INSULIN AND ORAL

HYPOGLYCEMIC
DRUGS

Kuswinarti
Truly Sitorus
Department of Pharmacology and Therapy
Medical School,Universitas Padjadjaran
INTRODUCTION
Pancreas

Endocrine gland produces Exocrine gland produces


Insulin Digestive Enzymes
(/B-cells islets Langerhans)

Glucagon Somatostatin
(2/A-cells islets Langerhans) (1/D-cells islets Langerhans)
INTRODUCTION (CONTINUED)
These hormones regulating the metabolic
activities of the body and maintain the
homeostasis of blood glucose
Hyperinsulinemia severe hypoglycemia
Relative /absolute lack of insulin (e.g . DM)
serious hyperglycemia
Administration of insulin/OHA (oral hypoglycemic
agents) prevent morbidity and reduce
mortality DM
Insulin is a hormone which lowers
the concentration of glucose in the
blood by :

1. Stimulating the uptake of glucose by the
tissues
2. Converting glucose to glycogen in the liver
where it is stored
3. Increasing the production of fat and protein





Fat Fat
formed

Liver Glucose
converted
to glycogen

Level of glucose
in the blood lowered

Others tissues provides energy
builds protein

THE METABOLIC EFFECTS OF INSULIN


Insulin
Glycogen

glucose
Increased metabolism
(e.g. exercise ) Insulin reduces
Reduce blood glucose blood glucose

Normal blood glucose
concentration





Calories increase illness and infection
Blood glucose increases blood glucose
and more insulin is required

BALANCING PATIENTS WITH DIABETES
Diabetes Mellitus
A syndrome characterized by an elevation
of blood glucose caused by a relative or
absolute deficiency of insulin
Diabetic
Insulin-dependent diabetes mellitus
(IDDM/Type I)
Non-insulin-dependent diabetes
mellitus (NIDDM/Type II)

HYPOGLYCEMIA

Tachycardia
Confusion
Vertigo
Diaphoresis
COMPARISON OF IDDM AND NIDDM
IDDM NIDDM
Age of onset Usually during childhood
or puberty
Frequently over age
35
Nutritional status at
time of onset of
disease
Frequently
undernourished
Obesity usually
present
Prevalence 10-20 % of diagnosed
diabetic
80-90 % of
diagnosed diabetic
Genetic predisposition Moderate Very strong
Defect or deficiency Cells destroyed
eliminating production of
insulin
Inability of Cells to
produce appropriate
quantities of insulin;
insulin resistance;
other unknown defects
Treatment Type I DM
Relies on exogenous insulin
Good control of blood glucose
Goal :
To maintain blood glucose concentrations as
close to normal
To avoid wide swing in blood glucose levels
may contribute to long-term complications


Treatment Type II DM
Good control of blood glucose
Delays long-term complications
Diet and exercise necessities
Treated by Oral Hypoglycemic Agents
and/ or insulin
Insulin in pregnancy or in severe illness

INSULIN SECRETION
Regulated by blood glucose levels, other
hormones, autonomic mediators
Secretion is triggered by high blood
glucose phosphorylated -cells
pancreas Adenosine Triphosphate
(ATP) & block K
+
channels
membrane depolarization & influx Ca
++

insulin exocytosis
Glucose injection has lower effect on
insulin secretion than glucose taken orally

INSULIN
Sources :
Pork, Beef, Human
Administration :
Parenteral : SC, IV
Human insulin > more quickly absorbed DOA <
Preparations :
Short acting insulins (soluble insulins) :
Regular (crystalline zinc insulin)
OOA (SC) 30 Minutes, DOA 8 Hours
Intermediate acting insulins :
Insulin zinc suspension (IZS)
Biphasic isophane insulins
OOA 1-2 Hours , DOA 16-24 Hours
Long-acting insulins :
Protamine zinc insulin (PZI)
OOA 6 Hours, DOA 24-30 Hours

ADVERSE EFFECTS OF INSULIN
Tachycardia
Confusion
Vertigo
Diaphoresis
Lipodystrophy
Hypersensitivity
ORAL HYPOGLYCEMIC AGENTS
Non-insulin-dependent diabetes (NIDDM)
Diabetes after age 40 & has diabetes < 5
years
Long-standing disease combination :
OHA + Insulin
SULFONYLUREAS
First generation : Tolbutamid
Second generation : Glyburide, Glipizide
(high potency)
Mechanism of action :
1. Stimulates insulin release
2. Reduces glucagon release
3. Increases insulin binding
Contraindications :
Hepatic or renal insufficiency
NIDDM Pregnant women : treated insulin
Avoided in elderly : Chlorpropamide

