2 n d S em es t er A Y 2 0 1 6- 2 0 1 7 / / M a rc h 8, 2017

PPHARMACOLOGY
5.06 Anti-thyroid Drugs
Dr. Glenn Guevarra

OUTLINE free free)

Produced exclusively by thyroid 80% comes from the
I. Overview gland conversion of T4 in tissues
II. Thyroid Hormone Synthesis Half-life: 1 week Half-life: 1 day
A. Iodide trapping 10x more preval;ent in serum 3-100x more potent than T4
B. Iodide Organification and Coupling than T3
C. Proteolysis Turnover Rate: 10% Turnover Rate: 60%
D. Peripheral Deiodination Extrathyroidal pool: 800ug Extrathyroidal pool: 54ug
E. Hormone Transport Clearance: 1.1L Clearance: 12.4L
III. Types of Thyroid Disorders Biological Potency: 1 Biological potency: 4
A. Hyperthyroidism vs Thyrotoxicosis T4 is less toxic, longer half-life, used as maintenance for
B. Primary Hyperthyroidism hypothyroidism, abundant in circulation
C. Secondary Hyperthyroidism T4 can produce the effects needed by the body but it needs
D. Thyrotoxicosis without Hyperthyroidism to be converted to T3
IV. Drugs that cause Hypothyroidism o Binding of T3 to the thyroid receptors is 10x more
V. Diagnostics potent than the binding of T4 especially in the liver and
VI. Graves Disease kidneys. This is the reason why T3 is the biologically
A. Graves Ophthalmopathy active hormone according to some books.
B. Goals of Treatment
C. Treatment Hormone Transport
VII. Anti-thyroid Treatment Thyroid-binding globulin (TBG)
A. Methimazole o Once it reaches the blood, most of the thyroid
B. Propyltiouracil hormones are bound to TBG
C. Beta-blockers o Although it is not the dominant protein in the blood, it
D. Iodides binds 80% of the thyroid hormones
VIII. Iodine Deficiency Transthyretin
A. Synthetic Thyroid Hormones o Can bind 10% of T4
IX. Drug Interactions o Binds less of your T3
A. Drugs and Substances that Interact with Albumin
Thyroid/Anti-thyroid Drugs o can bind 10% of T4 and 30% of T3
B. Complications
Why is it important to know the percentage binding of your
OBJECTIVES TBG? Certain conditions and drugs can increase/decrease
the level of your TBG. And when youre treating patients,
At the end of the lecture, the student should be able to: you need to consider this and titrate the dose later on.
1. Identify steps in thyroid hormone synthesis that can be
altered by substances Thyroid Hormone Function:
2. Compare and contrast PK and PD of thyroid drugs Increase the basal metabolic rate
3. Compare and contrast PK and PD of anti-thyroid drugs Affect protein synthesis
4. Identify drug interactions that affect TH levels Help regulate long bone growth (synergy with growth
hormone) and neural maturation
From book (Book used) Increase the body's sensitivity to catecholamines (such as
From old trans (Lecturer) adrenaline) by permissiveness.
Highlighted by lecturer
II. THYROID HORMONE SYNTHESIS
I. OVERVIEW
Once it reaches the area of the thyroid gland it will go in the
+ -
thyroid follicular cells through 2Na -1I symporter/NIS (iodide
Iodine vs Iodide trapping) iodide is oxidized by thyroidal peroxidase (TPO) to
Iodine (I2)- element; halogen iodine once theres oxidation reaction, Iodine will attach to
-
Iodide (I )- anion; combined with another substance Thyroglobulin to form your Iodothyronine (organification)
once it reaches the colloid, it will undergo coupling (one
Table 1. T3 vs. T4 (from 2017A) Monoiodothyronine + one Diiodothyronine = Triiodothyronine (T3);
T4 T3 Diiodothyronine + Diiodothyronine = Tetraiodothyronine (T4))
99.97% protein-bound (2mg/dl- 99.7% protein bound (0.4mg/dl-

