This document discusses insulin and antidiabetic drugs. It begins by describing the pancreatic axis and role of insulin and glucagon in maintaining glucose homeostasis. It then defines diabetes mellitus and describes the main types, Type 1 and Type 2 diabetes. It discusses treatment approaches for both types, including lifestyle changes and various drug classes. The mechanisms and preparations of insulin are outlined in detail. Finally, it reviews common oral antidiabetic drug classes like sulfonylureas, meglitinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors.
Controlling blood sugar (glucose) levels is the major goal of diabetes treatment, in order to prevent complications of the disease.
Type 1 diabetes is managed with insulin as well as dietary changes and exercise.
Type 2 diabetes may be managed with non-insulin medications, insulin, weight reduction, or dietary changes.
Medications for type 2 diabetes are designed to
increase insulin output by the pancreas,
decrease the amount of glucose released from the liver,
increase the sensitivity (response) of cells to insulin,
decrease the absorption of carbohydrates from the intestine, and
slow emptying of the stomach, thereby delaying nutrient digestion and absorption in the small intestine.
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from whic
Pancreas makes a hormone called insulin. It helps your cells turn glucose, a type of sugar, from the food you eat into energy. Diabetes happens when one or more of the following occurs:
Your pancreas does not make any insulin.
Your pancreas makes very little insulin.
Your body does not respond the way it should to insulin
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Excess of hyperglycemic hormones (glucagon, ete. ) obesity: ; cause relative insulin deficiency the β cells Tag behind
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Oral hypoglycemic drugs are used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin. Type 1 diabetes involves a lack of insulin and requires insulin for treatment. There are now four classes of hypoglycemic drugs:
Controlling blood sugar (glucose) levels is the major goal of diabetes treatment, in order to prevent complications of the disease.
Type 1 diabetes is managed with insulin as well as dietary changes and exercise.
Type 2 diabetes may be managed with non-insulin medications, insulin, weight reduction, or dietary changes.
Medications for type 2 diabetes are designed to
increase insulin output by the pancreas,
decrease the amount of glucose released from the liver,
increase the sensitivity (response) of cells to insulin,
decrease the absorption of carbohydrates from the intestine, and
slow emptying of the stomach, thereby delaying nutrient digestion and absorption in the small intestine.
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from whic
Pancreas makes a hormone called insulin. It helps your cells turn glucose, a type of sugar, from the food you eat into energy. Diabetes happens when one or more of the following occurs:
Your pancreas does not make any insulin.
Your pancreas makes very little insulin.
Your body does not respond the way it should to insulin
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Insulin is synthesized in the β cells of pancreatic islets as a single chain peptide Preproinsulin (110 AA) from which
Diabetes mellitus (DM):- It is a metabolicdisorder characterized by hyperglycaemia, (fasting plasma glucose ≥ 126 mg/dl and/or ≥ 200 mg/dl 2 hours after 75 g oral glucose),glycosuria, hyperlipidaemia, negative nitrogen balance and sometimes ketonaemia.
Diabetes mellitus, one of the major public health problems worldwide, is a metabolic disorder of multiple etiologies distinguished by a failure of glucose homeostasis with disturbances of carbohydrate, fat and protein metabolism as a result of defects in insulin secretion and/or insulin action.
According to International Diabetes Federation (IDF) report, elevated blood glucose is the third uppermost risk factor for premature mortality, following high blood pressure and tobacco use globally
Cardiovascular diseases, neuropathy, nephropathy, and retinopathy are among the major risks that are associated with diabetes.
These chronic complications may lead to hardening and narrowing of arteries (atherosclerosis) that could advance to stroke, coronary heart disease, and other blood vessel diseases, nerve damage, kidney failure, and blindness with time
Two major types of diabetes mellitus are
1. Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
2. Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Insulin-dependent diabetes mellitus (IDDM) / juvenile onset diabetes mellitus
There is β cell destruction in pancreatic islets; majority of cases are autoimmune (type 1A) antibodies that destroy β cells are detectable in blood, but some are idiopathic (type 1B)-no βcell antibody is found.
