Download 01 drugs used in hyperthyroidism

DRUGS USED IN
HYPERTHYROIDISM
Objectives
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At the end of 1st lecture the studetns will be able
to :
Classify common drugs used for treatment of
hyperthyroidism
Details the drugs regarding , mechanism of
action , pharmacological effects , clinical uses &
side effects
Recognize treatment of special cases of
hyperthyroidism such as pregnancy, breast
feeding , Grave,s disease & thyroid storm
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Hypothalamic –pitutary – thyroid axix
Thyroid regulation
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T3
T4
T3
T3
T3
T4
PB
T3
cytoplasm
Response
T3
Nucleus
Protein
PP
Pre-m RNA
mRNA
Mechanims
of action
of thyroid
Mechanism
of action
of thyroxine
at hormones
cellular level
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HYPERTHYROIDISM
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Elevated levels of T3 and T4 in the blood.
Causes :
 Adenomas / carcinomas
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 Thyroiditis
 Autoimmune
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GRAVES' DISEASE
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Most common cause of hyperthyroidism 60-80%.
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Autoimmune disorder associated with circulating
immunoglobulins that bind to and stimulate the
thyrotropin ( TSH) receptor , resulting in sustained
thyroid over activity & it can be familial.
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Manifestations of Hyperthyroidism
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Nervousness , irritability.
Tremors
palpitation
Weight loss
sweating
Heat intolerance
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|Manifestations cont’d
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Diarrhea
short breath
Itching
Xophthalmos
Thyroid Enlargement
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Treatment of Hyperthroidism
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Thioamides ( antithyroid drugs)
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Iodides
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Radioactive iodine
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Beta blockers
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Surgery
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THIOAMIDES:
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Methimazole
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Propyl thiouracil
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Mechanism of Action
Inhibit synthesis of thyroid hormones
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By inhibiting peroxidase enzyme that
catalyzes the iodination of tyrosine residues
in the thyroglobulin & couples iodotyrosines
to form T3 & T4.
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They block the conversion of T4 to T3
within the thyroid & in peripheral tissues
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Pharmacokinetic comparision between Propylthiouracil and
Methimazole
Propylthiouracil
Methimazole
Absorption
Both are rapidly and Absorbed from GIT
Protein binding
80-90%
Most of drug is free
accumulation
Both are accumulated in thyroid
Excretion
Kidneys as inactive
Excretion slow,60metabolite within 24 hrs 70% of drug is
recovered in urine in
48 hrs
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Pharmacokinetic comparision between Propylthiouracil and
Methimazole
Propylthiouracil
Methimazole
Half life
1.5 hrs ( short half-life)
6 hrs ( long half-life)
Administration
Every 6-8 hrs
As a single dose
Pregnancy
Both cross placenta &
fetal thyroid.
It is highly protein
bound ,crossing placenta
is less readily so
recommended in
pregnancy.
Concentrated in
Less secreted in breast milk
secreted
Breastfeeding
Not recommended in
pregnancy
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Adverse Effects
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Cutaneous reactions ( urticaria , maculopapular
rash )
Arthralgia
 GI upset , Hepatotoxicity ( cholestatic jaundice
mainly with methimazole)
 Most dangerous complication is agranulocytosis
occur within 90 days of treatment
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IODIDES:
Mechanism of action
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Inhibit thyroid hormone synthesis and release
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Block the peripheral conversion of T4 to T3 .
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They produce a temporary remission of
symptoms.
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Anti –thyroid agents ( Mechanissm)
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Clinical uses
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Prior to thyroid surgery to decrease vascularity
of the gland .
Following radio active iodine therapy.
Examples
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Organic iodides as :iopanoic acid or ipodate
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Precautions /toxicity:
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Should not be used as a single therapy
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Should not be used in pregnancy
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May produce iodism ( acniform rash,
swelling of salivary glands, mucous
membrane ulceration, metallic taste
bleeding disorders and rarely anaphylaxis ).
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RADIOACTIVE IODINE
 131
I isotope ( therapeutic effect due to emission of β
rays )
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Accumulates in the thyroid gland and destroys
parenchymal cells . Clinical improvement may take 2-3
months
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Half -life 5 days
Cross placenta & excreted in breast milk
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Easy to administer ,effective , painless and less
expensive
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Radioactive Iodine ( con.)
Available as a solution or in capsules
 Clinical uses
 Hyperthyroidism mainly in old patients
(above 40)
 Graves, disease
 Patients with toxic nodular goiter
 As a diagnostic
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Disadvantages
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High incidence of delayed hypothyroidism
Large doses have cytotoxic actions ( necrosis
of the follicular cells followed by fibrosis )
May cause genetic damage
May cause leukemia & neoplasia
(carcinogenic )
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ADRENOCEPTOR BLOCKING AGENTS:
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Adjunctive therapy to relief the adrenergic
symptoms of hyperthyroidism such as
tremor, palpitation, heat intolerance and
nervousness.
E.g. Propranolol, Atenolol , Metoprolol.
Propranolol is contraindicated in asthmatic
patients
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THYROIDECTOMY
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Sub-total thyriodectomy is the treatment of
choice in very large gland or multinodular
goiter
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THYROID STORM:
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A sudden acute exacerbation of all of the
symptoms of thyrotoxicosis, presenting as a life
threatening syndrome.
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There is hyper metabolism, and excessive
adrenergic activity, death may occur due to heart
failure and shock.
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Is a medical emergency .
Propranolol 1-2mg slows IV or 40-80 mg orally
every 6 hours
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Potassium iodide 10 drops orally daily or
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Propylthiouracil 250 mg orally every six
hours or 400 mg every six hours rectally.
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Hydrocortisone 50 mg IV every 6 hours to
prevent shock.
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If above methods fail peritoneal dialysis.
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Thyrotoxicosis during pregnancy
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Therapy with 131I or subtotal thyroidectomy prior
to pregnancy to avoid acute exacerbation during
pregnancy or after delivery
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During pregnancy radioiodine is contraindicated.
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Propylthiouracil is the better choice during
pregnancy.
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