rx for End-Stage Renal Disease?
- Rx for Hypothyroidism
- Potency of each preparation varies
- Thyroglobulin is a protein produced by thyroid cells (both normal and cancerous cells). After removal of the thyroid gland, Thyroglobulin can be used as a "cancer marker."
- Tx for Hypothyroidism
- Short acting w/ Rapid onset
- A synthetic form of natural T3 hormone with same actions as natural product; thyroid hormone raises basal metabolic rate, increases utilization and mobilization of glycogen store, and promotes gluconeogenesis
- Tx: Hypothyroidism, Nontoxic goiter, Myxedema, Myxedema coma
(KI and I2)
- a solution of elemental iodine and potassium iodide in water
- It was also used at one time as a first line treatment for Hyperthyroidism, as the administration of pharmacologic amounts of iodine leads to temporary inhibition of iodine organification in the thyroid gland, a phenomenon called the Wolff-Chaikoff effect.
Mechanism of PTH?
- PTH increases plasma Ca2+
- Stimulates adenylyl cyclase in target tissues
- Elevated cAMP inhances syn. of 1,25(OH)2D3
- Increasing bone resorption by activating Osteoblast --> Osteoclast and Stimulating Ca2+ transport from bone to extracellular fluids
Increases the synthesis of 1,25(OH)2D3 at the lvl of the Kidney
- Increases Renal tubular reabsorption of Ca2+
Mechanism of 1,25(OH)2D3
- 1,25 dihydroxycholecalciferol
- 7 dehydrocholesterol is converted to Cholecalciferol (D3) by UV light at the skin
- D3 is converted to 25(OH)D3 in the Liver
- 25(OH)D3 converted to 1,25(OH)2D3 (calcitriol) in the Kidney
- PTH stimulates 1α-hydroxylase, is the Kidney's converting enzyme.
- Increases plasma Ca2+
- Increasing the synthesis of Ca2+ binding transport protein in the Mucosal cells of the gut --> Increaseing absorption
- Increasing Ca2+ transport from Bone to Extracellular fluids (in large doses)
Mechanism of Calcitonin?
- Decreases plasma Ca2+
- Decreasing bone reabsorption by inhibiting activity of osteoclasts
- Decreasing tubular reabsortpion of Ca2+
Rx for Hypoparathyrodism?
- Tx: Dietary calcium and 1,25(OH)2D3
- PTH and Calcium gluconate mabe be used following surgical parathyroidectomy to prevent Hypocalemic tetany
Rx for Pseudohypoparathyrodism?
- PTH lvls are Normal or Elevated
- Serum Ca2+ is low
- End organs are insensitive to PTH
- Often abnormal Gs, the transducer that links PTH receptor to Adenylyl cyclase
- Tx: 1,25(OH)2D3 can correct Hypocalcemia, but it does not always improve Bone disease
Rx for Rickets and Osteomalacia?
- Inadequate miniralization of Bone matrix
- Lack of exposure to sunlight, resulting in impaired vitamin D3 synthesis in the skin
- Supplementing food and Vit. D2 has greatly reduced the incidence
- Tx: Administer Vit. D2 or D3
Rx for Vit. D-dependent Rickets?
- Autosomal recessive does not respond to Vit. D admin.
- Defect belived to be in the 1α-hydroxylase enzyme w/in the Kidney
- Tx: 1,25(OH)2D3
Rx for Drug-induced Osteopenia?
- The anticonvulsant drugs, Phenytoin, Phenobarbital, and Corticosteroids, suppress intestinal Ca2+ absorption w/ Secondary Hyperparathyroidism (elevated PTH)
- High doses of corticosteroids inhibit Osteoblast diff. and Collagen syn. --> decreased bone mass
- Tx: 25(OH)D3, D2, or D3 improve symptoms of Anticonvulsant-induced Osteomalacia (Osteopenia)
Rx for Paget's Disease?
- Overactive Osteoclast activity in bone resulting in Deminieralization of Osteoid tissue
- Painful, Multiple bone compression fractures
- Tx: Calcitonin via Nasal spray, Sodium Etidronate (bisphosphonate), also Alendronate and Risedronate, and even Ibandronate.
Rx for Postmenopausal Osteoporosis?
- Abnormal, rapid loss of bone, predisposing postmenopausal women to Fracture
- Tx: Estrogen replacement therapy w/ increased risk of Heart disease, Breast cancer, and Uterine cancer w/ HRT
- SERM - Raloxifene is safer
- Bisphosphonates: Alendronate, Risedronate, Ibandromate, or Zoledronic acid
- Teriparatide (Human PTH1-34) is effective for treating osteoporosis --> stimulates new bone growth and reduces vertebral fracture risk by 65%, injected daily
- SERM - Raloxifene is safer
Rx for Vitamin D intoxication?
- Hypercalcemia leading to Ca2+ deposition in soft tissues
- Tx: Stop Vit. D administration, Administer Glucocorticoids, such as Prednisone --> Block GI absorption of Ca2+
Rx Primary Hyperparathyroidism?