Pharmacology-Thyroid & Parathyroid

Question 1

Why is it important to test expecting mothers’ thyroid levels?

Answer 1

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.

Question 2

Why is hyperthyroidism particularly concerning for people with coronary heart disease?

Answer 2

T3/T4 sensitize beta-adrenergic receptors and make the heart beat harder.

Question 3

Why are people with hypothyroidism at increased risk for atherosclerosis?

Answer 3

T3/T4 increase LDL receptors in the hepatocytes. If T3/T4 is deficient, more LDL will circulate in the blood.

Question 4

Hypothalamic Pituitary Thyroid access

Answer 4

*

Question 5

What happens when TSH from thyrotrophs binds to follicular cells in the thyroid?

Answer 5

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.

Question 6

How is T4 activated and how is it deactivated?

Answer 6

Activated and deactivated by deiodination. Activation forms T3, deactivation form rT3.

Question 7

What drugs can deactivate thyroid hormone in peripheral tissues?

Answer 7

Amiodarone, beta-blockers and corticosteroids. These prevent the deiodination of T4 to form T3 and only allow for formation of rT3.

Question 8

How does T3 activate genes?

Answer 8

Acetylation releases gene repressors and allows activator to bind and induce transcription of DNA.

Question 9

Symptoms of myxedema/hypothyroidism?

Answer 9

Cold, eyelid edema, pallor, thin hair, lethargy, poor memory, bradycardia, weight gain, hypercholesterolemia, constipation, amenorrhea.

Question 10

Drug of choice for hypothyroidism

Answer 10

Levothyroxine (T4)

Question 11

Treatment of hypothyroidism prior to surgery or in myxedema coma?

Answer 11

IV sodium liothyronine (T3)

Question 12

Drug that is given in the natural ratio (4:1) of T4:T3.

Answer 12

Liotrix

Question 13

Why take T4 replacement of T3?

Answer 13

T4 has a longer half-life than T3

Question 14

Symptoms of hyperthyroidism

Answer 14

Hot, sweaty, palpitations, nervous, weight loss, insomnia, diarrhea and exopthalmos

Question 15

What activities are inhibited by thioamides? What are the thioamides?

Answer 15

Propylthiouracil (PTU), methimazole & carbimazole. They inhibit thyroid peroxidase and thus inhibit organification of iodine and T3/T4 synthesis.

Question 16

Why only use PTU in the 1st trimester?

Answer 16

PTU does not cross the placenta as much as methimazole, lowering the risk of hypothyroidism in the child.

Question 17

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?

Answer 17

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)

Question 18

Why are the parathyroids spared when you treat someone with I-131?

Answer 18

The beta particle of the radioactive iodine is destructive but does not travel very far.

Question 19

How do you follow up treatment of I-131?

Answer 19

Life-long levothyroxine supplementation due to loss of thyroid tissue.

Question 20

In the case of nuclear fallout, what can you give to prevent thyroid damage?

Answer 20

Prophylactic KI prevents uptake of radioactive iodine.

Question 21

3 hormones that regulate serum Ca2+

Answer 21

PTH, 1,25-dihydroxycholecalciferol, calcitonin

Question 22

How does PTH affect the kidney, intestine and bone?

Answer 22

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

Question 23

Where does the 25 hydroxylation of vitamin D take place?

Answer 23

Liver

Question 24

Usual treatment for hyperparathyroid adenomas

Answer 24

Surgery, you really only need one of you four parathyroids to survive

Question 25

Treatment for hypoparathyroidism?

Answer 25

The problem is low PTH, causing low serum Ca and high serum phosphate. You give dietary Ca and 1,25(OH)2D3.

Question 26

What happens in worst case scenario of hypoparathyroidism?

Answer 26

Tetany, convulsions and death.

Question 27

Pseudohypoparathyroidism treatment?

Answer 27

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

Question 28

Why can’t you treat hypoparathyroidism with milk?

Answer 28

You need PTH to convert D2 to D3, but PTH is low.

Question 29

Treatment for rickets or osteomalacia

Answer 29

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.

Question 30

Drugs that can cause osteopenia. How do you treat drug-induced osteopenia?

Answer 30

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.

Question 31

How can vitamin D cause kidney stones?

Answer 31

Overdosing on vitamin D caused too much Ca uptake from gut and Ca deposition in the kidney

Question 32

How do you treat Paget’s disease?

Answer 32

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.

Question 33

Bisphosphonates, what are the drugs and how do they work?

Answer 33

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.

Question 34

Side effect of using bisphosphonates for osteoporosis?

Answer 34

Osteonecrosis of the jaw

Question 35

Second-line drug for postmenopausal osteoporosis if bisphosphonates are not an option? Risks for this?

Answer 35

HRT: estrogen if no uterus, estrogen + progesterone if present. Increased risk for heart disease and breast cancer.

Question 36

Best drug to use for HRT

Answer 36

Raloxifene, a SERM, still has risk of vascular problems

Question 37

Injectable active form of PTH used to treat osteoporosis

Answer 37

Teriparatide. Stimulates bone growth and increases bone density. Used if bisphosphonates no longer work

Question 38

Anti-RANKL monoclonal antibody used for osteoporosis

Answer 38

Denosumab, down-regulates osteoclasts by sequestering RANKL

Question 39

Nasal spray inhibitor of osteoclast activity used for osteoporosis

Answer 39

Calcitonin