Flashcards in Diabetes Treatments - PHARM Deck (44)
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1
In which patients are insulin treatments ESSENTIAL?
Type I diabetes. These patients no longer have insulin and therefore you must treat them with insulin (making up for what they lack)
*they are indicated for late and progressive type ii diabetes that is not able to be controlled with non-insulin treatments and lifestyle changes
2
What are the bolus insulins used for prandial therapy?
• Humalog
○ Lispro
• Novolog
○ Aspart
• Glulisine
○ Aprida
• Inhaled insulin (Afrezza)
*these agents can be effectively used in insulin pumps
3
What is the time to onset of the bolus insulins? What is their clearance time?
These are rapid acting and should be used for prandial therapy
* Lispro, Aspart, Glulisine (Girls and Lads from sketchy)
*they lead to a 15minute or so onset of insulin action
*their peak action is about 1 hour
*their activity lasts 3-5 hours in total
*these agents can be effectivly used in insulin pumps
4
What are the short acting human insulins?
• Straight up regular insulin
• Humulin R
• Novolin R
○ Recombinant human insulin
5
When do you use intravenous insulin infusions?
• Think regular, recombinant insulin here
• DKA
• Hyperosmolar hyperglycemic state
• Inpatient hyperglycemia in which glycemic control is desired, like peri-operatively and ICU patients
• IV insulin has immediate effect and rapid off-set (15 min or so)
• Thus no benefit to using a rapid acting IV agent
6
What is the usual dose of regular, recombinant insulin in hospital setting therapy?
• Hospital setting b/c regular insulin not often used in outpatient setting because of the difference in physiological timing
• 5-15 units is the usual dose
• This leads to clearance after 6-8 hours
7
What are the pharmacokinetic profiles of the short acting human insulins?
• Regular insulin (recombinant insulin)
• Not often used in outpatient b/c kinetics do not match well with physiologic needs
• 30 min before meals
• 30-60 minute onset with 2 hr peek
• Duration is 6-8 hours if used in normal doses
• 5-15 units are the normal dose
8
What are the "basal" insulins?
• These are the long acting ones that mimic the basal action of insulin in the body
• These are not prandial, but provide the insulin necessary to handle normal glucose fluctuations throughout the day
○ Remember thought that WELL CONTROLLED diabetes HbA1C is still 7%
• Glargine (Lantus)
• Detemir (Levemir)
• Degludec (Tresiba)
• Glargine U-300 (toujeo)
9
What makes the long acting insulins "long acting"
• They are formulated in a way that allows for less rapid dissolving and incorporation into the plasma
• Glargine has extra arginines that makes it precipitate in the subcutaneous neutral pH
○ Onset is 1.5 hr and 24 hour duration, taken once a day
• Detemir has an additional fatty acid chain which allows it to be more liphophilic and bind serum protein better, increasing duration of action to 12-20 hrs. usually taken 2X a day
• Degludec is the newest and has 42 hours of duration and is injected once daily
10
As far as drug mixing goes (insulin) what about NPH insulin vs. glargine?
• Glargine can't be mixed with other insulins because it's stored in an acidic manner
• NPH insulin and regular insulin CAN be mixed up in the same delivery stystem
11
What are the pharmacokinetics of NPH and Humulin insulin?
• NPH = neutral protamine Hagedorn
• The brand names are Humulin N, Novolin N
• Another word to look for is sophane
• Cloudy solution
• 1-3 hour onset with 6-8 hour peek
• Lasts 12-16 hours and is mostly used for the lunch-time peak in glucose
12
What is meant by "pre-mixed insulins"?
• Human: %NPH/%regular
○ Usually 70/30 or 50/50
• Humalog/regular is an option for the analogs
○ Humalog 75/25
§ Or 50/50
○ Novolog 70/30
• Allows for short term benefit for meals with longer action basal coverage
• Analog mixed - Injected 5-15 minutes before meal and have pharmacokinetics that are more physiologic than NPH/regular b/c of basal and spike mix
13
What is meant by basal bolus therapy?
• This includes the basal, prandial and correctional insulin needs
• You are mimicking with injection the normal insulin release of the body
14
Glargine, Detemir and NPH are used for what purpose?
• These are basal insulin medications
• Used for a patient to cover normal daily cyclical glucose spikes or hormone swings
• Suppresses hepatic glucose output and lowers overall glucose levels throughout the day
• Type 1 patients will develop DKA if they do not inject their basal insulin doses while type 2 patients will develop severe hyperglycemia but usually have enough endogenous insulin secretion to prevent ketoacidosis
15
If you wanted to start a patient on insulin therapy what is the estimate you can use to figure out the starting dose?
