ANTIDIABETIC DRUGS

DEFINITION
Diabetes mellitus is
defined as an
elevated blood
glucose associated
with absent or
inadequate pancreatic
insulin secretion with
or without concurrent
impairment of insulin
action (Katzung B.G., 2009; WHO
2014)

Classification
Type 1 diabetes

Pancreas fails to
produce the insulin
which is essential
for survival.

Type 2 diabetes

the body's inability

to respond
properly to the
action of insulin
produced by the

Environmental fc
Lifestyle
changes

Genetic Factors

High fat/lack of exercise

Interaction

Obesity
Insulin resistance

Decreased insulin seretion

Relative insufficiency of insulin action

Development of type 2 diabetes

Factors causing increase in visceral fat

1

Stress-related factors
-overeating, especially excessive intake of simple
sugars
-smoking
-Increase in alkohol intake
-disorders of nervous and endocrine
systems:increase in cortisol, abnormality in sex
hormone secretion

2
3
4

Lowered energy consumption due to a lack of

exercise
Genetic factors
Aging

PREDIABETES
Reflects failing pancreatic compensation to an
underlying state of insulin resistance (caused
by obesity)
Current criteria: impaired glucose tolerance,
impaired fasting glucose, or metabolic syndrome
a 5-fold increase in future T2DM risk
The primary goal management : WEIGHT LOSS

PREDIABETES
Antihyperglycemic medications :
Metformin and acarbose
Reduce the risk of future DM in prediabetic patients
by tolerated
25 to 30%AND safe
Well
CV benefits

(Chiasson J.L., et al.1994; Gerstein H.C., et al.2006)

Thiazolidinediones

Prevented future DM in 60 to 70 % of subjects

with prediabetes,but have a number of AEs

PHARMACOTHERAPY

eving the glucose target and hemoglobin AIC g

AIC 6,5% for most patients
AIC > 6,5 % if the lower target cannot achieved
without AEs
In large clinical trialintensive gluc-lowering th/
(target AIC < 6% in pt with baseline AIC >8,5% was
associated with increased mortality in older and
middle-aged patients with longstanding diabetes who
were at high risk CVD
In other trial : higher AIC target for intensively treated
pt no- between group diff in CVD endpoints, CV
deaths, or overall death. (Duckworth W., et al. 2009 ; Gerstein H.C., et al.
2008)

Pharmacotherapy 2
Patients with recent-onset T2DM or
mild hyperglycemia (AIC < 7,5%)
TLC with monotherapy :
Metformin
Alternatives: GLP-I agonists,
ipeptidyl-peptidase-4 (DPP-4)
inhibitors, and alpha-glucoside
inhibitors
(AGIs)
TZD, Sulfonylureas
(SFUs) and glinides may also be
used but should be used with caution owing to the
potential for weight gain,
hypoglicemia, or other risk

Treatment
The mainstay of nonpharmacological diabetes
treatment is diet and physical
activity.
About 40% of diabetes sufferers
require oral agents for satisfactory
blood glucose control, and some
40% need insulin injections.
People with Type 1 diabetes are
usually totally dependent on
insulin injections for survival
The majority of people suffering
from diabetes have the Type 2
form.

An algorithm for the treatment of type 2 diabetes mellitus

bclass drugs used for Diabetes

INSULIN
SULFONYLUREAS
Meglitinides
BIGUANIDES
ALPHA-GLUCOSIDASE
INHIBITORS
THIAZOLIDINEDIONES

Lowering blood glucose

by stimulating insulin
Have been used for
secretion from the
treatment T2DM for
cells of the pancreatic
nearly 50 years
islets
SULPHONYLUREAs
The drugs bind
to the
-cell sulphonylurea
When sulphonylureas
receptor (SUR)-1
interact with
closes K-ATP
SUR1release of preCHANNELS)reduces
formed insulin
cellular potassium
granules adjacent to
efflux
the plasma
depolaritationope
membranc(first
ning voltagephase of insulin
dependent Ca
release)
channels influx of
Ca release insulin

