Antidiabetic Med Classes- FINAL Flashcards
Insulin
-Polypeptide hormone secreted by B cells
-MOA:
-Triggered by glucose levels
-Exogenous in Type 1 to REPLACE absent insulin
-Exogenous in Type 2 to SUPPLEMENT insulin secretion
-Pharm: made by recombinant DNA
technology using strains of E. coli or yeast that are genetically altered
-Broken down in the GI tract, so it cannot be taken orally
-ADE: Low blood sugar
Weight gain
-Local injection site reactions (lipodystrophy)
-Bronchospasm can occur with
inhaled insulin
Bolus Insulin Therapy
-A meal bolus is determined by: the amount of CHO to be ingested; this amount is divided by the insulin-to-CHO ratio [the number of grams of CHO that 1 unit of insulin covers]
-1 Unit covers approx 15 carbs
-Correction bolus is used: to quickly reduce BS back to normal; the dose is determined by the sensitivity factor
[the amount the BS will decrease with 1 unit of insulin]
-1 Unit covers approx 20mg/dl of blood sugar
-Sensitivity factor= is calculated by dividing 2000 by the total daily dose of insulin
Basal Insulin Therapy
-This is the steady background insulin that controls BS in the fasting state [overnight and in between meals]
-Enables stored fat and glucose to be released in appropriate amounts to sustain metabolism during time when fuel is not being consumed and metabolized
-Can be added to orals for better BS control
Considerations for insulins
(Functions)
-Secreted at a constant basal rate with intermittent bursts in response to stimuli
-Lowers blood sugar by enhancing transport of glucose into tissues
-Increases [NO] production in blood vessels
-Acts as a vasodilator; inhibits platelet aggregation
-In a person with normal insulin sensitivity, insulin plays a protective role against atherosclerosis
Rapid and Short-Acting Insulins
-Are given to mimic mealtime release
of insulin and control postprandial glucose
-Usually used in conjunction with longer-acting basal insulin that
provides control of fasting BS
- Rapid acting should be injected 15 mins before meal (30 for regular insulin)
-Onset: 5-15 mins
-Peak levels: 60 mins approx
-Rapid duration: Approx 2 hours
-Ex: regular, inhaled insulin= SHORT lispro, aspart, glulisine= RAPID
NOTE– with REGULAR insulin, onset is 30 mins, peaks in 2 hours, but hangs around for 5-6 which is why we’re using it a lot more now in tube fed patients
Side note for INHALED insulin (Abrezza)
-Most be older than 18
-Can use for type I or II
-eliminated more rapidly
-Provides higher insulin levels with peak effects in about 2 hours
-Dosed beginning with largest meal
-Can affect lung function contraindicated in COPD [risk of
acute bronchospasm]
-Patient must have baseline PFTs, then repeated every 6- 12 months
-Should not be used in smokers or in those with severe
asthma
What are the goals of treatment for diabetes mellitus (DM)?
Maintain blood glucose within normal limits, prevent long-term complications, reduce insulin resistance through lifestyle modifications, and use pharmacologic interventions as needed.
What is the action of insulin on the liver?
Insulin inhibits gluconeogenesis, promotes glycogen storage, and decreases hepatic glucose production.
What is the action of insulin on muscle tissue?
Insulin stimulates glucose uptake, promotes glycogen storage, and enhances protein synthesis.
What is the action of insulin on adipose tissue?
Insulin facilitates glucose uptake, promotes lipid synthesis, and inhibits lipolysis.
What are the phases of insulin release in the body?
1) Fed State (Phase 1): Immediate insulin burst post-meal. 2) Postabsorptive State (Phase 2): Blood glucose from glycogen breakdown. 3) Early Starvation (Phase 3): Blood glucose from gluconeogenesis. 4) Preliminary Prolonged Starvation (Phase 4): Liver/kidney gluconeogenesis. 5) Secondary Prolonged Starvation (Phase 5): Reduced glucose use and gluconeogenesis.
What is the role of Amylin in the body?
Amylin delays gastric emptying, decreases postprandial glucagon secretion, and enhances satiety.
What is the difference between basal and prandial (bolus) insulin?
Basal insulin provides steady background insulin levels for fasting states, while prandial (bolus) insulin is used to manage post-meal glucose spikes.
What are the types of insulin based on their action?
1) Rapid-acting (onset: 5-15 min, peak: 1-3 hrs, duration: 2-4 hrs).
2) Short-acting (onset: 30-60 min, peak: 2-4 hrs, duration: 6-12 hrs).
3) Intermediate-acting (onset: 2-4 hrs, peak: 6-10 hrs, duration: 10-16 hrs).
4) Long-acting (onset: 2 hrs, no peak, duration: 20-24 hrs).
Which types of insulin target fasting blood sugar (FBS) vs. postprandial blood sugar (PPBS)?
Basal insulins (intermediate, long-acting) target FBS. Lantus/glargine
Prandial insulins (rapid, short-acting) target PPBS.
Which insulins may be given IV?
Short-acting and rapid-acting insulins (Regular insulin, Insulin Aspart, Insulin Lispro, and Insulin Glulisine).
