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Flashcards in thyroid pharmacology Deck (57):

Which drugs can cause hypothyroidism

lithium, amiodarone, cholestyramine, phenytoin, carbamazepine



synthetic T4


Levothyroxine- time course

Resolution of symptoms begins within 2-3 weeks. Requires 6-8 weeks of maintenance dose to reach steady-state plasma levels . Thyroid function tests should be assessed at least 6-8 weeks after any dosage change


Levothyroxine- contraindications

cardiac disease


Hypothyroidism during pregnancy

Requires an increased dose (avg 25% increase) due to: 1. Increased levels of TBG (via  estrogen) decreases free T4-T3. 2. Increased placental metabolism of T4-T3.


Myxedema coma

An extreme form of hypothyroidism, so severe as to readily progress to death unless diagnosed promptly and treated vigorously. Na and glucose drop, hypothermia, shock and possibly death.


Myxedema coma treatment

1. large doses of T4- IV loading dose followed by daily IV dosing. 2. hydrocortisone to prevent adrenal crisis b/c T4 may increase its metabolism


Thyroid hormones absorption

Best in ileum-colon. bioavailability - T4: 65-85%, T3: 95%. May be modified by binding proteins (T4), food or intestinal flora. Absorption is impaired in severe myxedema, so IV only.


Levothyroxine- instructions for usage

empty stomach with water, 30-60 min before breakfast or 4 hours after last meal in evening


Levothyroxine- drugs that can impair absorption

•Metal ions (antacids, calcium and iron supplements). Ciprofloxacin, bile acid sequestrants, raloxifene, sucralfate. Avoid interaction by spacing levothyroxine dose 2 hrs before or 4-6 hrs after interacting drug


amount of free T3 and T4 in plasma

free T4 = 0.04%, free T3 = 0.4%


Levothyroxine- drugs that affect protein binding

Increased binding: estrogens/SERMs, methadone, 5-fluorouracil, heroin. Decreased binding: glucocorticoids, androgens, salicylates, anticonvulsants (phenytoin-carbamazepine), furosemide


Activation of thyroid hormones

•T3 (80%) utilized by peripheral tissues is derived from T4 deiodination in liver via 5'-deiodinase. T3 in brain and pituitary derived by intracellular deiodination


Drugs that inhibit conversion of T4 to T3

glucocorticoids, Beta blockers, amiodarone, propylthiouracil


Conditions which inhibit conversion of T4 to T3

acute/chronic illness, caloric deprivation, malnutrition, fetal/neonatal period


Inactivation of T3

•Deiodination to reverse T3, Deamination, decarboxylation, conjugation to glucuronide or sulfate


Conditions which cause increased/decreased metabolic clearance of thyroid hormones

•Increased in hyperthyroidism and CYP450 induction - decreased by hypothyroidism


Half life of T3 and T4

T4: 7 days (due to protein binding). T3: 1 day.


When should Thyroid function tests be monitored for hypothyroidism

6-8 weeks after any change in levothyroxine


Liothyronine MOA

aka triiodothyronine. Synthetic T3.


Liothyronine uses

NOT recommended for routine replacement due to short t1/2 (greater Cp fluctuations between doses), high cost.


Liothyronine contraindications

cardiac disease- T3 activity has greater risk of cardiotoxicity. Also may increase risk of osteoporosis


Liotrix - MOA

4:1 mixture of T4 and T3.


Liotrix uses

No advantage b/c T4 conversion to T3 in periphery results in near normal ratio. Rarely required, not recommended.


Liotrix adverse outcomes

May increase incidence of low TSH concentrations and increase markers of bone turnover


Thyroid USP MOA

Dessicated porcine thyroid extract containing T3 and T4


Thyroid USP disadvantages

1. Variable T4/T3 ratio and content - unexpected toxicities. 2. protein antigenicity. 3. instability.


Thyroid USP uses

Less desirable than levothyroxine - current recommendation is use in hypothyroidism should be avoided


Adverse reactions of thyroid hormones in children and adults

Children: restlessness, insomnia, accelerated bone maturation. Adults: anxiety, heat intolerance, palpitations-tachycardia, tremors, weight loss, diarrhea. Also sympathetic overactivity: can precipitate arrhythmias, angina, or MI in patients with cardiac dz


Drug interactions with thyroid hormones

•Increased adrenergic effect of sympathomimetics: epi or decongestants (pseudoephedrine - phenylephrine)


In general, treatment of graves disease

1. interfere with hormone production (synthesis inhibitors): thionamides, idodides. 2. Modify tissue response (symptomatic improval): beta blockers, corticosteroids. 3. glandular destruction: radioactive iodine or surgery


List thionamides

Methimazole, propylthiouracil


Who responds best to methimazole- PTU

mild dz, small gland, young patients


Benefits of specific beta blockers in graves disease

Used for symptom relief until hyperthyroidism is resolved. Propranolol: blocks T4 to T3 conversion. Metoprolol-atenolol: B1 selective, longer T1/2.