Sulphonylureas
2 additional mechanisms of action have
been proposed:
1. A reduction of serum glucagon levels
Mechanisme is unclear
Appears to involve indirect inhibition due to
enhanced release both insulin and
somatostatin which inhibit alpha-cell
secretion
2. Closure of potassium channels in
extrapancreatic tissue

armakokinetika golongan sulfonilurea

First Generation Sulphonylurea

Tolazamide

Chlorpropamide
has a shorter
a half-life of 32
duration of
hours and is
action. More
slowly
Tolbutamid metabolized in the slowly absorbed
liver to products
than the other
well absorbed. that
retain some sulphonylureas.
Rapidly
biology activity.
Half-life is 7
metabolized in
20-30% is
hours.
It
is
the liver.
excreted
metabolized to
Its duration of unchanged in the
several
urine.
effect is short.
compunds that
Dosage higher
Elimination
retain
half-life of 4-5 than 500 mg/d
hypoglicemic
increase jaundice
hours
effects. If more
Maintenance
than 500 mg/d
dosage : 250
are require
mg/d, SD in the

Second Generation
Sulfonylurea

Glyburide Glipizide

Glimepiri
de

GLYBURIDE
Metabolized : Hepar into
products with very low
hypoglycemia activity
Usual starting dosage: 2,5 mg/d
or less
Average maintenance :dosage :
5-10 mg/d, single morning dose
Maintenance > 20 mg/d not
recommended
A formulation micronized
glyburide is available in a
variety of tablet sizes

Glyburide
FDA recommends
careful monitoring
to retitrate dosage
when switching
1 from standart doses
or from other
sulfonylurea drugs
3

Flushing has
rarely been
reported after
ethanol ingestion

Few Aes,
potential for
causing
hypoglicemia

4
Contraindicatio
n : hepatic
impairment and
renal
insufficiency

Glipizi
de
Has the shorted half-life :2-4 hours
Ingestion : 30 minutes before breakfast
absorption is delayed by food
Recommended starting dosage : 5 mg/d 15
mg/d SD
Higher dosage should be divided, given
before meals
Total daily dosage recommended by the
manufacturer : 40 mg/d

Glipizide
90% of glipizide :
metabolized in the liver
to inactive products
10% is excreted
unchanged in the urine
Contraindication:
hepatic or renal
impairment

GLIMEPIRIDE
Once daily use as monotherapy or
combination with insulin
A single daily dose of 1 mg has been shown
to be effective
The recommended maximal daily dose :8 mg
Has a long duration of effect with a half-life
of 5 hours
It is completely metabolized by the liver to
inactive product

Meglitinides
Repaglinide
a new non-sulfonylurea insulin
secretagogue agent, the first available
from the meglitinide class.

Nateglinide
the newest member of the class, has
recently become available

The first
member of the
meglinitides
Very fast
onset, a peak
concentration
and peak
effect : 1 hour
after ingestion,
duration : 5-8
hours

Meglitinid
e:
Repaglinid
e
Have 2 binding
sites in common
with sulfonylurea
and one uniqe
binding site

Modulate
beta-cell
insulin release
by regulating
potassium
efflux through
the potassium
channels

Repaglinide

It is hepatically cleared by CYP3A4

Plasma half-life: 1 hour
Onset : rapid controlling glucose excursion
Should be taken before each meal in doses of 0,25
mg 4 mg (maximum 16 mg/d)
If the meal contains inadequate CH
hypoglycemia
Caution : renal and hepar impairment
Is approved as monotherapy or its combination with
biguanides
There is no sulfur in structure can be used by
T2DM with sulfur or sulfonylurea allergy

Nateglinide
Stimulates very rapid and transient
release of insulin from beta-cells
through closure of the ATP sensitive
K+ channel.
Ingestion : just before meal
Absorption : 20 minutes
Metabolism : hepar, by CYP2C9 and
CYP3A4
A half-life of 1,5 hours
The overall duration of action : < 4

BIGUANIDES
AN ANTIHYPERGLYCEMIC
AGENT its lowers blood
glucose concentration in
t2d without causing overt
hypoglicemia

INSULIN SENSITIZER
reduces insulin
resistance and significant
reduction of plasma
fasting insulin level

Metformin

Increases plasma levels of

glucagon-like peptide 1
(GLP-1) and induces islet
incretin receptor gene
expression through a
mechanism that is
dependent on PPAR(Maida et al)

Primary function : decrease

hepatic glucose
production, mainly by
inhibiting gluconeogenesis.