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Proteolysis: endocytosis enter thyroid follicular cells
interaction with a lysosome proteolysis MIT and DIT will be
degraded; free iodides and free TG will undergo recycling; T3 &
T4 will be released to the circulation.
Once it goes to the circulation, it will reach the cells, and there are
deiodinase enzymes in the different cells of the body; it converts
T4 to T3
Figure 1. Thyroid Hormone Synthesis
A. Iodide trapping
Iodide is actively transported from the blood stream into the
follicular lumen by the follicular epithelial cells against
+ -
chemical and electrical gradients by a 2Na -1I symporter
(NIS) located in the basolateral membrane of thyroid
epithelial cells. Consequently, Iodide is highly concentrated in
the thyroid gland compared to the rest of the body. This
process is called the iodide trap.
Two transporters involved in iodide transport:
NIS can be INHIBITED by anions such as thiocyanate,
pertechnate, or perchlorate via competetive inhibition.
o NIS gene expression is STIMULATED by:
TSH(primarily), cAMP and adenosine.
o NIS gene expression is INHIBITED by:
Iodide, cytokines(TGF-1, TNF-, IFN-),
Sphingomyelinase, Dexamethasone and
T3.
Pendrin (Iodine-chlorine transport), a passive transporter,
is located at the inner end or apical end of thyroid cells, that
transports iodide towards the colloidal space.
Absence of pendrin leads to Pendreds syndrome (hereditary
syndrome of goiter and deafness).
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Normally, a thyroid-plasma free iodide ratio of 30 is
maintained. A reduction in dietary iodide intake
depletes the circulating iodide pool and greatly
enhances the activity of the iodide trap. When
dietary iodide intake is low, the percentage of thyroid
uptake of iodide can reach 80% to 90%.
Katzung: recommended iodine intake:
> Adult:150 mcg/day
> Pregnant: 200 mcg/day
B. Iodide Organificaiton and Coupling
Thyroid Peroxidase, an enzyme present in the acellular
colloid of the follicular lumen, performs several key reactions:
It first generates I by oxidizing I- ions present in the
2
follicular lumen, as H2O2 is reduced.
It then "organifies" the generated I2 by covalently linking
it with the tyrosine residues present in Thyroglobulin.
This generates either single or doubly-iodinated species
of tyrosine, termed "Monoiodotyrosine (MIT)" and
"Diiodotyrosine (DIT)", respectively.
Finally, it combines MIT and DIT residues to generate T4
or T3 species within the thyroglobulin protein, a process
termed "Coupling". T4 is generated by combining two
DIT residues while T3 is generated by combining one
DIT residue with one MIT residue. (Importantly,
peroxidase is much more efficient at combining of two
DIT residues and thus generation of T4 occurs much
more readily, explaining why the thyroid gland primarily
produces T4 rather than T3. Notably, some MIT and DIT
residues do not get coupled and so peroxidase-
processed thyroglobulin will retain some MIT and DIT
residues).
C. Endocytosis of Peroxidase-processed Thyroglobulin
Peroxidase-processed thyroglobulin is then endocytosed by
follicular epithelial cells on a regulated basis whenever the
thyroid gland is stimulated to release thyroid hormone into the
circulation. Importantly, peroxidase-processed thyroglobulin
within the follicle can act as a reservoir for thyroid hormones
in the absence of stimulation for hormone release.
Importantly, this reservoir of peroxidase-processed
thyroglobulin is usually enough for months of use explaining
why defects in thyroid hormone synthesis often take months
to become clinically apparent.
D. Proteolysis
Once endocytosed into the follicular epithelial Cell, the
thyroglobulin is broken down by lysosomes, thus releasing
attached T4, T3, MIT, and DIT. T4and T3 are then transported
out of the follicular epithelial cells and into the circulation. The
iodine atoms of MIT and DIT are salvaged and transported
-
back into the follicular lumen as I .
E. Peripheral Deiodination
Deiodination, the convertion of abundant T4 in the
peripheral tissue to a more biologically active T3, is catalyzed
by iodothyronine deiodinase.

