Anti diabetic Flashcards
(14 cards)
Acarbose
Antihyperglycemic agent that reduces rate and amount of glucose absorbed and may be useful in dogs and cats with mild hyperglycemia
unlikely to be effective therapy for management of DM
competitively inhibits pancreatic alpha amylase and alpha glucosidases in small intestine, delaying digestion of complex carbs and disaccharides to glucose and other monosaccharides
contraindications - DKA, IBD, colonic ulceration, partial intestinal obstruction or predisposition to obstruct
AE: dose dependent loose stools, diarrhea, flatulence
Drug not as effective if not given with meals
Glipizide
Sulfonylurea antidiabetic agent
sulfonylureas lower BG concentrations in both diabetic and non diabetic patients with exact mechanism unknown, but thought to stimulate beta cells in pancreas to secrete additional exogenous insulin; also enhances tissue sensitivity to insulin and reduces production of hepatic basal glucose
May be useful in cats with nonketotic DM with mild to moderate signs and good physical condition, but may take 4-8 weeks for full effects
NOT recommended for dogs
contraindications - absolute insulin deficiency, DKA; use with cuation in patients with untreated adrenal or pituitary insufficiency, thyroid, renal, or hepatic function impairment
AE: GI, hypoglycemia, liver toxicity; increased amyloid deposit formation can occur, potentially causing further destruction of beta cells; hepatic adverse effects possible
Glyburide
Sulfonylurea antidiabetic agent
sulfonylureas lower BG concentrations in both diabetic and non diabetic patients with exact mechanism unknown, but thought to stimulate beta cells in pancreas to secrete additional exogenous insulin; also enhances tissue sensitivity to insulin and reduces production of hepatic basal glucose
May be useful in cats with nonketotic type 2 like DM
May be useful if glipizide is unavailable or if once daily dosing is important
NOT recommended for dogs
contraindications - absolute insulin deficiency, DKA; use with caution in patients with untreated adrenal or pituitary insufficiency, thyroid, renal, or hepatic function impairment
AE: GI, hypoglycemia, liver toxicity;
Metformin
Antihyperglycemic
controversial use
increases insulin’s ability to transport glucose across cell membranes in skeletal muscle without increasing lactate production, and inhibits the formation of advanced glycosylation end products; decrease hepatic glucose production and may decrease intestinal absorption of glucose; does not stimulate insulin production or release from pancreas so does not cause hypoglycemia
contraindicated with iodinated contrast agents, metabolic acidosis
potentially significant drug interactions
AE: GI in dogs; cats - GI, weight loss
Insulin - Lente
Porcine Zinc insulin
Intermediate acting
The primary action of insulin is to regulate glucose metabolism. Insulin and its analogues lower blood glucose by increasing glucose uptake in peripheral tissues, especially by skeletal muscle and fat. In the liver, insulin increases glucose storage (ie, glycogen) while also inhibiting gluconeogenesis. Insulin’s anabolic actions also enhance fatty acid and protein synthesis while inhibiting lipolysis and proteolysis.
2 peaks of activity in dogs, first is at 2-6 hours and the second is at 8-14 hours; duration of activity is between 14-24 hours
Cats - peak 1.5-8hrs and duration between 8-12 hours, may be too short for most cats
U40 syringes
Shake vigorously prior to administration
Insulin, aspart
Novolog
Rapid/short acting used to treat DKA in place of regular insulin
U 100 syringes
used in diabetic emergencies (eg, diabetic ketoacidosis [DKA]). As an insulin analogue similar in action to regular insulin (ie, rapid/short acting), insulin aspart could be considered for the same indications as regular insulin (eg, hyperkalemia) if regular insulin is not an option, although evidence in veterinary species is lacking. IV insulin administration is recommended in patients with poor tissue perfusion, shock, or cardiovascular collapse, as well as in those that require adjunct therapy for hyperkalemia.
