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Dr. Suriyan Thengyai, PhD
School of Pharmacy, WU
suriyan.te@wu.ac.th
Upper portion of
trachea and below
the larynx
Consist of 2 lobe
connected by
isthmus
About 25 g weight
Recall anatomy and physiology of thyroid
gland
04749891ensiafthyroidh
mmmm 1 0 51829
Follicle is a sphere, cyst-like
bringing 300mA
pabffffrae structure approximately 300
Ir
1 Apical m diameter and is filled
with gelatineous colloid
9 9 68800 02,40gelatin
Main component of colloids
TG
is glycoprotein called
glytoprotein
thyroglobulin (Tg)
rn
grnthyroglobuli
tag.morontoalcitonin
Recall anatomy and physiology of thyroid
gland
UB's
The follicle cells seem to fulfill the function of secretory and
mum
9008
absorptive cells 6090928418
vimeo.mn
intermediate
rain thyroid
Bringin I 382
damnit iodine 408M
MIT = monoiodo-L-tyrosine DIT = diiodo-L-tyrosine
T3 = 3,5,3 -triiodo-L-thyronine T4 = 3,5,3 ,5 -tetraiodo-L-thyronine
rT3 (Reverse T3) = 3,3 ,5 -triiodo-L-thyronine
Tg
Hormones of thyroid gland
t II
Glehoh8ET3gT4tb5UIodine4Uo7sn70fTfjjg6uMuInfeI5DITtO.s'T
Thyroglobulin (Tg) serves as the matrix for the synthesis of T 4
and T3 and as the storage form of the hormones and iodide
Biopolymers glycopeptides ohhonotamingo
my
Tg is a large glycoprotein with MW 660,000 Da which
account for about one-third of the weight of thyroid gland138098
Althgroi
6 10 fog MIT gland
Tg carries an average of 6 tyrosyl residues as MIT, 5 residues
5126 17 0.3 win Tg
14
as DIT, 0.3 residues as T3 and 1 residues as T4
vimeo.jo innit Ty 266458308 1
Normal thyroid gland contains enough potential T 4 to Inna
maintain a euthyroid state for 2 month without new synthesis
I
JPY02 I
8120
I
10808819 1
On 0
I
O
Os coupling
1 Dina
2 MIT DIT
I
anmetabo
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thyroidgl
Biosynthesis of thyroid gland
I 296906072765U
Active uptake of iodide by follicular cellsload
ohcond
The mechanism to iodide uptake is iodide pump which
regulated by TSH
mum
pituitary
Iodide pump maintain the ratio of thyroid iodide to serum
A2UnoYb6nTC0nc.oios9fwofggnwvnc.thyroidgland
iodide (T:S ratio) of about 20:1. If more than 100:1
R2UBWM8oT9I
hyperactive gland fgnai1serum206ri7
- -
This process may be blocked inorganic ions (SCN and ClO4 )
e
pump 070 In block
of 8 PM unaval II
q noo
g
Biosynthesis of thyroid gland
4202
I Or
Oxidation of iodide and formation iodotyrosines
I b giguotag
Iodide must be oxidized by H2O2 and thyroperoxidase (TPO)
-
to serve as an iodinating agent (OI ) higher oxidationstate
stabndotyrosineta
TPO is also essential for the incorporation of iodide into
tyrosine residues in Tg and coupling of iodotyrosyl residues
Hypothyroid Hyperthyroidism
T4, T3, DIT, and MIT are released from the proteolytic activity of GI
enzymes
o Strength : 25 – 300 g
Liotrix (Thyrolar)
o (+)-stereoisomer of T4
Radioiodine
131 125
Only isotopes I and I have been used consistently
Radioiodine
131
Absorption of I -radiation highly localized desctruction of thyroid
follicles advantage: avoid surgical risks
- -
Perchlorate (ClO4 ) and pertecnetate (99mTcO4 )
Iodide
Thyrotoxicosis
Bridging atom
Phenolic OH
Calcitonin
Parathyroid hormone
Vitamin D
Vitamin D
Disease states associated with abnormal
calcium homeostasis
Osteoporosis Pseudohypoparathyroidism
Osteopetrosis Hyperparathyroidism
Hypocalcemia Rickets and osteomalacia
Hypercalcemia Paget disease of the bone
Hypoparathyroidism
Drug therapies used to treat osteoporosis
Antiresorptive agent
Antiresorptive agent
Antiresorptive agent
Hormonal regulation of serum calcium level
Antiresorptive agent
SAR of SERM
Only pure antiestrogen are 7 -substituted estrogen
Antiresorptive agent
Bisphosphonates
Design to mimic pyrophosphate, where O in P-O-P is replaced by C to
create nonhydrolyzable backbone
Antiresorptive agent
Bisphosphonates
Drug therapies used to treat osteoporosis
Antiresorptive agent
SAR of bisphosphonates
Substitution at central C of geminal phosphonate affect
physicochemical and biological properties
Antiresorptive agent
32 amino acid
Antiresorptive agent
Bone-forming agents
Teriparatide
Since 2002, FDA approved for postmenupausal osteopososis,
glucocorticoid-induced osteopososis, and primary or hypogonadal
osteopososis
32 amino acid
Bone-forming agents
Inorganic salt
Calcium salts – 1,300 mg/day of elemental calcium for teenagers,
1,000 mg/d for premenupausal women and men, and 1,200 mg/d for
postmenupausal women
▪ Absorption of Ca at GI 25-40%
Miscellaneous
Strontium ranelate (Protelos)
Drug therapies used to treat
hyperparathyroidism
Zoledronate (Zometa)