thyroid drugs Flashcards
thyroid hormones
T3 and T4
T3
triiodothyronine
T4
thyroxine
controller of production of thyroid hormone
TSH
TSH causes
- increase blood flow to thyroid
- uptake of iodine into thyroid
- iodination of tyrosine in thyroglobulin
- formation of thyroglobulin associated T3 and T4
- release of stored T3 and T4
increases all steps
dietary form of iodine
iodide
movement of iodide
transported by high efficiency active transport into the cell
peroxidase strips off electron to make iodine into a radical
iodine binds tyrosine
3 iodines added to make T3 or 4 added to make T4
thyroglobulin
once properly iodinated is transported into the follicle and released under direction of TSH
taken up into vessicle where proteases cleave the protein and release the T3 and T4 amino acids and insert them into circulation
activity of thyroperoxidase
facilitates radicalisation and iodination and diodination
effects of thyroid hormones
- growth and maturation
- increased metabolic rate - increased uptake of amino acids and glucose, increased production of ATP
- adrenergic facilitation
effects of thyroid hormones
- growth and maturation
- increased metabolic rate - increased uptake of amino acids and glucose, increased production of ATP
- adrenergic facilitation
ligand for thyroid hormone receptor
T3
thyroid hormone receptor requires
retinoid x receptor
has to meet T3 together to become a transcription factor and enter the nucleus
TRE
thyroid hormone response element - the sequences of DNA recognised by the complex of thyroid hormone receptor and retinoid x receptor
hypothyroidism may be caused by
- autoimmune thyroid disease
- odine deficiency
- surgical removal or radio-iodine treatment
- drug induced (lithium, antithyroid drugs, amiodarone)
hyperthyroidism may be caused by
- graves disease (TSH receptor antibodies)
- thyroid adenoma
- thyroid hypertrophy (iodine sufficiency after deficiency)
- over production of TSH (rare)
replacing T3
more rapidly effective, eliminated more rapidly
available as IV formulation, for rapid treatment or life threatening hypothyroidism
also available as oral
replacing T4
longer half life
available oral formulation
adverse effects of supplementing T3 and T4
- sinus tachycardia and other arrhythmias
- angna
- restlessnesss
- tremor
hyperthyroidism
- remove gland and replace T4
- irradiate gland and replace T4
- inhibit thyroperoxidaase
- prevent peripheral deiodination of T4
- interfere with sympathetic nervous system facilitating action of T3 and T4
irradiate thyroid gland
taken orally as an iodide salt (radioactive form)
actively incorporated by thyroid epithelium
beta emission leads to death of thyroid tissue
half life of 8 days
patient ultimately becomes hypothyroid
then needs T4 replacement
thiourylenes
carbimazole (a pro-drug for mathimazole) and methimazole
propylthiouracil
short half life, so dosed 2-4 times daily
slow onset of action, depletes follicle contents over 3 to 4 weeks
adverse effects of thiourylenes
excessive suppression leads to hypothyroid
immunological, idiosyncratic
- marrow aplaasiaa or agranulocytosis
- skin rashes and other immune-mediated injuries
- severe liver toxicity with propulthiouracil
potassium iodide
big doses
very rapid suppression of hyperthyroidism
onset at around 12 hours
control is quickly lost
mechanism of potassium iodide
suppresses release of stored thyroid hormone
inhibits peripheral conversion of T4 to T3
clinical use of potassium iodide
fast, temporary suppression of hyperthyroidism
- life threatening hyperthyroidism
- hyperthyroid patient facing emergency surgery
monitoring T4 replacement and anti-thyroid drugs
- TSH level more generally useful
high TSH = needs more T4 or less antithyroid
low TSH = needs less T4 ore more antithyroid
free T4 measurement appropriate in some specific clinical situations
high TSH
high TSH = needs more T4 or less antithyroid
low TSH = needs less T4
low TSH
low TSH = needs less T4
beta adrenergic blockaade
antagonises thyroid hormone facilitation of sympathetic activity
adjunct in managing hyperthyroid-related tachyarrhythmias
suppresses sympathetic manifestations - tachycardia, tremor, eyelid retraction