There are two deiodinase enzymes but the one that binds
more to T4 is deiodinase-2 enzyme; found in the kidney,
brain, and liver
This step can be INHIBITED by:
Amiodarone, B-blockers, corticosteroids, iodides,
contrast media, severe illness or starvation.
Figure 2. Biosynthesis of thyroid hormones
Organification and coupling (-) by anti-thyroid drugs
(Thioamides)
Iodide trapping, organification and coupling are (-) by
Iodides; if theres a significant number of iodides in the
circulation, it can be an initial treatment and can inhibit thyroid
hormone synthesis including proteolysis
Iodide trapping, organification and coupling, including
proteolysis are (+) by TSH; TRH stimulates the synthesis and
release of thyrotropin (TSH)
II. TYPES OF THYROID DISORDERS
Table 2. Signs and Symptoms of Hypothyroidism.
Important S/Sx: weakness, dry skin, feeling cold, constipation,
weight gain.
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Table 3. Signs and Symptoms of Hyperthyroidism
Important S/Sx: Hyperactivity, heat intolerance, sweating,
palpitations, tachycardia, tremor.
A. Hyperthyroidism vs Thyroxicosis
Hyperthyroidism
Hyperthyroidism is a condition in which there is an increase
in thyroid function (increases T3 and T4 production).
Hyperthyroidism manifests hypermetabolic problems, such
as always hungry, not gaining weight, having bulging and big
eyes, tremors, diarrhea, fatigue, and muscle weakness. It is
diagnosed with a blood test via T3 and T4.
Thyrotoxicosis
Thyrotoxicosis, on the other hand, is defined as too much
thyroid hormones circulating in the blood which is more than
those of hyperthyroidism, due to another cause (other than
production of T3 & T4). It is also called a thyroid storm or
thyrotoxic crisis, an emergency situation which may cause
immediate death in the person having it. e.g.:
o patient ingested an overdose of thyroid hormones
o release of stored hormones after destruction of follicular
glands secondary to thyroiditis
o iatrogenic (RAI)
Thyrotoxicosis manifests an exaggerated manifestation of
hyperthyroidism plus life-threatening conditions, such as
tachycardia, increased bowel sounds, crackles, and
dysrhythmias.
B. Primary Hyperthyroidism
Graves' disease
o Most common primary hyperthyroidism
o also known as diffuse toxic goiter, is an autoimmune
disease that affects the thyroid, causeing a generalized
overactivity of the entire thyroid gland
Toxic multinodular goiter
o Hyperfunctioning of several nodules
o Different from Graves
Toxic adenoma
o Benign tumor leading to hyperthyroidism
Iodine Excess (Jod-Basedow phenomenon; amiodarone,
lithium)
o It is an iodine-induced hyperthyroidism, typically
presenting in a patient with endemic goiter (due to iodine
deficiency)
o 2 ways wherein Iodine can affect your thyroid hormone
synthesis:
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normal thyroid gland: elevated levels of iodnie destroy thyroid tissues to decrease hyperthyroidism to the
blockade for 1-2 days of thyroid hormone euthyroid state.
synthesis (Wolf-Chaikoff) adjustment of Iodine excess
thyroid gland resume production of thyroid o It can go through hyperthyroidism
hormone Iodine deficiency
diseased thyroid: hyperactive thyroid can o Can lead to enlargement of the thyroid gland and
inhibit production of hormone through the hypothyroid state because of the absence of you
different steps of hormone synthesis riodine
o this is why you give iodides in certain Secondary
hyperthyroid conditions like thyroid Hypopituitarism
storms Hypothalamic tumors and trauma
o can also increase production of thyroid o increasing production of TSH decreased
hormone via the Jod-Basedow production of T4 & T3
phenomenen Myxedema coma
o The Jod-Basedow effect typically occurs with o uncontrolled hypothyroidism
comparatively small increases in iodine intake, in people
who have thryoid abnormalities that cause the gland to II. DRUGS THAT CAUSE HYPOTHYROIDISM
function without the control of the pituitary (i.e., a thyroid
gland that is not normally suppressed by thyroid
Iodine excess
hormone driven loss of TSH secretion from the pituitary).
o All drugs and food containing iodine (amiodarone,
lithium, iodine containing compound and contrast
C. Secondary Hyperthyroidism
media)- it either goes to a Jod-basedow or inhibition of
your thyroid hormones
TSH-secreting pituitary adenoma Anit-thyroid drugs
o It increases the production of TSH. Salicylic acid (iodine containing compund)
Thyroiditis Interferon alpha/ cytokines
o Increase the function of the thyroid gland, or later on if
Aminoglutethimide
there is destruction of the thyroid tissue, the reserved
o hormonal treatment for metastatic breast cancer
thyroid hormones will be released.
Tytosine kinase inhibitors (sunitinib)
o It can be a cause of thyrotoxicosis.
Decrease the production of TG, tyrosine is important in
the production of TG also in the organification of your
D. Thyrotoxicosis without Hyperthyroidism
iodide

