Antidiabetic Drugs

Which of the following are Rapid Acting Insilin?

Insulin lispro (Humalog®)

Glulisine (Apidra®)

Aspart (Novolog®)

None

Which of the following is a Regular Acting Insulin?

Regular insulin (Humulin R®/Novolin R®)

None

Which of the following are an Intermediate Acting Insuling?

Neutral Protamine Hagedorn (NPH) insulin (Humulin N®)

None

Which of the following is a Long Acting Insulin?

Insulin glargine (Lantus®)

Insulin detemir (Levemir®)

None

Which of the following is an Antidiabetic Oral Drug?

Biguanides "metformin"

Sulfonylureas 2nd generations- "Glipizide"

Glinides (metglitinides) "Repaglinide"

TZD’s (Thiazolidinediones) "Pioglitazone"

Alpha-glucosidase inhibitors "Acarbose"

DPP-IV inhibitors (Dipeptidyl peptidase-4), Gliptins "Sitagliptin"

Sodium-Glucose Co-Transport 2 (SGLT-2) Inhibitor "Canagliflozin"

Which of the following is an Antidiabetic Non-Insulin Injectables drug?

Glucaon Like Peptide-1 (GLP-1) Receptor Agonist/ Incretin Mimetic "exenatide (Byetta®), liraglutide (Victoza®)"

Amylin Mimetic "pramlintide (Symlin®")

Miscellaneous "Glucagon"

None

Which of the following is true about Diabetes?

Diabetes is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

Insulin necessary for normal metabolism of protein, carbohydrates and fat

All Types of Diabetes are associated with insulin deficiency

Which of the following is true about "Insulin-Anabolic"

Promotes glycogen synthesis and storage Stimulates cellular uptake (transport ) of glucose, amino acids, nucleotides and potassium

Liver Glycogenesis- Glucose converted to glycogen

Skeletal Muscle Glycogenesis- Glucose converted to glycogen Amino Acids converted to proteins

Adipose Tissue lipogenesis- Storage of fatty acids in to triglycerides

None

Which of the following is true about Insuline-Catabolic"

Liver Glycogenolysis- Glycogen breaks down Gluconeogenesis- proteins converted to amino acids

Skeletal Muscle Glycogenolysis- Glycogen breaks down Protein breakdown

Adipose Tissue Lipolysis/Ketogenesis- Triglycerides break down to glycerol and free fatty acids/ketones (ketoacidosis)

None

Which of the following is true about Insulin, glucagon, and glucose homeostasis?

. Fasting State–In healthy humans plasma glucose is maintained in a range from 4.4-5 mM, and fatty acids near 400 μM. In the absence of nutrient absorption from the GI tract, glucose is supplied primarily from the liver and fatty acids from adipose tissue. With fasting, plasma insulin levels are low, and plasma glucagon is elevated, contributing to increased hepatic glycogenolysis and gluconeogenesis; low insulin also releases adipocytes from inhibition, permitting increased lipogenesis. Most tissues oxidize primarily fatty acids during fasting, sparing glucose for use by the CNS.

. Prandial State–During feeding, nutrient absorption causes an increases in plasma glucose, resulting in release of incretins from the gut and neural stimuli that promote insulin secretion. Under the control of insulin, the liver, sekletal muscle and adipose tissue actively take up glucose. Hepatic glucose production and lipolysis are inhibited, and total body glucose oxidation increases. The brain senses plasma glucose concentrations and provides regulatory inputs contributing to fuel homeostasis. The boldness of the arrows reflects relative intensity of action; a dashed line indicates little or no activity.

None

Are All insulins HIGH RISK MEDICATION/Serious potential for fatal harm?

False

True

Which of the following is true about insulin lispro (Humalog®)- SC?

Which of the following is true about regular insulin (Humulin R®/Novolin R®)-SC, IV!!?

Which of the following is true about Neutral Protamine Hagedorn (NPH) insulin (Humulin N®/Novolin N®)- SC?

Hypoglycemia is an adverse effect

The addition of the protein protamine as well as a higher zinc concentration allow for a delayed onset of action and increased duration of action

None

Which of the following is Insulin Mixtures/Fixed combinations?

Which insulins will be in Humulin 70/30 vs Humalog 75/25?

Humulin 70/30- NPH + Regular

None

If you have Humalog 75/25, which insulin is the 75, which is the 25?

