Pharm Chapter 31
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What does the Thyroid do?
- Control metabolism
- Promote normal growth and development
What does the parathyroid do?
- Regulates Ca++ homeostasis
- Maintains normal bone mineralization
What suggests that T4 is a precursor to T3?
- T3 may exert most of the physiologic effects on tissues
- (conversion occurs in peripheral tissues)
How are thyroid hormones synthesized?
- Adding iodine to residues of the aa tyrosine
- Add 1 iodine atom= monoiodotyrosine
- Add 2 iodine atoms= diiodotyrosine
- T3(triiodotyrosine): monoiodotyrosine + diiodotyrosine
- T4(thyroxine): diiodotyrosine + diiodotyrosine
How are thyroid hormones regulated?
- TRH from hypothalamus stimulates release of TSH from ant. pituitary
- TSH goes to thyroid gland to stimulate production of T3 and T4
- NEGATIVE FEEDBACK: increase inhibits TSH, prevents high levels of peripheral thyroid hormones
What are some physiologic effects of thyroid hormones?
- Can be direct or facilitate other hormones
- Thermogenesis: ↑ basal metabolic rate and heat production
- Growth/development: stimulates release and enhances effect of GH
- Cardio: ↑'s HR and myocardial contractility, ↑ing cardiac output
- Metabolic: ↑'s glucose availability and lipids for cellular activity
What is Thyrotoxicosis?
- treated w/drugs that attenuate thyroid hormones
- Can be cause by tumors and endocrine regulation problems
- Enlargement of thyroid or goiter
What is Diffuse toxic goiter?
- Graves disease
- Type of Hyperthyroidism
- Caused by problem of immune system
- Rx: Remove thyroid or administer radioactive iodine
What are drugs used to treat Hyperthyroidism?
- Antithyroid agents
- Radioactive Iodide
- Beta-adrenergic blockers
How do Antithyroid agents work? Examples?
- Inhibit thyroid hormone synthesis
- Inhibit thyroid peroxidase enzyme
- Prevent coupling of residues within thyroglobulin molecule
- Block conversion of T4 to T3 (propylthiouracil)
- Prophythioracil (Propyl-Thyracil), Methimazole (Tapazole)
How does iodide treat hyperthyroidism?
- Large doses cause rapid decrease in thyroid function (temporarily)
- Diminishes after 2 weeks
How does radioactive iodide work?
- Emits beta radiation to destroy thryoid follicle cells
- No damage to surrounding tissue in gland
- Permanently ablates thyroid gland
How do beta-adrenergic blockers help hyperthyroidism?
- Don't directly decrease hormones
- Suppresses symptoms such as tachycardia, palpitations, fever, restlessness
What are types of Hypothyroidism?
- Myxedema: adult
- Cretinism: Child
- Goiter (may be present in some forms of hypothyroidism): Lack of dietary iodine (endemic goiter)--->no negative feedback of TSH, so increase in thyroglobulin
What are some thyroid hormones?
- Natural and synthetic
- Liothyronine (Cytomel)
- Used to treat Hypothyroidism
What is the controlling factor of PTH?
- Ca++ in the blood
- Decrease in Ca++ activates receptor on cell membrane and increases PTH release
How does PTH release Ca++ into the bloodstream?
- Liberates Ca++ from bone--->increases bone turnover
- Enhances osteoclasts
What are the physiologic effects of PTH?
- Liberates Ca++ from bone
- ↑ renal reabsorption of Ca++ and ↑ phosphate excretion
- ↑ Ca++ absorption from GI tract (increases conversion of Vitamin D to calcitriol which stimulates Ca++ absorption from intestine)
What are the two primary fxns of bone?
- 1.) Rigid framework
- 2.) Provides Ca++ pool
How do PTH levels affect bone?
- High levels: accelerate bone breakdown (and fracture)
- Low levels: enhance bone formation (stimulate osteoblastic activity)
What regulates bone homeostasis?
- Vitamin D
- GC's (catabolic effect)
- Estrogens, androgens, insulin, thyroid hormone (enhance bone formation)
How does Vitamin D affect bone?
- Promotes muscle growth and increase strength and lean body mass
- From diet or UV light on skin
- ↑ supply of Ca++ and PO4 (GI absorption)
- Suppresses PTH
What is a PTH antagonist?
- Calcitonin (from thyroid gland)
- Lowers blood Ca++ by stimulating bone formation and ↑ incorporation of Ca++ into skeletal storage
What happens when Blood Calcium levels are not maintained?
- Falls below 6mg/100mL, then titanic muscle contractions ensue
- Levels greater than 12mg/mL depresses nervous function
What helps prevent bone loss?
- Alone will not prevent osteoporosis but is helpful with other Rx's
- Calcium carbonate (Tums)
- Calcium citrate (Citracal)
What does Vitamin D do?
- Precurosr for cmpds that
- ↑ intestinal absorption and decreases excretion of Ca++ and PO4
- Enhances bone mineralization
- Fat soluble, can lead to toxicity
What are bisphosphonates?
- Reduce bone resorption by inhibiting osteoclastic activity
- Used in Paget disease
- Used in neoplastic disease
- Can help prevent bone loss associated with prolonged administration of GC's
- Primary Rx's for osteoporosis (Improve bone health in women)
How does Calcitonin work?
- Decreases blood Ca++ levels and promotes bone mineralization
- Used to Rx hypercalcemia and decrease bone resorption in Paget's
- Human Calcitonin (Cibalcalcin)
What can help treat postmenopausal osteoporosis?
- ↑ bone mineral content and reduce risk of fractures
- Combined with Ca++ supplements
- Raloxifene (Evista)
- Synthetic form of PTH
- Calcimimetic agent (mimics endogenous Ca++)
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