Thyroid Pharm-IL- Thyroid-Leah :) Flashcards
How is IODINE taken up into follicular cells for thyroid hormone synthesis?
Thyroid:plasma ratio of iodine?
- Active absorption via Na/I symporter (requires ATP)
- Normal is 20-50:1
- Thyroid can concentrate iodine up to 100x more than plasma!
What inhibits follicular iodine uptake? (2)
stimulates? (1)
- uncouplers of ox phos (thiocyanate, perchlorate) inhibit uptake
- TSH stimulates
Describe the process of organification:
Step 1: oxidation of iodide via thyroid peroxidase + H2O2
Step 2: thyroglobulin is iodized at tyrosyl residues to form MIT/DIT (basically T1/T2 if such a thing existed)
How are T3/4 formed?
Where are these hormones formed?
- MIT + DIT –> T3
- DIT x 2 –> T4
- Catalyzed by thyroid peroxidase + H2O2 like organification
- stored in the center of follicles as “colloid”
How is thyroid hormone released from thyroid to blood?
- Endocytosis is stimulated by TSH
- Thyroglobulin taken up into lysosomes and broken down
- T3/4 sent to blood, MIT/DIT recycled for iodine
What inhibits thyroid hormone release? (2)
- iodine (inversely modulates secretion)
- lithium
What are the carriers of T3/4 in plasma? (2)
- Thyroxine Binding Globulin (TBG) carries both T3/4
- Transthyretin carries T4
Which thyroid hormone has the highest concentration in blood? Which is more active?
** IMPORTANT CARD!!!**
- T4 HAS HIGHEST PLASMA CONCENTRATION.
- T3 IS MORE ACTIVE
What enzyme converts T4 to T3?
What are the two important isoenzymes of this enzyme?
Which is responsible for MOST of the conversions?
Which is responsive to propylthiouracil?
iodothyronine 5′-deiodinase
D1: liver, kidney, thyroid – responsible for MOST conversion; INHIBITED by propylthiouracil
D2: brain, pituitary, cardiac/skeletal muscle
In what organ is the deiodinase enzyme most active?
How can this be increased even more than usual?
- Liver
- ^^ by CYP450 INDUCERS
Primary Hypothyroid lab findings:
Most common cause:
Two other causes?
- HIGH TSH, LOW T3, T4
- Autoimmune/ Hashimotos most common
- thyroid damage via Iodine radation/ surgical removal
Hormone findings and cause of SECONDARY hypothyroid?
-TSH LOW (pituitary lesion, loss of TRH from hypothalamus) –> T3, T4 LOW
Drug of choice for thyroid hormone supplementation?
Why?
How long does it take to reach steady state?
- levothyroxine (T4)
- consistent, long acting, once daily dosing
- t 1/2 = 6-7 days–> can take up to a MONTH to reach steady state.
What is liothyronine and when might it be used?
Why isn’t it the drug of choice for primary hypothyroid?
- T3, not used in primary hypothyroid but might be used in deiodinase deficiency
- variable response, short t1/2
In addition to INCREASING T4 levels, what can levothyroxine be used to do?
List 2 additional therapeutic uses.
DECREASE TSH via negative feedback–>
Treats thyroid carcinomas, goiters
When might levothyroxine be given IV?
- myxedema coma
- (severe hypothyroid)
What are four agents that may reduce levothyroxine bioavailability?
- cholestyramine, colesevelam (bile sequestrants)
- calcium carbonate
- aluminum hydroxide
How does estrogen effect levothyroxine?
Glucocorticoids?
- Estrogen INCREASES thyroid binding globulin (TBG)–> INCREASE levothyroxine doses if given with OCPs
- Glucocorticoids DECREASE TBG–> DECREASE levothyroxine doses
In addition to propylthiouracil, what drug inhibits deiodinase?
amiodarone
How does thyroxine effect warfarin?
- Thyroxine INCREASES anticoagulant activity–> DECREASE warfarin dose
- ^^ catabolism vitamin K dep. factors
Effects of levothyroxine on the cardiovascular system (3)?
-tachycardia
-palpitations
-HTN
(Sympathetic effects, just like T4)
Most common form of HYPERthyroidism?
Describe the pathogens is of this disorder.
What are the assc hormonal findings?
- Graves
- Ab’s bind TSHR/ Follicular cells to ^^ thyroid hormone production
- ^^ T3/T4, low TSH
Five treatments for HYPERthyroid?
- propanolol (cardio sx)
- NSAIDs (inflammatory sx)
- propylthiouracil (antithyroid)
- methimazole (antithyroid)
- radioablation therapy
Propylthiouracill and methimazole MOA (2):
Which has a longer t1/2 and is the DOC?
Which is the DOC in pregnancy?
- block organification (both)
- block MIT/DIT –> T3/4 (both)
- PROPYLTHIOURACIL ONLY blocks peripheral deiodinase (T4 –> T3)
- Methimazole has 6 hr t1/2 and is DOC
- Propylthiouracil is DOC in preggos