Humalog 75/25- NPH + Rapid

None

Insulin glargine (Lantus®)- SC is

Long Acting Insulin "Basal"

Glargine was modified to have a higher iso-electric point vs human insulin- forms precipitant detemir's B chain was modified to allow for binding to albumin, a depot like effect

Some argue that detemir is intermediate

Glargine has an iso-electric point (pI) of 6.7, compared to 5.4 of normal insulin. The normal physiologic pH is 7.4. Bringing the iso-electric point closer to our normal physiologic pH causes the glargine to cause a "reservoir" of tiny microprecipitants upon injection that slowly release over 24 hours

All insulin Adverse Effects

Hypoglycemia

Lipo-hypertrophy-rotate sites!

Hypokalemia- activates Na+/K+ATPase Typically a transient state, advantage for patients with hyperkalemia

Normal adverse effects of insulin Weight gain

None

All insulins have

Onsets

Peaks

durations

None

Adverse Effects of insulin

Transient hypokalemia "shift"

Hypoglycemia!!!!

Lipohypertrophy

None

Which id true about Dawn Phenomenon vs Somogyi Effect

Dawn Phenomenon- BG elevates in the morning when you wake up

Somogyi Effect- BG elevates in the morning when you wake up

Metformin(met FOR min) (Glucophage®)- PO, the GOLD STANDARD

)inhibits glucose production in the liver 2)sensitizes insulin receptors in skeletal muscle (and fat) 3) minimally reduces glucose absorption in the gut 4) has minimal reduction in lipids (LDL/TGs)

Adverse effects lactic acidosis- fatal! Gi upset- take w/food

Renal elimination- caution!

None

Metformin

1st line therapy/ drug of choice for DM2 and pre-diabetic patients "The Gold Standard"

The UK Prospective Diabetes Study (UKPDS) demonstrated a substantial beneficial effect of metformin therapy on cardiovascular disease (CVD) outcomes, with a 36% relative risk reduction in all cause mortality and a 39% relative risk reduction in myocardial infarction

Gestational Diabetes

Polycystic Ovary Syndrome (PCOS)

Metformin adverse effect

Commonly associated with GI issues- N/D Counter-act by taking with meals Can also slowly titrate up to max dose (2550mg/day) 5% patients stop therapy due to this

BOXED WARNING: Lactic Acidosis- can accumulate in renal impairment, rare...but can be deadly!

Weight Neutral! NO HYPOGLYCEMIA

Dermatologic- Rash, Photosensitivity

Decreased B12 and folic acid absorption

Metformin-DRUG-DRUG INTERACTIONS

Alcohol- both drugs prevent break down of lactic acid IV radiocontrast - avoid metformin 48 hours after

None

Metformin-Contraindications:

Heart Failure renal impairment New research has CrCl/GFR restrictions

Monitor: LFTs, SCr HgbA1C, BG

Lactic Acidosis

2nd generation –glipizide (GLIP I zide) (Glucotrol®)- PO

Sulfonylureas (1st oral diabetes class)

In pancreatic ß cells they inhibit potassium-ATP channels (retain K+)-> depolarizes cell-> Ca2+ influx-> stimulate insulin release

Adverse effects hypoglycemia- take w/food!!!

Hepatic metabolism renal excretion

Sulfonylureas

USED TO TREAT Only for DM2 Take with Food!

ADVERSE EFFECTS hypoglycemia- Take with Food! Weight gain (5-10 lbs) GI- N/V

PREGNANCY/LACTATION teratogenic in animals can cause hypoglycemia in infants manufacturer recommends to stop 1 month prior to due date

None

DRUG-DRUG INTERACTIONS Alcohol- disulfiram like reaction Hypoglycemic Drugs ß- blockers- mask s/s of hypo

All of the answers are correct

Repaglinide (re PAG li nide) (Prandin®)- PO

Meglitinides

Same MOA as sulfonylureas, stimulate insulin release from pancreatic ß cells, but faster acting and shorter duration

Rapid acting short half life ( 1 hour)

Meglitinides

USED TO TREAT Only for DM2

ADVERSE EFFECTS hypoglycemia- Take with Food! Miss a meal, miss a dose, weight gain Upper respiratory infections/ Flu like symptoms (11%)

Pioglitazone (PYE o GLIT a zone) (Actos®)- PO

Thiazolidinediones (TZD's)

None

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