Pharmacotherapy of Diabetes Mellitus: Dr. Ave Olivia Rahman, Msc. Bagian Farmakologi Fkik Unja

PHARMACOTHERAPY
of
DIABETES MELLITUS
dr. Ave Olivia Rahman, MSc.

Bagian Farmakologi FKIK UNJA
DIABETES MELLITUS (DM)
TYPE 1 TYPE 2
Insulin-dependent Non-insulin-
Diabetes Mellitus dependent diabetes
Destruction of Relative insulin
insulin-producing B deficiency, Insulin
cells in the pancreas. resistance.
GOAL OF THERAPY
BLOOD SUGAR CONTROL AT NORMAL

OR NEAR-NORMAL VALUE DIET,
EXERCISE, DRUG
TREAT ASSOCIAETED CONDITIONS &

COMPLICATION RISK CONTROL
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 glucose storage in the liver as
glycogen and in adipose tissue as triglycerides
and amino acid storage in muscle as protein
INHIBITS gluconeogenesis.
inhibits lipolysis, stimulates fatty acid
synthesis, decreases the hepatic
concentration of carnitine.
Enhances the transcription of lipoprotein
lipase in the capillary endothelium. This
enzyme hydrolyzes triglycerides present in
VLDL and chylomicrons
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
History of Insulin
Development
1930s : the first long-acting
preparation, protamine zinc insulin.
1950s : neutral protamine Hagedorn
(NPH) and insulin zinc (Lente) were
introduce.
1980s, : the development of purified
pork insulin and then recombinant
human insulin.
1990s : insulin analogues introduce.
Continue...
Type of Insulin...based on its acting
Type Onset Peak Duration

Ultra rapid- 15-30 30 minute-
acting minutes 2 hours
Short- 30 minutes-1 2-4 hours 6-8 hours
acting/Regular hours
Intermediate- 2-4 hours 1-8 hours 14-15
acting hours
Long-acting 1-3 hours Witout peak 24 hours
Continue...
lispro (humalog), Aspart
Ultra rapid- (novorapid), Glulisine
acting (apidra)
Short- Regular, Humulin R,

acting actrapid
Intermediat NPH, Humulin N

e-acting Insulatard, lente
Glargine (lantus), detemir,

Long-acting ultralente, protamine zinc
Type of Insulin..based on composition
Single
composition Human
70,30
humulin/mixtard
(70% NPH, 30%
reguler)
- 50,50 humulin
Premixed
Analogue insulin
-75/25 humalog
-50,50 humalog
- 70,30 novomix
- 50,50 novomix
Factors Affecting Insulin Absorption
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.
Indication of Insulin Therapy
DM type 1
DM type 2 uncontrolled with diet,
excersice, oral antidiabetic drugs
Gestational DM
DM with severe kidney and liver disease
DM with infection, major operation,
malnutrition, tumor, corticosteroid
therapy, graves disease
DM Ketoacidosis
Insulin Dosing
Insulin replacement therapy includes
long acting insulin (basal) and short
acting insulin to provide postprandial
needs.
Average dose of insulin : 0,2-1
U/kgBB/day
Pathophysiological Alterations Leading to
Hyperglycemia in Type 2 Diabetes and
Specific Types of Treatment.
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
Metformin. 1st line therapy in DM type 2.
Metformin is antihyperglycemic by
decreasing hepatic glucose production
(gluconeogenesis) and by increasing insulin
action in muscle and fat.
Does not bind to plasma proteins. Half life :
about 2 hours.
Only Metformin has been demonstrated to
reduce macrovascular events in type 2 DM (U.K.
Prospective Diabetes Study Group, 1998b).
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
TOLBUTAMIDE,
GROU ACETOHEXAMIDE,
TOLAZAMIDE,
P1 CHLORPROPAMIDE
GLIBURYDE
GROU (GLIBENCLAMID),
GLIPIZIDE,
P2 GLICLAZIDE,
GLIMEPIRIDE
SULFONYLUREAS : Stimulating insulin
release from pancreatic cells
SULFONYLUR
EAS
PHARMACOKINETICS
Effectively absorbed from the
gastrointestinal tract.
Variaty half-lives among agents
More effective when given 30 minutes
before eating.
90% - 99% bound to protein
(especially albumin)
Metabolism in hepar, excreted in urine.
INCREASED INSULIN
SECRETION
SIDE EFFECT : mild- severa hipoglycemia,
(glibenclamide cause up to 20-30%), nausea,
vomiting, cholestatic jaundice,
agranulocytosis, aplastic and hemolytic
anemias, hypersensitivity reactions,
hyponatremia.
DRUG INTERACTION : other sulfonamides,

