Second Threatment Options

Levothyroxine (T4) Levothyronine (T3) Liotrix (4:1 T4:T3) 1/4 line * more potent + PGA * dessicated animal thyroid Stable; long half-life * Faster onset of action dose adjusted Short half-life (1-2 days) 94-6wk not desirable for * proportions vary chronic use blw brands D-D Interactions * does not change T4 levels not Safe more difficult to monitor, more AE, Estrogen Cholesterol & Orgs * Phos, Fe, Ca Treatment of Hyperthyroidism: Propylthiouracil (PTU) * Methimazole * Iodides Reducing TH Activity - Strategies: i. interference @ TH production via the use of pharmacologic treatment ii. Blocking TH release via use of e.g. thioamides iii. Destruction of thyroid gland - RAI or surgery iv. Blockage of TH effects on target tissues v. Adjunctive Therapy for Symptom management - BBs, iodine supplements **Thioamides: MOA** Both inhibits TPO * Incorporating iodine into tyrosyl residues of TBG is inhibited ↳ Coupling of iodotyrosyl residues to form iodothyronines is also methimazole inhibited PTU * it takes 3-4 wks to work * does not affect TH storage or release PTU inhibits T4 to T3 conversion ONLY PTU **Thioamides: Pks** * PTU has 80% BA * Accumulates in Th Metabolized to glucuronide conjugate & excreted * * Both thioamides have short serum half life but long Functional half-life due to their accumulation in TG **PTU vs. Methimazole** کا Better in severe states Preferred in 1st trim of pregnancy Drug of choice (longer-half life + less frequent administration) where not CI -nor osea often Thionamides: Toxicity cross-sensitivity blw methimazole + PTU is ~50% SES: rash, fever, arthralgia, benign transient leukopenia Rare: jaundice, agranulocytosis, liver failure (only PTu) Other Anions: Perchlorate (ClO4-), pertechnate (TcO4-), thiocyanate (SCN-) & nitrate compete as iodine for transport into thyroid Adjunct & Other Treatments: i. RAI used to destroy thyroid tissue treatment option for hyperthyroidism, thyroid cancer rapid abs. accumulates in thyroid & emits β & γ radiation (0.4-2 mm) crosses placenta + breastmilk ↑ levels of I-131 are produced as a nuclear fission by-product released after detonations or uncontrolled rxns NRI can be taken immediately before or within 3-4h after exposure to compete for uptake into the thyroid ii. Potassium Iodide Hyperthyroidism >>> tachycardia, palpitations, arrhythmia Used for symptomatic relief by antagonizing the sympathetic effects of thyrotoxicosis ↓ TH → sympathetic tone of CV system iii. β-Blockers refer to pg 13 iv. Calcium channel blockers (refer to pg 13) v. Corticosteroids Block some T3 used during thyroid storm immunosuppressants may be added to thiamine therapy in Grave's Disease Various small drugs + anti-cancer drugs can also be used for thyroid cancer Pipelines diff. thyroid hormone receptor isoforms & tissue-specific diff. in level of expression Examples TRβ1 expressed in liver; agonists that ↓ cholesterol & T4 TRβ2 expressed in heart; agonists used for heart failure Or bradycardia TH antagonists may be developed for thyrotoxicosis