BIGUANIDE-METFORMIN
Accumulation of metformin in the liver has been
shown to be higher than in other tissues, reaching
hundreds of M in the periportal area
Deletion of the OCT1 gene in mouse dramatically
reduces metformin uptake in hepatocytes and
human individuals carrying polymorphisms of the
gene (SLC22A1) display an impaired effect of
metformin in lowering blood glucose levels (Shu Y, et al.2007)
(Wilcock C, et al. 1994)

BIGUANIDE-METFORMIN
The activation of AMP-activated protein
kinase (AMPK) was intimately associated
with the pleiotropic actions of metformin
( Zhou g., et al.2001)
AMPK is a heterotrimeric protein consisting
of a catalytic -subunit and two regulatory
subunits and and each subunit has at
least two isoforms.
AMPK is activated by increase in the
intracellular AMP-on-ATP ratio resulting from
imbalance between ATP production and
consumption.

BIGUANIDE-METFORMIN
Metformin most likely does not directly
activate either LKB1 or AMPK as the drug
does not influence the phosphorylation of
AMPK by LKB1 in cell-free assay (Hardie
D.G. 2006)
There is evidence that AMPK activation by
metformin is secondary to its effect on the
mitochondria, the primary target of the
drug.

BIGUANIDS-METFORMIN
First line therapy for T2DM
Does not increase weight or provoke
hypoglicemia
Decreases the risk of macrovascular
and microvascular disease
Also indicated for use in combination
with insulin secretagogues or
thiazolidinediones in T2DM in whom
oral monoth/ is inadequate

BIGUANIDS-METFORMIN
Eficacy: prevent the new onset T2DM in middle-aged,
obese person with impaired glucose tolerance and
fasting hyperglicemia
did not prevent diabetes in older, leaner prediabetics (the
landmark Diabetes Prevention Program)

the dosage : 500 mg 2,55 g/daily

Can be initiated as a once-daily dose a bedtime or
before a meal.
common schedule : fasting hyperglycemia begin with
a single 500 mg tablet
If tolerated wo/ GI dicomfort and hyperglicemia persist,
a second 500 mg tablet added to be taken with
breakfast or the midday meal or the larger (850 mg)
tablet 2 daily

BIGUANIDES-METFORMIN
Most common toxic effects : GI (anorexia,
nausea, vomiting, abdominal discomfort,
and diarrhea) occurs in up to 20% pt
Dose related
Occur at the onset of therapy
Persistent diarrhea stop (3-5% pt)
CI renal disease, alcoholism, hepatic
disease, conditions predisposing to tissue
anoxia coz of an increased risk of lactid
acidosis induced by biguanide drugs

THIAZOLIDINEDIONES

THIAZOLIDINEDIONES
Rosiglitazone
Pioglitazone
Combination preparations are also
available

THIAZOLIDINEDIONES
The principal mechanism

Stimulation of PPAR- enhance

insulin sensitivity
PPAR- is expressed at
highest levells in adipose
tissue, and less so in
muscle and liver

THIAZOLIDINEDIONES
ACTOS is a thiazolidinedione
antidiabetic agent that depends on
the presence of insulin for its
mechanism of action.
ACTOS decreases insulin resistance
in the periphery and in the liver
resulting in increased insulindependent glucose disposal and
decreased hepatic glucose output.