2.Noninsulin-dependent diabetes mellitus (NIDDM) / maturity onset diabetes mellitus
Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide.
There is no loss or moderate reduction in β cell mass: insulin in circulation is low. normal or even high. no anti-β -cell antibody is demonstrable: has a high degree of genetic predisposition: generally has a late onset (past middle age). Over 90% cases of diabetes are type 2 DM
Abnormality in gluco-receptor of β cells so that they respond at higher glucose concentration or relative β cell deficiency. In either way. insulin secretion is impaired: may progress to β cells failure.
Reduced sensitivity of peripheral tissues to insulin: reduction in number of insulin receptors, “down regulation” of insulin receptors.
Excess of hyperglycemic hormones (glucagon, ete. ) obesity: ; cause relative insulin deficiency the β cells Tag behind
Insulin history:
Insulin was discovered in 1921 by Banting and Best who demonstrated the hypoglycaemic action of an extract of pancreas prepared after degeneration of the exocrine part due to ligation of pancreatic duct.
It was first obtained in pure crystalline form in 1926 and the chemical structure was fully worked out in 1956 by Sanger.
Insulin is a two chain polypeptide having 51 amino acids and MW about 6000.
The A-chain has 21 while B-chain has 30 amino acids.
Oral hypoglycemic drugs are used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin. Type 1 diabetes involves a lack of insulin and requires insulin for treatment. There are now four classes of hypoglycemic drugs:
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2. PANCREATIC AXIS
INSULIN
-β cells secrete due to high
blood glucose levels
-Glucose uptake into tissues
increases
GLUCAGON
-α cells secrete when blood
glucose is low
-Glucose is released from tissues
back into blood
3. GLUCOSE HOMEOSTASIS
Body
Cells take up
more glucose
Liver takes
up glucose
and stores it as
glycogen
Blood glucose level
declines to a set point;
stimulus for insulin
release diminishes
Homeostasis: Normal blood glucose level
(about 90 mg/100 mL)
STIMULUS:
Rising blood glucose
level (e.g., after eating
a carbohydrate-rich
meal)
Beta cells
of pancreas stimulated
to release insulin into
the blood
High blood
glucose level
Blood glucose level
rises to set point;
stimulus for glucagon
release diminishes
Liver
breaks down
glycogen and
releases glucose
to the blood
Glucagon
Alpha
cells of
pancreas stimulated
to release glucagon
into the blood
STIMULUS:
Declining blood
glucose level
(e.g., after
skipping a meal)
Insulin
4. NORMAL GLUCOSE CONTROL
Post-absorptive period - normal individual-low basal levels of
circulating insulin maintained through constant β cell secretion-
suppression of lipolysis, proteolysis and glycogenolysis.
After ingesting a meal-burst of insulin secretion in response to
elevated glucose and amino acid levels.
When glucose levels return to basal levels- insulin secretion
returns to its basal level.
5. DIABETES MELLITUS
-Definition- Diabetes is a heterogeneous group of syndromes
characterized by the elevation of glucose levels due to a relative
or absolute deficiency of insulin.
-It is characterized by-
1. High level of glucose in urine and fasting blood
2. Polyuria
3. Polydypsia
4. Fatigue
5. Constant hunger
6. TYPES
Type 1 DM:
- “Childhood” diabetes (sudden onset, before age 15)
- Lack of functional pancreatic β-cells (T cell-mediated autoimmune response
destroys beta cells)
- Lack of functional β-cells prevents mitigation of elevated glucose levels and
associated insulin responses.
- Controlled by insulin injections.
Type 2 DM:
- “Adult” diabetes (after age 40, obese individuals)
- Insulin levels are normal or elevated but there is either a decrease in number of
insulin receptors or the cells cannot take it up.
