University:
University of Kentucky
Course:
NUR 101 | Academic Orientation and Introduction to Nursing
Academic year:

2023
Views:

210

Pages:

2
Author:

Joseph D.

Metabolism: T4 is the biologically active TH rT3 is biologically inactive 5' Deiodinase (enzyme in the kidney) converts T4 to T3 & to rT3 L-isomer more active SAR: COOH is essential carbon chain length 1-2 Bridging Atom 5 COOH | | 4 NH2 | | 3 * C3 & C6 alkyl & | | alkoxyl grps 2 | retain activity | | 1 | | V O Optimum activity | | A | | 3 C | | B 5 | | 4 C | | OH 6 | | V H Optimum activity C3 + C6 halogens are essential providing optimum activity Optimum activity T3 Thi o amides: PTU & methimazole Synthetic derivatives. Carbinazole prodrug used for hyperthyroidism i.e. inhibits TPO + 5' Deiodinase peripherally C2 thiokero & Unsub. Ni essential for activity Po Shorter half-life than methimazole BA pass through FPHM Highly regulated by a -ve feedback loop of hypothalamus + ant. pituitary T3 + T4 provide a -ve feedback when there is too much TSH, it reduces the amount that is produced & released by sending feedback signals to the hypothalamus & ant. pituitary Thyroid Receptors: 2 sub-types each in our isoforms: α & β | Hypervariable DNA binding region | Ligand binding domain | % | |---|---|---|---| | TRα1 | 100% | 100% | 514 | | TRα2 | 0% | 100% | 492 | | TRβ1 | 0% | 84% | 80% | 410 | | TRβ2 | 0% | 84% | 80% | 370 | ↑ metabolic rate, Oxygen consumption by tissues, heart rate, respiratory rate, catabolism of all fuels & body temperature Treatments of Hypothyroidism: Levothyroxine (T4) Levothyroxine (T3) T4 has higher binding affinity to TBG & it is more potent Most actions of the thyroid hormone are T3-mediated circulating TH are bound to TBG as well as other proteins The remaining that are unbound circulate freely & are unionized i.e. able to diffuse freely into target cells Thyroid Hormone Production: Controlled/regulated by the HPT axis Hypothalamus releases TRH TRH controls release of TSH from ant pituitary TSH stimulates production & release of TH Both regulated by a negative feedback loop ↑ levels of TH will stimulate a -ve feedback loop inhibiting thyrotropin production & TSH secretion ↑ levels of TH will stimulate the enhancement of TSH secretion to stimulate TH production Thyroid Hormone MoA: T4 to T3 via 5' deiodinase T3 binds to TR unliganded form, TR binds to thyroid response elements in the promoter/regulatory region of target genes & interacts & co-repressors of gene expression T3 binding interaction w/ co-activators of gene expression & transcription of gene