THIAZOLIDINEDIONES

Action of Pioglitazone in a
Diabetic Patient

THIAZOLIDINEDIONES
Rosiglitazone and pioglitazone rapidly
and nearly completely absorbed (1-2 hours
to peak concentration)
Absorption is slightly delayed when taken
with food
Both agents are extensively metabolised by
the liver
Rosiglitazone is metabolised mainly to very
weakly active metabolites with lesser
activity that are excreted in urine

THIAZOLIDINEDIONES
The metabolites of pioglitazone are
more active excreted mainly in
the bile
Pioglitazone is metabolised by
CYP3A4
No clinically significant reductions in
plasma concentration of other drugs
( e.g oral contraceptives)

THIAZOLIDINEDIONES
As a monotherapy in non-obese and obese
patients with type 2 diabetes in whom
diabetes is not adequately controlled by
nonpharmacologycal measures
Can be used in combination with other AD
drugs and in combination with insulin
Can cause fluid retention with increased
plasma volume, a reduced haemotocrit, and
a decreased in Hb concentration

THIAZOLIDINEDIONES
In Europe, CI CHF
AHA and ADA : patient treated with a
combination of insulin plus thiazolidinediones
higher risk of oedema careful clinical
monitoring (check : Hb before starting a
thiazolidinediones)
Liver function should be assessed by
measuring serum ALT before starting therapy
an subsequently at 2-monthly intervals
during the 1st year of treatment

THIAZOLIDINEDIONES
Rosiglitazone : 4 mg/d in combination
with sulphonylurea, increasing to 8
mg/d in combination with metformin
Pioglitazone : a once-daily dosage of 15
mg/d, increasing to 30 mg if necessary
If no effect is observed after 3 months
treatment stop the treatment
Can be used in the elderly, mild-tomoderate renal impairment

ALPHAGLUCOSIDASE
INHIBITORS

ALPHA-GLUCOSIDASE INHIBITORS
Acarbose and Miglitol

Competitive inhibitors of the intestinal

-glucosides and reduce post-meal
glucose excursions by delaying the
digestion and absorption of starch and
disaccharides

ALPHA-GLUCOSIDASE INHIBITORS
Acarbose
the first alpha-glucoside inhibitors
introduce in the early 1990s
Do not cause weight gain
Can reduce postprandial
hyperglycemia
Have lowered plasma triglyceride
concentrations in some studies (Lebovitz
H.E., et al. 1998)

ALPHA-GLUCOSIDASE INHIBITORS

ALPHA-GLUCOSIDASE INHIBITORS
Pharmcokinetics:
Is absorbed only < 2%
Is degraded by amilase in the small intestine
and by intestinal bacteria
Some of these degradation products are
systemically absorbed to be eliminated in
the urine
Can be used as monotherapy for pt T2DM
that is inadequately controlled by
nonpharmacological measures

ALPHA-GLUCOSIDASE INHIBITORS
Can be a useful first-line treatment in
pt who have a combination of only
slightly raised basal glucose
concentrations and more marked
postprandial hyperglycemia
STOP-NIDDM : confirmed the utility
of acarbose in preventing the
transition from impaired glucose
tolerance to diabetes (Chiasson J.L., et al. 2002)

ALPHA-GLUCOSIDASE INHIBITORS
When starting th/ ensure that pt is taking
diet rich in complex CH
Should be taken with meals
Starting with a low dose, for example 50
mg/day
Slowly titrating up over several weeks
High dosages can occasionally increase liver
enzyme concentrations transaminase
concentration are measured at intervals in pt
receiving the max dosage.

ALPHA-GLUCOSIDASE INHIBITORS
If liver enzymes are raised the dosage should
be reduced to a level at which normal enzyme
concentrations are re-etablished
Aes: gastrointestinal in th STOP-NIDDM trial:
31% of acarbose treated pt compared with
19% on placebo discontinued treatment early
If dosage is too high undigested
oligosaccarides pass into the large bowel
fermented by flora flatulance, abdominal
discomfort, and sometimes diarrhoea. can
be minimised by slow titration

ALPHA-GLUCOSIDASE INHIBITORS
Hypoglycemia in combination with
a sulphonylurea or insulin (Krentz A.J., et al. 1994)

ALPHA-GLUCOSIDASE INHIBITORS
Oral:
-Adults: Dosage must be individualized on the basis of effectiveness and tolerance
while not exceeding the maximum recommended dose
Initialdose: 25 mg 3 times/day with the first bite of each main meal.
Maintenancedose: Should be adjusted at 4- to 8-week intervals based on 1-hour
postprandial glucose levels and tolerance. Dosage may be increased from 25 mg 3
times/day to 50 mg 3 times/day. Some patients may benefit from increasing the dose
to 100 mg 3 times/day.
Maintenance dose ranges: 50-100 mg 3 times/day.

