Carbimazole and the Thioamide/Thioureylene family
The antithyroidal drugs Carbimazole, Methimazole and Propylthiouracil
all contain a thioamide group which is essential for antithyroid
Carbimazole, which is converted to Methimazole in the body is
widely used in the UK.
- Decreases output of thyroid hormones from thyroid leading
to a gradual reduction in symptoms.
- BMR and pulse rate return to normal over 3-4 weeks as stores
of hormones must be used up first.
- Prevent hormone synthesis by blocking thyroid peroxidase catalysed
reactions, hence I2 and thyroglobulin do not complex and MIT and
DIT are not formed.
- They also block the coupling of iodotyrosines.
- Propylthiouracil also reduces the de-iodination of T4 to T3.
Methimazole does this to a much lesser extent.
- There is little evidence that the bulging eyes typified by
Grave's disease are cured by Thioamides.
- All thioamides are taken orally.
Carbimazole and Methimazole
- Carbimazole is rapidly converted to Methimazole, which is
- Methimazole is distributed throughout the body water and has
a plasma half life of 6-15 hours, there is concentration in the
- Most is absorbed into the body but the time taken to be absorbed
- 65-70% is excreted in 48 Hours
- Despite the short plasma half life only small doses need be
given as the drug accumulates in the thyroid.
- A single 30-40 mg dose can exert an antithyroid effect for
24 hours. Thus in mild to moderate cases a single daily dose may
- 3-4 Weeks are required for the drug to take effect as the
thyroid may have large stores of hormone which must be depleted.
- Propylthiouracil is rapidly absorbed, reaching peak levels
after about 1 hour.
- About 50-80% are available for use in the body due to incomplete
absorption and break down by the liver.
- There is, again, some accumulation in the thyroid.
- Most of the ingested dose is excreted by the kidneys in 24
hours as inactive glucuronide.
- Propylthiouracil may acts more rapidly as it inhibits conversion
of T4 to T3.
- As a single 100 mg dose can inhibit 60% of iodine complexation
for 7 hours the drug can be taken at six hourly intervals.
Typical treatment pattern
- Initially a large dose of Propylthiouracil is administered.
This will be 100-150 mg every six hours. This is used in preference
to Methimazole as it has a faster antithyroidal effect.
- On responding to this treatment the dose ill be reduced. Often
the patient is placed on 30-40 mg of Methimazole daily. Methimazole
is preferred as is exerts its effect for a longer time than Propylthiouracil.
- Once the condition is under control the dose will be reduced
to a maintenance dose of 5-15 mg of Methimazole. It is at this
point that the side effects become rare and the immune system
- If at anytime the immune system becomes compromised treatment
is stopped and antibiotics administered.
- All thioamides cross the Placental barrier and appear in the
milk. They are concentrated by the foetal thyroid.
- Propylthiouracil is the preferred drug as this is more strongly
bound to plasma protein and thus crosses the placenta less readily.
It is also not secreted in sufficient quantities to rule out breast
- Adverse reactions occur in 3-12% of patients, normally early
on in the treatment.
- Most commonly a maculopapular pruritic rash (coloured, raised
patches, itchy) and possibly fever
- More rare adverse reactions are:
- Urticarial rash (itchy rash with individual swellings that
rapidly appear and disappear)
- Vasculitis (Patchy inflammation of the walls of a blood vessel.
Can lead to skin rashes, arthritis, pupura and kidney failure.)
- Arthralgia (pain in joint with no sign of swelling).
- Lupus like reaction (red scaly rash caused by inflammation
of connective tissue).
- Cholestatic jaundice (failure of normal amounts of bile to
reach the intestine resulting in obstructive jaundice. Causes
dark urine, pale faeces, and usually itching).
- Hypoprothrombinemia (reduction in clotting factor prothrombin
in blood resulting in an increased tendency to bleed).
- Lymphadenopathy (Diseased lymph nodes)
- Polyserositis (Inflammation of the membranes that line the
chest, abdomen and joint with the accumulation of fluids in the
cavities. If complicated by the infiltration of major organs by
a glycoprotein the disease usually proves fatal).
- The most serious complication is agranulocytosis, this is
the acute shortage of eosinophils. It occurs in 0.3-0.6% of patients.
The risk is increased in those over 40, and those on high doses
of Methimazole. The result is normally reversed soon after ceasing
to take the drug. Antibiotic treatment may be necessary to treat
resultant infections. There is a 50 % cross sensitivity between
Methimazole and Propylthiouracil; thus switching drugs is not
© 1996 Iain Chambers
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