Week 20 Pharmacology

T3 / T4.

  • Thyroxine is used to replace deficiencies – guided by TSH (aiming for low TSH)

 

Anti-thyroid drugs (basic understanding):

  • SE – nausea, GI upset, altered taste, maculopapular rash, fever, rarely – lymphadenopathy, exfoliative dermatitis, SLE like syn, arthralgia, hepatitis (can be fatal), agranulocytosis
  • ¬†Carbimazole.
    • Carbimazole converted to methimazole in vivo and is 10x more potent that PTU
    • Accumulate in thyroid
    • PK – similar to PTU
    • Cross placenta
    • PD – inhibit thyroid peroxidase, inhibit iodine organification, inhibit coupling of iodotyrosines. Do not block uptake of iodide by thyroid. Onset of action takes 3-4weeks.
  • Propylthiouracil (PTU)
    • PK – rapidly absorbed, peak level in 1hr, 50-80% bioavail, large first pass effect, Vd – total body water, plasma protein bound, excreted by kidney as inactive glucuronide
    • Accumulate in thyroid
    • Cross placenta
    • PD – inhibit thyroid peroxidase, inhibit iodine organification, inhibit coupling of iodotyrosines. Do not block uptake of iodide by thyroid. Block peripheral deiodination of T4 to T3. Onset of action takes 3-4weeks.

 

Anion inhibitors.

  • Block uptake of iodide by thyroid by competitive antagonism
  • Percholate, thiocyanate

 

Iodides.

  • Inihibit organification and hormone release
  • Decrease size and vascularity of the thyroid gland
  • Symptoms improve in 2-7days
  • Can induce hypothyroidism or hyperthyroidism
  • Iodide should be started after carbimazole or PTU and not used if radioactive iodine use is planned.
  • Not for monotherapy – effect will finish in -8weeks and withdrawal can produce sev exac of thyrotoxicosis

 

Radioactive Iodine.

  • 131 Iodine used for hyperthyroidism – oral solution.
  • Rapidly absorbed and concentrated in thyroid
  • No pain
  • Safe
  • Not for use in pregnant or nursing mothers

 

Thyroid storm.

  • Sudden exacerbation of thyrotoxicosis
  • Life threatening
  • Sx – hypertension, tachycardia, heart failure, fever,
  • Mx – propanolol/diltiazem, potassium iodide, propylthiouracil, prednisolone, in extreme circumstance peritoneal dialysis is used to remove excess thyroxine

 

Glucocorticoids:

  • Hydrocortisone – IV, naturally occurring.
  • Prednisone – oral and injectable, 4x more active than hydrocortisone
  • Effects — see physiology
  • Indications – addisons disease, autoimmune disease flare ups eg IBD, SLE. Asthma, thyroid storm, ARDS, cerebral oedema, immune suppression in transplant
  • Table of relative potencies (MCQ). – see physiology

 

Mineralocorticoids: Aldosterone. -see physiology

 

Viva questions:

  • Tell me about Thyroxine.
  • Compare and contrast T3 and T4.
  • Tell me about Hydrocortisone
  • How do glucocorticoids act ?
  • Compound with receptor and become a transcription factor by binding DNA and promoting certain genes to be rtanscribed –> proteins/enzymes –> cellular effects
  • Tell me about Aldosterone