Supplied
Tablet: 25 mg, 50 mg, 100 mg
Maximumdose:
60 kg: 50 mg 3 times/day
>60 kg: 100 mg 3 times/day

INSULIN

INSULIN
A small protein with a molecular
weight in humans of 5808
It contains 51 amino acids arranged
in 2 chains (A nd B) linked by
disulfide bridges
The entire human pancreas contains
up to 8 mg of insulin

Model of glucose-induced insulin release

The Key Elements in Insulin Secretion

Glucose transport 2 (GLUT2)

Glucokinase (GK)
Mitochondria
ATP-sensitive K+ channels (K+
ATPchannels)
Voltage-dependent Ca2+-channels
(VDCC)
Exocytosis

INSULIN DEGRADATION
The liver and kidney 2 main organs
that remove insulin from the
circulation
The liver normally clears blood of
approximately 60% of the insulin
released from pancreas, removing by
kidney : 35-40%
That atio is reversed in insulintreated diabetis receiving sc insulin
injections

Circulating Insulin
Basal insulin values : 5-15 U/mL
Peak rise to 60-90 U/mL during
meals

Diagrammatic structure of stimulation of the

insulin receptor

ulin-activated intracellular signal transduction pathwa

INSULIN PREPARATIONS

Principal types and duration of

action of insulin preparations
4 principal types of injected insulins
are available:
1. Rapid-acting , with very fast onset
and short duration
2. Short-acting, with rapid onset of
action
3. Intermediate-acting
4. Long-acting, with slow onset of
action

Rapid-acting insulin
Three injected rapid-acting insulin
analogs : Insulin Lispro, Insulin aspart
and Insulin glulisine
rapid onset and early peak action more
closely mimic normal endogenous prandial
insulin secretion than does regular insulin
Duration of action : rarely more than 4-5
hours decreases the risk of late postmeal
hypoglicemia

Rapid-acting insulin
Have the lowest variability of absorption (app.
5 %) of all available commercial insulins .
Lispro -> the first monomeric insulin analog to
be marketed, is produced by recombinant
technology : proline at position B28 has been
moved to B29 and lysin at position B29 has
been moved to B28
Lispro when injected SC quickly dissociates
into monomers and is rapidly absorbed with
onset of action 5-15 minutes and peak activity
1 hour.

Short-acting insulin
= regular insulin : a short acting acting
crystalline zinc insulin made by
recombinant DNA techniques
Its effect appears within 30 inutes
Peaks between 2 and 3 hours after SC
injection and generally last 5-8 hours
Shoul be injected 30-45 or more minutes
before the meal
Is the only type that should be
administrated IV diabetic ketoacidosis

Intermediate-acting and long-acting

insulins
NPH (Neutral protamine Hagedon, or
isophane)
absorption and onset of action are
delayed by combining insulin and protamine
onset : 2-5 hours
Duration : 4-12 hours
it is usually mixed with regular,
lispro,aspart, or glulisine insuline and given
2-4 times daily for insulin replacement
Variabiliy of absorption :> 50%

Intermediate-acting and longacting insulins

Insulin glargine :
Has a slow onset : 1-1,5 hours
achieves a max effect after 4-6 hours
Max activity maintained for 11-24
hours or longer
once daily
Should not be mixed with other insulins
Has 6-7 fold greater binding than native
insulin to the IGF-1 receptor

Intermediate-acting and longacting insulins

Mixtures of insulin:
Because intermediate-acting NPH insulin
require several hours to reach adequate
therapeutic levels requires supplements of
rapid- or short-acting insulin before meals
Mixed together in the same syringe before
injection
Insulin lispro, aspart and glulisine can be
acutely mixed just before injection with NPH
insulin without affecting their absorption

Catatan!
Rapid Insulin (Novorapid), insulin rapid action untuk
mengatasi lonjakan post prandial glucose.
Long Acting Insulin (Levemir) untuk mengatasi
kebutuhan insulin basal (GDP) efeknya 24 jam
menyerupai insulin endogen dan tidak mempunyai
puncak (peak) sehingga mengatasi nocturnal
Hypoglicemia.
Mixed Insulin (Novomix) gabungan antara basal dan
prandial insulin digunakan untuk meningkatkan
compliance px sebagai alternatif insulin basal plus
dan basal bolus

