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HY points about each drug followed by a quiz at the end
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Thyroid drugs
Thionamides
- Propylthiouracil (PTU)
- Methimazole
MOA of PTU methimazole?
- Both inhibit thyroperoxidase.
- PTU has a second MOA: inhibits 5-deiodinase.
- Thyroperoxidase converts iodide to iodine within the thyroid gland so that it can be added to thyroglobulin for thyroid hormone synthesis.
- 5-deiodinase converts T4 to T3 peripherally.
When are PTU and methimazole used?
- Graves, toxic adenoma, and toxic multinodular goiter (all ↓ TSH, ↑ T3, ↑ T4).
- TSH-secreting tumor (rare) prior to any type of surgery (↑ TSH, ↑ T3, ↑ T4).
- Do not treat subacute granulomatous thyroiditis (deQuervain) presenting with hyperthyroidism with thionamides; use aspirin or steroids.
Major side-effects of PTU and methimazole?
- Agranulocytosis (neutropenia) –> presents as mouth ulcers, sore throat, fever.
- 38F + treated four days ago for hyperthyroidism in hospital + now has a fever and a mouth ulcer; why? –> answer = “drug-induced neutropenia” (PTU or methimazole). This is on 2CK IM form.
- Hepatotoxicity (PTU > methimazole).
- Methimazole is teratogenic in first trimester (causes aplasia cutis congenita).
- In pregnant woman with Graves, PTU is used first trimester; methimazole is then used 2nd and 3rd trimester to spare the patient from PTU’s greater risk of hepatotoxicity with continued use.
Propranolol
- Beta-blockade decreases peripheral conversion of T4 to T3.
- Propranolol the classic beta-blocker used to treat tachycardia in hyperthyroidism.
- See here for a detailed post on beta-blockers and -agonists.
Levothyroxine (T4), Triioiodothyronine (T3)
- Levothyroxine is a T4 analogue (thyroxine is endogenous T4).
- Triiodothyronine is same as endogenous T3.
When are levothyroxine and triiodothyronine used?
- Hashimoto thyroiditis (↑ TSH, ↓ T3, ↓ T4).
- Increase dose by 50% in pregnancy (USMLE asks this detail on Step 3).
- Subclinical hypothyroidism (↑ TSH, normal T3 + T4) if 1) anti-Hashimoto antibodies, 2) pregnant, or 3) TSH >10 mIU/L (NR 0.5-5.0).
- Drug-hypothyroidism (e.g., due to lithium or amiodarone).
- 25F + started on medication for bipolar disorder + cold intolerance + weight gain + TSH is high + serum lithium levels within normal limits; what do we do? –> answer = keep dose of lithium the same + commence levothyroxine.
USMLE wants you to know important physiology with use of these agents:
- 40F + Hashimoto + started on levothyroxine; how will her TSH, T3, and T4 change as a result of this treatment? –> answer = ↓TSH, ↑ T3, ↑ T4; once again, these arrows are the mere changes in the patient’s serum values as a result of the T4 administration. Untreated (or insufficiently treated) Hashimoto will have (↑ TSH, ↓ T3, ↓ T4).
- 40F + Hashimoto + started on triiodothyronine; how will her TSH, T3, and T4 change as a result of this treatment? –> answer = ↓TSH, ↑ T3, ↓ T4. Student says, “Wait, what? Why is T4 down.” Because T4 is converted to T3 peripherally, but not the other way around. If we give thyroxine (T4), of course T4 is high, but so is T3 because it’s converted T4 → T3. However if we give T3, it’s not converted to T4, so T4 (which is already low) will go down further because the T3 induces negative feedback on TSH secretion, and the lower TSH will mean the thyroid gland is suppressed.
Vasopressin (anti-diuretic hormone; ADH) drugs
Desmopressin (DDAVP)
- Vasopressin analogue.
When is it used?
- Central diabetes insipidus (replaces vasopressin).
- von Willebrand disease (stimulates vWD production + release from vascular endothelium).
- Hemophilia A (stimulates factor VIII production + release from the liver and vascular endothelium).
Conivaptan, Tolvaptan
MOA of conivaptan and tolvaptan?
- Vasopressin receptor antagonists.
When are they used?
- SIADH (usually caused by small cell bronchogenic carcinoma or head trauma).
Demeclocycline
MOA of demeclocycline?
- Technically a tetracycline antibiotic, but not used for antimicrobial purposes because it causes nephrogenic diabetes insipidus (i.e., antagonizes vasopressin receptors). However this side-effect is advantageous and capitalized upon in order to treat SIADH.
- For USMLE, demeclocycline and the -vaptan agents are both used for SIADH.
Aldosterone drugs
Spironolactone, Eplerenone
MOA of spironolactone and eplerenone?
- Aldosterone receptor antagonists.
When are they the answer for USMLE?
- Spironolactone or eplerenone used as potassium-sparing diuretic in patients already on furosemide (the latter causes potassium wasting).
- 44M + liver failure + peripheral edema + already taking furosemide; what drug could be added to help with this patient’s edema? –> answer = spironolactone.
- (It should be noted that triamterine and amiloride, which are ENaC inhibitors, are correct answers for this Q as well; I’ve seen this Q with numerous answers).
- Hyperaldosteronism due to adrenal hyperplasia or Conn syndrome (aldosterone-secreting tumor).
- Spironolactone is used in heart failure when patient has low ejection fraction despite already being on an ACEi/ARB and a beta-blocker.
Hierarchy for drugs in heart failure (simplified but HY for USMLE):
- Start with ACE inhibitor or an angiotensin II receptor blocker (ARB) to improve ejection fraction (normal is 55-70%).
- If the patient is fluid overloaded (i.e., peripheral edema or pulmonary edema), attempt to achieve euvolemia by adding furosemide (loop diuretic).
- If insufficient ejection fraction with the ACEi or ARB, add a beta-blocker (metoprolol XR, bisoprolol, carvedilol, and nebivolol decrease mortality in heart failure; propranolol does not).
- If insufficient ejection fraction with ACEi/ARB + beta-blocker, add spironolactone (aldosterone receptor antagonist).
- If insufficient ejection fraction, add the combination of hydralazine + nitrates. Only the combo decreases mortality in HF. It is especially efficacious in African Americans (tend to have stiffer vessels).
- If insufficient ejection fraction when already on ACEi/ARB + beta-blocker + spironolactone + hydralazine + nitrates, add digoxin.
- If pharmacologic therapy insufficient, use implantable device.
Side-effects of spironolactone?
- Gynecomastia (HY for USMLE); eplerenone has much lesser risk.
- Hyperkalemia (potassium-sparing diuretic, but can inadvertently cause hyperkalemia in some patients).
Calcium/Phosphate drugs
Cinacalcet
MOA of cinacalcet?
- Calcimimetic (i.e., sensitizes calcium-sensing receptor on the parathyroid glands).
- Causes a decrease in serum PTH, thereby reducing serum calcium levels.
When is cinacalcet used?
- Secondary hyperthyroidism due to renal failure in patients on dialysis (i.e., once electrolytes are stabilized in patients with renal failure, cinacalcet can help lower the PTH levels).
- Primary hyperparathyroidism refractory to surgery.
What do I need to know for USMLE?
- USMLE is way more likely to ask what effect giving cinacalcet would have on a patient versus why it’s used –> answer = ↓ PTH; ↓ serum Ca2+.
Sevelamer
MOA of sevelamer?
- Phosphate-binder that binds phosphate in the small bowel and prevents its absorption.
- Decreases phosphate levels in patients with chronic renal disease.
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