Clofibrate Allopurinol
Phenylbutazone Probenecid
Salicylates Phenylbutazone
Sulfonamides Salicylates
Sulfonamides
Displace sulfonylureas Decrease urinary excretion of
from plasma proteins sulfonylureas or their metabolites





Reduce hepatic metabolism of sulfonylureas
Dicumarol
Chloramphenicol
Monoamine oxidase inhibitors
Phenylbutazone



DRUGS INTERACTING WITH SULFONYLUREA DRUGS
Sulfonylureas
Increased hypoglycemic action of sulfonylurea drugs
Sulfonylureas
ADVERSE EFFECTS OF OHA
Hypoglycemia
GI disturbances
Pruritus
Nausea
Anemia
BIGUANIDES
Metformine
Mechanism :
Inhibits gluconeogenesis

Reduces hyperlipidemia
SE : GI disturbances
Long-term used : Vit B
12
malabsorption
Contraindicated : renal & hepatic
insufficiency
Sulfonylurea
Biguanides
pancreas
Increased insulin
production
Gut liver
muscle
Decreased glucose
absorption
Decreased glucose
release
Increased
Glucose uptake







Comparison of the actions of sulfonylureas and biguanides
-Glucosidase inhibitor
Acarbose
NIDDM & Adjunct to insulin for IDDM
Inhibits -glucosidase in intestinal
decreases absorption of starch and
disaccharides
stimulate insulin release & increase
insulin peripheral tissues
hypoglycemia
SE : flatulence, diarrhea, abdominal
cramping
THE PHARMACOTHERAPY OF
THYROID DISORDERS
HORMON SYNTHESIS AND SECRETION

UPTAKE OF IODIDE ION :
-Stimulated by TSH
-Inhibited by Potassium Perchlorate
IODINATION :
-I
-
I
2
-I
2
+ Thyroglobulin MIT and DIT
-Inhibited by methimazole & PTU

CONDENSATION :
DIT and MIT T3 and T4
Inhibited by Methimazole and PTU

RELEASE :
Enter the general circulation
Inhibited by Iodide
Stimulated by TSH

TO ACT IN THE TISSUES :
T4 T3 + I
-
Inhibited by PTU and adrenergic antagonist
FUNCTIONS OF THYROID HORMONES
Facilities normal growth and maturation by
maintaining the level of metabolism
Two major thyroid hormones :
Triiodothyronine (T3)
Thyroxine (T4)
Is not essential for life, inadequate secretion
(hypothyroidism) bradycardia, poor resistance
to cold, mental & physical slowing (mental
retardation & dwarfism)
Hyperthyroidism tachycardia & cardiac
arrhythmias, body wasting, nervousness, tremor,
excess heat production
DRUG FOR HYPOTHYROIDISM
Levothyroxine (T4)
Long half-life
Given once a day
Steady state is achieved at 6 to 8 weeks
Toxicity manifests as hyperthyroidism
Nervousness, heart palpitations, tachycardia,
intolerance to heat, unexplained weight loss
Precautions ;
Heart disease
TREATMENT OF HYPERTHYROIDISM
(Thyrotoxicosis )
Accomplished by
Removing part or all of the thyroid gland
Inhibiting the synthesis of the hormones
Blocking the release of the hormones
Blocking the action of the hormones in the
tissue
REMOVAL OF THE THYROID
Surgical

Destruction by radioactive iodine (
131
I)
which emitted beta particles
INHIBITING HORMONE SYNTHESIS
Drugs :
Methimazole
Carbimazole
Active metabolite of Methimazole
Propylthiouracil (PTU)
Not effective for thyroid storm
Adverse effects :
Agranulocytosis
Rash
Edema
BLOCKADE HORMONE RELEASE
Drugs :
Iodide
Combined with PTU or Methimazole
Effective for thyroid storm
Administered prior to surgery
Decreases the vascularity of the gland
Not useful for longterm therapy
Adverse reactions :
Ulceration of mucous membranes
Metallic taste in the mouth
Rashes
BLOCKING THE ACTION
T
3
is the form that is active in the tissues

To act in the tissues T
4
T
3
Inhibited by PTU and adrenergic antagonist

adrenergic antagonist also normalizes heart
beat