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Farmakodinamik Obat Anti Diabetes
Farmakodinamik Obat Anti Diabetes
Diabetes Melitus
IR
a a
b b
P
IRS
PI3K
Glut4 Akt
P
cont
Insulin-mediated glucose transport signaling
pathway
Glucose Uptake Assay
Insulin
IR
glucose a a
b b
P
IRS
PI3K
Akt
P
insulin sulfonylurea
biguanida tiazolidindione
Alfa GLP-1
Agonist and
glukosidase DPP 4
inhibitor Inhibitor
INSULIN
Insulin is a small protein consisting of an A
A chain chain of 21 amino acids linked by two disulfide
(S—S) bridges to a B chain of 30 amino acids.
IR
a a
b b
P
IRS
PI3K
Glut4 Akt
P
cont
Insulin-mediated glucose transport signaling
pathway
Glucose Uptake Assay
Insulin
IR
glucose a a
b b
P
IRS
PI3K
Akt
P
Amino Acid Substitutons
A- B- chain Position
chai
n
Position
Source/ A21 B3 B28 B29 B30 B31
Type And
B32
Human Asn Asn Pro Lys Thr
Aspart Asn Aspartic Lys Thr
acid
Lispro Asn Lys Pro Thr
Glulisin Asn Lys Pro Glu Thr rapid-acting
e
Glargine Gly Pro Lys Thr Arg
Detemir Lys Myristic
acid long-acting
Bertram Katzung, Susan Masters, Anthony Trevor-Basic and Clinical Pharmacology, 11th Edition (LANGE
Sulfonylureas : stimulate β cells to produce more insulin
1st generation
2-(p-aminobenzenesulfonamido)-5-isopropyl -thiadiazole
(1)Orinase (tolbutamide)
bind to protein
(IPTD) was used in treatment of typhoid fever in 1940’s
hypoglycemia
Currently > 12,000
(3)Tolinase (tolazamide)
(6)Diabinese (chlorpropamide)
may become dislodged delayed activity
¨ 2nd generation
Rel. Potency
– (75)Glucotrol (glipizide)
– (150)Glucotrol XL (ex. rel. glipizide)
– (150)Micronase, Diabeta (glyburide)
– (250)Glynase (micronized glyburide)
¨ 3rd generation
– (350)Amaryl (glimepiride)
*Hydroxylation of the aromatic ring appears to be the most favored metabolic pathway
*Hydroxylated derivatives have much lower hypoglycemic activity
Mechanism action of sulfonilurea
Graham Rena & Ewan R. & Kei Sakamoto, 2013. Molecular mechanism of
action of metformin: old or new insights
https://www.drawittoknowit.com/term/physiology/endocrine-pancreas
diakses tanggal 14 november 2018
Katzung,Bertram G. . 2009. Farmakologi Dasar dan Klinik Edisi 11EGC :
Jakarta.
Lang, Veronica and Light, Peter E. . 2010. The Moleculer Mechanisms and
Pharmacotherapy of ATP-Sensitive Potassium Channel Gen Mutations
Underlying Neonatal Diabetes. Pharmacogenomics and Personalized
Medicine.Dove Medical Press Ltd. 3. 145-161