Diabetes Pharamcology Flashcards
What glucose transport protein does insulin binding up regulate?
GLUT4 on peripheral cells
- induces facilitated diffusion of glucose into cells
How does polyphagia occur in diabetes mellitus?
Improper insulin release results in poor GLUT4 upregulation which makes the cells think they are starving and signals ghrelin release from hypothalamus as well as lipolysis
This leads to polyphagia with weight loss
What are the 2 potential mechanisms for pathogenesis in insulin resistance
1) ectopic accumulation of lipids in liver and muscle
2) obesity-induced inflammation
At what percentage of B-cell dysfunction is the usual cutoff for asymptomatic-> symptomatic Type 2 diabetes?
50% of normal B-cell function
- at this point symptoms start to develop
How long does glycated hemoglobin last in the body
8-12 weeks
- this is why this level is monitored for losing-term blood glucose control
- *a fasting blood glucose can manipulated, this cant**
- fasting blood glucose only shows glucose levels for the past 8 hrs
What are diagnostics test cut offs for diabetes and prediabetes
Pre-diabetic mellitus
- FBG = 100-125 mg/dL
- A1C = 5.7-6.4%
- OGTT post 2hrs draw = 140-199 mg/dL
Diabetes
- FBG = >126 mg/dL
- A1C = >6.5%
- OGTT post 2hrs draw = >200 mg/dL
What is the rough conversion of mean plasma glucose: A1C?
A 3.5-4 mg/dL or 0.2 mmol/L increase in plasma glucose = 0.1% increase in A1C
A 36 mg/dL or 2.0 mmol/L increase in plasma glucose = 1% increase in A1C
Different between mealtime insulin’s and basal insulin’s
Mealtime = rapid and short acting
Basal = intermediate and long acting
- used to counter the liver gluconeogenesis that occurs overnight in patients
What are the three rapid acting insulin’s
“LAG”
1) Lispro
2) Aspart
3) Glulisine
All takes 20 minutes to onset and peaks concentration in 1hr
All have the same duration of 3-4 hrs
All are used after meals and acute hyperglycemia
can also used inhaled versions over IM injections
Short acting insulin
Two types and are normal insulin
1) novolin R
2) humblin R
Onset = 30 min-1 hr
Peaks within 2-3 hrs
Duration is 3-6 hrs
Used after meals, in acute hyperglycemia or to manage ketoacidosis
Concentrated regular insulin (insulin U-500)
Only used in severe insulin resistance (type-2 DM)
- patient requires >200 units of insulin daily
Onset = 30 min-1 hr
Peak = 4-8 hrs
Duration = 13-24hrs
Intermediate acting insulin
Three types
1) NPH isophane
2) Novolin N
3) Humulin N
All have an onset of 2-4 hrs
All have a peak of 4-6 hrs
All have a duration of 8-12 hrs
All are used for basal insulin, overnight coverage
Lon-acting insulin’s
Include the following three
1) glargine
2) Detemir
3) Degludec
All three have onset of 1-2 hrs
All have no peak and have durations greater than 24hrs
don’t mix with other insulin doses
How is NPH formulated
Combination of insulin and protamine
- the protamine is degraded by proteolytic tissues permitting insulin absorption
- this one can be mixed with other insulin’s
How is glargine formulated
Combined 2 arginine molecules
- are soluble in acidic only solutions but precipitates in neutral body pH after injection
The pH must be stable at 4.0 so DONT mix with other insulin’s
How are insulin detemir and degludec formulated
Detemir
- replaces threonine at B30 position with myositis acid at B29 lysine position
- induces self aggregetion of insulin in high levels, so DONT mix with other insulin’s
Degludec
- replaces threonine at B30 position with hexadecnoic acid at B29
- when injected, the solution forms multihexameric chains and dissolves into insulin monomers slowly.
- Because of the multihexameric chains, DONT mix with other insulin’s
Vial concentrations vs pen concentrations
Vial = less expensive but more inconvenient since you need to dose your self
Pen = more expensive but comes in select doses already so more convenient
both require you to throw it out in 30 days (they expire)
What are the insulin’s that are often mixed together?
Almost always it sNPH mixed with one foot he short acting (lisopril, aspart, glulisine)
ADRs of insulin
1 is hypoglycemic events
- inital stage = sweating/hunger/tremor and anxiety
- 2nd stage = confusion/weakness/drowsiness/warmth/dizziness/blurred vision
Others
- weight gain
- lipodystrophy (increased risk if you continue to inject at the same injection site)
- anti-insulin antibodies
- hypokalemia
What is the interaction between exogenous insulin and potassium levels
Exogenous insulin = promotes K+/Na+ channel and K+/ATPase action in muscles and fat cells
- this presents as mild hypokalemia if not replenished
What are additional ADRs for inhaled insulin
Coughing, throat pain and irritation
also has black box warning for:
- acute bronchospasms with asthma and COPD
DONT give to any patients with any chronic lung disease
Before initiating therapy, must perform spirometry and screen for lung diseases in patient
Why can bromocriptine and other dopamine receptor agonists be used as an adjuvant therapy for type 2 diabetes
When dopamine is low
- hepatic glucose goes up
- insulin resistance goes up
- FFA’s go up
- triglycerides go up
so if you use agonists, it will take all of the above
What is first line in type 2 diabetes always?
Lifestyle modifications and metforamin
You begin changes from this if the patient begins to be high risk of develops CKD/HF or if the A1C remains high
