Thyroid Pharmacology Flashcards
Briefly describe the histology of the thyroid gland
Thyroid gland is made up of thyroid follicles. Follicles are formed from cuboidal cells surrounding the colloid filled lumen. Produce thyroid hormones
Parafollicular cells (clear cells) secrete calcitonin. Respond to calcium levels
Where is thyroglobulin synthesised?
Made by the RER of the follicular cells and secreted through the apical membrane into the lumen of the follicle.
Role of thyroid peroxidase
Mediates conversion of iodide to iodine.
Catalyses the iodination of thyroglobulin to produce DIT/MIT and the coupling reaction to produce T3 and T4.
How does TSH mediate its effect on thyroid hormone production
TSH receptor is coupled to Gs, binding increases levels of cAMP.
Physiological conditions that cause impaired conversion of T4 to T3
fasting state
acute trauma
systemic illness
drug interactions
How are thyroid hormones carried in the circulation?
Bound to thyroid binding protein - much lower affinity for T3
Bound to albumin - serves as a carrier when high affinity proteins are saturated
Only free hormones are active. Low plasma protein levels or interactions which displace hormones will increase activity.
Drugs which increase TBG levels
Oestrogens, Tamoxifen - breast cancer 5-Flurouracil - colorectal cancer Heroin Methadone - heroine substitute
Drugs which decrease TBG levels
Androgens
Corticosteroids
Agents interfering with TBG binding
Phenytoin
Carbamazepine - used in treatment of hyperthyroidism
Salicylates - aspirin
Diazepam
Name four effects of thyroid hormone on the body
Foetal brain and skeletal maturation Increase in BMR Inotropic and chronotropic effects on the heart Increases sensitivity to catecholamines Stimulates gut motility Increases bone turnover Increase in serum glucose
Conditions causing excess thyroid hormones
Graves Toxic solitary adenoma (benign follicular adenoma) Pituitary tumour Thyroiditis Thyroid carcinoma Iodine induced (amiodarone)
Investigations in a patient with suspected thyroid problems
Asses goitre Assess thyroid eye disease ECG Thyroid autoantibodies Thyroid Ultrasound scan Raido-iodine uptake scan
Treatments for patients with thyroid problems
Beta blockers
Carbimazole
Propylthiouracil
Radioiodine
Thyroidectomy
Drug treatment for hyperthyroidism
Antithyroid medication:
Iodide - inhibits organification of iodine, proteolysis of thyroglobulin and angiogenesis in the glands. Given in thyorid storm
Thionamides: propothyouracil, carbimazole inhibit TPO. Reduces thyroid hormone synthesis and storage
Beta blockers: block peripheral conversion of T4>T3. Block adrenergic effects. Reduce tachycardia, BMR, tremor.
Adverse effects of thionamides
Agranulocytosis - results in recurrent infections, oral ulcers and fever
Skin rashes
Arthralgia and myalgia
Hepatic abnormalities (long term use)
