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DIABETES MELLITUS
Insulin-dependent
Diabetes Mellitus
Destruction of
insulin-producing B
cells in the pancreas.
TYPE 2
Non-insulindependent diabetes
Relative insulin
deficiency, Insulin
resistance.
GOAL OF THERAPY
BLOOD SUGAR CONTROL AT NORMAL
OR NEAR-NORMAL VALUE DIET,
EXERCISE, DRUG
PHARMACOTHERAPY OF
DM TYPE 1
INSULIN
REPLACEMENT
INSULIN ACTION
In healthy subjects, the amount of insulin is
automatically matched to blood glucose
concentration.
Continue...Insulin Action
Stimulates glikogenesis
Inhibits gluconeogenesis.
Inhibits lipolysis
Stimulates fatty acid synthesis
Insulin Replacement
Subcutaneous
administration
Absorption is
usually most rapid
from the abdominal
wall, followed by
the arm, buttock,
and thigh
Different type of
insulin according to
their duration of
action
Onset
Peak
Duration
Ultra rapidacting
15-30
minutes
30 minute2 hours
Shortacting/Regular
30 minutes-1
hours
2-4 hours
6-8 hours
Intermediateacting
2-4 hours
1-8 hours
14-15
hours
Long-acting
1-3 hours
Continue...
Ultra rapid-acting
Insulin
Basal
Insulin
Postprandial
Site of injection
Type of insulin
Subcutaneous blood flow
Smoking
Regional muscular activity at the side of
injection
Volume& concentration of injected insulin
Depth of injection.
Insulin Dosing
Insulin replacement therapy includes
long acting insulin (basal) and short
acting insulin to provide postprandial
needs.
IHT (Insulin Harian Total) = 0,5 U x
BB (kg)
IPT (Insulin Prandial Total) = 60% dari
IHT dibagi 3 dosis (sarapan, makan
siang, makan malam)
IBT (Insulin Basal Total) = 40% dari IHT
ORAL HYPOGLICEMIC
AGENTS
BIGUANIDE
INSULIN SECRETAGOGUES:
SULFONYLUREAS
NON SULFONYLUREAS (MEGLITINIDE): REPAGLINIDE,
NATEGLINIDE
THIAZOLIDINEDIONES
GLP-1 AGONIST : EXENATIDE
DIPEPTIDYL PEPTIDASE 4 INHIBITORS :
SAXAGLIPTIN, SITAGLIPTIN, VIDAGLIPTIN
ALPHA GLUCOSIDASE INHIBITORS
PRAMLINTIDE
BIGUANIDES
Continue...Metformin
CONTRAINDICATION : renal
impairement, hepatic disease, history of
lactic acidosis, cardiac failure, cronic
hypoxic lung disease.
SIDE EFFECTS: lactic acidosis, diarrhea,
abdominal discomfort, nausea, metallic
taste, anorexia.
Metformin can be administered in
combination with sulfonylureas,
thiazolizinediones, and/or insulin.
Available Fixed-dose combinations.
Dosing of Metformin
Available generic Tablet 500 mg,
forte 850 mg.
Dose : 2-3 x 500 mg daily with
meals, max 2,5 g/daily.
SULFONYLUREAS
GROUP 1
INCREASED INSULIN
SECRETION
Repaglinide
Stimulates insulin release by closing
ATP-dependent potassium channels
in pancreatic cells.
Side effects : hypoglicemicemia.
Initial dose 0,5 mg every timt before
meals. Max dose 16 mg/day
Nateglinide
Stimulates insulin secretion by
blocking ATP-sensitive potassium
channels in pancreatic cells.
Dose of 3x 120 mg, 1 to 10 minutes
before a meal.
Side effects : hypoglicemia (more
rare)
Thiazolidinediones
Troglitazone (withdrawn because
causing severe hepatic toxicity),
Rosiglitazone, and Pioglitazone.
Can be combined with insulin or other
classes.
Side effects : hepatotoxicity, anemia,
weight gain, edema, and plasma
volume expansion
Pioglitazone Dose : 1x 15-30 mg/day.
Mechanism of action
Thiazolidinediones are selective agonists
for nuclear peroxisome proliferator
activated receptor- (PPAR) activates
insulin-responsive genes that regulate
carbohydrate and lipid metabolism.
Increasing insulin sensitivity in peripheral
tissue, lowering glucose production by the
liver, increasing glucose transport into
muscle and adipose tissue
-Glucosidase Inhibitors
Acarbose, Miglitol.
Inhibition of -glucosidase enzyme in
the intestinal brush border slows
the absorption of carbohydrates.
Used in combination with other oral
antidiabetic agents and/or insulin.
SIDE EFFECTS : malabsorption,
flatulence, diarrhea, and abdominal
bloating.
Mechanism of Actions
Acarbos
e
Dosing of Acarbose
GLUCOBAY : acarbose 50, 100 mg.
Initial dose 3x 50 mg, can be increase
after 4-8 weeks 3x 100-200 mg