T10 pharmacology of thyroid drugs

hyperthyroidism - drugs

thioamides, anion inhibitors, radioactive iodine (131I), iodides, beta blockers, glucocorticoids, guanethidine

thioamides - drug names

PTU, methimazole, carbimazole

thioamides - mechanism

inhibit thyroid peroxidase → block hormone synthesis & iodine organification

PTU - mechanism

inhibits peripheral conversion of T4 to T3

methimazole - pharmacokinetics

half life 6 hours (good)

thioamides - pharmacokinetics

secreted in low breast milk concentration

thioamides - side effects

agranulocytosis, nausea, rash, GI upset, fever

agranulocytosis

suppress WBC → effect immune system

PTU - uses

preferred in 1st trimester pregnancy

anion inhibitors - drug names

perchlorate, thiocyanate, pertechnetate

anion inhibitors - mechanism

compete with iodine at Na+/I- symporter → block iodide uptake

anion inhibitors - uses

hyperthyroidism patients

anion inhibitors - side effects

aplastic anemia

anion inhibitors - contraindications

rare clinical use → high risk of toxicity

radioactive iodine (131I) - mechanism

concentrated in thyroid → destroys follicular cells via beta-emission

radioactive iodine (131I) - pharmacokinetics

oral, rapidly absorbed

radioactive iodine (131I) - contraindications

pregnancy & breastfeeding

iodides - mechanism

inhibit organification and hormone release, reduce gland size and vascularity

iodides - side effects

rash, salivary gland swelling, mucosal ulcers, rhinorrhea, fetal goiter if cross placenta

iodides - pharmacokinetics

not used alone or long-term → withdrawal worsen thyrotoxicosis

beta blockers - drug name

porpanolol

beta blockers - mechanism

inhibits T4 → T3 conversion

glucocorticoids - drug names

dexamethasone, hydrocortisone, prednisolone

glucocorticoids - mechanism

inhibits T4 → T3 conversion

glucocorticoids - uses

thyroid storm or severe thyrotoxicosis

guanethidine - mechanism

inhibits catecholamine release → reduce exophthalmos

graves disease - treatments

antithyroid drug therapy, thyroidectomy, radioactive iodine therapy, adjuncts to antithyroid therapy

antithyroid drug therapy - uses

young patients (< 50 years), mild/moderate thyrotoxicosis, small goiters

antithyroid drug therapy - drugs name

methimazole & PTU

antithyroid drug therapy - PTU - uses

1st trimester of pregnancy or thyroid storm

antithyroid drug therapy - period

long term therapy (12-18 months)

antithyroid drug therapy - purpose

restore euthyroid state

thyroidectomy - uses

very large thyroid glands, multinodular goiter

thyroidectomy - pharmacokinetics

antithyroid drugs (6 weeks), KI (10-14 days) pre-op

thyroidectomy - mechansim

near-total thyroid removal

heart disease / severe thyrotoxicosis / elderly - start with

antithyroid drug for euthyroid state

heart disease / severe thyrotoxicosis / elderly - stop antithyroid when

3-5 days before RAI

heart disease / severe thyrotoxicosis / elderly - after antythyroid drug

administer RAI

heart disease / severe thyrotoxicosis / elderly - after RAI

wait 6-12 weeks → thyroid gland shrinks

heart disease / severe thyrotoxicosis / elderly - after thyroid gland shrinks

develop hypothyroidism → levothyroxine lifelong

adjuncts to antithyroid therapy - uses

older patients, heart disease

adjuncts to antithyroid therapy - drug names

beta blockers → propanolol

adjuncts to antithyroid therapy - mechanism

control tachycardia, palpitations, hypertension

thyrotoxicosis / thyroid storm - what is it

sudden acute exacerbation of all symptoms of thyrotoxicosis (hyperthyroidism)

thyrotoxicosis / thyroid storm - treatments steps

block peripheral effect of TH → stop production of TH → inhibit hormone release → supportive therapy

thyrotoxicosis / thyroid storm - block peripheral effect of TH

propanolol (beta blocker) → control severe cardiovascular manifestation

thyrotoxicosis / thyroid storm - stop production of TH

PTU → inhibit conversion of T4 to T3 & prednisolone → protect against shock & block conversion of T4 to T3

thyrotoxicosis / thyroid storm - inhibit hormone release

KI → after giving antithyroid medication

thyrotoxicosis / thyroid storm - supportive therapy

control fever, heart failure, underylying disease

thyrotoxicosis during pregnancy - contraindicated treatment

radioactive iodine

thyrotoxicosis during pregnancy - safe management

PTU (first trimester)

thyrotoxicosis during pregnancy - mid-trimester

subtotal thyroidectomy if other medical therapy fails

neonatal graves disease - pathophysio

placental transfer of maternal TSH receptor antibodies OR inherited genetic mutations

neonatal graves disease - treatment

propranolol, PTU, lugol’s solution, prednisolone oral

nontoxic goiter - what is it

thyroid enlargement without excessive thyroid hormone production → due to iodine deficiency

nontoxic goiter - treatment

iodide to encourage consumption of iodine-rich foods

hypothyroidism - treatment

levothyroxine, liothyronine, liotrix

levothyroxine - formulation

oral sodium salt

levothyroxine - pharmacokinetics

half life 7 days, slow onset

levothyroxine - uses

first line therapy

levothyroxine - administation

taken on empty stomach

levothyroxine - contraindications

caution in cardiac patients

levothyroxine - advantages

stable, long half life, inexpensive, easy to monito

liothyronine - formulation

synthetic form of T3

liothyronine - pharmacokinetics

half life 24 hours, fast onset

liotrix - formulation

combined (4:1)

liotrix - pharmacokinetics

mimics physiological ratio but expensive

myxedema & coronary artery disease - concerns

elderly patients may have coexisting coronary artery disease

myxedema & coronary artery disease - treatment strategy

cardiac surgery → levothyroxine therapy

myxedema coma - concerns

hypothyroidism with decreased mental status and hypothermia

myxedema coma - treatment strategy

ICU with IV levothyroxine & IV hydrocortisone

hypothyroidism and pregnancy - concerns

thyroxine essential for fetal brain development

hypothyroidism and pregnancy - treatment strategy

increase levothyroxine dose by 25%, free form of T4 for placental transfer