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Pharmacology Test 2 > Thyroid and Antithyroid Drugs > Flashcards

Thyroid and Antithyroid Drugs Flashcards

1
Q

Thyroid

A
  • endocrine gland that makes thyroid hormones (TH) & calcitonin
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2
Q

Thyroid Hormone (TH) increases:

A
  • metabolic rates
  • O2 consumption
  • heat production
  • cardiac rate and output
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3
Q

TH is responsible for

A
  • growth
  • development
  • function
  • maintenance of all tissues
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4
Q

rT3

A

reverse T3

INACTIVE

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5
Q

NIS

Sodium/Iodide Symporter

A
  • target for treating thyroid disorder

- halt = decrease I in cell

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6
Q

T4

A

major hormone released

  • can become T3 in target tissues
  • very tightly bound to TBG
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7
Q

Thyroxide

A

T4 (4 I)

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8
Q

Triiodothyronine

A

T3 (3 I)

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9
Q

T3 potentcy

A
  • 3-4x more potent/active than T4
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10
Q

Deiodination

A

T4 -> T3 or rT3

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11
Q

Metabolism of TH

A
  • CYP3A stimulates T4->T3 conversion in liver
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12
Q

5-deiodinase inhibition

A
  • inhibits activation of T4->T3 => decreased T3 (most active version)

inhibited by:

  • amiodarone
  • iodinated contrast media
  • B-blockers
  • corticosteroids
  • severe illness
  • starvation
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13
Q

Low T4 levels stimulate

A

T4 production to maintain homeostasis

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14
Q

Deiodination/Deamination

A

metabolizes T3 & T4, removed in urine and bile

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15
Q

T4 vs T3

t1/2

A

T4: 7 days
T3: 1 day

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16
Q

What stimulates creation of TH

A

TSH

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17
Q

Hypothalamic-Pituitary-Thyroid Axis

activation

A

pyschosis or prolonged cold

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18
Q

TSH

release/inhibition

A
  • TRH stimulates TSH released

- somatostatin and dopamine inhibit TSH release

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19
Q

TSH stimulates

A

T4 and T3 synthesis and release

- increases TPO expression and vascularity

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20
Q

T4 & T3 inhibit

A
  • TSH synthesis and release

NEGATIVE feedback

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21
Q

High intrathyroidal iodide levels blcok

A

thyroid activity (autoregulation)

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22
Q

TRH/TSH/T4/T3 pathway

A

increased TRH -> increased TSH -> stimulates thyroid gland -> increased T4&T3 AND increased TPO

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23
Q

TPO

A

thyroid peroxidase

- very reactive

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24
Q

Thyroid Hormone Action

A
  • T4&T3 dissociate from TBP (thyroid binding protein)
  • FT4 & FT3 (free) enter cells
  • when directed T4 -> T3 by 5-deiodinase
  • T3 enters and binds T3R a or b
  • T3R-RXR activates gene transcription
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25
Q

5-deiodinase

A

converts T4->T3

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26
Q

T3 active because

A

I at T3 & T5: prevents ring rotation

27
Q

Hyperthryoidism

A
  • EXCESS thyroid hormones
  • high metabolic rate (skinny)
  • Suppressed TSH
  • – too much TH => decrease in TSH (- feedback)
  • thyroid storm => excessive adrenergic activity, fever, flushing, and sweating
28
Q

Hypothroidism

A
  • NOT ENOUGH thyroid hormones
  • more common in women
  • affect almost all metabolic processes
  • primary hypothyroidism (issue at thyroid glands)
29
Q

Prolonged hypothyroidism can lead to

A
  • myxedema: skin lesions
30
Q

Subclinical Hypothyroidism

A
  • no symptoms
  • high TSH, normal T4
  • ** TSH overcompensates for issues of decreased TH ***
31
Q

Hashimoto’s Thyroiditis

Chronic Lymphocytic Thyroiditis

A
  • autoimmune disorder
  • most common cause of hypothyroidism (most frequent in women)
  • caused by autoantibodies against Tg, TPO, or TSH receptor on thyroid glands
  • inflammation, swelling (goiter) and destruction of thyroid glands => lower T3 and T4; higher TSH
32
Q

Other Causes of Hypothyroidism

A
  • diet
  • drugs (amiodarone)
  • genetic
  • radiation
  • thyroidectomy
  • congenital
  • secondary or tertiary disorder
  • pregnancy
  • age & gender
33
Q

Management of Hypothyroidism

A
  • if caused by drugs, removed the drug

- other causes: thyroid replacement therapy

34
Q

Levothyroxine

A

T4
- synthetic natural hormone, long t1/2 (T4!)
- used as thyroid replacement therapy
BEST

35
Q

Liothyronine

A

T3

  • synthetic natural hormone, shorter t1/2
  • faster onset but greater risk of cardiotoxicity
  • used as thyroid replacement therapy