- Actual insulin levels may be normal or supra-normal but it is ineffective
(insulin resistance).
- Controlled by dietary changes and regular exercise.
7. TREATMENT
Type I DM :
- Depend on exogenous insulin to prevent hyperglycemia and avoid
ketoacidosis.
- The goal of therapy is to mimic both the basal and reactive secretion of insulin
in response to glucose levels avoiding both hyper- and hypo-glycemic
episodes.
Type II DM:
- The goal of treatment is to maintain glucose concentrations within normal
limits to prevent long term complications.
- Weight reduction, exercise and dietary modification decrease insulin resistance
- essential steps in the treatment regimen.
- Addition of hypoglycemic agents is often required, often insulin therapy is
also required.
8. INSULIN
Insulin- peptide hormone
synthesized in the beta cells of
islets of Langerhans in the
Pancreas.
Produced as a polypeptide- Pro
insulin (precursor)
Proinsulin converted to insulin
and C-peptide and stored in the
secretory granules.
Stimulation leads to release of
secretory granules.
9. MECHANISM OF ACTION
Secretion elicited by elevated glucose levels
Increased glucose levels in β-cells results in increased ATP levels, this results
in a block of K+ channels causing membrane depolarization which opens Ca2+
channels.
The influx of Ca2+ results in a pulsatile secretion of insulin.
Many insulin stimulated cascades are activated mainly translocation of GLUT
4 glucose transporters to plasma membranes causing-
1. Glucose diffusion into cells
2. Activates glycogen synthetase and thus glucose stored as glycogen
3. Stimulate uptake of amino acids, potassium and magnesium
4. Stimulate protein synthesis and inhibit proteolysis
1 unit of can account for 30 grams of carbohydrate
1 unit can lower 50 mg/dL blood glucose
10. ACTION OF INSULIN ON VARIOUS
TISSUES
LIVER MUSCLE ADIPOSE
↓ GLUCOSE
PRODUCTION
↑ GLUCOSE
TRANSPORT
↑ GLUCOSE
TRANSPORT
↑ GLYCOLYSIS ↑ GLYCOLYSIS ↑ LIPOGENESIS&
LIPOPROTEIN
LIPASE ACTIVITY
↑ TG SYNTHESIS ↑ GLYCOGEN
DEPOSITION
↓ INTRACELLULAR
LIPOLYSIS
↑ PROTEIN
SYNTHESIS
↑ PROTEIN
SYNTHESIS
11. The Synthesis and Release of Insulin is modulated by:
1. Glucose (most important) and ketone bodies stimulate release.
2. Glucagon and somatostation inhibit release
3. α-Adrenergic stimulation inhibits release (most important).
4. β-Adrenergic stimulation promotes release.
5. Elevated intracellular Ca2+ promotes release.
12. PHARMACOKINETICS
Elimination t ½ of IV insulin- 5 to 10 minutes
Metabolized by kidneys and liver
Insulin tightly bound to tissue receptors- so even though rapid clearance,
pharmacologic effects remain till 30-60 minutes.
Insulin secreted into portal venous system at rate of 1 unit/hour
Daily secretion of insulin is 40 units.
Insulin response to glucose is greater for oral ingestion than for iv infusion.
15. PREPARATIONS
Regular Insulin
- Fast acting (rapid acting)
- Only type which can be given IV as well as SC
- Six molecules linked with a zinc molecule to form hexamer
- For abrupt onset hyperglycemia or ketoacidosis
- Single iv injection 1-5Units/ continuous infusion of 0.5-2 units/hour
16. VERY RAPID ACTING- LISPRO/ INSULIN ASPART/ GLULISINE-
(ultrashort acting)
- More rapid than regular insulin and shorter duration
- Less Associated hypoglycemia but recurrent hyperglycemia before next meal due
to shorter duration of action.
- Given just 15 minutes prior to meals
- Provides a postprandial plasma insulin concentration like normal insulin.
