Professional Documents
Culture Documents
Kuliah Drug For DM
Kuliah Drug For DM
Insulin
hypoglycemia
Amylin
Mechanism of action
•Insulin acts via receptors that
are transmembrane
glycoproteins.
•Each receptors has two binding
sites. Receptor occupancy
results in:
1. Activation of insulin-dependent
glucose transport processes in
adipose tissue and muscle.
2. Inhibition of adenylyl cyclase-
dependent processes (lipolysis,
proteolysis, glycogenolysis).
Insulin
(-)
AC cAMP PD
ATP 3’,5’-AMP
(+)
Other abbreviations
which are used for insulins are:
•Hum- and -man (for human ),
•PP (purified preparation)
MAIN TYPES OF
INSULIN PREPARATIONS
•Short-acting
•Intermediate-acting
(they contain protamin or Zn)
•Long-acting
(they contain both protamin & Zn)
Injectors (with cartridge):
OptiPen, OptiSet, Penfill, etc.
Comparisons among insulins
Type Onset of Peak Duration
action activity
Short-
acting 10–20 min 1–2 h 5–7 h
Interme-
diate-act. 1–2 h 5–7 h 13–18 h
Long-act. 2–4 h 8–14 h 18–36 h
Insulins are used mainly in type 1 DM.
Patients with type 2 DM use
insulins in the following cases too:
•acute infections
•pregnancy
•surgical operations
•burn
•myocardial infarction
•ketoacidosis
Therapy of DM
with insulin is
a replacement
therapy.
High compliance!
s.c.:
6 sec
s.c.
Insulin pumps:
They infuse
subcutaneously
fast-acting
insulin through
small catheter
(very handy
and very
expensive).
1. Short-acting insulins
and analogues
a) Insulins: Actrapid , Humulin R
•Insulin glargine
(Lantus )
s.c. 20 min
before meal
once daily
Adverse effects of insulins
•hypoglycemia/coma
•allergic reactions
•insulin resistance
•lipodystrophia of subcutane-
ous fat at or near injection
•local fibrosis
II. Oral hypoglycemic and
other drugs, used
in DM type 2
1. Biguanides:
Metformin
•usually first line drug for type 2 DM
•reduces intestinal glucose absorption
•stimulates anaerobic glycolysis
•stimulates glucose uptake
•enhances insulin receptor binding
Metformin
•excreted exclusively
by the kidney
•does not increase weight
and preferable in the obese
•GI side effects
•rarely
lactic acidosis
2. Sulfonylureas
I generation:
•Chlorpropamide and Tolbutamide (Out)
II generation:
•Glibenclamide (Maninil: tab. 5 mg)
•Gliclazide (Diaprel MR)
•Glipizide
•Gliquidone
Mechanism of action
• promote enhanced insulin release
from the pancreas
• leads to a reduction in hepatic
glucose production
Unwanted effects
• Hypoglycemia, weight gain
• facial flushing following
alcohol ingestion
Sulfonylureas –
important drug interactions:
•displacement from protein binding sites
– salicylates and sulphonamides
•interference with hepatic metabolism
– inducers: rifampicin, phenytoin
– inhibitors: cimetidine
•reduction of renal elimination
– allopurinol, salicylates
3. Meglitinides: stimulate the release of insulin
from pancreas by closing ATP-dependent
potassium channels.
- Nateglinide
- Repaglinide
4. Glucosidase inhibitors
- Acarbose (Gluco Bay): p.o.
•Inhibits intestinal alpha-glucosidase
•Decreases intestinal absorption
of the mono- and polysaccharides.
•Produces flatulence and diarrhoea.
5. Thiazolidinediones (TZDs)
They increase tissue insulin sensitivity
but have serious ADRs and the EMA
recommended in Sept (2010) that they
be suspended from the EU market:
- Rosiglitazone (Avandia)
has high cardiovascular risks.
- Pioglitazone causes bladder tumors.
- Troglitazone causes hepatitis.
6. Glucagon-like peptide-1 (GLP-1)
agonists (in type 2 DM): increase
pancreatic secretion of insulin:
Exenatide
Bydureon (s.c./7 days):
$323/4 doses, resp.
$4200 per year
Liraglutid
is a GLP-1
agonist,
which reduces,
BM, HbA1C,
and systolic
Liraglutid blood pressure,
and improves
beta cell function
of the pancreas
(s.c. once a day)
7. Inhibitors of Dipeptidil
peptidase-4 (DPP-4): prevent
degradation of incretin GLP-1
Sitagliptin (p.o.)
Vildagliptin (p.o.)
8. Inhibitors of reabsorption
of glucose (SGLT2 inhibitors): p.o.
•Canagliflozin blocks in renal proximal
tubule sodium / glucose co-transporter
protein 2 (SGLT2), which re-absorbed
90% of the filtrated glucose.
The result is increased glucosuria and
plasma glucose levels are lowered.
ADRs: Hypoglycaemia, vulvovaginal candidiasis
urinary tract infections, polyuria, frequent urination.