thyroid pharmacology Flashcards
What drugs are commonly used to manage hypothyroidism?
Levothyroxine(T4) and Liothyronine(T3)
when do you use levothyroxine (T4)?
First line of treatment
- hypothyrodism (PO)
- Hashimoto thyroiditis (PO)
- myxedema coma, congenital hypothroydism (IV)
what are the things to take note when using levothyroxine? (food)
- Take with water only on an empty stomach in the morning before breakfast
- Wait 1 hour before taking food, soymilk, coffee, bulk forming laxative (fiber)
- Wait 4 hours before taking iron or calcium supplements or antacids
- Avoid bile salt binding resins (cholestyramine) as it reduces absorption
- Avoid soya products in infants with congenital hypothyroidism
- Cannot take caffeine
- Selenium, antacids, iodine, fiber all impair absorption of the drug
what are the things to take note for levothyroxine?
- Warn patient to keep taking it consistently as it may take 1-3 weeks before therapeutic benefits are felt
- Monitor TSH level as high level indicate that a increase in dose is needed
- Can take many months before dose is correctly titrated and must wait 4-6 weeks for each dose adjustment to take effect
what is the onset of levothyroxine?
oral: 1-3 days
IV: 6-8 hour
slow
what is the half life of levothyroxine ?
what is the duration of levothyroxine?
half life:6-8 days
duration: 1-3 weeks
slow
what is the absorption rate for levothyroxine?
40%-80% per manufacturer and is decreased by age , food and drugs
what are the adverse effect of levothyroxine (T4) in adults?
cardiac arrest hypertension palpitation tachycardia anxiety heat tolerance hyperactivity insomnia irritability weight loss
There will be increased risk if it is combined with epinephrine and norepineohrine
what are the effects of overdosing of levothyroxine (T4) in children?
insomnia
restlessness
accelerated growth
bone maturation
what is the absorption rate of liothyronine T3?
well absorbed (95% in 4 hours)
what is the onset of action of liothyronine ?
onset 2-4 hours (oral)
but Iv is faster
what is the half life of liothyronine T3?
1-2.5 days
when is liothyronine used?
used in emergency cases and when a rapid onset of action is needed
IV for myxedema for coma
what are the side effects of liothyroxine ?
cardiac arrhythmia, tachycardia
hypotension
myocardial infraction
why is levothyroxine used more commonly?
it has lower cardiovascular risk due to slower onset and it has to be converted to T3 in target tissues and organs
which patient must be cautious when using levothyroxine?
patients with cardiac symptoms
elderly patients with many comorbidities
women of childbearing age (30% increase dose once pregnant)
how often must the follow up be for patients with hypothyroidism ?
repeat tsh measurement after 4-12 weeks
every 6months when stable
if target not reached: consider reasons for treatment failure
if target is reached: annual serum TSH measurement
what are the medication used for hyperthyrodism?
thioamides( carbimazole or PTU)
idodies
radioidoine
what is the first line drug for hyperthyroidism ?
thioamide: carbimazole
what is the mechanism of thioamide?
Interfere with iodination and coupling 🡪 inhibit peroxidase enzyme 🡪 T3 and T4 cannot form
what is the mechanism that is only specific to PTU?
Inhibits deiodination of T4 to T3 too, hence there is a faster onset of action as there is usually storage of T4 and T3.
what are the half lives of thioamides?
carbimazole: 3-6 hours
PTU: 75 minutes
why is carbimazole preferred over PTU?
lower risk of severe hepatotoxicity
longer half life, allows for dosing once or twice daily dosing
what are the side effects of carbimazole?
most serious reaction is agranulocytosis, but is reversible when discontinued
- it is the reduced wbc count and it risk the patient of infection (sorethroat and infections)
can have rashes too
liver toxicity
what are the liver toxicty side effect in both PTU and carbimazole?
carbimaozole: jaundice
PTU: risk of severe liver injury and acute hepatic failure hence SHOULD NOT BE used by children unless they are allergic to carbimazole
What is the contra of thioamides?
both can readily cross the placecnta and can induce goiter and even cretinism , hence should be given sufficient but not excess dose
PTU:
- if used during pregnancy should be warned of the rare potential hazard to the mother and fetus of liver damage
- recommended in first trimester
carbimazole
- seconds and third trimester
- rare development of fetal abnormalies such as aplasia cutis and choanal atresia
what is the second line of medication for hyperthyroidism?
iodide
what are the formulations of idodie
- strong iodine solution (lugol solution)
- consist of 5% iodine and 10% potassium iodide
- the idodine is reduced to iodide in the intestine before absorption - potassium iodide tablets
what is the route for iodides?
what is the onset of action
oral administeration
onset 24-48 hours
what is the mechanism of action of iodide
- suppress thyroid hormone synthesis
- inhibit thyroid hormone release (useful in thyroid storm to prevent release of thyroid stores
- decrease the size and vascularity of the gland when given over 1-2 weeks (used 10-14 days pre operatively in patients scheduled for surgery to remove thyroid gland)
what are the adverse effect of iodide ?
- delay onset effect of thioamide therapy
- prevent use of 131I for several weeks as it competes for uptake by thyroid gland
- may produce severe exacerbation for thyrotoxicosis if the iodine escapes from the gland
- iodide is required for thyroid hormone synthesis but overloading with iodide triggers the shut down of hormone production and release
- lead to bleeding disorders, conjuntivitis, fever, inflamed salivary glands, ulceration, rash and rhinorrhoea
contra of iodide
breast feeding and in pregnancy s I- crosses the placenta and may cause fetus goitre
what medication to take if patient is allergic to thioamides?
radioactive iodine
what medication to take if patient is children is allergic to carbimazole?
PTU
what is radioactive idodine used for
1 . treatment choice for patients aged 35 and above
- alternative to thioamides (when they are allergic)
- in patients that are not suitable for surgery
what is the mechenism of radioactive iodine?
it destroys the cells of thyroid gland without damaging the surrounding tissue
the raioactivity of I 131 diappears after 2 months and the cytotoxic effect, cell death peaks after 2 months
what are the advantages of radioactive iodine?
they are convenient, administered outpatient
inexpensive
what are the disadvantages of radioactive iodine ?
slow onset cytotoxic effect
major adverse effect is development of hypothyroidism in later life
what is the contra for radioactive iodine?
CHilDREN (genetic damage, carcinogenesis)
pregancy (fetal thyroid)
nursing mothers (neonatal thyrod)
what are medication use for thyroid storm?
- thioamides (PTU)
- iodides
- cholestyramine
- beta blockers (propranolol)
- glucocorticoids (hydrocortisone or dexamethasone)
- paracetamol
what are the steps taken for thyroid storm?
- lowering thyroid hormone synthesis / secretion
- thioamides inhibit T4 to T3 conversion
- iodies suppress both synthesis and secretion of thyroid hormones - reduction of circulating thyroid hormones
- bile salt binding resin (colestyramine), as bile salt are usually secreted in the bile and reabsorbed in the small intestine, therefore the medication will prevent thyroid hormones to be excreted - control peripheral effects of thyroid hormones
- beta blockers (propranolol) helps to reduce CVS risk
- prop also helps reduce T4 to T3 conversion - control the peripheral effects of thyroid hormones
- glucocorticoids (hydrocortisone or dexamethasone) helps to protect risk of adrenal insufficiency
- reduce T4-3 conversion
- reduces fever - paracetamol
- antipyretic helps to reduce fever
DO NOT use aspirin or other salicytes as antipyretics as they increase free T3 and T4 levels by interfering with serum protein
