Pharmacology-Thyroid & Parathyroid Flashcards
Why is it important to test expecting mothers’ thyroid levels?
The fetus depends on mother’s thyroid hormone until 2nd trimester and will become mentally retarded if deficient. Since pregnancy adds extra burden to the thyroid, pregnancy may exacerbate subclinical hypothyroidism.
Why is hyperthyroidism particularly concerning for people with coronary heart disease?
T3/T4 sensitize beta-adrenergic receptors and make the heart beat harder.
Why are people with hypothyroidism at increased risk for atherosclerosis?
T3/T4 increase LDL receptors in the hepatocytes. If T3/T4 is deficient, more LDL will circulate in the blood.
Hypothalamic Pituitary Thyroid access
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What happens when TSH from thyrotrophs binds to follicular cells in the thyroid?
PKA turns on thyroid peroxidase and the Na/I symporter. Thyroid peroxidase makes iodine from iodide. Organification occurs as I is complexed to tyrosine on thyroglobulin to form MIT & DIT, which is stored in colloid. MIT and DIT combine to form T3 and T4 on thyroglobulin, which is then proteolyzed and T3/T4 are released and thyroglobulin is recycled.
How is T4 activated and how is it deactivated?
Activated and deactivated by deiodination. Activation forms T3, deactivation form rT3.
What drugs can deactivate thyroid hormone in peripheral tissues?
Amiodarone, beta-blockers and corticosteroids. These prevent the deiodination of T4 to form T3 and only allow for formation of rT3.
How does T3 activate genes?
Acetylation releases gene repressors and allows activator to bind and induce transcription of DNA.
Symptoms of myxedema/hypothyroidism?
Cold, eyelid edema, pallor, thin hair, lethargy, poor memory, bradycardia, weight gain, hypercholesterolemia, constipation, amenorrhea.
Drug of choice for hypothyroidism
Levothyroxine (T4)
Treatment of hypothyroidism prior to surgery or in myxedema coma?
IV sodium liothyronine (T3)
Drug that is given in the natural ratio (4:1) of T4:T3.
Liotrix
Why take T4 replacement of T3?
T4 has a longer half-life than T3
Symptoms of hyperthyroidism
Hot, sweaty, palpitations, nervous, weight loss, insomnia, diarrhea and exopthalmos
What activities are inhibited by thioamides? What are the thioamides?
Propylthiouracil (PTU), methimazole & carbimazole. They inhibit thyroid peroxidase and thus inhibit organification of iodine and T3/T4 synthesis.
Why only use PTU in the 1st trimester?
PTU does not cross the placenta as much as methimazole, lowering the risk of hypothyroidism in the child.
A patient comes to the ED complaining of palpitations, fever, flushing and sweating. ECG reveals atrial flutter tachycardia and labs show high levels of T3 and T4. How do you treat this patient?
She has thyroid storm, thyrotoxic crisis due to super sensitization of beta-adrenergic receptors. You treat with beta blockers (propranolol or atenolol) and can use Lugol’s solution (KI + I2) to diminish vasculature of the thyroid temporarily (Wolff-Chaikoff Effect)
Why are the parathyroids spared when you treat someone with I-131?
The beta particle of the radioactive iodine is destructive but does not travel very far.
How do you follow up treatment of I-131?
Life-long levothyroxine supplementation due to loss of thyroid tissue.
In the case of nuclear fallout, what can you give to prevent thyroid damage?
Prophylactic KI prevents uptake of radioactive iodine.
3 hormones that regulate serum Ca2+
PTH, 1,25-dihydroxycholecalciferol, calcitonin
How does PTH affect the kidney, intestine and bone?
Kidney: decreases Ca excretion and increases PO4 excretion, increases 1-hydroxylase activity. Intestine: 1,25(OH)2D3 made from 1-hydroxylase increases Ca uptake from gut. Bone: induces expression of RANKL and activates osteoclasts
Where does the 25 hydroxylation of vitamin D take place?
Liver
Usual treatment for hyperparathyroid adenomas
Surgery, you really only need one of you four parathyroids to survive
Treatment for hypoparathyroidism?
The problem is low PTH, causing low serum Ca and high serum phosphate. You give dietary Ca and 1,25(OH)2D3.
What happens in worst case scenario of hypoparathyroidism?
Tetany, convulsions and death.
Pseudohypoparathyroidism treatment?
PTH is high but serum Ca is still low. Usually the problem is low or abnormal Gs signaling protein. Treat with 1,25(OH)2D3
Why can’t you treat hypoparathyroidism with milk?
You need PTH to convert D2 to D3, but PTH is low.
Treatment for rickets or osteomalacia
PTH is secreted, but D3 is low from lack in diet or sunlight so increased bone resorption occurs and bones soften and bend.This is treated by sunlight and food supplementation with D2 or D3.
Drugs that can cause osteopenia. How do you treat drug-induced osteopenia?
Drugs that interfere with Ca absorption from the gut are phenytoin, phenobarbital and glucocorticoids. You treat this with 25(OH)D3, D2 or D3 administration.
How can vitamin D cause kidney stones?
Overdosing on vitamin D caused too much Ca uptake from gut and Ca deposition in the kidney
How do you treat Paget’s disease?
Paget’s disease is a result of overactive osteoclasts and abnormal bone restructuring. This puts patients at risk for compression fractures. You treat this with calcitonin injections or orally active bisphosphonates.
Bisphosphonates, what are the drugs and how do they work?
Na-etidronate, alendronate, risedronate, pamidronate, ibandronate, zoledronic acid. These impregnate bone and are taken up by osteoclasts and thus inhibit the osteoclasts as long as they are inside the osteoclast.
Side effect of using bisphosphonates for osteoporosis?
Osteonecrosis of the jaw
Second-line drug for postmenopausal osteoporosis if bisphosphonates are not an option? Risks for this?
HRT: estrogen if no uterus, estrogen + progesterone if present. Increased risk for heart disease and breast cancer.
Best drug to use for HRT
Raloxifene, a SERM, still has risk of vascular problems
Injectable active form of PTH used to treat osteoporosis
Teriparatide. Stimulates bone growth and increases bone density. Used if bisphosphonates no longer work
Anti-RANKL monoclonal antibody used for osteoporosis
Denosumab, down-regulates osteoclasts by sequestering RANKL
Nasal spray inhibitor of osteoclast activity used for osteoporosis
Calcitonin