Catatan 2!
Insulin long acting (Levemir) berfungsi 24
jam dan tidak ada puncak (no peak)
sehingga dapt menghindari hipoglikemia
Nocturnal. Intermediate hanya 12-20 jam
sehingga saat tidur bisa hipoglikemia

Catatan 3!
Kapan diberikan IV? Yaitu pada saat krisis
Hiperglikemia
1.KAD (klinis : ketonuri, Kussmaul, Asidosis
metabolic)
2.HONK (pake rumus 3 yes 1 No, hiperglikemi, keton
(-), Kussmaul (-) osmolaritas >325
3.Infark Myocard
4.CVA
5.Sepsis
6.Steroid dosis tinggi

THYROID AGENTS

Thyroid Physiology
The normal thyroid gland secretes amounts of the
thyroid hormones
Triiodothyronine (T3)
Tetraiodothyronine (T4,thyroxine)
These hormon contain 59% and 65% (respectively) of
iodine
T4 and T3 are critically important for normal growth and
development and for controlling energy metabolism.

Calcitonin, the second type of thyroid hormoneis

involved in the control Calsium plasma and is used
to treat osteoporosis and other metabolic bone
diseases

Thyroid Physiology
The thyroid secretes about 80 micrograms of T4,
but only 5 micrograms of T3 per day.
However, T3 has a much greater biological activity
(about 10X) than T4.
An additional 25 micrograms/day of T3 is produced
by peripheral monodeiodination of T4
The main steps in the synthesis, storage and
secretion of thyroid hormon:
Uptake of plasma iodide by the follicle cells
Oxidation of iodide and iodination of tyrosine residues of
thyroglobulin
Secretion of thyroid hormone

Iodine
Metabolism
Dietary iodine is absorbed in the GI tract, then taken up by
the thyroid gland (or removed from the body by the
kidneys).
The transport of iodide into follicular cells is dependent
upon a sodium/iodine co-transport system.
Iodide taken up by the thyroid gland is oxidized by
peroxide in the lumen of the follicle:
peroxidase+
II

Oxidized iodine can then be used in

production of thyroid hormones.

Byosynthesis of Thyroid Hormones

The thyroid hormones thyroxine (T4)

and T3 are formed within the thyroid
gland
Once taken up by the thyroid gland,
iodine undergoes a series of
enzymatic reactions before it
converts into active thyroid
hormones

Thyroid Hormone
Synthesis
The first step in the synthesis of thyroid
hormones is the organification of iodine
Iodide is taken up, converted to iodine, and then
condensed onto tyrosine residues which reside
along the polypeptide backbone of a protein
molecule called thyroglobulin.
This reaction results in either a mono-iodinated
tyrosine (MIT) or di-iodinated tyrosine (DIT)
being incorporated into thyroglobulin.
This newly formed iodothyroglobulin forms one
of the most important constituents of the colloid
material, present in the follicle of the thyroid
unit.

Thyroid Hormone
Synthesis
The other synthetic reaction, that is closely
linked to organification, is A COUPLING
REACTION.
Where iodotyrosine molecules are coupled
together. If two di-iodotyrosine molecules
couple together, the result is the formation of
thyroxin (T4). If a di-iodotyrosine and a monoiodotyrosine are coupled together, the result is
the formation of tri-iodothyronine (T3).

Thyroid Hormone
Synthesis
The major coupling reaction is the diiodotyrosine coupling to produce T4.
Although T3 is more biologically active
than T4, the major production of T3
actually occurs outside of the thyroid
gland. The majority of T3 is produced
by peripheral conversion from T4 in a
deiodination reaction involving a
specific enzyme which removes one
iodine from the outer ring of T4.

Thyroid Hormone
Synthesis
The T3 and T4 released from the
thyroid by proteolysis reach the
bloodstream where they are bound to
thyroid hormone binding proteins.
The major thyroid hormone binding
protein is thyroxin binding globulin
(TBG) which accounts for about 75%
of the bound hormone.

