Professional Documents
Culture Documents
Treatments
Diana Holidah
DIANA HOLIDAH
Bagian Farmasi Klinik dan
Komunitas
Fakultas Farmasi-Unej
Management of
Diabetes Mellitus
HbA1c (%)
6
7
8
9
10
11
12
Management of DM
The major components of the treatment of diabetes are:
Oral hypoglycaemic
therapy
Insulin Therapy
A. Diet
Diet is a basic part of management in every case.
Treatment cannot be effective unless adequate
attention is given to ensuring appropriate nutrition
Exercise
Physical activity promotes weight reduction and improves
insulin sensitivity, thus lowering blood glucose levels.
Together with dietary treatment, a programme of regular
physical activity and exercise should be considered for
each person.
People should, however, be educated about the potential
risk of hypoglycaemia and how to avoid it.
Repaglinide
Nateglinide
Biguanides
Thiazolidinediones
Acarbose
Miglitol
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Insulin secretagogues
Insulin sensitizers
Inhibitors of CHO
absorption
Sulfonylureas :
stimulate cells to produce more insulin
1st generation
Rel. Potency
bind to protein
(1)Orinase
(tolbutamide)
(3)Tolinase (tolazamide)
(6)Diabinese (chlorpropamide)
2nd generation
(glipizide)
(150)Glucotrol XL (ex. rel. glipizide)
(150)Micronase, Diabeta (glyburide)
(250)Glynase (micronized glyburide)
(350)Amaryl
(75)Glucotrol
(glimepiride)
*Hydroxylation of the aromatic ring appears to be the most favored metabolic pathway
*Hydroxylated derivatives have much lower hypoglycemic activity
GLUT2
K+
Sulfonylureas
KIR K+
Na+
K+
K+
Ca2+
Pancreatic
cell
Ca2+
Insulin granules
Vm
Ca2+
Voltage-gated
Ca2+ channel
Mechanism of Action
Sulfonylureas interact with receptors on pancreatic
b-cells to block ATP-sensitive potassium channels
This, in turn, leads to opening of calcium channels
Which leads to the production of insulin
Half-life - 2 to 4 hours
HN O
S
O
Potency - High
O
(2.5 to 40 mg/d)
N
N
C NH
N
H
Oxidized to weakly
active metabolites
HN O
S
O
Half-life - 6 hours
Duration of action-
24 hours
Potency - High
(1.25 to 20 mg/d)
C NH
Cl
N
H
OCH3
CH3
O
HN
O
S
O
C2H5
N
C2H5
C NH
N
H
Choice of Sulfonylurea
Consider:
Duration of action, potency, metabolism, side effects
In presence of renal dysfunction:
- Dual routes of elimination
Glyburide or glimepiride
- Metabolized to inactive metabolites
Glipizide
Second generation SUs bind nonionically to plasma albumin
and have fewer drug interactions than earlier SUs, which
bind albumin ionically and compete with other drugs for
binding sites
Metformin
Glucophage, Fortamet,
Riomet
H
N
H
N
N
H
HCl
Metformin is a widely used monotherapy, and also used in combination with the
sulfonylureas in treatment of type 2 diabetes
Biguanides
First Generation- Phenformin
Phenethylbiguanide
Adverse Effects
Lactic acidosis
Risk of cardiovascular disorder
CH2H2C
NH2
NH2
C
N
H
N
H
NH2
guandino
H3C
N
H3C
NH2
NH2
C
N
H
NH2
Biguanides
Mechanism of action: antihyperglycemic
Correct elevated hepatic glucose output
Inhibit gluconeogenesis
Inhibit glucose-6-phosphatase activity glycogen sparing
insulin resistance
Mediated by activation of 5AMP-activated protein kinase
(AMPK) in hepatocytes and muscle
Do not increase insulin secretion
Not hypoglycemic, even at high doses
Metformin
Excreted unchanged in the urine
Half-life - approximately 2 hours
Does not bind to plasma proteins
Should not be used with renal or hepatic dysfunction
Also approved for prevention of Type 2 diabetes in high
risk individuals
Use also for polycystic ovary syndrome: insulin
resistance with ovarian hyperandrogenism