Occurs when secondary hyperthyroidism goes into a III. DIAGNOSTICS

subacute stage
o Silent throiditis
Most important in diagnosing hyper/hypothyroidism: TSH, Free T3
o Subacute thyroiditis
& T4
o Iatrogenic (RAI)
A. Diagnostics
All of this can lead to thyrotoxic crisis (thyroid storm) if
you cannot control hyperfunctioning thyroid with your anti-
thyroid treatment regimen. TSH: 0.4-4 mlU/l
FT4: 0.7-1.86ng/dL
E. Hypothyroidism
DIAGNOSIS FT3:145-348pg/dL
Primary Total T4: 4-12.3ug/dL (60-160nmol/L)
Autoimmune (Hashimoto) thyroiditis- most common Total T3: 60-181 ng/dL (0.9-2.7 nmol/L)

nd
Iatrogenic- 2 most common; TSI: <125
o Anti-thyroid Tg Ab: <20IU/L
o If still uncontrolled: RAI, thyroidectomy Anti TPO: <0.8IU/L
With RAI, you dont destroy the whole thyroid gland, there THBR: 0.9-1.1
are still remaining normal functioning thyroid tissues that Free T4 index: 4-11
wil be left. That is the reason why there are still levels of Free T3 index: 80-180
your T3 & T4 (already in hypothyroid state) TGB: 12-39mg/L
Thyroidectomy: they dont remove everything. But
because most of it is removed, you will have your Increase in TSH decreased T3 and T4
hypothyroid state later on. hypothyroidism (not always the case)
Some doctors aim for euthyroid state, they do partial Decrease in TSH T3 and T4 increase = hyperthyroidism
thyroidectomy and RAI is underdosed just enough to (Not always the case)

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Total T3 and T4 helpful in pregnancy, drug use, etc.; it
constitutes the bound and the unbound, it can affect the T3
and T4
TSI (Thyroid Stimulating Immunoglobulin)- you get this in
Graves disease when you find an equivocal TSH, T3 and
T4 but you eye findings and the patients is complaining of
tremor.
Tg Ab and Anti TPO- your order this when have
subclinical graves or hashimoto; both can increase Tg Ab
and Anti TPO but only graves can increase TSI
B. Other diagnostic tests
Thyroid Scan
o Nuclear study
o Reasons for ordering thyroid scan
If there are nodules, you either identify if it is hot or
cold. Hot nodules- rarely the case is cancer; cold
nodules- always suspect malignancy
In preparation of RAI you want to know the
behaviour of your radioactive iodine, but use weak
dose then you would be able to know the
absorption of your radioactive isotope in your
thyroid; you will know what does to give for your
RAI.
RAIU
o Definitive treatment for younger thyroid patients
o 1-131 is the radioactive iodine used
Can be the initial treatment after initiation of
thioamides o
Can be the treatment of choice for relapses
o Within few weeks of administration, destruction of thyroid
parenchyma is evidenced by epithelial swelling and
necrosis, follicular disruption, edema and leukocytic
infiltration
Main function is destruction of thyroid tissues and
the target is to attempt at hypothyroid state
May cause thyroid storms (because its still an
iodide) and can cause Jod-Basedown phenomenon
o Initial thioamide treatment should be done before RAI
treatment
Stop 3 days before RAI treatment for Methimazole
Stop 2-4 weeks prior to RAI treatment for PTU
o Avoid exposure of patient to children and pregnant
women for 1-2 weeks due to radiation emission
o Repeat after 6 months if patient is still hyperthyroid and
manifesting thyrotoxicosis
UItrasound
o To know if its cystic, solid
FNA biopsy
definitive diagnosis for malignancy
IV. GRAVES DISEASE
60-80% thyrotoxicosis
More common in women; 20-50 years
Autoimmune hyperthyroidism; diffuse goiter
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Due to stress, smoking, sudden increase in iodine intake,
postpartum, antiretroviral, alemtuzumab
Most common form of Hyperthyroidism
o Manifestations: Pretibial dermopathy, retraction of the
upper lid of the eyes with wide stare, periorbital edema,
exophthalmos, diplopia, Increase in sympathetic activity
of the body.
Remission is possible
If it reaches restrictive myopathy and exophthalmos or
there is compression of the optic nerve use steroids
A. Graves Ophthalmopathy
Grave ophthalmopathy is always present in Graves
disease
Cytokines play a major role due to the infiltration of your T
cells inside the orbit
o most of the time it is in the extraocular muscles but
sometimes there is also increase in the quantity of
fat ans asoft tissues inside the orbit
The petrusion of the eyeball (exopthalmos) is associated with
increased volume of the retroorbital connective tissues and
extra ocular muscles.
Leads to fibrosis late in the illness if uncontrolled
Manifestations:
o Dry eyes, lid retraction (scleral show), restrictive
myopathy (diplopia), exophyhalmos (proptosis; exposure
keratopathy), loss of vision (optic neuropathy)
B. Goals of Treatment
Alleviate signs and symptoms
Reduce or increase thyroid hormone synthesis
C. Treatment
Anti-thyroid- Thionamides
Iodides
Especially in Thyroid storms
Used to be given in other types hyperthyroidism
Beta Blockers
o To decrease sympathetic activity
Radioactive Iodine / Thyroidectomy
o For toxic goiters and Graves
V. ANTI-THYROID TREATMENT
If you will wait for remission, this is the definitive treatment,
you give anti-thyroid. Sometimes if its uncontrolled, you
start with anti-thyroid drugs and then prepare the patient
for RAI. The same is true if you will refer the patient for
surgery, you give anti-thyroid prior to surgery.
WHY do you need to give anti-thyroid prior to RAI or
surgery?
to prevent thyroid storms
there is destruction of thyroid tissue increased
activity of functional thryoid cells thyroid storm
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A. Methimazole You only use PTU during thyroid crisis (Thyroid Storm),
st
DRUG OF CHOICE for Graves Disease 1 trimester of pregnancy and when there are adverse
Single daily dose, good compliance, less toxic, long plasma reactions to Methimazole.
intrathyroidal half-life and long duration of action
Given in most cases of hyperthyroidism LIFTED FROM 2018A Trans Table 1