Retrospective studies have shown that early administration (ie, within 6 hours of presentation) of insulin aspart as an IV CRI to canine DKA patients led to resolution of hyperglycemia, acidemia, and ketonemia while being safe and well tolerated.1 When compared with an intensive SC glargine administration protocol, insulin aspart administered as an IV CRI to cats in the early stages of treatment for diabetes mellitus was shown to decrease long-term insulin requirements and increase remission rates.2
In patients with DKA, initial aggressive fluid replacement therapy is of paramount importance to restore tissue perfusion and begin correcting electrolyte or acid-base derangements. Once the patient is stabilized, longer-acting insulin products can be started for maintenance insulin therapy. It is strongly encouraged to consult a veterinary emergency and critical care and/or endocrinology specialist or reference when treating this complex condition
Cats - onset within 0.25 hrs and duration 2.5-3 hours;
Insulin, Lispro
Humalog
Rapid/short acting
used to treat DKA, can be used in place of regular insulin
diabetic emergencies (eg, diabetic ketoacidosis [DKA]) and for control of the complicated diabetic patient. As an insulin analogue similar in action to regular insulin (ie, rapid/short-acting), insulin lispro could be considered for the same indications as regular insulin (eg, hyperkalemia) if regular insulin is not an option, although evidence in veterinary species is lacking. IV insulin administration is recommended in patients with poor tissue perfusion, shock, cardiovascular collapse, or in those that require adjunct therapy for hyperkalemia.
Insulin lispro is not commonly used for maintenance insulin therapy in diabetic dogs and cats; however, it could be considered in complicated diabetic patients that cannot be regulated using more standard insulin preparations, particularly those in which a profound postprandial hyperglycemic response exists.
Insulin lispro is less likely to form hexamers, and its rapid absorption results in a fast onset and short duration of effect.
U100 syringes
Although published studies are lacking, the pharmacokinetics of insulin lispro given IV to dogs and cats appear to be comparable with that of humans. After SC administration in diabetic dogs, the onset of hypoglycemic effect is within 0.5 hours, and the peak effect occurs over 1 to 3 hours.
Insulin, NPH
Neutral protamin hagedorn
Humulin N, Novolin N
Intermediate-acting
Used for treatment in patients newly diagnosed with diabetes mellitus and for long-term maintenance therapy
Not recommended for use in cats because of its short duration of action in that species
Animals presenting with ketoacidosis, anorexia, lethargy, and/or vomiting should first be stabilized with appropriate therapy, including short-acting insulin.
U100, gently roll
NPH to 10 diabetic dogs, the median onset of effect was 1.5 hours, median peak effect was 4 hours, and median duration was 8.5 hours.5
In healthy cats given NPH insulin (bovine/porcine source), peak insulin concentration was reached ≈1.5 hours after SC injection, and insulin concentration returned to baseline ≈6 to 8 hours postinjection
Insulin, Glargine
long acting
U100 and U300
Used for treatment in patients newly diagnosed with diabetes mellitus and for long-term maintenance therapy. Also may be used to stabilize cats with diabetic ketoacidosis (DKA)
There are no absolute contraindications, except during episodes of hypoglycemia; avoid concurrent use with SGLT2 inhibitors in cats
Despite differences in their concentrations, one unit of U-300 glargine produces a similar glucose lowering effect as one unit of U-100 glargine
After SC injection of U-100 insulin glargine, the acidic solution is neutralized, and microprecipitates that slowly release small amounts of insulin glargine are formed, resulting in a relatively constant concentration/time profile over 24 hours, with no pronounced peak. smaller injection volume delivered by U-300 insulin glargine produces an even more gradual and prolonged release of insulin when compared to U-100 insulin glarine.
dogs, peak hypoglycemic effect occurred 7 hours after SC injection of U-100 insulin glargine. In diabetic dogs receiving U-100 insulin glargine SC, a hypoglycemic effect was noted 2 hours after administration and persisted for 12 hours
nondiabetic dogs given U-300 insulin glargine, the onset of effect occurred at 4 hours, the peak effect occurred at 6.3 hours, and the duration was 16.3 hours
9 healthy cats compared equal doses of U-100 insulin glargine, protamine zinc insulin (PZI; mixed beef/pork), and purified pork lente insulin. Results showed no significant difference in onset of action (0.8-1.8 hours) or nadir glucose concentrations among different insulin types; time to reach nadir glucose concentration was longer for insulin glargine (≈14 hours) versus PZI insulin (≈4 hours) and lente insulin (≈5 hours)
nondiabetic cats, the onset and duration of effect for U-300 insulin glargine is ≈2 hours, and 12 to 17 hours, respectively. U-300 glargine produced a more evenly distributed metabolic effect over a 24-hour period when compared to U-100 insulin glargine
Duration was significantly shorter for lente insulin (10 hours) than for insulin glargine (22 hours) or PZI (21 hours), with glargine and PZI not appearing to be significantly different. This study also showed definite peaks in glargine concentration and in its glucose-lowering effects
The duration of glargine effect is significantly shortened when given IV or IM, or when diluted. Microprecipitates are not formed with these routes
Hypersensitivity reaction reported to have occurred in a cat
Insulin, Protamin Zinc
Protamine Zinc Recombinant Human Insulin (PZI)
ProZinc
long lasting
U40 syringes, gently roll
rPZI 0.5 units/kg SC at a single site to healthy (ie, nondiabetic) dogs, median onset of action was 3 hours (1-14 hours), time to glucose nadir was 16 hours (6-16 hours), and duration was 20 hours (16 to greater than 24 hours). After administration of rPZI 0.8 units/kg SC at a single site to healthy (ie, nondiabetic) dogs, median onset of action was 3.5 hours (0.5-10 hours), time to glucose nadir was 14 hours (5 to greater than 24 hours), and duration was more than 24 hours (16 to greater than 24 hours)
rPZI doses ranging from 0.1 – 0.99 units/kg SC to cats (nondiabetic and diabetic), onset of activity was 0.5 to 1.5 hours, peak effect was 3 to 9 hours, and duration of effect was 7 to 18.5 hours.
