Pharm endocrine (Thyroid) drugs

Question 1

LevoThyroxine (T4)

Answer 1

• Treatment of choice for replacement therapy in HYPOthyroid pts
• 1/2 life 7 days = 1 a day
• Circulates bound to thryroxine-binding globulin protein (TBG)
• Circulating depot allowing for normal regulatory target tissue conversion of T3
• Liothyronine (T3)
• Active hormone, short 1/2 life MORE expensive

Question 2

Hypothyroid Pharm

Answer 2

• MOA (T3&T4)
• Activation of nuclear receptors results in gene expression w/ RNA formulation = protein synthesis
• PK:
• T4 converted to T3 @ target tissues (liver, kidney)
• T3 MORE potent than T4-preferred in myxadema (severe hypo) rapid onset IV
• Adverse effects:
• Symptoms of HYPERthyroidism
• Osteopenia (low bone density), pseudotumor cerebri, MI
• Contraindications:
• MI, uncorrected adrenal cortical insuff, Untreated Hyperthyroidism

Question 3

Hypothyroid Pharm (interactions)

Answer 3

• Drug interactions:
• Cholestyraine (reduce bile acids) & sodium polystyrene sulfonate (reduce hyperkalemia) decrease absorption of T3/T4
• Rifampin (TB) & Phenytoin (anticonvulsant) Increase metab of T3/4
• Conditions that alter TBG levels require dose-adjustment-
• Increase binding = estrogens, pregers (hypothyroid women require high doses)
• Chronic liver disease
• HIV
• _Decrease binding _
• Acute liver disease
• Glucocorticoids
• Androgens
• Acute illness

Question 4

Iodide Uptake Inhibitors

Answer 4

• _MOA: _
• Compete w/ Iodide for uptake into the thyroid follicular cells via Na-iodide symporter
• OVERALL effect decrease in iodide available for thyroid synthesis
• DRUGS:
• Perchlorate
• Thiocyanate
• Pertechnetate
• Clinical uses: Hyperthyroidism
• Adverse effects:
• GI
• Aplastic anemia (RBCs in bone marrow)

Question 5

Radioactive Iodine (131-I)

Answer 5

• Isotope used to treat thyrotoxicosis
• MOA:
• emits both beta & gamma particles - destroys gland tissue
• PK: 99% of radioactivity gone after 2 mnths
• Adverse effects:
• Pts can become hypothyroid - managed with T4
• Common = sore throat
• Contraindications - Pregers & lactation
• Used to measure iodine uptake & thyroid imaging (emits gamma particles & 1/2 life 13hrs)

Question 6

Iodides: K+ iodide & inorganic iodide

Answer 6

• End result to decrease circulating thyroid hormone
• Inhibit organification (active T3)
• Decrease size & vascularity of hyperplastic gland
• PK:
• Oral admin - HIGH doses
• Acute onset with 2-7 days
• Effect reversible & transient - NOT for long-term gland immune after 14 days
• Clinical use:
• Prep for surgical thyroidectomy = temp suppression of thyroid gland function
• Adverse effects:
• May worsen hyperthyroidism
• Lugol’s solution = antiseptic or to purify drinking water

Question 7

Thioamides

Answer 7

• PTU (propylthiouracil) & Methimazole
• MOA:
• Inhibit thyroid peroxidase = block iodine organification & coupling rxns
• PTU also INHIBITS T4 -> T3
• PK: oral w/slow ondet (4weeks)
• Clinical uses:
• Hyperthyroidism
• Prep patients for thryoidectomy
• Adverse effects:
• Nausea, GI, Rash, Hepatitis, hypothryroidism
• Agranulocytosis (bone marrow failure WBCs)
• Considerations: methimazole preferred lower issue of side effects
• BOTH are class D (high retriction)

Question 8

Beta-Blockers

Answer 8

• Symptoms of HYPERthyroidism “look like” non-speific beta adrenergic activation
• AKA thyroid storm (tachycardia, tremor, sweating)
• Beta blockers help control these effects
• Beta blockers inhibit conversion of T4-T3
• Propranolol = NOT drug of choice for this
• ESMOLOL = preferred due to rapid onset & short 1/2 life