• 0.2 units/kg/day is the weight based method
• Titrated according to individual needs and circumstances
• Type 2, which has some insulin resistance in it, think more along the 0.5 units/kg/day for basal insulin
16
Describe the treatment paradigm of prandial insulin
• Used to metabolize nutrients in a meal or snack and cover the postprandrial rise in glucose
• The rapid-acting insulins are used for this
○ Humalog, novolog, apidra
○ Girls and Lads - Glulisine, Aspart and Lispro
• You can estimate the dose according to the carbohydrate to insulin ratio (C:I)
• Number of grams of carbohydrates that 1 unit of insulin is anticipated to cover for that individual
○ Insulin sensitive individuals may require a C:I ratio of 15:1 or 20:1
○ Resistant is more 10:1 or 8:1
17
How do you go about determining the dose of insulin for CORRECTION?
• Correctional doses of insulin are used to correct a high blood glucose level
• Humalog, novolg, apidra and inhaled insulin all used
• Usually added to a prandial insulin dose
• You determine the correction factor or sensitivity factor by dividing a constant, 1600, by their total daily dose of insulin
• The resulting number is the number of mg/dL that the blood glucose is expected to drop with each unit of insulin given as a correction dose
• Normal sensitivity might have a correction factor of 50
○ 1 unit of rapid acting insulin would be expected to drop the glucose by 50mg/dL
• Resistence might look like a correction factor of 20
○ 1 unit will drop glucose 20mg/dL
• USE TARGET GLUCOSE OF 100mg/dL
18
Describe the general, overall treatment paradigm of type 1 diabetes patients
• standard care is intensive multiple-dose insulin or basal bolus therapy
• This provides more physiologic replacement of insulin
• Allows for flexibility in timing, size and composition of meals
• Pre-meal doses can be fixed according to carbohydrate content of a given meal
• Must take into account lifestyle, motivation and preferences as well as cost
• Glargine injected once daily provides basal coverage for about 24 hours (detemir is 2X daily))
• Bolus dose is added to this before meal and additional correctional doses can be added as well according to correction factor
• Also think of the glucose pumps and the artificial pancreas
19
Describe the overall and general treatment paradigm for type 2 diabetes
• Essentially use insulin in patients who have not achieved good control before
• With data from home glucose monitoring, doses of rapid-acting insulin are added successively until glycemic control is achieved
• In this case though, consider the use of all non-insulins before starting insulin therapy
• Usually add insulin after 2-3 non-insulins are tried and are not effective in controlling the glucose target/goal
• In cases of severe insulin deficiency you should use insulin right away
• Fasting over 250, random over 300 and A1c over 10%
• Use insulin at first and see if you can titrate down or off
• Also use insulins in hyperglycemic hyperosmolar state or DKA
• Discharge with insulin and maybe taper with outpatient follow up
20
What are the different targets for treatment of diabetes?
• ADA recommends:
○ Less than 7% A1c
○ Fasting glucose - 70-130mg/dL
○ 2 hr post-meal glucose is less than 180mg/dL
21
What are the lifestyle recommendations made in the treatment of diabetes?
• Less calorie-dense foods
• More complex carbohydrates (as opposed to simple like high fructose corn syrup?)
• Higher fiber, lean proteins, smaller portions
• Increase physical activity
• Weight loss to normal range
22
What is metformin?
• Biguanide drug
• Potentiates the suppressive effect of insulin on hepatic glucose production
• Does not stimulate insulin secretion or increase circulating insulin levels
• Risk of lactic acidosis lower than a different drug in this class which is pulled off the market
○ But the risk still exists
• Use eGFR to guide use, since renal failure may precipitate lactic acidosis
23
What are the pros and cons to metformin use?
• Pros
○ Mechanism of action is more or less safe
○ No hypoglycemia
○ Inexpensive
○ No weight gain (slight weight loss)
○ Combinations are possible
§ Sulfonylureas
§ Thiazolidinediones
§ DPP-4 inhibitor
§ SGLT-2 inhibitor
• Cons
○ GI side effects - nausea, bloating, diarrhea
○ Risk of lactic acidosis - contrast media, CHF, renal insufficiency, liver disease
24
If metformin is not enough in your type 2 diabetes patient, and they have CV comorbidities, now what do you recommend?
• Add SGLT-2 or GLP-1RA to the regimen
25
You have a 51 year old woman with a 9yr histor of T2DM, A1c of 8.4% and is only on metformin right now. What additional therapies can be recommended at this point
• Again, have the lifestyle change conversation (always)
• Drugs (essentially just add another one)
○ Sulfonylurea
○ Thiazolidinedione
○ Basal insulin
○ GLP-1 receptor agonist
○ DPP-4 inhibitor
○ SGLT-2 inhibitor
26
What are the drug-specific considerations for thinking through additive glucose-lowering therapies?
