Beta Blockers

ii- Beta Blockers • any BB w/out ISA • Propanolol has shown to be the only one w significant inhibition on peripheral conversion of T4 to T3 • Useful for symptomatic relief - fatigue - nervousness - palpitations - weight loss - heat intolerance - diaphoresis iii- Calcium Channel Blockers • use of non-dihydropyridine CCBs may alleviate symptoms • used when BBs are CI • useful in management of ophthalmopathy, thyroid storm, pretibial myxedema, RAI pre-treatment iv- Corticosteroids Chemistry-based discipline involving biology, medicine & pharmaceutical Sciences invention, discovery, design, identification, & preparation of biologically active compounds metabolism, MOA, SARs Pharmaceutical Chemistry: Medicinal chem + development, manufacture & analysis of drug products/formulations Thyroid Function: - thyroid gland produces TH that regulates body's metabolism - disorder leads to hyperthyroidism, hypothyroidism or thyroid cancer - RISK Factors: - congenital (born with it) - drug-induced - RAI - viral infections - Female sex - Surgical removal Physiological Functions Hormones that play an important role in normal body functioning & development (esp. growth & development) Synthesis of TH 1. Thyroglobulin (TBG) is synthesized & released in the lumen 2. Iodides (I-) are taken up into the cell & oxidized into iodine (I2). I2 released into the lumen 3. TPO attaches iodine to tyrosine (T.) forming MIT & DIT 4. MIT + DIT = T3; DIT + DIT = T4 5. T3 + T4 are endocytosed & cleaved in the lysosomes & diffuse into blood stream Pharmacotherapy: - Thyroid Replacement Therapy: natural or synthetic - Antithyroid drugs: sodium iodide, thiamides, Lugol's Solution (conjunctive therapy used for symptomatic relief in hyperthyroidism) - Thyroid Imaging Agents: BB3 Others: CTXs Synthetic TH: - derived from L-tyrosine - L-thyroxine has an extra iodine making it more lipophilic (has a longer half-life) compared to L-triiodothyronine L-T4 used to treat hypothyroidism has greater binding affinity to TBG - Liotrix is a mix of T3 + T4 in a 4:1 ratio - either PO or IV TBG Stays 90% unionized in plasma It has a less lipophilic nature It has a faster onset of action SARs for TH Action: - depending on what functional group is attached will reflect the type of binding affinity to TBG R Gened B B Antithyroid activity L-Ala OH 100 T Comp. # has 666 L-Ala H OH 500 T binding affinity to the amino acid that is attached L-Ala H OH <0.01 DL-Ala OH 0 DL-Ala 1 H OH 137 DL-Ala 1 CH H OH 300 L-Ala Pr H OH 786 L-Ala 1 H NH <1.5 L-Ala H -150 *cis geometry exhibits 10 LA 1 H OCH, 225 better binding affinity to thyroid receptors