nd rd
May be used during the 2 and 3 Trimester of Pregnancy C. Beta-blockers
st
after initial treatment with PTU during 1 Trimester. Controls sympathetic stimulation
st
May cause congenital malformations in the 1 Trimester or Use beta blockers without ISA (propranolol, metoprolol,
pregnancy. atenolol)
REPLACE BLOCK METHOD is another technique being Only PROPRANOLOL blocks peripheral T4-T3 conversion in
used where high doses of Methimazole (40mg) is combined 20% of hyperthyroid patients
with Levothyroxine. By doing this, you can aim for euthyroid Some doctors use propranolol in patients who
state in 6 months but may increase risk of hyperthyroidism d/t present with tremors, sweating, tachycardia etc. and
Levothyroxine especially in patients under multiple drug the symptoms are found to be resolved. These
therapy (drug interactions). patients may be in subclinical hyperthyroidism.
40-80mg q6 (160mg/day)
Table 4. Thioamides METOPROLOL 100mg q12
Anti-Thyroid Drugs (Thioamides) ATENOLOL 100mg OD
METHIMAZOLE PROPYLTHIOURACIL (PTU)
Thyroid Storms: beta blockers should be given to reduce
MOA: Blocks organification MOA: Blocks organification
and coupling (10x more potent) and coupling tachycardia