• Mechanism of action
• Glucose-lowering effectiveness
• Side effects
• Cost
• Convenience
• Pharmacokinetics
• Non-glycemic beneficial effects
27
What are the patient-specific considerations for thinking through additive glucose-lowering therapies?
• Baseline control
• Stage of diabetes
• Co-existing medical conditions
• Tolerability of side effects
• Social situation
• Financial situation
• Preference of therapy
28
If a DM patient has primarily a problem with insulin resistance, what are the drugs of choice?
• Metformin
• GLP-1RA
• DPP-4i
• TZD
• Insulin
29
How many times per year should A1c be measured in a diabetic patient?
• 2-4 times per year in ALL diabetic patients
• At that point you re-hash goals and talk about risk/benefit
30
How much of a reduction in A1c can the standard T2DM non-insulin drugs be expected to give you?
• Metformin - 1-2% reduction
• Every other drug but insulin will give you a 0.5% reduction
• The other exception is sulfonylureas, which can be expected to give you about the same reduction as does metformin
31
What are the Incretins?
• GLP-1 = glucagon-like peptide 1
○ Very effective for lowering glucose in diabetes
• GIP = gastric inhibitory peptide
○ Secreted by cells in GI tract in response to food intake
○ Augments insulin secretion only if blood glucose is elevated
32
What are incretins supposed to treat?
• The incretin effect
• This is the fact that there is insufficient insulin secretion AND insufficient glucagon supression in response to a meal in type 2 diabetes
33
What are all the ways that GLP-1 lowers glucose?
• Food intake will stimulate GLP-1 secretion from L cells of ileum
• This stimulates glucose-dependent insulin secretion and SUPRESSES postprandial glucagon secretion
• This leads to decreased hepatic glucose output, slowed gastric emptying and inhibited food uptake
• The end result is a normalized blood glucose
34
What is DPP-4 and why must it be inhibited?
• DPP-4 is what breaks down GLP-1
• DPP-4 = dipeptidyl peptidase 4
• Inhibit it to allow GLP-1 agonists to do their work of inhibiting glucagon secretion
35
What are the GLP-1 agonists you should know about?
• Exenatide
○ byetta
• Liraglutide
○ victoza
• Exenatide qwk
○ bydureon
• Albiglutide
○ tanzeum
• Dulaglutide
○ Trulicity
36
What are the pros and cons of GLP-1 agonists?
• Pros
○ Multiple mechanisms of action to lower postprandial glucose
○ Effects are glucose-dependent
○ Weight loss
○ Recent trial suggests CV benefit
• Cons
○ SC injections
○ Side effects
○ expensive
37
What are the DPP-4 inhibitors to know about?
• Sitagliptin
• Saxagliptin
• Linagliptin
• Alogliptin
○ Just remember the clips on the old hag's nose in the sketchy picture
38
What are the pros and cons to the use of DPP-4 inhibitors?
• Pros
○ Multiple mechanisms of action to lower postprandial glucose
○ Oral admin
○ Once daily admin
○ Weight neutral drugs
○ Combination pill with metformin
• Cons
○ Less potent glucose-lowering effect
○ Expensive
○ Side effects
39
What are the SGLT-2 inhibitors to know about?
• Sodium glucose co-transporter 2 is what is being inhibited - in proximal tubule
• Canagliflozin
○ invokana
• Dapagliflozin
○ farxiga
• Empagliflozin
○ Jardiance
40
What level of glucose can the normal kidney handle?
• Filtered glucose load of about 180 g/day
• Urinary glucose less than 0.5g/day
• Glucose reabsorption occurs in the proximal tubule though the action of SGLT1 and 2
41
What are the pros and cons of SGLT2 inhibitors?
• Pros
○ Novel mechanism for controlling glucose
○ Weight loss
○ Pill
○ At least 1 available as a combo pill with metformin
○ Recent trial suggesting CV benefit
• Cons
○ Increased risk for urinary tract and GU infections
○ Increased risk for low potassium
○ Expensive
○ Questionable long-term safety because they are new and not all that well studied far out
42
What is the mechanism of action for sulfonylureas?
• Close the ATP-sensitive K+ channels in the beta cell
• Closing of the potassium channels will depolarize the beta cell and lead to influx of calcium and secretion of insulin granules
43
What are the sulfonylureas to know?
• Glyburide
• Glipizide
• glimepiride
44
