Thyroid and Antithyroid drugs DSA Flashcards
1
Q
Thyroid agents
A
- Levothyroxine (T4)
- Liothyronine (T3)
- Liotrix (4:1 of T4:T3)
- Thyroid desiccated
2
Q
Antithyroid agents
A
- Radioactive iodine (131) sodium
- Methimazole
- Potassium iodide
- PTU (propylthiouracil)
3
Q
TH biosyn
A
- NIS (sodium/iodide symporter) transports iodine into the thyroid gland
- pendrin- controls the flow of iodide across the membrane
- iodide is oxidized to iodine by thyroidal peroxidase
- iodine iodinates tyrosine residues in thyroglobulin- form MIT (monoiodotyrosine) and DIT (diiodotyrosine)
- 2 molecules of DIT combine with thyroglobulin- forms T4
- 1 molecule of DIT and MIT combine- forms T3
- T4, T3, MIT, DIT released from thyroid gland
- T4:T3 ratio within thyroid gland is 5:1
4
Q
TH transport
A
-T4 and T3 are bound to TBG (thyroxine-binding globulin) in plasma
5
Q
peripheral metabolism of THs
A
- T3 is deiodinated to T3 (4x more potent than T4) or reverse T3 (metabolically inactive)
- T4 may be inact by deamination, decarboxylation, or conjugation
6
Q
THs- pharmacokinetics
A
- oral bioavailability of T4- 80%- t1/2 7 days
- oral bioavailability of T3- 95%- t1/2 1 day
- abs may be affected by myxedma with ileus (but not by mild hypothyroidism)
- T4 and T3 clearance- inc with pts with hyperthyroidism; dec with hypothyroidism
7
Q
drug effects and thyroid fxn- inhibit conversion of T4 to T3 and in reverse T3 levels
A
- radiocontrast agents iopanoic acid and ipodate
- amiodarone
- B-blockers
- corticosteroids
- admin to reduce T3 levels in pts who are experiencing a thyroid storm!
8
Q
drug effects and thyroid fxn- dec T4 abs
A
- antacids (aluminum hydroxide, calcium carbonate
- ferrous sulfate
- cholestyramine
- colestipol
- ciprofloxacin
- proton pump inhibitors
- bran, soy, coffee
9
Q
drug effects and thyroid fxn- induce CYP450s
A
- rifampin, phenobarbital, carbamazepine, phenytoin, imatinib, protease inhibitors
- inc metabolism of T4 and T3
10
Q
TH- moa
A
- TR is bound to DNA at the TRE
- in absence of H- TR homodimer is bound to corepressor proteins (inactive)
- T4 and T3 enter cell- T3 enters nucleus- binds to TR- corepressor is released- coactivator binds- homodimer separates
- TR binds to RXR and gene transcription occurs
11
Q
Thyroid preparations
A
- synthetic or of animal origin (rarely used)
- T4 (levothyroxine)- preparation of choice for thyroid replacement tx- stability, low cost, lack of allergic foreign protein, easy lab measurement of serum levels, long t1/2- once-daily admin
- T3 is 3x more potent- not recommended for routine replacement tx- short t1/2, higher cost, diff of monitoring
12
Q
Antithyroid agents
A
- thioamides
- anion inhibitors
- iodides
- radioactive iodine
- B-blockers
13
Q
Thioamides- pharmacokinetics
A
- PTU- rapidly abs, 50-80% bioavailability, renal excretion, accum in thyroid gland, 3-4 doses a day
- Methimazole- completely abs, accum in thyroid gland, slower renal excretion than PTU, once-daily dosing
14
Q
Thioamides- moa
A
- inhibits the thyroidal peroxidase rxns and blocks iodide organification (blocks the oxidation of iodide in the thyroid gland)
- also inhibits coupling of MIT and DIT to form T3 and 4
- PTU- blocks peripheral conversion of T4 to T3
- hormone synthesis is inhibited!!- requires 3-4 wks of therapy before stores of T4 and T3 are depleted
15
Q
Thioamides- toxicity
A
- maculopapular pruritic rash- most common
- rare- urticarial rash, vasculitis, lupus-like rxn, LA
- most serious complication- agranulocytosis- can be reverse with drug discontinuation and CSFs
16
Q
Anion inhibitors- moa
A
perchlorate, pertechnetate, thiocyanate
-block thyroid gland uptake of iodide by inhibiting the iodide transport mech
17
Q
Iodides- moa, clinical use
A
- inhibit organification and H release- dec the size and vascularity of the hyperplastic thyroid gland
- thyroid storm, preoperative reduction of a hyperplastic thyroid gland, block thyroidal uptake of radioactive isotopes of iodine in a radiation emergency
18
Q
Iodides- toxicity
A
- acneiform rash, swollen salivary glands, mucous memb ulcerations, conjunctivitis, metallic taste
- avoid during pregnancy- can cause fetal goiter
19
Q
Radioactive iodine
A
- tx thyrotoxicosis
- admin orally
- causes destruction of thyroid parenchyma
- ease of admin, effectiveness, low expense, absence of pain
- contraindicated in women who are pregnant or breast feeding
20
Q
B-blockers
A
- w/o intrinsic sympathomimetic activity (metoprolol, propranolol, atenolol)- tx thyrotoxicosis
- propranolol- most common
- improve sx of hyperthyroid
21
Q
drug of choice for replacement therpy
A
levothyroxine
- given on an empty stomach
- 6-8 wks to reach steady-state levels
22
Q
Hypothyroidism management- myxedema coma
A
- end state of untreated hypothyroidism- progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock and death
- give IV due to poor absorption!
23
Q
Hypothyroidism management- myxedema and CAD
A
-correction of myxedema with T4 must be done cautiously to avoid arrhythmia, angina, or acute MI
24
Q
Hypothyroidism management- pregnancy
A
- are typically infertile until restoration of normal thyroid levels
- maintenance of normal levels is crucial to fetal brain development dep on maternal T4
25
Q
Grave’s disease- management
A
- Antithyroid drug therapy- young pts with small glands and mild dz- methimazole (preferred- once daily) or PTU (pregnancy)- admin until remission
- thyroidectomy- very large glands or multinodular goiters- require thyroid supplementation
- radioactive iodine- preferred tx for pts > 12 yo- 80% develop hypothyroidism and require replacement tx
- adjuncts to antithyroid tx- B-blockers (control tachycardia, HTN, a fib); diltiazem when B-blockers contraindicated
26
Q
Thyroid storm- management
A
- B-blockers- control arrhythmia
- potassium iodide- prevent release of THs
- PTU or methimazole- block H syn
- IV hydrocortisone- prevent against shock and block conversion of T4 to T3
- supportive therapy
