Levothyroxine (T₄)

Propylthiouracil – PTU

Methimazole – MMI

Potassium iodide – KI

Radioactive iodide ¹³¹I

Thyroid Hormone Synthesis:

Thionamides: Propylthiouracil (PTU) and Methimazole (Tapezol)

• PTU and Methimazole inhibit the peroxidase enzyme throughout the pathway.
• PTU has the additional effect of blocking the peripheral conversion of T₄ to T₃ by inhibiting the 5′-iodinase.
• Actions reversible when drug is stopped
• Some think that these drugs have some immunosuppressive actions which may be useful in Grave’s disease.
• Side effects:

1)     rash and itching; give anti-histamines

2)     agranulocytosis (1%)

• another mode of treatment: KI (potassium iodide) in high doses is used to inhibit the I^- pump for short term (Wolff-Chaikoff effect); used in the preparation of thyroid surgery. The theory is that you swith the cellular machinery into iodine uptake and storage. But you better hurry and do surgery or give Iodine¹³¹ because with all that new iodine there will be an even bigger surge of thyroid hormone in the next 1-3 days.

Major Actions of Thyroid Hormones

• required for normal growth and development
• major metabolic effects: O₂ consumption, temperature, Basal Metabolic Rate, Carba nd Lipid metabolism
• CV effects: mimic sympathetic stimulation in excess states
• Nervous System: restlessness, irritability, tremor, “hyper” in excess

Mechanism of Action of Thyroid Hormones

• nuclear receptor that functions to regulate the transcription of target genes
• T₃ has > affinity for receptors than T₄

Hypothyroidism

• very common
• Can be caused by:

1)     hypothalamic or pituitary disease or destruction

2)     abnormalities in thyroid gland development or function

3)     surgery

4)     pharmacological ablation (¹³¹I)

5)     treatment with anti-thyroid drugs

6)     immunological

• TREATMENT

Ø  Levothyroxine (T₄) is most frequently used

Ø  Side effects

1)     hyperthyroidism

Ø  Drug interatactions

1)     Cholestyramine decreases absorption of orally administered thyroid hormone

2)     Barbituates increase metabolism

3)     May displace salicylates/anti-inflammatory and anti-epileptic drugs from binding sites on serum proteins

• Myxedema Coma

Ø  end stage hypothyroidism

Ø  comatose, hypothermis, and in shock

• Pediatrics

Ø  neonatal hypothyroidism is fairly common

Hyperthyroidism

• common
• Can be caused by:

1)     thyroid or pituitary disease

2)     treatment with exogenous thyroid hormones

3)     Grave’s Disease

• TREATMENT – above

Ø  Thiourea derivatives – PTU and MMI

-        may require 2-3 weeks in order to deplete stored thyroglobulin

-        actions of drugs reversible when treatment is stopped

Ø  Iodide (KI)

-        inhibits both the synthesis and release of thyroid hormones from the gland

-        thyroid “escapes” this effect within weeks.

-        Used for surgical removal of thyroid tissue

Ø  Radioiodine

-        irreversible because the tissue is destroyed

-        most patients become hypothyroid

-        STOP PTU before giving the ¹³¹I or the PTU will prevent the incorporation of the radioactive agent into the thyroglobulin

Ø  Propranolol

-        tachycardia and tremor

• Thyroid Storm

Ø  rare but life threatening

Ø  DO NOT give aspirin or salicylates for the accompanying fever

• Hyperthyroidism during pregnancy

Ø  PTU and MMI may be used

Ø  PTU often preferred

Ø  Avoid iodide and propranolol

Ø  ¹³¹I contraindicated

Tags: agranulocytosis, Cholestyramine, comatose, hyperthyroidism, hypothalamic or pituitary disease, hypothermis, hypothyroidism, Levothyroxine, Methimazole, pharmacological ablation, Propylthiouracil, Thionamides, Thiourea derivatives, Thyroid Hormone Synthesis, Thyroid Hormones

This entry was posted on Thursday, August 13th, 2009 at 5:00 am and is filed under Pharmacology. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.