Endorcrine pharmacology - HYPER AND HYPOTHYRODISM Flashcards
What can be used to treat a Hypothyroid coma?
Liothyronine (T3)
3- molecules of iodine
Intravenous injection - emergency use (faster onset, but shorter duration of action)
What medication is the typicla medication used to treat hypothyroidism?
Levothyroxine (T4)
50-100 micrograms a day
4 molecules of iodine
Prodrug - T4 converted to T3 in cell to act on a nuclear receptor
What is the mechanism of action of levothyroixine ?
IT DOES NOT WORK ON A CELL MEMBRANE OR CYTOPLASM RECEPTOR.
IT WORKS ON A NUCLEUS RECEPTOR.
Remember, levothyroxine is a prodrug metabolised to triiodothyronine (T3) by iodinase enzymes in the cell membrane.
Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA.
What are the pharmacological effects of levothyroxine?
Note + increased sensitivity to catecholamines means this will effect how you treat the symptoms.
What is the enzyme that adds iodine to tyrosine amino acids contained within the protein thyroglobulin?
Thyroperoxidase enzyme
Therefore you need an inhibitor in hyperthyroidism.
Funciton of carbimazole
Works QUICKLY However, effect takes 2-4 weeks – depletion of thyroid and plasma stores of T4 required.
How do you treat hyperthryodism ?
Inhibitors of Thyroperoxidase
Mechanism of Action
Competitive inhibitors for substrate binding site on thyroperoxidase.
Inhibit the iodination of tyrosyl residues in thyroglobulin
What are the two Inhibitors of Thyroperoxidase
Carbimazole – oral prodrug (active metabolite methimazole) rapid inhibition of enzyme (12h). However, effect takes 2-4 weeks – depletion of thyroid and plasma stores of T4 required.
Propylthiouracil – additional mechanism: reduces the deiodination of T4 to T3 in peripheral tissues may work more quickly. Preferred in thyroid storm
What hyperthyroid medication is preferred in a thyroid storm ?
Propylthiouracil
What does potential for block and replace mean in hyperthryoidm ?
A graded reduction in thyroxine levels in hyperthyroidism can be difficult to achieve.
A system called block and replace may be used where thyroxine synthesis is prevented completely but then levothyroxine is administered orally to maintain normal levels just as it is in hypothyroidism.
Please take care with inhibitors of thyroperoxidase as some 1% of patients suffer from neutropenia and agranulocytosis the symptoms of which may start with a sore throat but include rash, headache and joint pain.
What is a severe adverse effect of inhibitors of thryoperoxidase ?
Please take care with inhibitors of thyroperoxidase as some 1% of patients suffer from neutropenia and agranulocytosis the symptoms of which may start with a sore throat but include rash, headache and joint pain.
Important to measure the level of neutrophils within the system.
What are catecholamines
Catecholamines are hormones made by your adrenal glands, two small glands located above your kidneys.
How would you treat the symptoms of hyperthyroidism?
This occurs due to the sensitivity to catecholamines.
Due to the increase in sensitivity to catecholamines, a symptom of hyperthyroidism is tachycardia and arrhythmia due to stimulation of the sympathetic nervous system. It is important to understand that the acute cardiac effects of hyperthyroidism are treated with Beta-blockers such as propranolol, rather than antithyroid drugs.
