Transcript Chapter 36 Insulin and oral hypoglycemic agents
Chapter 37 Insulin and oral hypoglycemic agents
Metabolic disorder of multiple etiology characterized by hyperglycemia (insulin resistance).
with carbohydrates, fat, and protein metabolic alterations that result from a decrease in the circulating concentration of insulin (insulin deficiency) and a decrease in the response of peripheral tissues to insulin
Characteristics of DM
hyperglycemia disturbance in metabolism of lipids, carbohydrates and proteins
Symptoms of diabetes
Polyuria (urinating frequently) Polydipsia (very thirsty) Continuous hunger Weight loss
Other diabetes symptoms
Fatigue Dry skin Frequent infections Feet ulceration Loss of sensibility in inferior extremities (legs)
Classification of DM
DM (insulin-dependent diabetes mellitus, IDDM)
DM (non-insulin-dependent diabetes mellitus, NIDDM) Other type: secondery
Treatment and control
(insulin vs. hypoglycaemic agents) Increase physical activity
at least walk for 30 min. most days Appropriate diet
fruit low in fat and carbohydrates Lifestyle changes
Classification of drugs (1) Insulin (2) Orally hypoglycemic agents Insulin sensitizers Sulfonylureas Biguanides Inhibitor of
-glycosidase Chinese herbs
PART 1 insulin
: small protein with a MW of 56 KD (in human) Two chains (A and B)
: once from bovine and porcine pancreas, now by recombinant DNA techniques
will be degraded in the gastrointestinal tract if taken orally.
often administered by subcutaneous injection.
Half life:9-10 min Elimination in liver and kindney
分类 制剂 短效 中效 半慢胰岛素锌混悬 液 低精蛋白锌混悬液 长效 正规胰岛素 慢胰岛素锌混悬液 精蛋白锌胰岛素 特慢胰岛素锌混悬 液 给药途径 皮下 脉 皮下 皮下 皮下 皮下 皮下
0 1~2 1~2 4~6 4~6
2~4 2~8 6~12 6~12 14~20 16~18
5~8 12~16 18~24 18~24 24~36 20~36
给药时间、 次数 餐前
日， 急症 餐前
The main effects of insulin are affecting metabolism of glucose, lipids and protein.
1.Effects on glycometabolism (hypoglycemia)
Increase the synthesis and storage of glycogen stimulating the uptake and metabolism of glucose by muscle and adipose tissue
2.Effects on lipometabolism
inhibiting the hormone-sensitive lipase in adipose tissue→ inhibiting the hydrolysis of triglycerides Increasing transfer of fatty acid →stimulates synthesis of fat
Pharmacological effects of insulin
3.Effects on protein metabolism
(positive nitrogen balance) stimulating amino acids uptake and protein synthesis inhibiting protein degradation in muscle and other tissues
4.Influence on kalium in blood Decrease kalium in blood 5.HR (heart rate), increase the contractility of myocardium, decrease renal blood flow [Mechanism of action]
The goal is the normalization not only of blood glucose but also of all aspects of metabolism.
:the only effective drug Patient with IDDM must rely on injected insulin daily in order to control hyperglycemia all his lifetime.
The most common site of subcutaneous injection is abdomen.
: not adequately controlled by diet and oral hypoglycemic agents (Weight reduction, exercise and dietary modification can correct the hyperglycemia in some patients) For NIDDM patients, the goal is to maintain blood glucose concentrations within normal limits and to prevent the development of long-term complications of the disease.
3.DM associated with acute or serious
complications: Ketoacidosis, hyperosmolar nonketotic coma
4.DM patients under stress conditions:
serious infection, consumptive diseases, pregnancy, trauma, operation
5. Hyperkalemia and intracellular hypokalemia GIK: 10
1.Hypoglycemia : most common may result from an inappropriately large dose of insulin or delayed food intake.
Short effect agents: sweating, hunger, palpitations, tremor and anxiety, Long effect agents: neuroglycopenic symptoms (such as difficulty in concentrating, confusion, weakness, drowsiness, even loss of consciousness)
2.Insulin allergy: The most frequent allergic manifestations are IgE-mediated local cutaneous reactions.