Insulin, Regular (crystalline zinc)
rapid/short acting
used to treat diabetic ketoacidosis (DKA) and as adjunctive therapy to treat hyperkalemia
There are no absolute contraindications, except during episodes of hypoglycemia
U100 syringes
In patients with DKA, initial aggressive fluid replacement therapy is of paramount importance to restore tissue perfusion and begin correcting electrolyte or acid-base derangements. In one study, early administration (ie, within 6 hours of presentation) of insulin to patients with DKA leads to earlier resolution of hyperglycemia, acidemia, and ketonemia while being safe and well tolerated.
Regular insulin may also be given IV concomitantly with dextrose IV to treat hyperkalemia. In dogs and cats, ECG changes seen in critical patients with hyperkalemia may be affected by concurrent metabolic derangements (eg, metabolic acidosis, hypermagnesemia, hypocalcemia) and thus may not typify the expected ECG changes (eg, bradyarrhythmias, loss of P wave, wide QRS complexes, peaked T waves) previously described for hyperkalemia. In humans, treatment for hyperkalemia is recommended when serum potassium is greater than 5.5 mEq/L if there are ECG changes or when serum potassium is greater than 6 mEq/L, regardless of ECG findings.
IV to dogs and cats, it has an immediate onset of action, with maximum effects occurring at 15 minutes; duration of action is 1 to 4 hours. After SC administration, onset is generally 10 to 30 minutes, peak is 1 to 2 hours, and duration is 5 to 6 hours. Half-life is 16 to 18 minutes. Following IM administration, onset is 10 to 30 minutes, peak is 1 to 4 hours, and duration is 3 to 8 hours
Exenatide
Glucagon like Peptide 1 receptor agonist
An incretin mimetic that is administered SC for adjunctive management of diabetes mellitus in cats
Exenatide is NOT an insulin substitute and cannot be used to treat diabetic ketoacidosis; it should not be used as monotherapy to manage type 1 diabetes mellitus.
Contraindications include hypersensitivity, severe GI disease, severe or end-stage renal disease, medullary thyroid carcinoma, and multiple endocrine neoplasia syndrome type 2.
Use with caution in patients with impaired renal function or history of renal transplant, history of pancreatitis, or drug-induced immune-mediated thrombocytopenia (DIIMT); occurrence of pancreatitis or DIIMT precludes further exenatide use
Adverse effects include nausea, vomiting, diarrhea, anorexia, and weight loss. Hypoglycemia is unlikely unless exenatide is used in conjunction with other hypoglycemic agents (eg, insulin).
The National Institute for Occupational Safety and Health (NIOSH) has determined that exenatide meets the definition of a hazardous drug; use appropriate precautions when handling.
Obtaining doses for cats from exenatide formulations intended for use in humans may prove challenging.
