Anti-thyroid drugs Flashcards
What is the recommended sodium intake per day?
150mcg
What transports Iodide to colloid which will be oxidized to Iodine via thryopoietin?
Pendrin
What are the 2 phenomenon that induces hyper- & Hypothyroidism?
Wolff-Chaikoff effect -> Hypothyroidism
Jod-Basedown Phenomenon -> Hyperthyroidism
What occurs in Wolff-Chaikoff effects & Jod-Basedown phenomenon?
Jod-Basedow phenomenon –> Impaired auroregulation –> escape from neg feedback –> Hyperthyroidism
Wolff-CHaikoff effect –> protective autoregulatory inhibition of organification –> protects TG –> hypothyroidism
What is the difference betw the duration of Wolff-Chaikoff effects & Jod-Basedown phenomenon?
WC effect –> transient physiologic response (24-48hrs)
HB phenomenon –> pathologic response that can lead to a thyroid storm
In what conditions do Wolff-Chaikoff effect & Jod-Basedown phenomenon occur?
Hashmito’s thyroiditis -> WC effect
Graves’ Disease –> JB Phenomenon
What are the 2 types of hypothyroidism & what is its difference?
Primary –> problem within the TG –> Iodine deficiency
Central hypothyroidism –> problem in either PG or Hypothalamus –> TSH deficit
What is the problem in secondary & tertiary central hypothyroidism?
2ndary => pituitary disease –> TSH deficit
3ary => Hypothalamic disease –> TRH deficit
What are the diff conditions that causes primary hypothyroidism?
Congenital hypothyroidism => Dyshormonogenesis, Dysgenesis
Hashimoto’s thyroiditis => Autoimmune destruction of thyroid via anti-TPO
Iatrogenic hypothyroidism => After iodinated contrast media
Which of the 2 thyroid hormones (T3 & T4) are absorbed better orally?
T3 = 95%
Which of the thyroid hormones is more protein-bound?
T4 = 99.96%
Which of the thyroid hormones is more potent biologically?
T3
Which of the thyroid hormones has a greater total & free serum concentration?
T3
What can impair T4 absorption?
interactions with food like brain, fiber, soy, coffee
What is the thyroid function test result in Hypothyroidism?
HIGH = TSH
LOW = Total T4, Total T3, Free Te & T4
What is the result of thyroid function test result in HYPERthyroidism?
HIGH = Total T3 & T4, Free T3 & T4
LOW = TSH
Why is it that T3 is more biologically active than T4?
because TH receptor has a greater affinity to T3 than T4
What are the diff effects of Thyroid hormones?
Growth & Development (brain & repro tissues)
Metab of CHO, Fats, CHON, vitamins, & drugs
Secretion & Degradation rates of all other hormones
INC Beta-adrenergic receptors and amplification of its signal (Palpitations, tachycardia, tremor, sweating, anxiety, heat intolerance)
What are the clinical uses of T3 & T4?
Levothyroxine replacement therapy in HYPOthyroidism –> regression on nontoxic goiter if present
–> TSH suppression –> post thyroidectomy in thyroid cancer –> DEC risk of tumor recurrence
What are the 2 preparations of T3, T4?
Synthetic T3 (Liothyronine)
Synthetic T4 (Levothyroxine)
Which of the 2 preparations of Thyroid hormones is used for SHORT term TSH suppression to DEC risk of cardiotoxicity due to elevations in peak levels?
Synthetic T3 (Liothyronine) –> T3 + T4 combination
Why is Synthetic T4 (Levothyroxine) the preparation of choice between the 2?
stability & content uniformity
lack of allergenic foreign protein
long halflife (7 days)
easy lab monitoring & low cost
What is the basis for T4 monotherapy?
peripheral T4 to T3 conversion
How much Levothyroxine is given in px?
50-100mcg/day
-> INC dose in pedia, preggos & thryoid cancer px
-> DEC dose in elderly & cardiac px
What are the special instructions for administration & monitoring of Levothyroxine?
Take on an empty stomach 1hr before or 4 hrs after meal
Measure serum TSH & FT4 before any change in dosage
What are the possbile implications of T4 toxicity when administering Levothyroxine?
Pedia: restlnessness, accelerate bone growth
Adult: symptoms of hyperthyroidism
Elderly: A-fib & Osteoporosis
At what point after administering Levothyroxine do you administer activated charcoal ?
Thyroxine toxicity
In what case do you decrease the dose of Levothyroxine?
Androgen, antibiotic steroids, asparaginase administration can DEC TBG
In what case do you INC the dose of Levothyroxine?
to INC metabolism of TH ,TBG (Enzyme inducers, Estrogen, Tamoxifen, Raloxifene, Methadone) & DEC peripheral conversion (Propanolol, Corticosteroids, Amiodarone)
What are the important C/Is of Levothyroxine?
Uncorrected adrenal insufficiency –> adrenal crisis
BBW –> DO NOT use to tx obesity/promote weight loss
What is the end state of untreated/decompensated HYPOthyroidism associated with progressive weakness, STUPOR, hypothermia, hypoventilation, hypoglycemia, hyponetremia, H2O intoxication, shock, & Death?
Myxedema coma
What should be given in px in Myxedema coma?
IV Levothyroxine 300-400mcg loading dose
50-100mcg daily
What are the diff causes of HYPERthyroidism?
Iodine excess
Amiodarone-induce thyrotoxicosis
Graves disease
Toxic nodular goiter (Plummer disease)
Subcute thyroiditis
Pregnancy
Pitutary adenoma
What condition has a goiter caused by a single toxic nodule?