Pioglitazone
- Actos,
Avandia
O
S
NH
O
5-{4-[2-(5-Ethyl-pyridin-2-yl)-ethoxy]-benzyl}-thiazolidine-2,4-dione
PPAR -
Thiazolidinediones: Rosiglitazone
AGIs
- Precose (acarbose),
Glucobay
H
- Glyset (miglitol)
O
H
O
N
H
1-(2-Hydroxy-ethyl)-2-hydroxymethylpiperidine-3,4,5-triol
a glucosidase inhibitors
Mechanism of action:
Clinical use:
For mild to moderate fasting hyperglycemia with significant postprandial
hyperglycemia
Taken with the first bite of a meal
Do not produce hypoglycemia or significant weight gain
Effective regardless of age, genetic factors, body weight, duration or
severity of disease
Acarbose
Metabolized within the digestive tract by enzymes and
intestinal bacteria
Low systemic bioavailability
< 2 % is absorbed as intact molecule
Adverse effects: Gastrointestinal disturbances
Flatulence
Nausea
Diarrhea
Use gradual dose titration
Contraindicated for inflammatory and obstructive
bowel disease, colonic ulcers
Meglitinides
O
N
OH
NH
- Prandin (repaglinide)
2-Ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid
NH
O
- Starlix (nateglinide)
O OH
2-[(4-Isopropyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionic acid
Dipeptidyl-Peptidase 4 Inhibitors
Agent in Class: Sitagliptin, Saxagliptin
Mechanism of action:
slows the inactivation of incretin hormones (glucagon-like
peptide 1 and glucose-dependent insulinotropic
polypeptide)
Increases glucose-stimulated insulin secretion
Causes glucose-stimulated glucagon suppression
primarily lowers postprandial glucose levels but has also
been shown to reduce fasting plasma glucose
INSULIN
Who need insulin medicine
Type I (insulin dependent) diabetes patients whose body
produces no insulin.
Type 2 diabetes patients that do not always produce
enough insulin.
Treatment
subcutaneous injection
Insulin Preparations
from LillyDiabetes.com
lispro
Ultra fast/ultra
short-acting
regular
Short-acting
Long-acting
Plasma [Insulin]
Intermediate-acting
NPH
lente
ultralente
glargine
Ultra long-acting
0
from lantus.com
12
16
20
24
Short-acting insulin
Regular insulin (insulin injection)
denoted on vial by R
zinc insulin crystals in a neutral, nonbuffered,
suspending solution
Intermediate-acting insulin
NPH insulin (Neutral protamine Hagedorn,
isophane insulin suspension)
denoted on vial by N
stoichiometric mixture of regular and protamine zinc
insulin (complexed with excess of positively charged fish
sperm protamine)
Long-acting insulin
ULTRALENTE insulin (extended insulin zinc
suspension)
denoted on vial by U
delayed onset
prolonged action
acetate buffer
excess zinc
large crystals with low solubility
glargine
ASN
GLY
ARG
ARG
B- chain Position
Source/
Type
A21
B3
B28
B29
B30
Human
Asn
Asn
Pro
Lys
Thr
Aspart
Asn
Aspartic
acid
Lys
Thr
Lispro
Asn
Lys
Pro
Thr
Glulisin
e
Asn
Pro
Glu
Thr
Glargine
Gly
Pro
Lys
Thr
Lys
Myristic
acid
Detemir
Lys
B31
And
B32
rapid-acting
Arg
long-acting
total
regular
lente
am
12
pm
12
am
12
12
am
regular
lente
4
am
12
pm
12
am
lispro
glargine
12
12
12
am
pm
12
am
pm
12
12
am
Continuous
infusion
regular or
lispro
am
12
pm
12
am
12
Special Considerations
Pregnancy
Both hyperglycemia and hypoglycemia adversely affect fetal
growth and differentiation
Increased insulin requirement during 2nd half
Pediatric diabetes
Approximately 75% of Type 1 diabetics are diagnosed before 18
years of age
Hypoglycemic unawareness in younger children
Higher frequency of other illness
Self-Care
Patients should be educated to practice self-care.
This allows the patient to assume responsibility
and control of his/her own diabetes
management. Self-care should include:
Thank you