Bexagliflozin
Bexacat
Antidiabetic, SGLT2 inhibitor
Sodium-glucose cotransporter 2 (also known as sodium-glucose–linked transporter 2 [SGLT2]) is expressed in the proximal convoluted tubules of the kidneys and is responsible for reabsorption of the majority (≈90%) of glucose from the glomerular filtrate back into the circulation. Bexagliflozin inhibits SGLT2, which reduces renal glucose reabsorption and lowers the renal threshold for glucose and thereby increases urinary glucose excretion. also inhibit renal sodium reabsorption, delivering an increased sodium load to the distal tubules
Sodium-glucose cotransporter 1 (SGLT1) is responsible for glucose absorption from the intestinal lumen. Bexagliflozin is suspected to also inhibit SGLT1, which may be responsible for the adverse GI effects (eg, loose stool, diarrhea) associated with this drug class
bexagliflozin is contraindicated in cats that were previously or are currently treated with insulin, and cats that have insulin-dependent diabetes mellitus. Do not use bexagliflozin in cats with evidence of hepatic disease or reduced renal function
Bexagliflozin increases the risk for potentially fatal DKA and euglycemic DKA, which can occur at any time during treatment. Do not initiate the drug in cats:
That are currently anorexic, dehydrated, or lethargic, have evidence of DKA,
With clinical signs or other objective evidence (fPL level greater than 5.3 micrograms/L, diagnostic imaging) consistent with pancreatitis, or with a history of pancreatitis, A BHB cutoff of 25 mg/dL (2.4 mmol/L) for all cats has been suggested.
AE: Bexagliflozin-induced glucosuria results in an osmotic diuresis. Persistent polyuria and/or polydipsia, with a resulting increased risk for dehydration, have been noted in 20% to 30% of treated cats. Inappropriate urination may be noted in some cats. The drug may also increase the risk for urinary infections. Long-term use of bexagliflozin may increase the risk for urothelial carcinoma;
hypercalcemia, increased liver enzymes, GI, pancreatitis, hemolytic anemia, death, DKA, euglycemic DKA, marked hypertriglyceridemia
Velagliflozin
Senvelgo
SGLT 2 inhibitor
Sodium-glucose cotransporter 2 (also known as sodium-glucose–linked transporter 2 [SGLT2]) is expressed in the proximal convoluted tubules of the kidneys and is responsible for reabsorption of the majority (≈90%) of glucose from the glomerular filtrate back into the circulation. Velagliflozin inhibits SGLT2, which reduces renal glucose reabsorption and lowers the renal threshold for glucose and thereby increases urinary glucose excretion. also inhibit renal sodium reabsorption, delivering an increased sodium load to the distal tubules
Sodium-glucose cotransporter 1 (SGLT1) is responsible for glucose absorption from the intestinal lumen. Velagliflozin is suspected to also inhibit SGLT1, which may be responsible for the adverse GI effects (eg, loose stool, diarrhea) associated with this drug class
velagliflozin is contraindicated in cats that were previously or are currently treated with insulin and in cats that have insulin-dependent diabetes mellitus. Use velagliflozin with caution in cats with a baseline serum creatinine of 1.6 to 2 mg/dL; these cats should be monitored closely for weight loss or signs of volume depletion or dehydration.
Velagliflozin is associated with an increased risk for potentially fatal DKA and euglycemic DKA, which can occur at any time during treatment, including in cats with improved glycemic control. Do not initiate the drug in cats:
That are currently anorexic, dehydrated, or lethargic, ketonuria or ketonemia
(blood or serum beta-hydroxybutyrate [BHB] values greater than 2.4 mmol/L has been suggested as a cutoff)
With current or a history of DKA
With clinical signs or other objective evidence (eg, fPL level greater than 12 micrograms/L, diagnostic imaging) within the previous month consistent with pancreatitis
With chronic or unresponsive diarrhea
With cachexia
With bilirubin greater than 0.5 mg/dL
With creatinine greater than 2 mg/dL (Note: Velagliflozin has been safely used in cats with International Renal Interest Society [IRIS] stage 1 and stage 2 kidney disease.
Most frequent: diarrhea/loose stool (53%, self-limiting in most cases), weight loss (44%), and vomiting (37%)
In 10% to 20% of cats (in decreasing frequency): polyuria, polydipsia, hyporexia/anorexia, hypersalivation and/or gagging, dehydration, and elevated BUN (typically less than 1.5 times the upper limit of normal)
In 1% to 10% of cats (in decreasing frequency): lethargy, polyphagia, UTIs, DKA or euglycemic DKA, hypercalcemia, inappropriate urination or incontinence, ketonuria, death, elevated liver enzymes (1/3 of which were greater than 2 times the upper limit of normal), hypertriglyceridemia, hyperphosphatemia, elevated fPL, pancreatitis, elevated creatinine, and hepatic lipidosis
Velagliflozin may cause DKA, euglycemic DKA, or ketonuria; additionally, pancreatitis, hepatic lipidosis, and hepatopathy have been rarely reported. Although ≈80% of these serious adverse effects occurred within the first 7 days of treatment, they may occur at any time during treatment and may result in death or euthanasia