Plummer disease/Toxic (uni- or multi-) nodular goiter
What condition develops Ab against TSH receptors where instead of attacking/destroying them, they stimulate it?
Graves’ disease
anti-TSH-Receptor
What condition has Amiodarone causing the disease of peripheral conversion of T4 to T3 and results in hypothyroidism? What causes this condition hyperthyroidism?
Amiodarone-induced thyrotoxicosis
Presence of iodine in Amiodarone that can induce hyperthyroidism (~3% only)
What is the diff betw HYPERthyroidism & Thyrotoxicosis?
Hyperthyroidism = INC synthesis & secretion of TH
Thyrotoxicosis = Excess circulating TH
What are important clin manifestations of HYPERthyroidism?
Retracted upper lids, bulging eyes, moist skin, INC HR, INC BMR, Heat intolerance, INC hormone degradation, anxiety, INC drug metabolism, DEC weight loss
What are the 6 anti-thyroid drugs?
Thioamides
Anions
Iodides
Radioactive Iodine
Beta blockers w/o ISA
Glucocorticoids
What are the 2 thioamides?
Methimazole
Propylithiouracil
Which of the 2 thioamides is more potent, higher transfer across placenta, longer DOA?
Methimazole (MMI)
Distribution = concentrated by Thyroid Gland
What is the DOC betw the 2 thioamides? What is preferred during 1st trim of preggos?
Methimazole
Preggos: Poprylthiouracil
What is the MOA of Thioamides & Clinical use?
MOA: inhibits iodine organification & coupling of MIT/DIT
-> PTU: inhibits peripheral deiodination of T3 &T4
Use:
-> HYPERthyroidism (primary tx)
-> adjunct to thyroid surgery for toxic multinodular goiter
What are the diff Anions (anti-TD)?
Perchlorate, Pertechnetate, Thiocyanate
What is the MOA, use, & Serious AE of Anions?
MOA: Blocks Iodide uptake through competitive inhibition of Na iodide transporter
Use: Amiodarone-induced hyperthyroidism type I
AE: Aplastic anemia (Disuse)
What are the 2 Iodides (anti-TD)?
KI and Lugols’ soln
What is the primary tx of HYPERthyroidism/
Methimazole
What are the actions of Iodides on TG?
DEC size
Inhibits proteolysis, DEC hormone release
Symptomatic, rapid relief in thyroid storm
Adjuvant to thyroid surgery
SHORT-TERM clinical use
What condition can form if there is persistent Wolff-Chaikoff?
Fetal goiter; that’s why it is avoided during preggos
Should Iodides be administered w/ food or diluted fluids?
YES
What is the MOA of radioactive iodine?
emission of beta rays –> destruction of Thyroid parenchyma
What are the clinical uses of Radioactive iodine?
Permanent cure of thyrotoxicosis
Tx of inoperable thyroid cancer
Adjuvant therapy to surgery for thyroid cancer
What are C/I of Radioactive iodine & important AEs?
C/I: Preggos & lactation
AE: permanent hypothyroidism
What is the MOA of beta-blockers w/o ISA?
competitively blocks beta-adrenergic receptors, ameliorating clinical signs and sympotoms of thyrotoxicosis & thyroid storm
Atenolol, Metroprolol, Propranolol
Which BB inhibits peripheral conversion of T4 to T3 & REDUCES T3?
Propranolol @ >160mg/day
What are the uses of BB in thyroid diseases , AE, & C/I?
Use: Control tachycardia, HTN, A-Fib
AE: Bronchospasm, bradycardia, hypotension
C/I: Bronchial asthma, Severe HF
What anti-inflam agent is used in severe hyperthyroidism?
Glucocorticoids
What conditions uses Glucocorticoids during severe HYPERthyroidism?
to manage thyroiditis in Amiodarone or infection
Relieves Sx of Graves ophthalmopathy
Manages severe metabolic stress in neonatal Graves’ disease
What conditions thyroid diseases use Oral Prednisone?
AIT type II
Severe subacute thyroiditis
Severe Graves’ disease
What thyroid disease uses Topical Triamclinolone covered w/ occlusive dressing? !!!!!
Graves’ dermopathy
What thyroid disease uses IV Hydrocorticosterone to protect the px against shock & reduce circulating TH levels by peripheral inhibition?
!!!
Thyroid storm
What are diff special problems in special populations?
Graves’ ophthalmopathy
Thyroid storm
Neonatal Graves’ disease
What drug is given in CVS symptoms of Thyrotoxicosis?
Propranolol
What is the prevention of progression of Graves’ ophthalmopathy?
Smoking cessation
What DOC is given to Graves’ opthalmopathy?
Oral Prednisone
Alt: irradiation of posterior orbit
What are tx of underlying thyroid dis & management of complications?
Tx of underlying thyroid dis: Surgery or RAI
Management of complications:
-> threatened visual loss: SURGICAL DECOMPRESSION OF ORBUT
-> residual eyelid/eye muscle problems: SURGERY
What drugs are used in cases of thyroid storm?
Propanolol
Propylthiouracil
Hydrocortisone
What is the cause of neonatal graves’ dis?
Passage of maternal TSH-R Ab through placenta into fetus
What are the drug measures for neonatal Graves’ dis?
PROPYLthiouracil
Propanolol
K Iodide (Lugol’s soln)
Prednisone
What is given in 1st, 2nd, & 3rd trimester of preggo mothers w/ HYPERTHYROIDISM
1st trim = Polythiouracil
2nd & 3rd trim = Methimazole
What is given in preggos mothers with HYPOTHYROIDISM?
Levothyroxine
What is a definitive therapy given in subtotal thyroidectomy in 2nd trimester?
Methimazole
