Type One Diabetes
- Due to no or very litle insulin
- Seen more in children
Type Two diabetes
- Tissue is resistant to insulin
- Seen in adults and the obese
Type 4 diabetes
Where are insulin recepters found?
- Adipose tissue and skeletal muscle
What are the regulators of Insuline secretion?
Chemical--- Glucose Concentration and AAs
Hormonal--- GH, Corticosteroids, adrenaline and glucagon
What are the Effects of Insulin?
- Promotes Potassium Uptake
- Enhances Glucose uptake and Storage (glycogen)
- Increases triglycerides and VLDL production
- Decreases breakdown of Proteins
insulin actions on:
- enhances Glucose uptake
- decreases the breakdown of proteins for energy and enhances their synthesis
Enhaces lipogenesis and glucose uptake
What is added to Insulins to increase the stability, duration of action and shelf life?
Where is insulin metabolized?
Zinc and Protamine
In the Liver and Kindney
What is the Function of Long or intermediate acting Insulins?
What is the function of Short Acting insulins
- To maintain the background or basal level of insulin
- to control postprandial hyperglycemia
Ultra-rapid onset of action and very short
acting Insulins are? They dont LAG
- Insulin lispro,
- Insulin aspart,
- Insulin glulisine
What are the Therapeutic uses of insulin?
- -All Type 1 DM patients
- -Only the type II patients that fail to maintain blood glucose
- Gestational DM
- Diabetic Ketoacidosis ( regular insulin)
Rapid onset - Short acting Insulin
- Crystalline Zinc insulin (Regular type)
- -Only insulin given in ketoacidosis !!!
- -Leads to early postprandial hyperglycemia and late postprandial hypoglycemia
Intermediate Onset ?
Slow Onset & Long Acting insulins (takes to GD long)
Insulin Glargine and Insulin Detemir
Prevents hyperglycemia between the doses.
Ultra-rapid onset and regular insulin types control?
- postprandial hyperglycemia &
- administered just before meal
Intermediate onset and Slow onset control what?
maintain basal insulin levels and control blood glucose between meals
When will you see Hyperosmolar, hyperglycemic syndrome (nonketotic coma)?
occurs in elderly patients with type II DM
Have hyperglycemia and dehydration
Treat: Faster fluid replacement and low dose insulin
What are the Main Clinical Symptoms of Diabetic ketoacidosis?
- Dehydration (due to deep slow respirations)
- and Tachycardia
- See elevated Ketones in the urine
- Low blood pH
What do you do to treat diabetic Ketoacidosis?
- -Insulin (Regular) by IV
- -IV fluids (normal saline or with glucose)
- - Monitor Potassium levels (because it would be peeed out when trying to concentrat the urine)
What is Hyperosmotic Hyperglycemic syndrome?
- Seen in elderly patients with Type II
- See Hyperglycemia and dehydration
- decline in mental status and convulsions (see NO acidosis)
- - Faster replacement of fluids
- - prophylatic heparin
What are the signs and symptoms of Hypoglycemia?
Sweating, anxiety, palpation, tremor, diziness and weakness.
Sever--> Seizures and Coma
- Mild- Sugar tablet
- Sever-- 50% Glucose IV, Glucagon
What is the Effect of Betablockers on Insulin?
Prolongs Hypoglycemia by:
- Decreasing warning signs
- Inhibit Glycogneolysis
What are the Effect of Thiazides, Furosemie and Vifedipine on insulin?
Corticosteroids act by?
They inhibit insulin secretion.
increaseing the Blood sugar and decreasing the effectivness of insulin
ORAL HYPOGLYCEMIC AGENTS
(OHA), what are they?
- 1. Insulin secretagogues-- increase insulin production
- 2. Biguanides-- decreaseglucose production by the liver
- 3. Thiozolidinediones-- Increase uptake of sugar my muscle
- 4. Alpha- glucosidase inhibitors-- slow suger absorption in the gut
- 5. Incretin based therapy
1. Insulin secretagogues, what are they?
Name the different ones
how do they work?
what are the newer ones?
