Drugs for thyroid disorders Flashcards
What will you see in the thyroid levels of someone w/ hypothyroidism?
Dec T3
Dec T4
Inc TSH
What will you see in the thyroid levels of someone w/ hyperthyroidism?
Inc T3
Inc T4
Dec TSH
Outline the normal mechanism of thyroid hormone release
Hypothalamus –> TRH –> anterior pituitary —> TSH –> thyroids –> T3/T4 –> target cells
Outline the basic phases of thyroid hormone synthesis as well as how T3 and T4 is made (what is combined)
Synthesis = tyrosine –> iodine + thyroid (thyroxine peroxidase) –> mono-iodotyrosine (MIT) –> Di-iodotyrosine (DIT)
MIT + DIT –> T3 triiodothyronine
DIT + DIT –> T4 (thyroxine)
What is the role of thyroid hormone in growth?
Growth formation
Bon maturation
What is the role of thyroid hormone in CNS?
Maturation of CNS in pregnancy
What is the role of thyroid hormone on basal metabolic rate?
Inc Na+K+ ATPase
Inc O2 consumption
Inc heat production
Inc BMR
What is the role of thyroid hormone in metbolism?
Inc glucose absorption
Inc glycogenolysis
Inc gluconeogenesis
Inc lipolysis
Inc protein synth & degradation (net catabolic)
What is the role of thyroid hormone in cardiovascular system?
Inc CO, HR, Stroke vol –> sensitisation to catecholamines
T3, T4 will cause tachycardia
What are the indications of levothyroxine (T4)?
hypothyroidism
goitre
thyroiditis, thyroid cancer
Replacement therapy after thyroid block in hypothyroidism
What are the pharmacokinetic properties of levothyroxine (T4)? (T1/2, absorption, SS)
High protein binding in circulation
Long plasma half-life = 6-7 days
SS 4-5 weeks to reach
Taken on empty stomach
Why is liothyronine (T3) no commonly used for replacement therapies?
Although 3-4 times more potent
Has short t1/2, requires multiple doses
Higher cost, monitoring is difficult –> need lab tests to see if you’re getting proper levels
Best used for short-term suppression of TSH in emergency - myxoedema coma
What is the MOA of radioidine?
Radioisotope = 131I isotope
Emits beta and gamma rays within thyroglobulin
Beta rays –> thyroid follicle –> destruction of follicular cells
dose is not repeated
What are the thioureylenes (thioamides) used in hyperthyroidism?
Carbimazole
propylthiouracil
methimazole
What is the MOA of thiourea derivates?
Inhibit iodination of tyrosyl residues in thyroglobulin
Inhibit thyroperoxidase catalysed oxidation reactions
Propylthiouracil - reduces de-iodination of T4 to T3 in peripheral tissue (and in cells)
What are some pharmacokinetic properties of thioamides? (t1/2, therapuetic effect)
Carbimazole (prodrug)–> methimazole
Class = t1/2 6-15 hrs
Therapeutic effect is delayed due to preformed thyroid hormones
- PTU = 17 weeks for full effect
- Carbimazole = 7 weeks for full effect
What are the ADRs seen with thioamides?
Bone marrow suppression –> agranulocytosis
Allergic reactions
- vasculitis, lupus-like syndrome - myopathy - cholestatic jaundice
GI upset, headache, arthralgia
Carbimazole crosses placenta –> foetal hypothyroidism
What is the MOA of iodine and Lugol solution in hyperthyroidism?
Inhibit H2O2 generation –> inhibit iodination of thyroglobulin
*mainly used in preparation for hyperthyroid surgery or severe thyrotoxicosis
What are some ADRs of iodine/iodide/lugol’s solution use in hyperthyroidisms?
Angio-oedema
rashes
drug fever
lacrimation
conjunctivitis
cold-like syndrome
