THYROID PREPARATIONS

MOA/PK

• A preparation of thyroxine (T4)

→ T4 is converted to T3 intracellularly

→ Administration of T4 produces both hormones

• Equi-effective dose: 100mcg

THYROID PREPARATIONS

MOA/PK

• Preparation of T3

• 3-4x more potent

• Shorter half-life: 24 hrs

THYROID PREPARATIONS

MOA/PK

• Best used for short term suppression of TSH

→ Multiple daily doses, higher cost, greater difficulty of monitoring its adequacy

→ Not recommended for routine replacement therapy

• Equi-effective dose: 37.5mcg

THYROID PREPARATIONS

Adverse effects

• Risk of cardiotoxicity

→ Avoided in patients with cardiac disease

THYROID PREPARATIONS

MOA/PK

• Mixture of thyroxine and liothyronine

• More expensive

THYROID PREPARATIONS

MOA/PK

• Disadvantages: Has protein antigenicity, product instability, variable hormone concentrations, difficulty in laboratory monitoring

• Equi-effective dose: 100mg

ANTI-THYROID DRUGS

MOA/PK

• Suppress secretion of T3 and T4 to subnormal levels

• ↑ TSH

• Produces glandular enlargement (goiter)

→ Can also be seen when eating kelp, cassava, cabbage

• Destruction with radiation or surgery

ANTI-THYROID DRUGS

MOA/PK

• Blocks iodine organification

• Blocks coupling of the iodotyrosines

• Do not block iodide uptake

• Onset of action is slow

→ Synthesis, NOT the release of hormones is affected

ANTI-THYROID DRUGS

Adverse effects

→ Maculopapular pruritic rash

→ Nausea

→ GI distress

→ Risk of fetal hypothyroidism

ANTI-THYROID DRUGS (THIOAMIDES)

MOA/PK

• Inhibits peripheral deiodination of T4 and T3

• Rapidly absorbed

→ Incomplete absorption, large first-pass effect

• Most is excreted by kidney as inactive glucuronide w/in 24 hrs

• Plasma t1/2: 1.5 hrs

ANTI-THYROID DRUGS (THIOAMIDES)

Indications

• 1st trimester of pregnancy

• Thyroid storm

• Methimazole allergy

ANTI-THYROID DRUGS (THIOAMIDES)

Adverse effects

→ Severe hepatitis

ANTI-THYROID DRUGS (THIOAMIDES)

MOA/PK

• 10x more potent than PTU

• 3-4x more potent than Levothyroxine

• Serum half-life: 24 hrs

• Completely absorbed

• Slower excretion

ANTI-THYROID DRUGS (THIOAMIDES)

Indications

• DOC in adults and children

• Best used for short-term suppression of TSH

ANTI-THYROID DRUGS (THIOAMIDES)

Adverse effects

• Congenital malformations

• Cholestatic jaundice

• Altered sense of taste or smell

• Agranulocytosis

ANTI-THYROID DRUGS (THIOAMIDES)

MOA/PK

• Converted to methimazole in vivo

ANTI-THYROID DRUGS

MOA/PK

• Block uptake of iodide by the gland

• Competitive inhibition of the iodide transport

ANTI-THYROID DRUGS

• PERCHLORATE (ClO4-)

• PERTECHNETATE (TCO4-)

• THIOCYANATE (SCN-)

ANTI-THYROID DRUGS (ANION INHIBITORS)

Indications

→ Iodide-induced hyperthyroidism (e.g.amiodarone-induced hyperthyroidism

ANTI-THYROID DRUGS (ANION INHIBITORS)

Adverse effects

→ Aplastic anemia

ANTI-THYROID DRUGS

• LUGOL’S SOLUTION

• POTASSIUM IODIDE (KI)

ANTI-THYROID DRUGS

MOA/PK

• Inhibit organification and coupling

• Inhibition of thyroglobulin proteolysis

• ↓ size and vascularity of the hyperplastic gland

• ↑ intraglandular stores of iodine

ANTI-THYROID DRUGS

Indications

• Thyroid storm

→ improvement occurs rapidly within 2–7 days

• Preoperative preparation for surgery

• Thyroid blocking effects of KI can protect glands from subsequent damage if administered before radiation exposure

ANTI-THYROID DRUGS

Adverse effects

• Hyperthyroidism (Jod-Basedow phenomenon)

• Hypothyroidism (Wolff-Chaikoff phenomenon)

ANTI-THYROID DRUGS

Adverse effects

• Should not be used alone

→ may produce severe exacerbation of thyrotoxicosis in an iodine-enriched gland

• Chronic use in pregnancy should be avoided

→ can cause fetal goiter

ANTI-THYROID DRUGS

Adverse effects

• Acneiform rash (similar to that of bromism), swollen salivary glands, mucous membrane ulcerations, conjunctivitis, rhinorrhea, drug fever, metallic taste, bleeding disorders, and rarely, anaphylactoid reactions

ANTI-THYROID DRUGS

MOA/PK

• Administered orally in solution as sodium 131I

• Rapidly absorbed, concentrated by the thyroid, incorporated into storage follicles

ANTI-THYROID DRUGS

MOA/PK

• Destruction of thyroid parenchyma

→ epithelial swelling and necrosis, follicular disruption, edema, and leukocyte infiltration

• Easy administration, effectiveness, low expense, absence of pain

ANTI-THYROID DRUGS

Indications

• Only isotope used for treatment of thyrotoxicosis

ANTI-THYROID DRUGS

Adverse effects

• Should not be used by pregnant women or nursing mothers

• Radiation-induced genetic damage, leukemia, and neoplasia

ANTI-THYROID DRUGS

MOA/PK

• Beta blockers without intrinsic sympathomimetic activity

ANTI-THYROID DRUGS

• METROPROLOL

• PROPRANOLOL

• ATENOLOL

ANTI-THYROID DRUGS

Indications

• Therapeutic adjuncts in management of thyrotoxicosis

→ Symptoms mimic those associated with sympathetic stimulation

• Clinical improvement of hyperthyroid symptoms without altering thyroid hormone levels

ANTI-THYROID DRUGS (ADRENORECPTOR-BLOCKING)

MOA/PK

• ↓ T3 levels approximately 20% by inhibiting peripheral conversion of T4 to T3

• Most widely studied and used in thyrotoxicosis