Term
What do the following cells secrete?
(a) Alpha cells
(b) Beta cells
(c) D cells
(d) PP F cells |
|
Definition
(a) Glucagon
(b) Insulin
(c) Somatostatin
(d) pancreatic polypeptide |
|
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Term
What are the 3 effects of glucagon? |
|
Definition
Stimulates production of glucose in liver
(gluconeogenesis)
Stimulates breakdown of glycogen into
glucose in skeletal muscles and liver cells
(glycogenolysis)
Stimulates breakdown of triglycerides in
adipose tissue and fatty acid release
(lipolysis) |
|
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Term
|
Definition
1. Accelerates glucose uptake and utilization by
cells
2. Stimulates glycogen formation (glycogenesis)
3. Stimulates triglyceride formation in adipose
tissue (lipogenesis)
4. Stimulates amino acid absorption and
protein synthesis |
|
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Term
Normal blood glucose levels when
(a) fasting
(b) 2 hours after meals (PP2) |
|
Definition
(a) 70-110 mg/dl
(b)<180 mg/dl |
|
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Term
Abnormal blood glucose
– Hypoglycemia:
– Hyperglycemia:
• Impaired glucose tolerance:
• Diabetes mellitus: |
|
Definition
- < 70 mg/dl
- >110 mg/dl
-110-180 g/dl
>180mg/dl |
|
|
Term
Causes of secondary diabetes: |
|
Definition
Pancreatic disease: e.g., pancreatitis, tumor
– Endocrine disease: e.g., Cushing’s syndrome
– Drug induced: e.g., thiazide diuretics
– Infection: e.g., congenital rubella |
|
|
Term
|
Definition
|
|
Term
Clinical manifestations of DM: |
|
Definition
Polydipsia
• Polyuria + nocturia
• Glycosuria
• Complications |
|
|
Term
Complications of DM
• Acute: |
|
Definition
– Diabetic ketoacidosis (DKA)
– Hyperosmolar non-ketotic (HONK) coma |
|
|
Term
Complications of DM
Chronic: |
|
Definition
Angiopathy:
• Microangiopathy:
– retinopathy - neuropathy - nephropathy
• Macroangiopathy:
– E.g., coronary artery disease (CAD) |
|
|
Term
Other complications of DM: |
|
Definition
infection - skin complications |
|
|
Term
|
Definition
Diet control
• Antidiabetic agents
• Treatment of complications |
|
|
Term
|
Definition
Insulin
• Oral hypoglycemic agents |
|
|
Term
Indications of Insulin Therapy |
|
Definition
Type I diabetes
• Type II diabetes:
– Inadequate control by oral hypoglycemic agents
– Stressful conditions: e.g., infection
– During pregnancy
• Gestational diabetes |
|
|
Term
|
Definition
• Bovine
• Porcine
• Human recombinant:
– Least antigenic
– Standardized to 100 U/ml |
|
|
Term
Administration of source of insulin |
|
Definition
Injection: SC, IV, IM
– Alternative methods: e.g., pump |
|
|
Term
|
Definition
|
|
Term
|
Definition
Regular (crystalline) insulin |
|
|
Term
|
Definition
NPH (Neutral Protamine Hagedorn) insulin
– Lente insulin: reasonably soluble zinc preparation |
|
|
Term
|
Definition
Ultralente: poorly soluble zinc preparation |
|
|
Term
Mixed types (combinations): |
|
Definition
– Rapid onset & prolonged duration |
|
|
Term
Insulin Regimens
• Conventional therapy: |
|
Definition
One or two injections per day
– Daily self monitoring of glucose
– Lower risk of hypoglycemia |
|
|
Term
Insulin regimens:
Intensive therapy |
|
Definition
Multiple daily injections
– Daily self monitoring of glucose and dose adjustment
– Reduction in retinopathy, nephropathy, and
neuropathy
– Higher risk of hypoglycemia (3-fold more than
conventional regimen) |
|
|
Term
|
Definition
|
|
Term
Absorption of SC Insulin
• Highly variable: |
|
Definition
Among different patients
– Between doses in same patient |
|
|
Term
Factors affecting absorption of SC insulin: |
|
Definition
Blood flow to site of injection
– Site of injection:
• Abdomen > arm > buttock > thigh
– Depth of injection
– Exercise increases absorption
– Massage of the area increases absorption |
|
|
Term
Alternatives to Insulin Injection (5) |
|
Definition
Insulin pumps
• Insulin pens (insulin containing cartridges)
• Inhaled insulin
• Transdermal patches
• Oral formulas (designed to resist insulin
digestion in the GIT) |
|
|
Term
2 characteristics of Insulin pumps: |
|
Definition
Indwelling catheter delivers basal insulin
•
Patient can program device to modify delivery rate
|
|
|
Term
What is a promising alternative to insulin injection? |
|
Definition
Inhaled insulin (Exubera) |
|
|
Term
Exubera:
(a) Preparation
(b) powder
(c) delivery |
|
Definition
(a) Short - acting insulin preparation
(b) fine dry powder
(c) Non-invasive insulin delivery |
|
|
Term
What enters the blood faster? Inhaled insulin or SC injection?