Methimazole-PTU MOA

Inhibits thyroid peroxidase blocking T4/T3 synthesis. Blocks iodine organification and iodotyrosine coupling. At high doses PTU blocks peripheral conversion of T4 to T3.


Time course of methimazole- PTU actions

requires 3-4 weeks to deplete T4


Methimazole- PTU uses

Only for thyrotoxicosis from excess production (Graves disease - high RAI) NOT excess release (low RAI)


methimazole- PTU absorption

rapid. PTU is incomplete. Methimazole is complete


Methimazole- PTU distribution

Both can cross placenta and are concentrated by fetal thyroid, so use with caution in pregnancy. PTU is more protein bound so it crosses the placenta less readily and has less secretion into breast milk.


Methimazole-PTU elimination/ half lives

Short half lives (PTU 1-2 hrs, methimazole 5-13 hrs) - but drugs accumulate in thyroid - thus clinical actions longer. PTU given 2-3 times per day. Methimazole once daily


Methimazole-PTU uses

Clinical resolution of thyrotoxicosis within 2 weeks. Biochemical resolution in about 6 weeks.


Situations where methimazole-PTU alone are effective in graves

small goiter, low level of anti-TSH receptor Ab, and mild-to-moderate hyperthyroidism


remission with methimazole-PTU for graves

•Remission within 12-18 months. 1/3 will have lasting remission. 60-70% will have recurrence of graves


Methimazol -PTU adverse rxns

Agranulocytosis is most dangerous. Pruritic rash, GI intolerance, arthralgias more common. For PTU only, hepatotoxicity is rare but serious.


Compare methimazole vs PTU

Methimazole generally preferred: efficacy at lower doses, once-daily dosing, and lower side effect incidence. PTU is safer to fetus - treatment of choice in pregnancy


list iodides

SSKI (super saturated potassium iodide) and Lugols solution (potassium iodide/iodine)


SSKI- Lugols solution MOA

•Inhibit T4-T3 synthesis (via elevated intracellular [I-]). Inhibit T4-T3 release (via elevated plasma [I-]) > block Tg proteolysis


SSKI- Lugols uses

1. severe thyrotoxicosis-thyroid storm b/c rapid onset. 2. decrease size and vascularity of hyperplastic gland before surgery.


SSKI- Lugols disadvantages

variable effects, rapid reversal when withdrawn, potential to produce new T3 and worsen hyperthryoidism


SSKI- Lugols adverse rxns

acneform rash, rhinorrhea, metallic taste - swollen salivary glands (selective accumulation)


Radioactive iodine MOA

Administered orally- concentrates in thyroid. Beta radiation causes slow inflammatory process that destroys the parenchyma of gland over a period of weeks to months.


Radioactive iodine advantages

easy administration, effective, low expense, no pain


Radioactive iodine disadvantages

slow onset (2-6 months and 10% require second dose), radiation thyroiditis via release of preformed T3 may cause cardio complications in elderly, worsening of ophthlamopathy, causes hypothyroidism.


Who should not receive radioactive iodine

pregnant or nursing women, elderly


Use of surgery for graves dz

Less commonly used b/c radioactive iodine has better benefit to risk ratio. 50-60% require thyroid supplementation afterwards due to iatrogenic hypothyroidism. Can be used in 2nd trimester of pregnancy if needed


What is a thyroid storm

Sudden acute exacerbation of thyrotoxicosis causing fever, flushing, sweating, tachycardia-atrial fibrillation, delirium, coma. May occur if patients are non-compliant, incompletely treted, undiagnosed and have an acute stressor. Sx are due to hypermetabolism and excessive adrenergic activity


Treatment of thyroid storm

1. Propranolol- IV or PO to control CVS sx plus block T4 to T3 conversion. 2. NaI (IV) or KI (oral) to slow hormone release. 3. PTU blocks hormone synthesis plus blocks T4 to T3 conversion. 4. Hydrocortisone protects against shock plus blocks T4 to T3 conversion plus modulates immune response