Blocks peripheral D. Iodides

deiodination (2x)
-the conversion of your T4 to
T3 in distant tissues
Can be used during 1
st
trimester of pregnancy (unlike
Methimazole which cannot be
used during pregnancy)
PK: lower excretion (48 hours); PK: lower bioavailability (40-
good thyroid absorption; t1/2 80%); good thyroid absorption;
6hrs; can cause malformations t1/2 1.5hrs; tightly protein
10-20mg bid, 3-4 weeks bound (good for first trimester
pregnancy)
Maintenance: 2.5-10mg od 100-200mg tid-qid, 3-4 weeks
50-100mg tid
Remission: 1-24 months
*For maintenance, shift to Remission: 18-24 months
Methimazole
*SHORT ACTING!!!
More important for our patient:
if you want to reverse
IMMEDIATELY the s/sx of
thyroid storm
IT IS GIVEN TID
AE: AE:
Common: rash, urticaria, Common: rash, urticaria,
feverish, nausea, GI distress feverish, nausea, GI distress
Altered taste and smell Vasculitis, lupus-like reaction,
Vasculitis; lupus-like reaction, hepatitis
hepatitis, agranulocytosis Agranulocytosis
(more seen if taking 40mg/d
methimazole)
B. Propylthiouracil (PTU)
More helpful in uncontrolled Hyperthyroidism especially
Thyroid Storms since PTU is shorter acting than
Methimazole.
st
Can be given in the 1 Trimester of pregnancy because it is
highly protein-bound and does not cross the placenta. Shift
nd rd
to Methimazole during the 2 and 3 Trimester.
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Previously the drug of choice of thyrotoxicosis
because it can reverse the s/sx of hyperthyroidism in
a short period of time
with an elevated dose of iodide, it blocks
organification and coupling in the production of
thyroid hormone
Wolf-Chaikoff effect/Jod-Basedow phenomenon
o Jod basedow - a chronically starved thyroid (read
iodine deficient. Also, this phenomenon does not
occur in normal individuals) finally gets some iodine
to make t3/4 and goes into overdrive.
so : iodine induced hyperthyroidism (sort of
o Wolff chaikoff - normal thyroid encounters large
iodine load and shuts down production ( a form of
internal regulation) - used therapeutically with KI
tablets following radiation (I think)
so : iodine induced hypothyroidism.
Used in thyroid storms, radiation exposure emergencies
Inhibits iodide trapping, organification, coupling, TG
proteolysis, deiodinase
Potassium Iodide (KI)
RDI: 150mcg (0.15.g) per day
1.5-150mg/day produces Wolff-Chaikoff effect
Thyroid storm: >6mg/day for 2-7 days; initiate Thioamides
prior to KI use
o Use PTU 500-1000mg LD. 250mg q4 for initiation
prior to Potassium Iodide
Your methimazole, PTU, and Iodides blocks the
organification and coupling in the formation of
thyroid hormones, but Iodides can also stimulate
through the Jod-Basedow phenomenon the
production though organification and coupling. By
blocking it initially with thionamides, theres no way
for the iodides to stimulate it, the only effect of
Iodides will be blocking the organificatio
Saturated Solution KI (SSKI) 5 gtts/drops q6; Ipodate or
Iopanoic Acid 500mg q12; NaI 250mg TIV q6
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Escape from iodide block: 2-8 weeks (so you only use this to o CHILDREN: 90-120 ug/day
control thyroid storm and not for maintenance) o PREGNANT AND LACTATING: 250 ug/day
Not used prior to RAI treatment / limit use in pregnant
women A. Synthetic Thyroid Hormones
Prep: Tablets, Saturated Solutions
Synthetic Thyroid Hormones
Radiation exposure emergencies Dessicated
Levothyroxine Liothyaronine Liotrix
Potassium iodide- 130mg/day (30-100mg) Thyroid
Lugols Solution (5% iodine, 10% KI) -8mg/gtt; 16-36mg (2- T4 (most T3 T4 and T3 T4 and T3
6gtts) TID common) (4:1 mixture) (4:1)
SSKI- 50mg/gtt; 50-100mg (1-2gtts) TID Natural:
bovine/
Iodides adverse effects
porcine
GI distress, rash
PK: absorption PK: absorpion
Iodism: uncommon, reversible; presents with rash, swollen
(40-80%) (100%)
salivary glands, mucus membrane, ulcerations, rhinorrhea,
decreased by decreased by
drug fever, bleeding disorder and anaphylactoid reactions
food, food,
malabsorption, malabsorption,
Radioactive iodine (sodium iodide)
drugs, dietary drugs, dietary
Definitive treatment for patients with hyperthyroidism
fibers, 99% fibers, 99%
used for treatment is Isotope (131I) and diagnosis is Isotope
protein bound, protein bound,
(123I)
excreted excreted
For diagnosis of thyroid diseases (thyroid scan): (123I) kidneys, t1/2 9- kidneys,
Initial treatment; for relapses 10 days t1/2 24 hrs
Destroys thyroid tissues
ADV: long ADV: faster More AEs, Greater
Indications: Graves disease, young patients without risks of
acting, stable onset (2-4hrs) rarely used variability /
cancer, old patients with heart disease, poor surgical
and and shorter batch, more
candidates, toxic goiter
predictable, acting, more Aes, variable
Effective dose depends on size of thyroid, iodide uptake, rate
cheap, widely frequent ratio of TH,
of release of RAI for weeks
studied dosing, not high risk for
131 used for anaphylaxis
Radioactive iodine ( I)
chronic
185-555mBq / 80-150mCi (attempt at hypothyroid than
replacement
euthyroid state)
Initial Thioamide therapy (stop Methimazole for 3 days and
Levothyroxine
PTU for 2-4 weeks prior to RAI)
o Synthetic T4
Often leads to hypothyroidism / may cause thyroid storms
o given in most cases
Hyperthyroidism for 2-3 months (because of the release of
o t1/2: 9-10 days
your T3 and T4 due to the destruction of thyroid tissues); use
o Daily dose: 1.6ug/kg/day (100-150ug/day) 30mins
thioamides / beta blockers
before breakfast; titrate 12.-5ug
Repeat RAI dose after 6-12 months if still hyperthyroid
o Replacement: 75-125 ug/day
Avoid exposure to children, pregnant women, family o Follow up for hypothyroidism is 2 months
members for 1-2 weeks Expect in 3-6 months that the patient will
80% effective in first dose; 20% on second dose be in euthyroid state
Advantages: no deaths, no thyroid surgery, low cost, out- maintained for 2-3 years
patient o Kung nagmiss siya ng one dose, you can tell the
Disadvantages: hypothyroidism, long time to control patient that s/he can take two doses the next day.
hyperthyroidism (2-3 months), worsening of ophthalmopathy, The patient will not experience adverse reactions.
radiation thyroiditis, salivary gland dysfunction Liothyronine
o Given to patients with Myxedema coma
VI. IODINE DEFICIENCY o Synthetic T3
o T1/2: 24 hours
Common in mountainous area o Given 3x a day
2 billion are iodine defiecient (WHO) Liotrix
leads to endemic goiter or diffuse non-toxic goiter o Synthetic
Most common cause of preventable mental deficiency o High risk for adverse reactions
Iodine supplementation: Dessicated Thyroid
o ADULTS: 150-250 ug/day o Organic
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o High risk for anaphylaxis because it is extracted iodides (incl. Amiodarone, interferon, lithium),
from animals thioamides, tyrosine kinase inhibitors
o Not preferred anymore Can competitively inhibit iodine trapping
B. Myxedema Coma inhibition of thyroid hormone release & iodide
synthesis
Medical emergency (20-40% mortality rate) What to do: DECREASE DOSE
There is decreased sensorium, seizures,
hypothermia(most common cause of death) Altered TH transport and TT4 / TT3 (N FT4 and TSH)
Occurs in the elderly o Increased TBG
precipitated by impaired respiration (pneumonia, drugs Estrogen, tamoxifen, methadone (long-acting
like sedatives, CHF, MI) morphine), 5-fluorouracil
If theres increased TBG there will be more of the
Treatment:
unbound that will bind to the protein decreased
o LT4 50ug IV bolus LD, 50100ug/dL
FT4 INCREASE DOSE
o Liothyronine 10-25ug IV q8-12h
o Decreased TBG
You can give LT4 but its helpful to give Liothyronine
Androgen, glucocorticoids
because this is the biologically active drug.
What to do: DECREASE DOSE
Since you give this 3x a day, you can shift later on when
o Displacement of T3 and T4 from TBG
the patient becomes stable, to Levothyroxine.
Salicylates, fenclofenac, mefenamic acid,
furosemide
VII. DRUG INTERACITONS There will be more FT4 DECREASE DOSE

