Thyroid pharm

Question 1

Thyroid Agents

Answer 1

• Levothyroxine [T4]
• Liothyronine [T3]
  Liotrix [4:1 ratio of T4:T3]
  Desiccated thyroid (animal origin, difficult to monitor)

Question 2

Antithyroid Agents

Answer 2

• Methimazole
• Propylthiouracil [PTU]
• Potassium iodide
  Radioactive iodine (131I) sodium

Question 3

comparison of levothyroxine and liothyronine

Answer 3

Levothyroxine (T4):
longer half-life
one dose daily

Liothyronine (T3):
more bioavailability
multiple doses daily
3-4x more potency

typically prefer to give T4- easier to monitor, fewer doses

Question 4

signs and symptoms of hyperthyroid

Answer 4

warm, moist skin, sweating, fine, thin hair

increased heart rate, arrhythmias, angina

increased appetite and frequency of bowel movements

nervousness, agitation

hyperglycemia, increased drug metabolism, decreased warfarin requirement

Question 5

signs and symptoms of hypothyroidism

Answer 5

pale, cool, puffy skin, brittle hair and nails
decreased heart rate; bradycardia
decreased appetite and frequency of bowel movements
lethargy/ fatigue; weakness
delayed degradation of insulin, decreased drug metabolism; increased warfarin requirement

Question 6

Thyroxine Toxicity

Answer 6

Children
Restlessness, insomnia, accelerated bone maturation and growth

Adults
Increased nervousness, heat intolerance, episodes of palpitations and tachycardia, or unexplained weight loss

Chronic overtreatment with T4 (especially in elderly) can increase risk of atrial fibrillation and accelerated osteoporosis

Question 7

Which of this patient’s following medical problems may be aggravated initially by starting low doses of levothyroxine?
Acid reflux 
Angina
Constipation
Depression
Hypercholesterolemia

Answer 7

Angina

Question 8

Thyroid-Pituitary Relationships

Answer 8

Hypothalamic cells secrete thyrotropin-releasing hormone (TRH) –> TRH stimulates synthesis and release of thyrotropin (thyroid-stimulating hormone, TSH) –> TSH stimulates the thyroid cell to increase synthesis and release of T4 and T3

T4 and T3 serve in a negative feedback fashion to the hypothalamus and pituitary to inhibit synthesis and release of TRH and TSH

Question 9

What is expected after TSH receptor activation? Activation of:
Adenylyl cyclase
Gene transcription
Jak/Stat signaling pathway
MAP kinase pathway
Thyroid hormone receptor

Answer 9

Adenylyl cyclase

Question 10

An agent is administered that blocks iodide organification.
Hepatitis is of concern.

Which agent was most likely prescribed?
Bromocriptine
Isoniazid
Perchlorate
Propylthiouracil
Radioactive iodine

Answer 10

Propylthiouracil

inhibits thyroidal peroxidase-catalyzed reactions and blocks iodide organification; blocks hormone synthesis

Question 11

how does radioactive iodine work?

Answer 11

rapidly incorporated into the thyroid; beta-emissions result in extensive local tissue damage

Question 12

when do we choose PTU over methimazole?

Answer 12

1st trimester of pregnancy- doesn’t cross the placenta, but still risk to the fetus (brain development) so be careful!

thyroid storm - because of the additional mechanism of action: prevents peripheral conversion of T4 to T3

Question 13

The patient is prescribed PTU every 8 hours. After 4 weeks of therapy, she returns to the clinic with complaints of flulike symptoms (chills, fever, sore throat), which have occurred over the past 2 days. She also reports a 2-day history of a temperature of over 101°F.

At this time, which of the following lab results may be found in this patient and could explain her presenting symptoms?
AST – 50 units/L (11-47 units/L)
Creatinine – 2.1 mg/dL (0.6-1.1 mg/dL)
FT4 – 0.3 ng/dL (0.7-1.9 ng/dL)
HCT – 25% (36.1-44.3%)
Neutrophils – 450 cells/mm3 (1500-5000 cells/mm3)

Answer 13

neutrophils suggest an infection, possibly agranulocytosis

Question 14

What course of action will most likely improve a patient’s agranulocytosis?  Discontinuation of PTU and:
Alprazolam
Cyanocobalamin (vitamin B12)
Epoetin-alpha
Filgrastim
Pyridoxine (vitamin B6)

Answer 14

Filgrastim- a granulocyte colony stimulating factor (G-CSF)

Question 15

Amiodarone intro Dysfunction

Answer 15

Amiodarone associated with:
Both hypo- and hyperthyroidism

Contains two iodine atoms:
~3 mg of inorganic iodine released after liver metabolism for every 100 mg dose
Average iodine intake in typical diet = 0.3 mg/day
Thus, 6 mg iodine released with a 200 mg dose will markedly increase iodine load

Question 16

Amiodarone and Thyroid Dysfunction

Answer 16

Intrinsic Effects
Inhibits 5’-monodeiodination of T4, decreasing T3 production and increasing rT3

Iodine Effects

• Normal auto-regulation prevents patient from becoming hyperthyroid after iodine load – iodine transport and hormone synthesis transiently inhibited
• Those with underlying disease have defects in auto-regulation

Question 17

DDI between cholestyramine and levothyroxine

Answer 17

cholestyramine interferes with T4 absorption

separate administration times

Question 18

What drugs inhibit conversion of T4 to T4 (peripheral)

Answer 18

ABC-RT:

amiodarone
beta blockers
corticosteroids

radiocontrast agents
TPU

Question 19

drugs that increase hepatic metabolism

Answer 19

rifampin
phenobarbital
phenytoin
HIV protease inhibitors

Question 20

drugs that interfere with T4 absorption

Answer 20

Oral bisphosphonates
bile acid sequestrants
ciprofloxacin
PPIs
antacids