Monitor increased risk of cardiotoxicity; faster; immediate stimulation

36
Q

Liotrix

A

T4 & T3

not in US

37
Q

Desiccated Thyroid

A
  • higher risk of toxicity; never justified
38
Q

Levothyroxine Side Effects

A
  • cardiotoxicity (but less than liothyronine (T3))
  • osteoporosis
  • hyperthyroidism
  • allergic reactions
39
Q

Myxedema with Coronary Artery Disease

A
  • do coronary artery surgery first
40
Q

Myxedema Coma

A
  • medical emergency; death can occur
  • large loading dose to saturate TBG
  • liothyronine for faster action
41
Q

Pregnancy

A
  • relatively infertile

- daily dose of T4

42
Q

Hyperthyroidism/Thyrotoxicosis

A
  • excess thyroid hormones
  • high metabolic rate
  • suppressed TSH
  • Thyroid storm
43
Q

Thyroid Storm

- avoid

A
  • acute thyrotoxicosis resulting in excessive adrenergic activity, fever, flushing, and sweating
  • life threatening; fatal if untreated
  • avoid aspirin
  • propranolol, PTU, then Iodide; dexamethasone
  • figure out what’s causing the issue and remove it
44
Q

Graves Disease

A
  • most common cause of hyperthyroidism; defect in suppressor Tcells & Bcells
  • genetic
  • diffuse toxic goiter (swelling)
45
Q

TSH-R Ab

A
  • Graves disease
  • autoantibodies activate TSH-receptor on thyroids
  • T4 &T3 elevated
  • TSH suppressed
46
Q

Exophthalmos

A

Graves

  • caused by TSI stimulation of TSH-R on eye
  • bulging eyes
47
Q

Pretibial Myxexedema

A

Graves

- waxy, discolored induration of the skin

48
Q

Other causes of Hyperthyroidism

A
  • toxic nodular goiter
  • thyroid adenoma
  • amiodarone
49
Q

Management of Hyperthyroidism

A
  • anti-thyroid drug therapy
  • destruction of thyroid gland: radioiodine
  • surgical thyroidectomy
  • block iodide uptake: anionic inhibitors
  • modify tissue responses: B blockers (propanolol)
50
Q

Anti-thyroid drug therapy

A
  • inhibit thyroid gland from making too much TH

- thioamides: PTU and MMI

51
Q

Propylthiouracil

A

PTU; thioamide

  • 6-n-propylthiouracil
  • binds and inhibits TPO, blocking iodide oxidation
  • inhibits 5-deiodinse peripherally
  • 2-4 months to take effect (more rapid than MMI)
  • non-pregnant adults
52
Q

PTU Adverse Effects

A
  • agranulocytosis
  • thrombocytopenia
  • hepatoxicity
53
Q

Thioamides

A

PTU & MMI

  • both inhibit TPO (PTU also inhibits 5-deiodinase)
  • effects take time (PTU more rapid)
  • not recommended for pregnancy (category D)
  • Adverse effects: agranulocytosis & hepatotoxicity
54
Q

Pregnant PTU vs MMI

A

not used unless benefits outweigh risks

  • PTU during 1st trimester
  • MMI preferred later
55
Q

Methimazole

A

MMI; thioamide

  • indicated for hyperthyroidism, adjunct to surgery
  • inhibits TPO (DOES NOT BLOCK T4->T3 like PTU)
  • LONGER t1/2 (5-6 hrs)
  • first line in nonpregnant because lower risk of hepatotoxicity
56
Q

MMI Adverse Events

A
  • agranulocytosis, liver failure, vaculitis
57
Q

Difference between PTU and MMI

A
  • PTU additional mechanism (inhibits 5-deiodinase: T4->T3 in peripheral tissues)
  • MMI longer t1/2
  • PTU more rapid
58
Q

Radioiodine

A

RAI; destruction of thyroid gland

  • antithyroid drugs fist
  • single oral dose
  • no use in pregnant or nursing mothers; low cancer isk
  • 131 Iodide; no other iodides used during treatment
59
Q

Adjuncts to Anti-thyroid

A
  • Propranolol: used for tachycardia, hypertension, and atrial fibrillation
  • Dexamethasone

Propanolol; PTU, Iodide; Dexamethasone

60
Q

Propranolol

Thyroid Storm

A
  • block end-organ effects
61
Q

Dexamethasome

Thyroid Storm

A
  • block all peripheral activation of T4
62
Q

Iodide

A
  • block TPO and proteolysis of Tg
  • QUICK (1-2 days)
  • reduce size and vascularity of thyroid gland prior to surgery
  • body adapts: can cause severe withdrawal symptoms
  • leaves thyroid LOADED w IODIDE: problematic for RAI and thiamide therapy
63
Q

Anionic Inhibitors

A
  • monovalent anions
  • block uptake of iodide by competing w/ NIS
  • major use in iodide-induced hyperthryoidism
64
Q

Surgical Thyroidectomy

A
  • for large goiters

- antithyroid drugs->KI->thyroid replacement

Pharmacology Test 2 (8 decks)

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