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Pharmacology Test 2 > Thyroid and Antithyroid Drugs > Flashcards

Thyroid and Antithyroid Drugs Flashcards

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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
5-deiodinase
converts T4->T3
26
T3 active because
I at T3 & T5: prevents ring rotation
27
Hyperthryoidism
- 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
Hypothroidism
- NOT ENOUGH thyroid hormones - more common in women - affect almost all metabolic processes - primary hypothyroidism (issue at thyroid glands)
29
Prolonged hypothyroidism can lead to
- myxedema: skin lesions
30
Subclinical Hypothyroidism
- no symptoms - high TSH, normal T4 * ** TSH overcompensates for issues of decreased TH ***
31
Hashimoto's Thyroiditis | Chronic Lymphocytic Thyroiditis
- 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
Other Causes of Hypothyroidism
- diet - drugs (amiodarone) - genetic - radiation - thyroidectomy - congenital - secondary or tertiary disorder - pregnancy - age & gender
33
Management of Hypothyroidism
- if caused by drugs, removed the drug | - other causes: thyroid replacement therapy
34
Levothyroxine
T4 - synthetic natural hormone, long t1/2 (T4!) - used as thyroid replacement therapy BEST
35
Liothyronine
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
Liotrix
T4 & T3 | not in US
37
Desiccated Thyroid
- higher risk of toxicity; never justified
38
Levothyroxine Side Effects
- cardiotoxicity (but less than liothyronine (T3)) - osteoporosis - hyperthyroidism - allergic reactions
39
Myxedema with Coronary Artery Disease
- do coronary artery surgery first
40
Myxedema Coma
- medical emergency; death can occur - large loading dose to saturate TBG - liothyronine for faster action
41
Pregnancy
- relatively infertile | - daily dose of T4
42
Hyperthyroidism/Thyrotoxicosis
- excess thyroid hormones - high metabolic rate - suppressed TSH - Thyroid storm
43
Thyroid Storm | - avoid
- 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
Graves Disease
- most common cause of hyperthyroidism; defect in suppressor Tcells & Bcells - genetic - diffuse toxic goiter (swelling)
45
TSH-R Ab
- Graves disease - autoantibodies activate TSH-receptor on thyroids - T4 &T3 elevated - TSH suppressed
46
Exophthalmos
Graves - caused by TSI stimulation of TSH-R on eye - bulging eyes
47
Pretibial Myxexedema
Graves | - waxy, discolored induration of the skin
48
Other causes of Hyperthyroidism
- toxic nodular goiter - thyroid adenoma - amiodarone
49
Management of Hyperthyroidism
- anti-thyroid drug therapy - destruction of thyroid gland: radioiodine - surgical thyroidectomy - block iodide uptake: anionic inhibitors - modify tissue responses: B blockers (propanolol)
50
Anti-thyroid drug therapy
- inhibit thyroid gland from making too much TH | - thioamides: PTU and MMI
51
Propylthiouracil
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
PTU Adverse Effects
- agranulocytosis - thrombocytopenia - hepatoxicity
53
Thioamides
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
Pregnant PTU vs MMI
not used unless benefits outweigh risks - PTU during 1st trimester - MMI preferred later
55
Methimazole
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
MMI Adverse Events
- agranulocytosis, liver failure, vaculitis
57
Difference between PTU and MMI
- PTU additional mechanism (inhibits 5-deiodinase: T4->T3 in peripheral tissues) - MMI longer t1/2 - PTU more rapid
58
Radioiodine
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
Adjuncts to Anti-thyroid
- Propranolol: used for tachycardia, hypertension, and atrial fibrillation - Dexamethasone Propanolol; PTU, Iodide; Dexamethasone
60
Propranolol | Thyroid Storm
- block end-organ effects
61
Dexamethasome | Thyroid Storm
- block all peripheral activation of T4
62
Iodide
- 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
Anionic Inhibitors
- monovalent anions - block uptake of iodide by competing w/ NIS - major use in iodide-induced hyperthryoidism
64
Surgical Thyroidectomy
- for large goiters | - antithyroid drugs->KI->thyroid replacement

Pharmacology Test 2 (8 decks)

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