clofibrate, and salicylates, ethanol.
CONTRAINDICATIONS : type 1 DM, pregnancy,

lactation, significant hepatic or renal
insufficiency for the older preparations
Dosing of Sulfonylureas
Glibenclamide :
Available in generic tablet 5 mg.
Initial Dose ; 1x -1 tablet ,can be increased < 2,5 mg
during 1 week until reached controled DM or max dose
20 mg has been given.
Glimepiride:
Available in generic tablet 1,2,3 mg
Initial Dose : 1x 1 mg , can be increased during 1 week
based on glucose monitoring, max dose 8 mg/day
Gliquidone:
Available in generic tablet 30 mg
Initial Dose : 1x 1 5mg , can be increased until 45-50
mg/daily divided dose 2-3 times. Max dose 120 mg/day.
Repaglinide
Stimulates insulin release by closing

ATP-dependent potassium channels
in pancreatic cells.
Absorbed rapidly from the
gastrointestinal tract, peak blood
levels : within 1 hour, half-life :
about 1 hour, metabolism in hepar
and renal.
Side effects : hypoglicemicemia.
Dosing of Repaglinide
NOVONORM : Repaglinide 0,5 mg, 1, 2 mg

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 120 mg, 1 to 10 minutes
before a meal.
Metabolism in hepar, excreation in
urine.
Side effects : hypoglicemia (more
rare)
Dosing of Nataglinide
STARLIX : Nataglinide 125 mg

Dose 3x1 tab/day
Thiazolidinediones
Troglitazone (withdrawn because causing
severe hepatic toxicity), Rosiglitazone, and
Pioglitazone.
Can be combined with insulin or other classes.
Rosiglitazone and pioglitazone are taken once
a day, absorbed within about 2 hours,
maximum clinical effect observed within 6 to
12 weeks, Metabolized in hepar.
Side effects : hepatotoxicity, anemia, weight
gain, edema, and plasma volume expansion
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
Dosing of Pioglitazone
PIONIX : pioglitazone 15 mg, 30 mg;

GLIABETES, DECULIN, etc
Dose : 1x 15-30 mg/day.
GLP-1 AGONIST
EXENATIDE, LIRAGLUTIDE
GLP-1 is incretin (hormon that
released after meals and stimulate
insulin secretions). Also inhibit
glucagon release, delay gastric
emptying, reduce food intake,
normalizes fasting and postprandial
insulin secretaion.
DPP 4 Inhibitors
Increase AUC GLP-1 and GIP
(Incretins) when their secretion.
-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
PRAMLINTIDE
Bind to amylin receptor reduction
in glucagon release, delayed gastric
emptying.
Posttest
1. First line obat antidiabetik oral adalah....;
mekanisme kerjanya .....
2. Acarbose termasuk golongan .......;
mekanisme kerja.....
3. Glibenklamid termasuk golongan.......;
mekanisme kerja .....
4. Tipe insulin berdasarkan onset kerja .....
5. Efek samping dari insulin dan obat
antidiabetik oral yang paling sering
adalah ....
kasus
Tn M, 50 tahun datang berobat untuk kontrol
gula darah, sebelumnya kadar gula
darahnya tinggi dan didiagnosa DM tipe 2.
Sebagai langkah pertama, telah dilakukan
konseling perubahan pola diet dan exercise.
Ternyata setelah 3 bulan kontrol, tekanan
gula darah masih tinggi. Dokter
memutuskan untuk memberikan
antidiabetik oral. Tuliskan resep antidiabetik
oral yang akan diberikan untuk tn M.

Pharmacotherapy of Diabetes Mellitus: Dr. Ave Olivia Rahman, Msc. Bagian Farmakologi Fkik Unja

Uploaded by

Copyright:

Available Formats

Pharmacotherapy of Diabetes Mellitus: Dr. Ave Olivia Rahman, Msc. Bagian Farmakologi Fkik Unja

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pharmacotherapy of Diabetes Mellitus: Dr. Ave Olivia Rahman, Msc. Bagian Farmakologi Fkik Unja

Uploaded by

Copyright:

Available Formats

PHARMACOTHERAPY

dr. Ave Olivia Rahman, MSc.

BLOOD SUGAR CONTROL AT NORMAL

TREAT ASSOCIAETED CONDITIONS &

Type Onset Peak Duration

Short- Regular, Humulin R,

Intermediat NPH, Humulin N

Glargine (lantus), detemir,

DRUG INTERACTION : other sulfonamides,

CONTRAINDICATIONS : type 1 DM, pregnancy,

Stimulates insulin release by closing

NOVONORM : Repaglinide 0,5 mg, 1, 2 mg

STARLIX : Nataglinide 125 mg

PIONIX : pioglitazone 15 mg, 30 mg;

GLUCOBAY : acarbose 50, 100 mg.

You might also like