Drugs used in Thyroid Disorders Flashcards
Which hormone is released by the hypothalamus and controls thyroid hormone secretion?
Thyrotropin-Releasing Hormone (TRH).
Which hormone is released by the pituitary gland and controls thyroid hormone secretion?
Thyroid Stimulating Hormone (TSH)
How are TRH and TSH secretions controlled?
Negative feedback by T4 and T3
What is thyroid peroxidase enzyme’s role in thyroid hormone biosynthesis?
- Oxidation of iodide
- Iodination of tyrosyl residues to form mono or di-iodo tyrosyl residues, also known as organification
What is the half life of T3 and T4?
T3 - about a day, T4 about a week
State 5 causes of hypothyroidism
- Hashimoto thyroiditis
- pitituary failure
- hypothalamus failure
- congenital
- IODINE DEFICIENCY
What would be expected of the TSH and T4 levels in a person with primary hypothyroidism?
High TSH, Low T4
What would be expected of the TSH and T4 levels in a person with subclinical hypothyroidism?
Higher than normal TSH, normal T4
Name 5 symptoms of hypothyroidism
Fatigue/lethargy
Mental slowness
Dry skin
Weight gain
Irregular menses
Hair loss
Cold intolerance
What drugs are commonly used to manage hypothyroidism?
Levothyroxine and Liothyronine
What precipitates myxedema coma and how would a patient with myxedema coma present?
Myxedema:
hypothyrodism
= insufficient T3/4 produced
= decrease metabolic rate
= low turnover rate of protein breakdown and metabolism
= glycosaminoglycans (hyaluronic acid, chondrotitin sulfate) accumulate in EXTRAcellular space
= retention of water within glycosaminoglycans, and decreased collagen synthesis
= non pitting edema and dry skin
Precipitated by: systemic illness (infection, heart attack)
long standing untreated hypothyrodism –> myxedema coma
Symptoms:
- altered mental status
-low body temperature
- hypoglycemia
- low blood pressure.
How often do we monitor TSH levels after initiating levothyroxine treatment?
6 to 8 weeks
What could cause persistently elevated TSH levels after initiation of treatment?
Poor medication compliance, malabsorption, drud/food interactions, inadequate dosing,
How does cholestyramine (lipid lowering medication) interfere with levothyroxine absorption?
cholestyramine
= bile acid sequesterant
= bind to bile acids in GIT
= forms insoluble complex
= levothyroxine cannot be absorbed in the intestines into the blood stream
= decreased efficiency of levothyroxine
How does estrogen interfere with levothyroxine absorption?
increase estrogen
= increase production of thyroid binding globulin (TBG)
= TBG binds to levothyroxine
= decrease free levothyroxine (T4) concentration in the blood
How would you expect levothyroxine requirements to change as one ages?
older individuals
= decrease metabolism
= levothyroxine degraded slower
= decreased levothyroxine required when older
How would you expect levothyroxine requirements to change during pregnancy?
Increase by about 30% - 50% early in pregnancy
How should levothyroxine be dosed in patients with ischemic disease and why?
levothyroxine increases metabolism
= has inotropic (contraction) and chronotropic (rate) effects
= can cause acute coronary disease if started at a full dose in HF patients
= should do slow upward titration till euthryrodism is achieved
Name 5 symptoms of hyperthyroidism
Increased motor activity, metabolism, increased heat production (flushed, warm moist skin),Increased appetite, weight loss with insufficient intake,
Increased heart rate, anxiety, nervousness
What would be expected of the TSH and T4 levels in a person with hyperthyroidism?
Low TSH, High T4
Name 3 classes of drugs that are used to downregulate thyroid hormone levels in patients suffering from hyperthyroidism
- Anti thyroid drugs - Thioamides (carbimazole, propylthiouracil, thiamazole)
- iodine (Lugol’s solution / Potassium iodide),
- Radioactive iodine therapy (I131)
What is the mechanism of action thioamides?
thioamides
1. propylthiouracil
2. carbimazole
thioamides (propylthiouracil) inhibit thyroid peroxidase
= prevent deiodination
= decrease T3/4 levels
carbimazole and propylTHIOuracil
= inhibit coupling of iodotyrosyl residues
What are the advantages carbimazole has over PTU?
Less frequent dosing, and lesser hepatotoxicity.
PTU has a black box warning due to its hepatotoxic effect.
What are some important adverse effects of thioamides that we need to look out for?
- Agranulocytosis = body does not have enough neutrophils
(do FBC if signs of infection appear) - Cholestatic jaundice due to liver damage or bile duct injury (carbimazole)
- Liver failure (PTU) –> hepatotoxicity (since it is a black box label)
What are anti-thyroid drugs commonly used to treat?
- hyperthyrodism (eg. graves disease)
- thyroid storm
Which of the thioamides is prescribed during the first trimester of a pregnancy?
PTU is preferred in the first trimester. Switch to carbimazole after first trimester
What is iodide used to treat?
Thyroid storm (an hour after anti thyroid drugs) It prevents the release of thyroid hormones.
In preparation for thyroidectomy, reduces size and vascularity of the gland,
Endemic goiter (iodine deficiency) as iodine replacement
How long does iodides take to have an onset of action?
24 to 48 hours
What are the signs and symptoms of iodism?
Metallic taste, gastrointestinal discomfort (diarrhoea, vomiting), lacrimation, severe headache, sore teeth and gums
Which radioactive iodine isotope is used for diagnosis of toxic nodular goiter and which is used in the treatment?
123I (diagnosis) and 131I (treatment)
patient given small dose of radioactive iodine
= absorbed by the thyroid gland
= in toxic MNG, there is somatic mutation of TSH receptors
= some nodules will take up more iodine than normal
= the nodules that do not take up iodine are malignant
How does radioactive iodine therapy work?
Radioactive iodine is rapidly and efficiently trapped by the thyroid sodium-iodide transporter, into the follicular cells, from which it is slowly liberated. Destructive β particles act almost exclusively on the follicular cells to destroy them , with little or no damage to surrounding tissue.
Does 123I emit beta rays?
No, only 131I. 131I emits goth beta and gamma rays
What advantage does radioactive iodine therapy have over thyroidectomy?
No hospitalisation, low cost, ease of administration (oral), low rate of complications.
What are the contraindications for radioactive iodine therapy?
Pregnancy, Extra caution in patients with active (moderate to severe Graves’ ophthalmopathy) as it may worsen the condition
Can radioactive iodine therapy be con-administered with thioamides?
No, must stop thioamides at least 3 days before. Been found to otherwise reduce effectiveness of RAI
How could beta blockers help in a thyroid storm?
Beta blockers limit the positive ionotropic and chronotropic effects of thyroid hormones, slightly decrease T4 conversion to T3.
What is the utility of glucocorticoids in thyroid disorders?
They are useful in a thyroid storm as they can reduce the conversion of T4 to T3. Used in Graves’ ophthalmopathy to reduce inflammation and swelling.
