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Endocrine System > Drugs for Thyroid Diseases > Flashcards

Drugs for Thyroid Diseases Flashcards

1
Q

What are the treatments for HYPOthyroidism?

A

–> Iodine for insufficient iodine from the diet
–> Levothyroxine for chronic autoimmune (Hashimoto’s), surgical removal, destruction by radioactive iodine, insufficient TSH/TRH

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2
Q

Which hyperthyroidism disease presents with exophthalmos?

A

Grave’s disease but not Plummer’s

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3
Q

What is Plummer’s disease?

A

Toxic nodular goiter, thyroid adenoma

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4
Q

What are the treatments for HYPERthyroidism?

A
  1. Surgical removal
  2. Radioactive iodine
  3. ANtithyroid Drugs
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5
Q

What are examples of antithyroid drugs?

A
  1. Methimazole
  2. Propylthuouracil
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6
Q

What is the preferred lab measurement for hypothyroidism? What are its uses?

A

TSH: most sensitive, screening and diagnosis of hypothyroidism, differentiating primary from secondary hypothyroidism, monitoring of therapy

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7
Q

What is the preferred lab measurement for hyperthyroidism?

A

Free T3 and T4 with TSH for hyperthyroidism (prefer T3 as it rises sooner than T4)

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8
Q

What are the drugs for HYPOthyroidism ?

A

Levothyroxine
Liothyronine

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9
Q

What is Levothyroxine?

A

Synthetic T4 (identical)

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10
Q

What is the drug of choice for patients requiring thyroid hormone replacement?

A

Levothyroxine

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11
Q

What is the half-life of Levothyroxine?

A

Prolonged half-life:
–> Needs about 1 month to reach steady state
–> Half-life of about 7 days

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12
Q

How many times is Levothyroxine administered daily?

A

Once daily

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13
Q

What are the PK of Levothyroxine?

A
  1. Absorption is reduced by food (has to be taken on an empty stomach)
  2. Gets converted to T3, so no need to give T3
  3. Broken down by CYP450 (CYP3A4)
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14
Q

Why is the half-life of Levothyroxine so long?

A

Because it is highly protein bound (99.97%)

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15
Q

What are the advantages of Levothyroxine having a long half-life?

A

Levels stay steady even with a once-a-day dosing; suitable for lifelong therapy

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16
Q

What are the disadvantages of Levothyroxine having a long half-life?

A

It takes one month (4 half-lives) to reach a steady state, onset of full effects is delayed

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17
Q

What are the therapeutic uses of Levothyroxine?

A

All forms of hypothyroidism
–> Simple goiter, myxedema, cretinism, and primary hypothyroidism

–> Also used for hypothyroidism resulting from insufficient TSH or insufficient TRH

–> Also used to maintain levels of thyroid hormones following thyroid surgeries, irradiation, or treatment with anti-thyroid drugs

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18
Q

What are the adverse effects of Levothyroxine at acute overdose?

A
  1. Tachycardia and angina
  2. Tremor, nervousness
  3. Insomnia
  4. Hyperthermia, heat intolerance and sweating
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19
Q

What are the adverse effects of Levothyroxine at chronic overdose?

A
  1. Accelerated bone loss –> increased risk of fractures
  2. Increased arterial fibrillation –> especially in older patients
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20
Q

What are the drug interactions of Levothyroxine?

A
  1. Increased metabolism by CYP3A4 inducers
  2. Accelerates the degradation of Vitamin - K-dependent clotting factors –> effects of warfarin are enhanced
  3. Thyroid hormones increase cardiac responsiveness to catecholamines,echolamine-induced arrhythmia thus increasing the risk
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21
Q

What are examples of CYP3A4 inducers?

A

Rifampin
Phenobarbital
Phenytoin

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22
Q

Which drugs reduce the absorption of Levothyroxine? (9)

A
  1. H2R antagonists
  2. PPIs
  3. Sucralfate
  4. Orlistat
  5. Cholestyramine
  6. Colestipol
  7. Al-containing antacids
  8. Ca supplements
  9. Fe supplements
    –> should be taken with a 4 hour interval in between
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23
Q

What is Liothyrine?

A

Synthetic T3

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24
Q

What are the differences between Liothyronine and Levothyroxine?

A

Liothyronine has:
1. Shorter half-life
2. Faster onset
3. Is more expensive

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25
Q

Out of Levothyroxine and Liothyronine which one is preferred and why?

A

Liothyronine is LESS desirable because of its price and shorter half-life

However, when the effects are needed promptly, Liothyronine is superior

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26
Q

What are the thioamides used for HYPERthyroidism?

A

Methimazole
Propylthiouracil (PTU)

27
Q

What is the MOA of thionamides?

A

Suppress thyroid hormone synthesis:
–> Inhibit peroxidase enzyme to prevent oxidation of iodide and inhibit incorporation of iodine into thyroxine

28
Q

What is Carbimazole?