What are they used for?
- 1st Generation – Tolbutamide, Chlorpropamide, Tolazamide
- 2nd generation – Glyburide, Glipizide, Glimepiride
-close the ATP sensitive K+ channels-->insulin released
- - Newer drugs - Repaglinide & Nateglinide
- - post prandial hyperglycemia in type II patients
What is its mechanism?
-Inhibiting gluconeogenesis and Enhance tissue glucose uptake & utilization
- Lactic acidosis
3. Thiazolidinediones / glitazones
Pioglitazone & Rosiglitazone
binding to Peroxisome proliferator activated receptor –gamma (PPAR-γ)-->Increase tissue glucose uptake
4. Alpha-glucosidase inhibitors
- Acarbose & Miglitol
- -Decrease digestion & absorption of
Adverse effects: Flatulence
Newer drugs used to control postprandial glucose?
- 1. Pramlintide
- by inhibiting glucagon release
- 2. Exenatide
- Increase insulin release
- 3. Sitaglipin
- Prolongs effect of GLP-1
What are the Glucocorticoid drugs?
which are short acting and which are long acting?
- -Short acting - Hydrocortisone
- (cortisol), cortisone
-Intermediate acting - Prednisone , Prednisolone, Methylprednisolone, Triamcinolone,
-Long acting - Betamethasone, Dexamethasone
What are the mineral corticoid drugs?
Glucocorticoids – pharmacological actions?
& immunosuppressive effects
- -Predominantly act on peripheral leukocytes (IL-2), decreasing their production by Inhibiting activation of phospholipase A2 (PLA2)
- -Inhibits macrophages and APC
Glucocorticoids – pharmacological actions 2?
Effects on metabolism of carbohydrates,
proteins & fats.
Prolonged use leads to?
- Stimulate gluconeogenesis, Increase serum glucose
- Breaks muscle proteins, Induce lipolysis & redistribution of fat.
When is glucocorticoids used for replacement theropy?
1. Acute adrenal insufficiency (Addison’s crisis):
2. Chronic adrenal insufficiency / Addison’s disease
3. Congenital adrenal hyperplasia
What are some Non-endocrine uses of Glucocorticoids?
Should you use it for HSV?
- (a) Allergic diseases
- (b) Bronchial asthma
- (c) Collagen vascular disorders
- (d) Autoimmune diseases
- (e) Ocular diseases
- f) Skin diseases
- (h) Gastrointestinal diseases
- (i)To reduce cerebral edema
- (j) Malignancies
- (k) To prevent organ transplant rejection
- (l) In preterm labor
NO!!! it is Contraindicated
Adverse effects of Glucocorticoids
- -Sudden withdrawal
- leads to Acute adrenal insufficiency
- -Iatrogenic Cushing’s
- syndrome: redistribution of fat -moon
- face, thin extremities, buffalo hump
- -Thin skin (fragile)
- with purple striae and easy bruising
- -Hypertension &
- -Myopathy & muscle wasting
- -Susceptible for
- infection: TB, candidiasis etc
- -Peptic ulcer
- -Hypomania, acute psychosis & depression
- -Posterior subcapsular Cataract
- & glaucoma
- -Delays wound healing
- -Growth retardation in children
Contraindications / cautiously used
- -Peptic ulcer
- -Diabetes Mellitus
- -Hypertension & congestive heart failure
- -Varicella & tuberculosis infections
- -Pregnancy (esp 2nd trimester)
What is the Drug?used in? what is a AE?
replacement therapy in hypoadrenalism
Edema due to Na retention
What are some Adrenalcorticoal Antagonists?
- Inhibitors of glucocorticoids synthesis
- Aldosterone receptor blockers
- Spironolactone & eplerenone