Thyroid Hormone
Synthesis
In order to attain normal levels of thyroid hormone synthesis, an
adequate supply of iodine is essential.
The recommended minimum intake of iodine is 150 micrograms a day.
Intake of less than 50 micrograms a day is associated with goiter.
High iodine levels inhibit iodide oxidation and organification.
Additionally, iodine excess inhibits thyroglobulin proteolysis (this is the
principal mechanism for the antithyroid effect of inorganic iodine in
patients with thyrotoxicosis).

Transport Of Thyroid Hormones

T4 and T3 in plasma are reversibly bound to

protein, primarily TBG
0,04% of total T4 and 0,4% of T3 exist in
the free form

DRUGS USED IN DISEASES OF THE THYROID

HYPERTHYROIDISM
Treated by pharmacologically or
surgically
RADIOIODINE

First line th/ for hyperthyroidism

The isotope used is 131I
Dose: 5-15 millicuries
Given orally, it is taken up and processed
by the thyroid in the same way as the
stable form of iodide, eventually becoming
incorporated into TG

RADIOIODINE
Emits both and radiation.
The rays pass through the tissue without
causing damage
The rays have very short range and
exert a powerful cytotoxic action resulting
in significant destruction of the tissue
T1/2: 8 days, so by 2 months its
radioactivity has dissapered
Single dose

RADIOIODINE
Graves diseases is treated by
Radioiodine, and after treatment
hypothyroidismcan be managed by
replacement therapy with T4
Avoided in children and pregnant
patients
Can be used diagnostically as a test
of thyroid funcion

THIOUREYLENES
Comprises: carbimazole, methimazole, and
propylthiouracyl (PTU)
Chemically, they are related to thiourea and the
thiocarbimide (S-C-N) group is essential for antithyroid
activity
Mechanism of action
Thyoureylenes decrease the output of thyroid hormones from the
gland and cause a gradual reduction in the signs adn symtomps of
thyrotoxicosis, the basal rates and pulse rate returning to normal over
a period of 3-4 weeks.
The mechanism is not completely understood, but there is evidence
that they inhibit the iodination of thyroyl residues in TG.
PTU has additional effect of reducing the deiodination of T4 to T3 in
peripheral tissues

THIOUREYLENES
Given orally
Carbimazole is rapidly converted to
its active metabolite methimazole
An average dose of carbimazole
produces more than 90% inhibition of
thyroid incorporation of iodine within
12 h

Comparisons of PTU and

methimazole
PTU

Methimazole

Serum protein
binding

75%

Nil

Serum half-life

75 minutes

4-6 hours

GI absorption

Almost complete

Almost complete

Peak serum
concentration

1 hour after
ingestion

1 h after ingestion

Duration of action

12-24 h

Possibly >24 h

Metabolites

Glucuronide

Not-well
characterized

Transplancetal
passage

Lower

Higher

Levels in breast milk

lower

higher

Effects of Antithyroid Drugs:

peripheral

Effects of Antityhroid Drugs :

intrathyroidal

The Uses of Antithyroid Drugs

2 contexts of antithyroid drug use .
Short Term Therapy (weeks-months)
To cool down the patient prior to
radioiodine.

Long-Term Therapy (1-2 years)

remission, that may or may not occur,
usually followed by radioiodine therapy

HYPOTHYROIDISM
There are no drugs that spesifically augment the synthesis or release of
thyroid hormones
It is caused by iodine deficiency iodide
The only effective treatment for hypothyroidism is to administer the
thyroid hormones themselves as replacement th/.
Thyroxine (official names: levothyroxine) and tri-iodothyronine (official
names :liothyroxine) are synthetic compounds, identical to the natural
hormones, and are given orally.
Thyroxine as the sodium salt in dose of 50-100 g/day is the usual firstline drug of choice.

HYPOTHYROIDISM
Liothyroxine has a faster onset but a
shorter duration of action, and is
generally reserved for acute
emergencies such as the rare
condition of myxoedeme
Overdoseunwanted effects:
hyperthyroidism and angina pectoris,
cardiac dysrhythmias or cardiac
failure

Thank You