Acute resistance: stress Chronic resistance: 1) AIRA (antiinsulin receptor autoantibody) 2) down regulation of receptor 3) dysfunction of glucose transfer
Preparations of insulin
Portable pen injection Continuous subcutaneous insulin infusion devices (CSII, insulin pumps) Inhaled insulin
胰岛素制剂比较 分类 药物 给药途经 作用时间 开始 高峰 维持 给药时间
Short-acting Moderate -acting Regular iv
insulin sc 0.5 2-3 6-8
Neutral protamine 2-4 8-12 18-24 Hagedorn sc
sc 2-4 6-10 12-18 Protamine zinc insulin 3-6 16-18 24-36
Part 2 Oral hypoglycemic agents
Common characteristics (1) Orally effective and convenient (2) Slow and weak (3) NIDDM
) Englitazone (
( 曲格列酮 )
Pharmacological action 1.Improve insulin resistance, lower hyperinsulinemia and hyperglycemia
Limosis and after-meal BS
Blood insulin and blood fatty acid
used in combination with other drugs
Low incidence of hypoglycemia
2.Correct lipodystrophy ↓
TG，↑TC and ↑HDL－C
3.Improve complication of NIDDM anti-atherosclerosis effect delay occurrence of albuminuria 4.Improve β-cell function
NIDDM and IR
general reaction heptic toxicity
The first generation
: Tolbutamide(甲苯磺丁脲), chlorpropamide(氯磺丙脲).
The second generation
美脲) : glyburide(格列本脲), glipizide(格列 吡嗪), gliquidone, glimepiride(格列
The third generation
Distribution: PPBR Elimination: liver Excretion:kidney
Hypoglycemic action: weaker than Insulin (1)Increasing the release of Insulin from pancreatic βcell: (2) Enhancing the sensitivity of target cell to insulin ① Increasing the numbers of insulin receptors ② Increasing the affinity of insulin receptors
(3) Decreasing the release of glucagons from pancreatic A cell by stimulating the release of somatostatin
↑secretion of ADH 3.Effects on coagulation ↓adhesion and agregation of PLT ↑synthesis of plasminogen ↓sensitivity of microvessel to CA
control hyperglycemia in NIDDM who can not achieve appropriate control with exercise and dietary modification alone.
(1)alone (2)plus insulin 2.Diabetes insipidus
（ 尿崩症 ）
1. Hypoglycemia reactions 2. Gastrointestinal tract reactions: 3. Anaphylactic reaction 4.Hepatic damage
[Drugs interaction] 1.Some drugs increase actions of sulfonylureas (1)Aspirin.butazolidin.SNS.coumarins (2) Penicillin.probenecid
2.Some drugs decrease actions of sulfonylureas Glucocorticoids.
metformin phenformin introduced in 1957 and were widely used. Phenformin was withdrawn in many countries during the 1970s because of an association with lactic acidosis .
Metformin has been associated only rarely with that complications and has been widely used in Europe and Canada. It became available in the United States in 1995.
1.Hypoglycemic action: (2) Slowing the absorption of glucose (3) Promoting the use of glucose (3) inhibiting release of glucagon (1) Promoting the effects of insulin 2.Regulating blood lipid 3.Antiplatelet effects
NIDDM patients with obesity
2.Ketonuria and acidemia phenformin
Mechanism of action :Inhibiting α-Glycosidase
(1)decreasing the formation of glucose (2) slowing the absorption of glucose
used in combination with other oral anti-diabetic agents and/or insulin
: 1.gastrointestinal reaction: 60%, mal-absorption, flatulence, diarrhea, abdominal bloating 2.hypoglycemia: 3%
Other types agents: Repaglinide
stimulating the pancreas to release insulin Mimicking physiological secretion of insulin
Chinese traditional medicine xiaokewan [Actions] 1.Absorption
2.Expansive action 3.Increase intestine peristalsis 4.Nourishing action [Uses]