Where must the drug reach? |
|
Definition
Inhaled insulin
Alveoli in the lung |
|
|
Term
Complications of Insulin Therapy
|
|
Definition
Hypoglycemia → most dangerous
–
Insulin allergy → rare with human insulin
–
Insulin resistance
|
|
|
Term
Complications of Insulin Therapy
Local |
|
Definition
Lipoatrophy
–
Hypertrophy
|
|
|
Term
Oral Hypoglycemic Agents
(5) |
|
Definition
Sulfonylureas
•
Biguanides
•
Meglitinides
•
Thiazolidinediones (TZDs, glitazones)
•
Alpha-glucosidase inhibitors
|
|
|
Term
Mechanism of action of sulfonylureas: |
|
Definition
Inhibit K channels on β-cell → causing depolarization → ↑ calcium entry → ↑ insulin release
|
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|
Term
Where do sulfonylureas potentiate insulin action? |
|
Definition
|
|
Term
What do sulfonylureas require?
Which diabetes are they useful for? |
|
Definition
Functional B cells to work
Only useful for type 2 not type 1 |
|
|
Term
What do sulfonylureas bind to?
(b) metabolised
(c) excreted |
|
Definition
(a) Plasma proteins
(b) Liver
(c) Kidney |
|
|
Term
Exaggerated effects of sulfonylureas are in: |
|
Definition
(a) Elderly
(b) Renal disease
(c) Liver disease |
|
|
Term
Where are sulfonylureas contraindicated? |
|
Definition
Pregnancy. They can cross the placenta and have teratogenic effects. |
|
|
Term
Which drugs increase hypoglycemic effects? |
|
Definition
NSAIDs, coumarins, alcohol, MAO inhibitors, some antibacterials (sulfonamides, chloramphenicol)
–
Cimetidine (inhibits metabolism)
|
|
|
Term
Which drug inhibits insulin release? |
|
Definition
|
|
Term
What can mask the symptoms of hypoglycemia? |
|
Definition
|
|
Term
First generation sulfonylureas (least potent) |
|
Definition
tolbutamide, chlorpropamide |
|
|
Term
2nd generation sulfonylureas: |
|
Definition
Glipizide, Glibenclamide, Ggliclazide |
|
|
Term
3rd generation sulfonylureas: |
|
Definition
|
|
Term
Side effects of sulfonylureas: |
|
Definition
Hypoglycemia (esp. chlorpropamide)
Gi disturbances
Jaundice
Allergic skin reactions
|
|
|
Term
Why does chlorpropamide have more side effects? |
|
Definition
More side effects especially hypoglycemia because prolonged duration of action. |
|
|
Term
Mechanism of action of biguanides: |
|
Definition
Decrease gluconeogenesis in liver
Increase glucose uptake in skeletal muscles |
|
|
Term
Indications of biguanides: |
|
Definition
First choice drug in patients with Type 2 DB
Can be combined with sulfonylureas and insulin |
|
|
Term
|
Definition
Do not cause hypoglycemia as they do not alter insulin levels. |
|
|
Term
Side effects of biguanides: |
|
Definition
Anorexia: Dose dependent can be severe
Nausea, diarrhea, metallic taste
Lactic acidosis (acidification of blood) |
|
|
Term
Contraindications of biguanides: |
|
Definition
|
|
Term
What is the only approved form of biguanides?
What are its 2 forms? |
|
Definition
Metformin (dimethylbiguanides)
- Glucophage™
- Glucophage XR™ (extended-release tablets)
|
|
|
Term
What are meglinitides?
What are they similar to?
Duration of action? |
|
Definition
Short acting insulin secretagogues.
Similar in action to sulfonylureas.
Half life is 1 hour. |
|
|
Term
Indications of meglitinides: |
|
Definition
Type 2 DM.
Can be combined with metformin. |
|
|
Term
Side effects of meglitinides: |
|
Definition
|
|
Term
Examples of meglitinides:
|
|
Definition
|
|
Term
Mechanism of action of TZDs: |
|
Definition
- Activate a transcription regulator, PPARγ (peroxisome proliferator-activated receptor gamma) →
- modulate lipogenesis in adipocytes
- improve glucose uptake in skeletal muscles
- reverse insulin resistance
|
|
|
Term
|
Definition
Type 2 DM
–
Alone or combined with metformin, sulfonylurea
|
|
|
Term
|
Definition
Congestive heart failure
Myocardial ischemia
May cause liver injury (monitor liver f unction) |
|
|
Term
|
Definition
|
|
Term
Alpha-glucosidase Inhibitors |
|
Definition
Inhibits α-glucosidases in intestine → reduces absorption of carbohydrates • Not absorbed from intestine • Control post-prandial glucose levels not adequately controlled by diet and sulfonylureas • Side effects: – GI upset and flatulence • E.g., Acarbose |
|
|
Term
What do you use for (a) Impaired insulin secretion
(b) Glucose uptake and utilisation |
|
Definition
(a) Sulfonylureas and meglitinides
(b) Metformin and TZDs |
|
|