OBAT ANTI DIABETES MELLITUS

anom murdhana

Bahan Bacaan : Katzung Bertram G.; Susan B. Masters; Anthony J Trevor, 2012
Basic & Clinical Pharmacology
a Lange Medical Book, 12th Edition, Mc Graw Hill, 743-766

Prasyarat : Memahami fisiologi hormon insulin dan hormon intestinal.

OBAT ANTI DIABETES, 2016

Diabetes mellitus  meningkatnya glukose darah dengan atau tanpa disertai

ketidak cukupan sekresi insulin oleh pankreas, dengan
atau tanpa gangguan efek insulin.

TIPE SEL PANKREAS DAN PRODUKNYA

TIPE SEL SEKRESI EFEK

Alpha Glucagon, Pro glucagon Katabolik -- Hiperglikemik
Betha Insulin, Pro Insulin, C-Peptide, Anabolik -- Hipoglikemik
Amylin
Delta Somatostatin Hiperglikemik
G Gastrin Hiperglikemik
F Pancrearic Polipeptide (PP)
OBAT ANTI DIABETES, 2016
SEKRESI INSULIN
REGULASI INSULIN
 FAKTOR YG MEMPENGARUHI PRODUKSI INSULIN

STIMULATORS INHIBITORS
Glucose Somatostatin
Mannose 2-Deoxyglucose
Amino Acids Mannoheptulose
Intestinal hormones (GIP, GLP-1 (7-36), Α-Adrenergic stimulators (nor-
Gastrin, Secretin, CCK, Others epinephrine, epinephrine)
β-Keto acids β-Adrenergic blockers
(propranolol)
Acethylcholine Galanin
Glucagon Diazoxide
Cyclic AMP and various cAMP- Thiazide diuretics
generating substances
β-Adrenergic stimulators K-depletion
Theohylline Phenytoin
Sulfonylureas Alloxan
Microtubule inhibitors
Insulin
OBAT ANTI DIABETES, 2016
SEKRESI INSULIN

INSULIN : Sekresi (basal) -- 1 U /jam  rata – rata per hari 40 U

Fasting (normal) vena perifer -- 5-15 µU/ml
Puncak (saat makan) – 60 – 90 µU/ml
Half life dalam plasma  3 - 5 menit
Degradasi  liver ( 60%), ginjal 35 – 40 % 
injeksi  ginjal 60 %, 40 % liver.

Klasifikasi diabetes mellitus :

Tipe 1 -- insulin-dependent diabetes mellitus
Tipe 2 -- non-insulin-dependent diabetes mellitus
Tipe 3 -- diabetes tipe lain
Tipe 4 -- diabetes gestasional
OBAT ANTI DIABETES, 2015 PREPARAT INSULIN

TIPE DAN LAMA KERJA

* Rapid acting -- lispro (B 28, 29) , aspart (B 28), glulisine (B 3, B 29) -- monomer
onset 5 – 15 menit, puncak 1 jam, durasi 4-5 jam  prandial
sub – cutan  continous s.c infusion

* Short acting -- R I  soluble crystalline zinc -- hexamer.

onset 30 menit, puncak 2-3 jam , durasi 5-8 jam
sub cutan,, intra vena.

* Intermediate & long acting – sub cutan

- NPH (neutral protamine Hagedorn, isophane) –intermediate
onset 2-5 jam, durasi 4-12 jam, gabung dgn RI atau Short.
- Glargine – (B–2 arginine, A 21- gly), long acting, peakless,
onset 1-1,5 jam, puncak 4-6 jam, durasi 11-24 jam
pemberian terpisah.
- Detemir – (B 30 hilang, B 29 dg C 14).
onset 1-2 jam (dose dependent), durasi > 12 jam.

KONSENTRASI  100 U/ml, 500 U/ml.

OBAT ANTI DIABETES, 2016

ONSET dan DURASI

OBAT ANTI DIABETES, 2016 I N S U L I N

Cara Pemberian
* Standar --- subcutaneous, alat suntik disposibel
* Portable Pen Injectors -- alat suntik khusus (dosis
terukur, jarum diganti)
* Continous Subcutaneous Insulin Infusion
(insulin pumps)
* Intravena (infus)

Efek Samping dan Komplikasi

* Hypogycemia

* Immunophatology -- allergy
resistance
lypodystrophy
cancer risk
OBAT ANTI DIABETES, 2016

ORAL ANTI DIABETIKUM

 TEMPAT KERJA O A D

Alpha –glucosidase inhibitors

Glucagon-like polypeptide-1 (GLP-1) Receptor Agonists -- Exenatide
Dipeptidyl peptidase-4 inhibitors -- Sitagliptin
Amylin analog –Pramlintide
Bile acid sequestrant – Colesovelam hydrochloride
OBAT ANTI DIABETES, 2015

ORAL ANTIDIABETIK

Insulin Secretagogues Sulfonylureas

Meglitinide\
Nateglinide

Biguanides -- Metformin

Insulin Receptor --- Thiazolidinediones - Pioglitazone; Rosiglitazone

Alpha- Glucosidase Inhibitor -- Acarbose, Miglitol

Intestinal Hormones – GLP-1 (glucagon-like polypeptide -1) Receptor Agonist

-- Exenatide, Liraglutide

DPP-4 (dipeptidyl peptidase-4) inhibitor --

-- Sitagliptin, Saxagliptine, Linagliptine
OBAT ANTI DIABETES, 2016 ORAL ANTIDIABETIK
SULFONYLUREA
Mekanisme kerja :

Efek samping -- hipoglikemia

Generasi 1 -- tolbutamide, chlorpropamide, tolazamide
Generasi 2 -- glebenclamide, glipizide, glimepiride
OBAT ANTI DIABETES, 2016
ORAL ANTIDIABETIK

BIGUANIDES  Metformin -- euglycaemic agent, mekanisme kerja ??

menghambat gluconeogenesis hepar, renal.
ekskresi oleh ginjal—kontra indikasi -

ALPHA – GLUCOSIDASE INHIBITOR  Acarbose --

menghambat alpha gucosidase di usus 
tidak terbentuk monosaccharida

GLP-1 (glucagon-like polypeptide -1) receptor agonist  Exenatide ; Liraglutide

- potensiasi glucose-mediated insulin secretion
- menekan sekresi glucagon postprandial
- pengosongan gaster dihambat
- nafsu makan (sentral) ditekan

Dipeptidyl peptidase -4 (DPP-4) inhibitors  Sitagliptin, Saxagliptin, Linagliptin

Mekanisme kerja :
GLP-1 & GIP (glucose-dependent insulinotropic polypeptide (mucosa usus)
 sirkulasi  ensim DPP-4 (1-7 menit )

Inhibitor (Sitagliptin, Saxagliptin, Linagliptin)

 terima kasih, selamat belajar

semoga menjadi dokter yang profesional