INTERMEDIATE ACTING- LENTE (NPH)
- Absorption delayed due to conjugation with protamine(0.005mg/unit)
LONG ACTING- ULTRALENTE, GLARGINE
- Given as single bedtime injection
- Lesser nocturnal hypoglycemia
17.
18. ADVERSE EFFECTS OF INSULIN
Hypoglycemia
Allergic reactions
Lipodystrophy
Insulin resistance
Hypokalemia
Weight gain
19. ORAL HYPOGLYCEMICS
These agents are useful in the treatment of Type 2 DM who do not respond
adequately to non-medical interventions (diet, exercise and weight loss).
Newly diagnosed Type 2 DM (less than 5 years) often respond well to oral
agents
Patients with long standing disease (often diagnosed late) require a
combination of agents with or without insulin.
The progressive decline in β-cell function often necessitates the addition of
insulin at some time in Type II DM. Oral agents are never indicated for Type I
DM.
20. SULFONYLUREAS
Promote the release of insulin from β-cells (secretogogues)
Mechanism of action:
These agents require functioning β-cells, they stimulate release by blocking
ATP-sensitive K+ channels resulting in depolarization with Ca2+ influx
which promotes insulin secretion.
They also reduce glucagon secretion and increase the binding of insulin to
target tissues.
They may also increase the number of insulin receptors
-Adverse Effects: Weight gain, Hyperinsulinemia and Hypoglycemia. Hepatic or
renal insufficiency causes accumulation of these agents promoting the risk of
hypoglycemia.
Tolbutamide is asociated with a 2.5 times rise in cardiovascular mortality.
21. Onset and Duration
Short acting: Tolbutamide
Intermediate acting: Glipizide ,Glyburide
Long acting: Chloropropamide, Glimepride
22. MEGLITINIDES
Agents -Repaglinide and Nateglinide act as Secretogogues.
Prompt peak effect (1 hour) and shorter duration of action (about 4 hours)
Taken 15-30 mins before meals
Decreases risk of prolonged hypoglycemia due to short duration of action.
When used in combination with other oral agents they produce better control
than any monotherapy.
23. BIGUANIDES
METFORMIN
- Classified as an insulin sensitizer- increases glucose uptake and utilization by target
tissues
- Mechanism of action : Reduces plasma glucose levels by inhibiting hepatic
gluconeogenesis.
- It also reduces hyperlipidemia (↓LDL and VLDL cholesterol and ↑ HDL). Lipid
lowering requires 4-6 weeks of treatment.
- Metformin also decreases appetite.
- It is the only oral hypoglycemic shown to reduce cardiovascular mortality.
- Adverse effects: Hypoglycemia occurs only when combined with other agents.
Rarely severe lactic acidosis is associated with metformin use particularly in
diabetics with CHF. Drug interactions with cimetidine, furosemide, nifedipine and
others have been identified.
24. THIAZOLIDINEDIONES (GLITAZONES)
PIOGLITAZONE and ROSIGLITAZONE
These agents are insulin sensitizers
They do not promote insulin secretion from β-cells but insulin is necessary for
them to be effective
Act principally at adipose tissue and skeletal muscles to decrease insulin
resistance
Clinical effect takes 4-12 weeks to be evident
SIDE EFFECTS- Weight gain, can induce hepatic dysfunction
25. ΑLPHA-GLUCOSIDASE INHIBITORS
Acarbose and miglitol are two agents of this class used for type 2 diabetes
Mechanism of action: These agents are oligosaccharide derivatives taken at the
beginning of a meal ; delay carbohydrate digestion by competitively inhibiting
α-glucosidase, a membrane bound enzyme of the intestinal brush border.
Adverse Effects: Flatulence, diarrhea, cramping.
Metformin bioavailability is severely decreased when used concomitantly.
These agents should not be used in diabetics with intestinal pathology.