What laboratory monitoring is important for diabetic patients?
Hemoglobin A1C (every 3 months), fasting blood glucose, postprandial glucose, kidney function (creatinine, albuminuria), lipid profile, and blood pressure monitoring.
Which insulins can be used in pregnancy?
Regular insulin, NPH, Insulin Lispro, Insulin Aspart, Insulin Detemir, Insulin Glargine.
How do you adjust insulin dosage when switching between types? How do you convert intermediate insulin to base insulin?
Switching from rapid to basal insulin requires dose calculation based on total daily insulin needs. Switching from intermediate to basal insulin requires a 20% dose reduction for starting dose.
What are common complications and side effects of insulin use?
Hypoglycemia, weight gain, injection site reactions, lipodystrophy, and risk of bronchospasm with inhaled insulin.
How do Biguanides (Metformin) work?
Decreases hepatic glucose production, increases insulin sensitivity, and decreases intestinal glucose absorption.
What are the advantages and disadvantages of Biguanides?
Advantages: No hypoglycemia, weight neutral, cardiovascular benefits. Disadvantages: GI disturbances, risk of lactic acidosis, contraindicated in renal impairment.
What is the mechanism of action of Sulfonylureas and Glinides?
Stimulate insulin release from pancreatic beta cells by closing ATP-sensitive potassium channels.
Sulfonylureas Glipizide
Glinides repaglinide
What are the advantages and disadvantages of Sulfonylureas?
Advantages: Effective in reducing blood glucose. Disadvantages: Risk of hypoglycemia, weight gain, and loss of efficacy over time.
What are the indications for IV insulin use?
DKA, HHS, perioperative glycemic management, and severe hyperglycemia in hospitalized patients.
Metformin
MOA, A1C reduction, targets fasting or postprandial? Can be used in children? Pregnancy?
MOA: Decreases hepatic glucose production, increases insulin sensitivity
A1C: 1-1.5%
Fasting.
Children: Yes > 10
Pregnancy Yes (B)
Metformin
Advantages, disadvantages, side effects and drug interactions
Adv: Weight neutral, CV benefits, no hypoglycemia.
Disadv: GI side effects, lactic acidosis risk.
Side effects: diarrhea, nausea, B12 deficiency, lactic acidosis (rare).
Interactions: Contrast, alcohol, cimetidine
Sulfonylureas/Meglitinides
MOA, A1C reduction, targets fasting or postprandial? Can be used in children or pregnancy?
MOA: Stimulates pancreatic beta cells to release insulin. A1C: 1-2%. Suldonylreas both fasting and post prandial, Meglitinides: post prandial Children: Limitied to Glyburide. Pregnancy: limited to glyburide (not first line)
Sulfonylureas/Meglitinides (Glinides)
Advantages, disadvantages, side effects and drug interactions
Adv: rapid action, effective early on.
Disadv: hypoglycemia, weight gain, loss of efficacy over time.
Interactions: Betablockers, ETOH, CYP2C9 inhibitors
Thiazolidinediones
MOA, A1C reduction, targets fasting or post prandial can be used in children? Pregnancy?
MOA: increases insulin sensitivity.
Fasting.
A1C 1-1.5%.
Children: No
Pregnancy: No
Thiazolidinediones
Advantages, disadvantages, side effects, and drug interactions
Adv: no hypoglycemia
Disadv: weight gain, edema, CHF risk, fractures.
ADE: bladder cancer (with pioglitazone).
Interactions: CYP2C8, Insulin
Alpha-Glucosidase Inhibitors
MOA, A1C, targets fasting or post prandial. Children? Pregnancy?
MOA: inhibits intestinal alpha-glucosidase, delays carb digestion.
Postprandial.
A1C: 0.5-0.5%.
Children: No.
Pregnancy: No.
Acarbose
Alpha-Glucosidase Inhibitors
Advantages, disadvantages, side effects and drug interactions
Adv: no systemic effects, weight neutral.
Disadv: GI issues, frequent dosing.
Side effects: flatulence, bloating, diarrhea.
Interactions: Affects absorption of other drugs
DDP-4 Inhibitors
MOA, A1C, targets fasting or postprandial, Children? Pregnancy?
Inhibiting DDP-4 anzyme increases incretin hormones.
Post prandial.
A1C: 0.5-1%.
Children: No.
Pregnancy: No
Gliptin: sitagliptin
DDP-4 Inhibitors Advantages, disadvantages, side effects, drug interactions
Adv: Weight neutral, low hypoglycemia risk.
Disadv: Pancreatitis risk, only modest A1C reduction.
Side Effects: N/V/D, pancreatitis, thyroid cancer??
Interactions: delays gastric emptying affecting oral drug absorption
Increase GLP1& GIP = sitagliptin
GLP-1 Agonists
MOA, A1C, targets fasting or postprandial, Children? Pregnancy?
Mimics GLP-1, enhances insulin, decreases glucagon and appetite.
Both fasting and postprandial.
A1C: 1-2%.
Children: Liraglutide in >10 only.
Pregnancy: No
GLP-1 Agonists
Advantages, disadvantages, side effects, drug interactions
Adv: weight loss, decreased CV risk, low hypoglycemia risk.