A. Drugs and Substances that Interact with Thyroid/Anti-
thyroid Drugs
Drugs that decrease absorption
o Albumin, PPI, suralfate, cholestyramine, colestipol, Ca
carbonate, chromium, food, iron, lactose intolerance,
raloxidene, soy
o What to do: INCREASE DOSE
If Im treating a hypothyroid with LT4 and theres
decreased absorption because of these drugs, will I
increase my dose or decrease? INCREASE.
Altered T4/T3 metabolism (no change in TSH)
o Increased metabolism (more degradation of TH)
Even if the TSH levels are normal, because it can
increase the metabolism of circulating T4 & T3
INCREASE DOSE
Nicardipine, phenytoin, carbamazepine, rifampin,
phenobarbital, sunitinib
o Inhibition of deiodinase (decreased T3)
Iopanoic acid, ipodate, amiodarone, propranolol,
corticosteroids, PTU, flavonoids
What to do: INCREASE DOSE

Drugs that increased metabolism B. Complications

o Rifampin, carbamazepine, sertraline, phenytoin
o What to do: INCREASE DOSE
Causes impaired T4-T3 conversion
o Amiodarone
o Given to patients with arrhythmia
o What to do: INCREASE DOSE
Multifactorial
o Estrogen, pregnancy, ethionamide, tyrosine kinase
inhibitor (sunitinib, imatinib), simvastatin
Tyrosine kinase inhibitor less tyrosine for Cretinism
organification INCREASE DOSE
Change in TH synthesis
o Inhibition of TRH adn TSH (w/o hypo or hyper)
dopamine, bromocriptine, levodopa, corticosteroids,
somatostatin
Decreased thyroid hormone production
What to do: INCREASE DOSE
o Drugs that decrease TSH (i.e., Meetformin)
What to do: INCREASE DOSE
o Inhibition of synthesis or release (w/ hypo)- anions
(perchlorate, thiocyanate, pertechnetate, nitrates),
Graves ophthalmopathy
o Thioamides, iodides, RAI, steroids, eye lubricant
o You have to reverse the hypothyroidism and add
steroids and lubricants.
Thyroid storm
o Start with Thionamides, but the definitive treatment
would be Iodides, beta blockers, anti-arrhytmia
o You can go to RAI if its still uncontrolled
Myxedema coma
o Liothyronine
o Congenital hypothyroidism
o For most cases, its Levothyroxine
SUMMARY
Most common cause of hyperthyroidism (Graves)/
hypothyroidism (Hashimoto thyroiditis)
Hyperthyroidism is treated with thioamides, RAI, iodides,
subtotal thyroidectomy
Hypothyroidism is treated with synthetic TH (LT4,
Liothyronine)

