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Endocrine System > Drugs for Thyroid Diseases > Flashcards

Drugs for Thyroid Diseases Flashcards

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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
Out of Levothyroxine and Liothyronine which one is preferred and why?
Liothyronine is LESS desirable because of its price and shorter half-life However, when the effects are needed promptly, Liothyronine is superior
26
What are the thioamides used for HYPERthyroidism?
Methimazole Propylthiouracil (PTU)
27
What is the MOA of thionamides?
Suppress thyroid hormone synthesis: --> Inhibit peroxidase enzyme to prevent oxidation of iodide and inhibit incorporation of iodine into thyroxine
28
What is Carbimazole?
A pro-drug that gets converted to its active form --> Methimazole
29
What is the bioavailability of the different thionamides?
Methimazole: 80 to 95% PTU: 80 to 95%
30
What is the plasma protein binding of the different thionamides?
Methimazole: 0% PTU: 75 to 80%
31
What are the levels in breastmilk of the different thionamides?
Low for both
32
What is the transplacental passage of the different thionamides?
Methimazole: Higher PTU: Low
33
What is the half-life of the different thionamides?
Methimazole: 6 to 13 hours PTU: 1 to 2 hours
34
What is the dosing frequency of the different thionamides? (initial therapy)
Methimazole: 1 to 3 times a day PTU: 3 to 4 times a day
35
What is the dosing frequency of the different thionamides? (maintainance therapy)
Methimazole: once a day PTU: 2 to 3 times a day
36
Is there agranulocytosis of the different thionamides?
Yes, for both
37
Which thionamide causes liver injury?
PTU
38
What are the therapeutic indications for the different thionamides?
Methimazole: first line in almost all cases PTU: Pregnancy (1st trimester)
39
What are the therapeutical uses of Methimazole?
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
Prior to which surgery is Methimazole given?
Subtotal thyroidectomy
41
What are the adverse effects of Methimazole?
1. Agranulocytosis 2. Hypothyroidism 3. Effects in Pregnancy 4. Lactation --> It does affect thyroid function or intellectual development in breast-fed infants
42
What happens if agranulocytosis occurs during the administration of Methimazole?
Stop Methimazole; agranulocytosis will suffice, and adding G-CSF accelerates recovery
43
How could hypothyroidism occur from Methimazole?
This could result when used in high doses
44
What are the effects of Methimazole in pregnancy?
Neonatal hypothyroidism, goiter, and even cretinism --> avoid during 1st trimester
45
What kind of treatment are PTUs?
Second-line treatment, because it is more toxic and requires MANY daily doses
46
What are the 4 signifiacnt differences between PTU and Methimazole?
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
What are the uses of PTU?
1. Pregnant women (but only during the 1st trimester) 2. Thyroid storm 3. Patients intolerant of methimazole
48
Why is PTU preferred during a thyroid storm?
It can also inhibit peripheral conversion
49
What are the adverse effects of PTU?
1. Hepatotoxicity (hepatitis) --> This can be so severe that transplants may be required 2. Agranulocytosis 3. Rash
50
What is radioactive iodine therapy?
Emits beta particles and gamma rays
51
What is the use of radioactive iodine therapy?
Destroys thyroid tissue in hyperthyroidism, safe --> it does not travel outside of the thyroid
52
What is the half-life of radioactive iodine therapy?
Decays rapidly --> half-life 8 days
53
What are the contraindications of radioactive iodine therapy?
Pregnancy and lactation
54
What is the risk associated with radioactive iodine therapy?
High risk of chronic hypothyroidism
55
What are the advantages of radioactive iodine therapy?
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
What are the disadvantages of radioactive iodine therapy?
1. Effective treatment is delayed 2. Treatment is associated with a significant incidence of delayed HYPOthyroidism
57
What is the use of beta-blockers?
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
In which other pathologies (related to the thyroid) are beta blockers useful in?
Beneficial in thyrotoxic crisis, in the absence of contraindications, all patients should be started on beta blockers IMMEDIATELY
59
What are the contraindications for beta blockers?
Asthma and heart disease
60
What is Lugol's solution?
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
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Endocrine System (25 decks)

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