Disadv: injection, N/V/D.
Side effects: N/V/D, pancreatitis, thyroid cancer risk.
Interactions: Delays gastric emptying affecting absorption of other drugs
Amylin Mimetics
MOA, A1C, targets fasting or postprandial, Children? Pregnancy?
MOA: slows gastric emptying, reduces glucagon.
Postprandial.
A1C: 0.5-1%.
Children: No.
Pregnancy: No
Amylin Mimetics
Advantages, disadvantages, side effects, drug interactions
Adv: Weight loss, adjunct to insulin.
Disadv: Injection, hypoglycemia risk with insulin.
Side effects: N/V, hypoglycemia.
Interactions: delays oral drug absorption, enhances insulin effects
SGLT2 Inhibitors
MOA, A1C, targets fasting or postprandial, Children? Pregnancy?
MOA: inhibits renal SGLT2 increasing urinary excretion of glucose.
Fasting.
A1C: 0.5-1%.
Children: Yes >10.
Pregnancy: No
SGLT2 Inhibitors
Advantages, disadvantages, side effects, drug interactions
Adv: weight loss, CV and renal benefits, low hypoglycemia risk.
Disadv/side effects: UTIs, dehydration, ketoacidosis, amputations?!
Interactions: Diuretics, RAAS inhibitors (hyperkalemia)
What is the role of bromocriptine (Cycloset) and colesvelam (Welchol) in diabetes management?
Neither are first line agents. They are used with patients need additional A1C lowering but can’t tolerate other medications. They are usually adjuncts to metformin whe other options are contraindicated. Bromocriptine is helpful for patients with diabetes and CV disease, while colesevelam is helpful for patients with diabetes and dyslipidemia.
What are some complications of insulin use that could decrease patient compliance?
Injection site reactions, allergies, complexity of regimens, fear of needles, social stigma, weight gain, hypoglycemia.
Why is Urine albumin to creatinine ratio important to monitor in DM patients?
Screens for diabetic nephropathy. Should be done annually. Indicates the need for ACE inhibitors or ARB.
Why are LFTs important to monitor in DM patients?
Screens for fatty liver disease or medication toxicity. Should be done annually. Adjust TZDs or statins as needed.
Why is TSH important to monitor in DM patients?
Detects thyroid disfuction that is common in DM. Hypothyroidism can affect blood glucose control. Should be done annually.
Why is C-peptide & Autoantibody (GAD, IA-2, ZnT8) checked in a DM patient?
Differentiates type 1 from type 2 DM. Only needed at the time of diagnosis. Helps determine if the patient is insulin dependent.
Intermediate acting insulin
-Only one formulation available in US (NPH–Novolin N or Humulin N)
-Is usually given with rapid or short acting insulin to cover mealtime—it can only be given SQ
-Should never be used when rapid BS lowering in needed
-Onset of action—2 hours; peaks in 5-6 hours, duration of action 12 hours (has a wide variation in effective action time—hypoglycemia risk)
-CLOUDY (and CAN be mixed with short acting)
Examples of Biguanides
Metformin (first line type 2)
Example of Sulfonylureas & Glinides
Sulfonylureas: Glipizide
Glinides: Repaglinide
Example of Thiazolidinediones (TZDs)
Pioglitazone
Example of Alpha glucosidase inhibitors
Acarbose
Example of DDP4 Inhibitors/Gliptins
Sitagliptin
Example of GLP-1 AGONISTS
Exenatide, liraglutide, semaglutide
Example of GLP-1/GIP agonist
Tirzepatide
Example of Amylin Mimetics
Pramlintide
Example of SGLT2 Inhibitors
Empaglifozin
Long acting insulins
-Lantus=PROTOTYPE
-Are used for basal control and
should only be given SQ—they should not be mixed with any other insulin
-Releases insulin over an extended time— slower onset and a flat prolonged blood sugar lowering effect with NO peak
-Onset of action in 2-3 hours; duration of action near 24 hours
-To initiate:
Adding to oral agents—start 10 units
evening dose—14 hours before first
meal of the day
-↑Glargine until fasting glucose target
of 100 mg/dL reached; then stop—that is the maximum dose
-Ex. Glargine, Detemir, Degludec
Mixed Insulins
-Targets both basal & postprandial glucose levels
-Cloudy suspension
-Pro: Limits number of injections
-Con: More difficult to adjust components as needed
Standard vs. Intensive Insulin Treatment
-Standard; injections twice per day
-Intensive: 3 or more injections per day (not recommended for those with long standing DM, microvascular issues, old age, hypoglycemia unawareness)
-Intensive therapy much more likely to achieve ADA goals of A1C of < 7% with target BS < 154
Insulin Prescribing guidelines
-Ketotic, infected, stressed—larger doses needed
-Decreased renal function requires less insulin
-Starting dose—0.6U/kg/day for adults [0.25-0.5 U/kg/day for
children]
-Teenagers may need more—1-1.5 u/kg/day
-Each insulin pen delivers 300 units
-ALWAYS order in Units
NOTE* MOST all insulins are pregnancy safe*
