Lecture 89 - Thyroid Pharm + Bone Mineral Pharm Flashcards
Describe the process of thyroid hormone biosynthesis central and peripheral
Iodide transport and Organification
Tyrosine iodination –> MIT, DIT by peroxidase
Coupling of MIT/DIT = t3 or t4, by peroxidase
5:1 T4:3
Exocytosis
Tranasport by TBG
Reaches target tissues where 5’ Deiodinase converst t4 –> t3
how is thyroid hormone transported in the blood
TBG
how is thyroid hormone activated in the periphery
T4/T3 dissociate from TBG
5’ De iodinase (in the periphery) – T4 —-> T3
what tissues are highly responsive to thyroid hormone
which are not responsive?
responsive: Pituitary, Kidney, Heart, Lung, Skeletal muscle, intestines
Unresponsive: Spleen, testes
what is the mainline treatment for hypothyroid
hormone supplement
what drugs can sometimes induce hypothyroid?
steroids, Beta blockers
first line medical therapy for hypothyroid?
how long does it take to see improvement?
Synthetic T4 - Levothyroxine –
takes a few weeks to see improvement in symptoms
why is synthetic T4 prefered over synthetic T3?
T4 is less potent; less side effects and body regulates the amount it wants to convert to T3
side effects of t3 supplements?
liothyronine
Hyperthyroid symptoms
Afib, tachycardia
pathophysiology for some cases of hypothyroid during pregancy…how should you adjust the medical regimen?
There is an increased TBG, therefore patients may be effectively hypothyroid (need to increase dose of synthetic thyroid)
treatment for myxedema coma
IV therapy – but avoid excess
Loading dose of T4 to fill the empty TBG
Then give active dose
Toxicity of thyroid hormone replacement
Symptoms of Hyperthyroid
Older patients – sensitive to T4; cardiotoxicity (afib, tachycardia), osteoporosis
two classes of drugs used to treat hyperthyroid
Thiomides
Anion Inhibitors:
name three thiomides and mechanism of each
Carbimazole – pro drug of methimazol
Methimazol (blocks peroxidase)
Propylthiouracil (PTU): blocks peroxidase and 5’ deiodinase
how long before effects of thiazides?
side effects of methimazole
Onset of action will be slow, bc stops synthesis;
May take 3-4 weeks before effects
Possible Teratogen; Agranulocytosis, Hepatotoxicity
how do anion inhibitors work?
which anion inhibitors are used?
indications :
Percholate (CLO4-), Thiocyante (SCN-)
block uptake of Iodide through competitive inhibition of iodide transport mechanism
Thyroid Storm
Pre thyroidectomy
what medical therapy is used for thyroid ablation ?
how does this work?
Radioactive Iodine – (I 131)
Mechanism: taken up by thyroid; secretes Beta Rays Destruction of the thyroid Parenchyma —
contraindications for RAI
Pregnant or Nursing women
what other medication may be used to help manage symptoms of thyrotoxicosis
Propranolol
what drugs can be used for treatment of thyroid storm
Propranolol
Diltiazem (if prop can be used bc of heart failure)
Saturated Potassium Iodide
PTU
Barbiturates - T4 –> rT3
Hydrocortisone - T3 –>rT3
how do glucocorticoids lead to stunted growth in kids and osteoporsis in adults
Antagonizes Vit D stimulated Calcium Transport
Stimulates renal calcium excretion
Blocks Collagen syntehsis
Increases PTH stimulated bone resorption
How does menopause lead to bone loss?
Estrogen Receptors on Bone == Bone remodeling
what drugs which act on the ER may be used to protect from bone loss?
SERM (Selective estrogen receptor Modulator)
such as Riloxifene
what non hormonal therapy is used for bone stabilization
theories of its mechanism
Bisphosphonates
increased risk for ____ with bisphosh use
Atypical Subtrochanteric femur fracture
what antibody therapy is used for bone stabilization. how does it work?
RANKL inhibitor (Denosumab) OB RANKL activates OC RANK; therefore this antibody blocks OC activaiton