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Life threatening complications include thyroid storm and

myxedema coma 8. Which antithyroid drug inhibits iodide trapping in thyroid
Identification of drug interactions play an important part in follicular cells?
achieving your desired therapeutic goals a. Thiocyanate
b. Interferon
c. Lithiu
REFERENCES
d. Amiodarone
Trans 2018A, 2017A
th
Katzung (13 ed.) and Goodman and Gillman
9. Which drug increases the displacement of T4/T3 from
Lecturers Presentation and Recordings TBG?
GUIDE QUESTIONS a. Estrogen
1. Propylthiouracil (PTU) is preferred over methimazole in b. Fluorouracil
the management of thyroid storm due to its greater c. Rifampin
inhibition of: d. Furosemide
a. Iodine trapping
b. Iodine organification and coupling 10. Rody Dudirty, 70 y/o male from Davao City, on
c. Thyroglobulin proteolysis propanolol for hypertension is also being treated for
Graves disease with methimazole 20mg od. He
d. Peripheral deiodination
complains of easy fatigability, poor appetite, weakness
and weight gain, and is found to be bradycardic. Of the
2. Which of the following medications can decrease the following, what will be the appropriate management
intestinal absorption of synthetic levothyroxine? option?
a. iodinated contrast media a. Increase methimazole to 20mg bid
b. amiodarone b. Decrease methimazole to 10mg od
c. esomeprazole c. Shift to PTU 200mg every 6 hours
d. sertraline d. Maintain on current methimazole dose

3. Which of the following statements is true of thioamides? 11. Datu Mar, 58 y/o male from Cubao, on quadruple anti-
a. Methimazole is more protein bound compared to Koch therapy for TB is being treated with levothyroxine
PTUamiodarone 25 mcg. His recent laboratory results the following:
TSH 7 mIU/L (0.4 4)
b. Methimazole is a prodrug of carbimazole
FT4 0.2 ug/dL (0.7 1.86)
c. PTU usually causes bothersome metallic taste
FT3 110 pg/dL (145 348)
d. PTU has a shorter half life compared to
The best thing to do is:
methimazole
a. discontinue the anti-Koch treatment
b. shift to dessicated throid
4. Which of the following drugs is used to prevent radiation- c. increase levothyroxine to 50 mcg/day
exposure hypothyroidism? d. decrease levothyroxine to 12.5 mcd/day
a. I131
b. Potassium iodide
c. Perchlorate 12. Onli Vinay, 73 y/o male from Makati, taking mefenamic
d. Carbimazole acid for osteoarthritis, was treated with radioactive
ioidine. 3 weeks prior to current consult. On follow-up.,
5. In the treatment of a patient with Graves disease, which he claims to have worsening of tremors and palpitations.
of the following laboratory findings can help in deciding What will you recommend?
when to increase PTU? a. give another dose of radioactive iodine
a. increased anti-TPO b. provide potassium iodide
c. initiate levothroxine
b. decreased unbound T3
d. start methimazole
c. increased TSI
d. decreased TSH
13. Grace Poon, 47 y/o female from California has been on
Tamoxifen for breast cancer/ Three months prior to
6. Patients given radioactive iodine need to be isolated consult, she was diagnosed with Hashimotos thyroiditis
from other people for at least: and was eventually given levothyroxine 25 mcg.
a. One day Essentially normal findings are observed on PE. The
b. One week current laboratory results reveal
c. One month TSH 3 mIU/L (0.4 4 mIU/L)
d. One year FT4 1.5 ng/dL (0.7 1.86)
Total T4 17 mcd/dL (4.5 11.5)
FT3 310 pg/ dL (145 348)
7. Which of the following drugs can decrease serum total
What will be the next best thing to do?
T4 levels
a. discontinue tamoxifen
a. Tamoxifen
b. maintain on current medications
b. Triamcinolone c. decrease levothyroxine to 12.5 mcg
c. Fluorouracil d. increase levothyroxine to 50 mcg
d. Methadone d,c,d,b,d,b,b,a,d,b,c,d,b
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