MELITUS
IInsulin adalah hormon yang diproduksi pankreas untk mengontrol kadar gula
darah. Bisa terjadi karena kekurangan insulin, atau resisten terhadap insulin.
Diabetes Melitus:
Symptoms
Kadar gula darah tinggi dapat menimbulkan banyak
masalah:
Pemandangan kabur
Perasaan haus sangat
Letih
Sering kencing
Lapar
Berat badan menurun
1. Rapid acting :
- onset cepat pendek kerjanyauration
- lama kerjanya : 3-5 jam
2. Short acting: onset cepat :
- onset : dalam 30 minutes
- lama kerja : 5-8 jam
3. Kerja itermediate
4. 4. Long acting : onset lamabt
Insulin musti disuntikkan karena ia suatu
protein enzim ini akan dicerna diperut
Lokasi penyuntikan insulin yang dianjurkan
Perut : absorpsi cepat
Lengan : absorpsi sedang
Paha : absorpsi lambat
Gluteus : absorpsi lambat
3. Obat yang
memperlambat absorpsi Alpha-glucosidase
kabohidrat dari saluran inhibitors
cerna
Oral Antidiabetic Agents
Insulin secretagogues : sulfonylureas
1st generation
1. Tolbutamide :
- well absorbed but rapidly metabolized in the liver
- duration of effect : short
- t1/2 : 4-5 hours
- safest for elderly diabetics
- dicumarol, phenylbutazone, some sulfonamide
inhibit the metabolism tolbutamide
hypoglycemia
Sulfonylureas
1st generation
- tolbutamide
- tolazamide
- chlorpropamide
Rel. Potency
2nd generation
– Glipizide
– glyburide
- glimepiride
Oral Antidiabetic Agents
Insulin secretagogues : sulfonylureas
3. Glimepiride
- t1/2 : 5 hours
- long duration of effect
- once daily use as monotherapy or in combination
with insulin ~ compliance
- lowets dose of anysulfonylurea compound : 1 mg
single daily dose, maximal 8 mg.
Oral Antidiabetic Agents
Insulin secretagogues : D- phenylalanine derivative
Nateglinide
• the latest insulin secretagogue to become clinically available
• stimulate release of insulin very rapidly and transiently from
B cells through closure of the ATP-sensitivie K+ channel
• ingested just prior to meal
• absorbed within 20 minutes after oral administration
• t1/2 1,5 hours
• metabolized by CYP2C9 and CYP3A4
• hypoglycemia : lowest
• safe in : very reduced renal function
Oral Antidiabetic Agents
Biguanides
Mechanisms of Action
1. Direct stimulation of glycolisis in tissues
2. Reduced hepatic & renal gluconeogenesis
3. Slowing of glucose absorption from GIT
4. Reduction of plasma glucagon levels
Metabolism & Excretion
Metformin :
- t1/2 : 1,5-3 hours
- Is not bound to plasma protein
- Is not metabolized
- Is excreted by the kidney as the active compound
Oral Antidiabetic Agents
Thiazolidinediones
Pioglitazone (Actos), rosiglitazone (Avandia),
[troglitazone (Rezulin) - (muncul 1997, ditarik tahun 2000 karena dicurigai
menyebabkan idiosinkratik hepatoselular)
Decrease : insulin resistance
Oral Antidiabetic Agents
Alpha Glucosidase Inhibitors
Alpha-glucosidase inhibitors block the enzymes that digest starches in
the small intestine slowing the rise in B.G.L.
Efficacy
– Decrease peak postprandial glucose 40-50 mg/dl (2.2-2.8 mmol/L)
– Decrease fasting plasma glucose 20-30 mg/dl (1.4-1.7 mmol/L)
Other Effects
– Flatulence or abdominal discomfort
– No specific effect on lipids or blood pressure
– No weight gain
– Contraindicated in patients with inflammatory bowel disease or
cirrhosis
Examples:
– acarbose (Glucobay),
– miglitol (Glyset) absorpsi oral yang lebih baik daripada acarbose