Pharmacology: Diabetews Flashcards
What are the 4 ADA diagnostic criteria for diabetes?
- FBS > 126 mg/dL on more than 1 occasion
- Random glucose over 200 mg/dL (with symptoms)
- Abnormal GTT
- A1C > 6.5%
What are 4 actions of insulin?
- Induces LPL on adipose tissue capillary
- Inhibits intracellular hormone sensitive lipase
- Stimulates glycogenisis, suppresses gluconeogenesis
- Stimulates protein synthesis
What hydrolyzes TG in blood so free FAs can enter adipose?
LPL
What hydrolyzes TG in adipose cell to break down fat and release FFAs into blood, stimulated by glucagon?
HSL
What kind of insulin is Lispro and Aspart?
Short-acting
When should short acting insulin be taken?
Very close to a meal… it has the most rapid onset of action
What type of insulin is NPH?
Intermediate acting
What is a long acting insulin?
Glargine
In conventional insulin therapy, when is insulin given?
Before breakfast and before the evening meal
What is in conventional insulin therapy?
Combination of short and intermediate acting insulins
What is honeymoon phase with conventional insulin therapy?
After 1-3 weeks of treatment, insulin requirements decrease…temporarily regain own insulin secretory capacity… this may last weeks to months
How is intensive insulin therapy given?
Long acting in AM and then 3 doses of regular or lispro insulin at the 3 main meals
What are the 4 actions of drugs for Type 2 DM?
- Decrease glucose production
- Increase insulin secretion
- Increase insulin sensitivity
- Decrease glucose absorption
What are the 2 actions of metformin?
- Decreases hepatic glucose production (gluconeogenesis)
2. Increases insulin sensitivity- Increases peripheral glucose uptake and utilization
What type of drug is metformin?
Biguanide
What are 2 advantages of metformin over other type 2 DM drugs?
- Doesn’t produce hyperinsulinemia
2. Doesn’t produce hypoglycemia
Glucose is taken up into the cell by what transporter?
GLUT 2
What traps glucose in the cell?
Glucokinase
What is glucose metabolized to once in the cell?
ATP
When ATP is produced, it closes what channels leading to depolarizaton?
K
What does depolarization do?
Opens the voltage gated Ca channels
What does Ca do?
Stimulates the fusion of the synaptic vesicle with the cell membrane and releases insulin
What do sulfonylureas do?
Block the K channel…this makes the cell look like there is an influx of glucose (depolarizes the cell), which will increase the release of insulin
What are 2 AE of sulfonylureas?
- Disulfram reactions
2. Hypoglycemia
What are the 3 actions of thiazolidinediones?
- Increase insulin sensitivity
- Increase glucose uptake
- Decrease hepatic glucose production (gluconeogenesis)
What is a complex oligosaccharide that decreases digestion of ingest carbs?
Alpha glucosidase inhibitors
How do alpha-glucosidase inhibitors work?
Competitive, reversible inhibition of intestinal brush border enzymes
What is the primary effect of alpha glucosidase inhibitors?
Affects postprandial blood glucose… decreases by 40-60 mg/dL
What is 1 advantage of rDNA-produced insulin over bovine insulin?
It is less antigenic….bovine insulin causes allergic reactions to impurities and to insulin molecule itself
What is the Somogyi Phenomenon?
Early morning hyperglycemia (7am) secondary to late evening (2am) hypoglycemia
What causes 2AM hypoglycemia and what does this cause?
Long or intermediate acting insulin- This stimulates counter regulatory (glucagon) hormones to increase blood glucose
What needs to be done to compensate Somogyi phenomenon?
Decrease long acting insulin
What are 3 adverse effects of insulin?
Hypoglycemia, weight gain, lipodystrophy
What is the most potentially dangerous AE to metformin?
Lactic acidosis
What increases the risk of lactic acidosis due to metformin?
Renal dysfunction and age
What does metformin reduce the absorption of?
B12
What are 2 CI to metformin?
Renal failure and CHF
What are 2 AE to thiazolidinediones?
- Exacerbates CHF
2. Check transaminases…heptaic issues
What binds to sulfonylurea receptors and closes ATP-sensitive channels, but has a short half life?
Glinidines
What blocks the K channels making the cell look like there is an influx of glucose, resulting in the increased release of insulin?
Sulfonylureas
How do dipeptidyl peptisase inhibitor-4 work?
Increase incretins by inhibiting DPP-4
What is the effect of increasein incretins?
Increase glucose mediated insulin secretion and suppress glucagon secretion
What inactivates incretins?
DDP-4
What are 2 incretins?
GLP-1 and GIP
What should be done until adequate glycemic control is achieved and how long might this take?
Increase dose of oral agent or add 2nd agent…4-8 weeks
Who should insulin be added for?
Newly diagnosed type 2 diabetics with markedly symptomatic and/or elevated blood sugars
What can be added to oral antihyperglycemic agent regimen when needed?
Insulin
What is eventually needed for may patients with type 2 DM because it is a progressive disease?
Insulin therapy
What is the level of HA1C expected with adequate glycemic control?
Under 7%
What is the portion of proinsulin that is cut out in processing?
C-peptide
-So there is one C-peptide molecule for every pro-insulin
What is an indicator of endogenous proinsulin, and thus insulin production?
C-peptide
-Synthetic insulin doesn’t contain C-peptide
What are the diadvantages of metformin?
- GI side effects
- Risk of lactic acidosis
- Can NOT be used in patients with renal dysfunction
- Should be held in pts receiving IV contrast or undergoing surgical procedure until stable renal function is established.
What are the disadvantages of sulfonylureas?
- Potential for severe, prolonged hypoglycemia
2. Weight gain
What are the disadvantages of thiazolinediones?
- Weight gain and fluid retention
- Contraindicated in NYHC III or IV
- Increase fracture risk in women
- Some questions about cardiovascular events. There has been recent news concerning Avandia.
- Some question linking these to higher incidence of bladder cancer.
What are the disadvantages of alpha glucosidase inhibitors?
Increased deliverly of CHO to colon results in flatulence and diarrhea
What is released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion?
Incretin hormones
-glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1)
What are the effects most relevant to metabolic dysfucntion of incretin hormones?
- Stimulation of insulin
2. Suppression of glucagon (resultant reduction in fasting and post-prandial glucose
What is impaired in type 2 DM?
Incretin secretion and/or action
What is the enzyme responsible for the short half-life of endogenous incretins?
DDP-4 (dipeptidyl peptidase)
What can be done to help with issues with incretin secretion and action in type 2 DM?
Adminiter long-acting DDP-4 resistant peptides that bind to and activate the GLP-1 receptor