A

A pro-drug that gets converted to its active form –> Methimazole

29
Q

What is the bioavailability of the different thionamides?

A

Methimazole: 80 to 95%
PTU: 80 to 95%

30
Q

What is the plasma protein binding of the different thionamides?

A

Methimazole: 0%
PTU: 75 to 80%

31
Q

What are the levels in breastmilk of the different thionamides?

A

Low for both

32
Q

What is the transplacental passage of the different thionamides?

A

Methimazole: Higher
PTU: Low

33
Q

What is the half-life of the different thionamides?

A

Methimazole: 6 to 13 hours
PTU: 1 to 2 hours

34
Q

What is the dosing frequency of the different thionamides? (initial therapy)

A

Methimazole: 1 to 3 times a day
PTU: 3 to 4 times a day

35
Q

What is the dosing frequency of the different thionamides? (maintainance therapy)

A

Methimazole: once a day
PTU: 2 to 3 times a day

36
Q

Is there agranulocytosis of the different thionamides?

A

Yes, for both

37
Q

Which thionamide causes liver injury?

A

PTU

38
Q

What are the therapeutic indications for the different thionamides?

A

Methimazole: first line in almost all cases
PTU: Pregnancy (1st trimester)

39
Q

What are the therapeutical uses of Methimazole?

A
  1. As sole form of therapy for Grave’s disease
  2. As an adjunct to radiation therapy until the side effects of radiation become manifest
  3. To suppress thyroid-hormone synthesis in preparation for surgery
  4. To treat patients with thyrotoxic crisis
40
Q

Prior to which surgery is Methimazole given?

A

Subtotal thyroidectomy

41
Q

What are the adverse effects of Methimazole?

A
  1. Agranulocytosis
  2. Hypothyroidism
  3. Effects in Pregnancy
  4. Lactation –> It does affect thyroid function or intellectual development in breast-fed infants
42
Q

What happens if agranulocytosis occurs during the administration of Methimazole?

A

Stop Methimazole; agranulocytosis will suffice, and adding G-CSF accelerates recovery

43
Q

How could hypothyroidism occur from Methimazole?

A

This could result when used in high doses

44
Q

What are the effects of Methimazole in pregnancy?

A

Neonatal hypothyroidism, goiter, and even cretinism –> avoid during 1st trimester

45
Q

What kind of treatment are PTUs?

A

Second-line treatment, because it is more toxic and requires MANY daily doses

46
Q

What are the 4 signifiacnt differences between PTU and Methimazole?

A

PTU:
1. Cause liver injury
2. Has a shorter half-life
3. Crosses the placenta LESS easily
4. Blocks conversion of T4 to T3 in the periphery

47
Q

What are the uses of PTU?

A
  1. Pregnant women (but only during the 1st trimester)
  2. Thyroid storm
  3. Patients intolerant of methimazole
48
Q

Why is PTU preferred during a thyroid storm?

A

It can also inhibit peripheral conversion

49
Q

What are the adverse effects of PTU?

A
  1. Hepatotoxicity (hepatitis) –> This can be so severe that transplants may be required
  2. Agranulocytosis
  3. Rash
50
Q

What is radioactive iodine therapy?

A

Emits beta particles and gamma rays

51
Q

What is the use of radioactive iodine therapy?

A

Destroys thyroid tissue in hyperthyroidism, safe –> it does not travel outside of the thyroid

52
Q

What is the half-life of radioactive iodine therapy?

A

Decays rapidly –> half-life 8 days

53
Q

What are the contraindications of radioactive iodine therapy?

A

Pregnancy and lactation

54
Q

What is the risk associated with radioactive iodine therapy?

A

High risk of chronic hypothyroidism

55
Q

What are the advantages of radioactive iodine therapy?

A
  1. Low cost
  2. Patients are spared of the risks, discomfort, and expenses of thyroid surgery
  3. Death is extremely rare
  4. No tissues other than the thyroid are injured
56
Q

What are the disadvantages of radioactive iodine therapy?

A
  1. Effective treatment is delayed
  2. Treatment is associated with a significant incidence of delayed HYPOthyroidism
57
Q

What is the use of beta-blockers?

A

Can suppress tachycardia and other symptoms of Grave’s disease
–> Benefits derived from blocking beta receptors, NOT from reducing levels of T3 and T4

58
Q

In which other pathologies (related to the thyroid) are beta blockers useful in?

A

Beneficial in thyrotoxic crisis, in the absence of contraindications, all patients should be started on beta blockers IMMEDIATELY

59
Q

What are the contraindications for beta blockers?

A

Asthma and heart disease

60
Q

What is Lugol’s solution?

A

An iodine solution that inhibits the organification of iodide and hormone biosynthesis, a phenomenon known as the Wold-Chaikoff effect

–> Inhibits the release of thyroid hormones in the acute setting

61
Q
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62
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63
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Endocrine System (12 decks)

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