Drugs for Thyroid Disorders Flashcards
Drugs for hypothyroidism and hyperthyroidism
Name the most common autoimmune cause of hypothyroidism. How does this disorder result in hypothyroidism?
Hashimoto’s thyroiditis (also known as Hashimoto’s disease). Autoantibodies against thyroid gland proteins, typically against thyroid peroxidase (TPO), trigger inflammation of the thyroid gland and chronically impair the production of thyroid hormones.
What is the first line drug for chronic hypothyroidism?
Levothyroxine. Levothryoxine replaces T4 and is converted to the approximately 1000-fold more active T3 in the liver, by gut microflora (including on enterohepatic recirculation), and in many target tissues and organs.
What advice should the patient be given on when to take levothyroxine?
Take levothyroxine once per day on an empty stomach 30 min to 1 hour before food. As the stomach is usually most empty after overnight fasting, it is usually taken before breakfast.
Why is it important to take levothyroxine on an empty stomach?
Oral bioavailability is decreased by many drug-food and drug-drug interactions.
List common foods and drugs that interfere with absorption of levothryoxine.
Wait 1 hour before taking food, soya milk, coffee, or bulk-forming laxatives. Wait 4 hours before taking iron or calcium supplements or antacids.
Why is it important to continue to administer the same brand of levothyroxine?
Oral bioavailability is highly variable (from 40% to 80%) between different manufacturers’ formulations. It is therefore best to keep using the same brand once an appropriate dose has been titrated, especially as the long half-life means that it takes a month or longer to reach a new steady state when the dose absorbed changes.
What is the half-life of levothyroxine?
6 to 8 days
How long does it take to reach steady state after changing the dose of levothyroxine?
About 4 to 6 weeks (least 5 x the half-life of 6 to 8 days).
What are the adverse effects of overdose of levothryoxine?
Cardiac arrest, hypertension, palpitations, tachycardia, anxiety, heat intolerance, hyperactivity, insomnia, irritability and weight loss. In children, overdosing can cause insomnia, restlessness, accelerated growth and bone maturation.
How fast is the onset of clinical action of levothyroxine?
Oral: 1-3 days; IV: 6-8 hours.
Due to the long half-life, it usually takes 1-3 weeks of daily dosing for plasma levels to accumulate sufficiently to see clinical improvement on first treatment. It takes 3-4 weeks of daily dosing to approach steady-state and achieve peak action.
How fast is the onset of clinical action of liothyronine?
Oral: 2-4 hours; IV: immediate. Liothyronine replaces T3, which is approximately 1000-fold more potent than T4.
Why is liothyronine not routinely used for treatment of chronic hypothyroidism?
Liothyronine (replacing T3) has a much faster onset of action than levothyroxine (replacing T4) and is much more potent. Liothyronine, therefore, has a markedly higher acute risk of adverse cardiovascular events (e.g., cardiac arrhythmia, tachycardia, and even myocardial infarction).
When is liothyronine usually administered?
Liothyronine has a much faster onset of action than levothyroxine and so is the drug of choice for intravenous administration in myxoedema coma due to severe untreated hypothyroidism.
What is the first line drug for chronic hyperthyroidism?
Carbimazole.
What is the active metabolite of carbimazole?
Thiamazole. Thiamazole (known as methimazole) can itself be used for the treatment of
hyperthyroidism but carbimazole is usually preferred here as it has a longer clinical duration of action due to the combined half-life of the pro-drug (carbimazole) and its active metabolite (thiamazole).
What is the MOST IMPORTANT adverse effect of carbimazole?
Although rare, agranulocytosis is a potentially life-threatening adverse effect of carbimazole as it puts patients at risk of opportunistic infection. Patients must be warned to report any sudden onset of signs of infection (e.g., sore throat or fever).
Why does propylthiouracil have a faster onset of clinical action than carbimazole?
Both carbimazole and propylthiouracil reduce thyroid gland production of thyroid hormones but the thyroid gland stores large amounts of thyroid hormones so it can take 3 to 12 weeks to see the onset of clinical action by this mechanism. Propylthiouracil additionally blocks T4 to T3 conversion and so has a faster onset of clinical action.
How fast is the action of radioiodine?
Radioiodine is rapidly concentrated into the thyroid gland but it takes about 1 to 2 months before a clinically significant reduction in thyroid function is seen and a further 2 months until the peak cytotoxic effect is achieved.
How fast is the onset of action of iodide
Oral iodide has an onset of action in the treatment of hyperthyroidism of about 24-48 hours. The peak effect is seen 10-15 days after continuous therapy.
Why is iodide used in patients scheduled for surgical thyroidectomy?
Iodide is commonly used for 10-14 days pre-operatively in patients scheduled for thyroidectomy surgery as it decreases the size and vascularity of the gland when given over 1-2 weeks.
List drugs used in the management of thyrotoxic crisis (thyroid storm). Briefly explain why they are used.
Lowering thyroid hormone synthesis and/or secretion:
(1) Thioamides - Propylthiouracil is preferred as it inhibits T4 to T3 conversion and so has a faster onset of action.
(2) Iodides – suppress both synthesis and secretion of thyroid hormones
Reduction of circulating thyroid hormones:
(3) Bile salt binding resins e.g., colestyramine
Control of the peripheral effects of thyroid hormones:
(4) Beta-blockers e.g., propranolol
- Help to reduce cardiovascular effects
- Propranolol also helps to reduce T4 to T3 conversion
Control of the peripheral effects of thyroid hormones:
(5) Glucocorticoids (e.g., hydrocortisone or dexamethasone):
- Protect against the risk of adrenal insufficiency
- Antipyretic – helps to reduce fever
- Reduce T4 to T3 conversion
(6) Paracetamol: Antipyretic – helps to reduce fever
