Lecture 1: Thyroid Pharmacology Flashcards
What is most circulating TH bound to?
what is result of this?
TBG (thyroxin binding globulin) = plasma protein
- results in longer t 1/2 and low amt free hormone
Does TBG bind to more T4 or T3? (which TH hormone has higher free levels)
TBG binds to more T4 –> more T3 is free
What type of hormones can the pituitary respond to?
FREE hormones only
What are 2 causes of incr thyroid binding proteins?
- Drugs (estrogen, methadone)
2. Pregnancy
What is the result on the levels of TH when incr thyroid binding proteins? (whole process)
TH levels incr
(less free hormone–> pituitary sees less–> incr TSH–> incr TH levels –> levels of TSH and free THs return to normal (euthyroid)
Which isomers of thyroid hormones are naturally occurring and have more activity?
L-isomers
Where is T4 best abosrbed from
duodenum and ileum
How does hyperthyroidism affect clearance of T4 & T3?
Hypothyroidism?
Hyperythyroidism–> incr clearance T4/3 (shorter half life)
HYPOthyroidism –> decr clearance T4/3 (longer half life)
T4 vs T3:
- which has longer half life (only need once daily dosing)
- which has more potency/affinity for receptors
T4 = longer half life T3 = more potency & affinity for rec
What modifies the body’s secretion and degradation rates of basically ALL other hormones
thyroid status (hyper, hypo, eu)
what is the physiologic effect of TH in nervous system
Others:
- incr heart effect, carb abs, BMR, O2 consumption
- breakdowns fats/proteins
- promotes normal growth/skeletal devel
- forms LDL rec
promotes normal brain development
3 indications for TH replacement therapy
- Adult HYPOthyroidism
- Infantile HYPOthyroidism (cretinism)
- Endemic Goiter
MC type and cause of Adult HYPOthyroidism
MC type = primary (thyroid gland defective)
MC cause = Hashimoto’s thyroiditis
What is Hashimoto’s thyroiditis?
What is characteristically seen w/this d/o?
autoimmune destruction of thyroid gland
assoc w/Abs to thyroid gland proteins
3 main features of Infantile HYPOthyroidism
MC areas for this type of hypothyroidism?
- Neuro impairement
- deaf-mutism
- Developmental failures
MC in iodine defic areas (prev w/screening)
Why is Endemic goiter rare in developed countries
Tx for endemic goiter
How is full dose of TH benefical
b/c iodide added to salt
Dietary supplementation of iodide
Full dose TH–> may hasten regression of goiter
Which thyroid prep has greater risk of cardiac toxicity and is CI in pts w/heart dz
T3
- Liothyronine sodium, L-triiodothyronine
Which thyroid prep is ToC for replacement therapy in hypothyroidism?
T4
- levothyroid sodium, L-thyroxin
What are the cardiac Sxs assoc w/T4?
What population must you use caution in w/T4?
palpitations, angina
caution in elderly
what is the thyroid prep given at T4 to T3 ratio of 4:1
Liotrix
Why is Liotrix not necessary for most pts
Who may it be benefical in?
body converts T4–> T3
may be beneficial in pts w/genetic polymorphism in deiodinase enzyme (cant convert T4–> T3)
What 2 drugs interactions w/T4? their effects?
- Rifampin (incr clearance of T4)
2. Cholestyramine (decr GI abs of T4)
indication for ANTIthyroid therapy
hyperthyroidism
What is MC form of hyperthyroidism
Graves dz
What type of d/o is Grave’s dz and what is characteristicially seen w/it
autoimmune d/o –> IgG antibodies
Role of IgG antibodies in Grave’s dz
IgG antibodies that bind to TSH rec/mimics its effects and stim thyroid–> incr TH levels
Hyperthyroidism looks like sympathetic NS overactivity but how do you know its not?
Catecholamine levels are NOT increased
What are the 4 main classes/types of drugs for Hyperthyroidism
- Thioamide class
- Anion inhibitors
- Iodides
- Radioactive Iodide
What are the 2 drug prototypes for the Thioamide class?
MOA for both?
- MMI (Methimazole)
- PTU (Propylthiouracil)
MOA = blocks iodide organification (TH production) and blocks coupling of iodotyrosines
What is the additional MOA for PTU
Acts peripherally to block conversion of T4 –> T3
Why do PTU and MMI have a slow onset of action
mechanism = inhibit hormone synthesis –> takes 3-4 wks to deplete hormone
3 major AEs a/w MMI and PTU
Others: skin rash, joint pain
- Agranulocytosis
- Hepatotoxicity (worse w/PTU)
- Birth defects (more w/MMI)
Recommendation for pregnant women on taking MMI vs PTU
PTU in 1st trimester –> then MMI
What dz is MMI and PTU the major drugs of Tx for?
Thyrotoxicosis
What is benefit of giving high enough conc to suppress gland for 2 yrs w/MMI or PTU
possible permanent remission
3 types of Anion inhibitors for Txing hyperthyroidism
- Perchlorate (ClO4-)
- Pertechnetate (TeO4-)
- Thiocyanate (SCN)
MOA for potassium perchlorate
major use?
blocks thyroidal uptake of iodine
Txs iodine induced HYPERthyroidism
common drug that causes iodine induced HYPERthyroidism
amiodarone (iodine rich)
Major AE a/w Anion inhibitors?
Aplastic Anemia
What 2 ways do iodides work to tx hyperthyroidism
- inhibit organification and hormone rel
2. decr size of hypertrophic gland
What do iodides precipitate
Wolff-Chaikoff effect
In what situation is the Wolff-Chaikoff reversed w/ time?
term for this reversal effect
effect reverses over time – if iodides used ALONE
escape
When are iodides CI? why?
Pregnancy –> fetal goiter
3 uncommon AEs that are usu reversible when iodides stopped?
- acneiform rash
- swollen salivary glands
- mucous mem ulcerations
When are iodides used? w/what other drugs
rarely used today
used w/PTU and b-blockers for thyroid storm
After radioactive iodide concentrates in thyroid follicle cells what is its MOA
Beta particles selectively destroy thyroid gland
w/out injury to adj cells
What is common eventual AE of radioactive iodide in most pts?
2 CIs
HYPOthyroidism
CI = kids, preg
What dz does radioactive iodide Tx
thyrotoxicosis
2 benefits of radioactive iodide Tx
- euthyroid in 6-8 wks
2. no incr CA risk
3 Things given for PREoperative Tx before subtotal thyroidectomy?
- Thioamide drug
- KI (potassium iodide)
- beta blocker
How long give Thioamide drug for PREoperative Tx before subtotal thyroidectomy?
til euthyroid (~6 wks)
When give Kl as PREoperative Tx before subtotal thyroidectomy? Why?
10 days before surg
- decr gland size/vascularity –> decr surgical risk
Why give beta blocker as PREoperative Tx before subtotal thyroidectomy?
antagonize cathecholamine effects –> sx relief
