Endocrine Pancreas Flashcards
possible goals of endocrine drug therapy
o Replace a hormone deficiency
o Reduce the formation of excess hormone
o Reduce effects of excess hormone
purpose of insulin in the body, when it is released
- insulin is produced by the islets of langerhans of the pancreas
- released primarily in response to glucose (but also other possible stimulating factors)
- primary hormone for controlling the uptake, utilization, and storage of cellular nutrients > overall anabolic effect
- stimulates liver to store glucose in the form of glycogen
- in the abscence of insulin, the liver will switch to releasing glucose from glycogen stores
- to maintain control of liver and glucose release, insulin is tonically released
- released in larger amounts following ingestion of carbohydrate-rich meal to facilitate uptake of glucose by the rest of the body
> facilitates placement of glucose transporters onto cell membranes, which are recycled back into the cytoplasm when insulin levels fall
diabetes mellitus, type 1
- what is it?
- what animals does it mostly occur in?
- Incidence?
- not common in what animals?
(Insulin-dependent; IDDM)
o Occurs most frequently in the dog and cat
o Incidence: 0.5-1.0%; middle-aged & older
o Type 1 most common form diagnosed in dog
o Rare in horses, ruminants, exotics
Type 1 diabetes mellitus pathogenesis, how clinical signs arise?
Intracellular glucose deficiency, due to lack of insulin
o net energy shortage for the cell
o switch to fat metabolism—ketosis
> ineffective long-term
o catabolic state ensues
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Extracellular hyperglycemia
o hyperosmotic plasma yielding cell dehydration
o glycosuria yielding polyuria, diuresis & polydipsia
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glucose toxicity yielding….
o reduced insulin release
o susceptibility to infections
o cataracts
o peripheral neuropathy
aims of therapy for diabetes mellitus
- Abolish clinical signs
- Restore lost condition/weight
- Reduce risk of complications
o Hyperglycemia
o Ketoacidosis
o Peripheral neuropathy - Enhance quality of life
therapeutic approaches for type 1 diabetes
o Insulin
o Oral hypoglycemics
o Diets formulated for diabetic cats
o Weight reduction if obese
o Cessation of diabetogenic drugs
o Control of other disorders
what is 1 IU of insulin in mass?
1 IU of insulin equals 36 μg insulin
how can insulin be formulated?
- what do we do to protect the protein? eg. temp, pH, light
- what other ingredients are included in insulin formulations?
- how is it administered?
Formulated as solutions or suspensions
o If suspension; gently mix versus shake
o Refrigeration can protect insulin; do not freeze
o Avoid heat and extreme sunlight
o Dilute with recommended diluent only; pH concerns
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o Formulated with zinc, +/- buffers, +/- protamine
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Insulin delivered by needle/syringe o Pen injectors, needleless injectors
difference between short, intermediate, and long lasting insulin preparations
short acting have a quick onset of action, short duration - get into circulation quickly, also get eliminated quickly > often the most commonly used in initial therapy
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intermediate acting are in the middle
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long acting are longer
commonly used short-acting insulin product
Regular insulin
commonly used intermediate acting insulin products
Lente
NPH
commonly used long-acting insulin products
Glargine
Insulin Determir
Protamine Zinc Insulin
regular insulin
- how fast does it act?
what are the properties of the solution?
- when is it used?
- routes of admin
Short-acting
o Clear solution, zinc, no added protein, +/- buffer (pH 7.2-7.4)
o Used as initial insulin therapy until patient stable; emergencies
o IV, IM, SC, CRI
Lente
- what is this drug?
- what animals is it approved for
- concentration, dosage availability
- suspension properties
- what are its components, and when do they peak? duration?
- admin route
- advantage
Intermediate acting insulin preparation
o Approved for use in dogs and cats
o U40 concentration (40 IU/mL)
o 1.0 and 0.5 mL syringes available
o Cloudy suspension, zinc, acetate buffer
o Purified porcine insulin
> 30% amorphous insulin:
peak (3 hrs) and duration (~8 hrs)
> 70% crystalline:
peak (7-12 hrs) and duration (~24 hrs)
o SC administration
o Less likely to stimulate immune response
NPH (Neutral Protamine Hagedorn)
- what is this
- properties of suspension
- admin route
Intermediate acting insulin preparation
o Cloudy suspension, zinc, phosphate buffer, protamine
o SC administration
o Similar in performance to Lente
Glargine
- what is this? what animal? how is it prepared? considerations for duration, efficacy. admin route.
long-acting insulin preparation, use limited largely to cats
o Clear solution, no buffer, pH (4.0)
o 2 arginine residues added to insulin b-chain, and an asparagine is replaced with a glycine residue in the a-chain
o Produces consistent flat blood glucose profile
o pH of 4.0 important for long duration
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o Do not dilute or mix with other insulins
o Administered SC
Insulin Determir
- what is it? for what animal?
- how does it work?
- possible advantage
long-acting insulin preparation used more commonly in dogs
- SC admin
o Fatty acid (myristic acid) is bound to lysine on b-chain; after absorption it binds to albumin in blood and slowly dissociates from this complex
o May be more potent than glargine or other insulins
Protamine Zinc Insulin
- what is this, for what animal
- properties
- availability
- admin route
Long-acting insulin preparation, licensed for use in cats
o Cloudy suspension, zinc, protamine, phosphate buffer
o Can be compounded in Canada from regular insulin, but less so with PZI available
o Administered SC
is insulin duration of activity longer in dogs or cats?
Insulin duration of action is generally less in cats than dogs
what are the intermediate-acting insulin preparations, and what is their dosing regime for dogs and cats?
(NPH and lente)
o once or twice daily in dogs
o TWICE daily in cats
what are the long-acting insulin preparations, and what is their dosing regime for dogs and cats?
(Glargine and PZI)
o once daily in dogs
o once, OR TWICE, daily in cats
advantage of twice per day dosing for insulin preparations
Twice daily injections can afford greater control of blood glucose
o Less swings in glucose levels
o Less complications with hypoglycemia
what type of monitoring can we do when administering insulin for diabetes mellitus?
Monitoring therapy necessary for control & dose adjustments
o Blood glucose curves
o Clinical signs: water intake, polyphagia
o Fructosamine levels
o Urine monitoring
diabetes mellitus type 2 (Non-insulin dependent; NIDDM)
- what animal is this common in? what defines this condition? what are risk factors?
o Relatively frequent occurrence in cats
o Reduced insulin secretion
o Reduced insulin action–insulin resistance
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o Risk factors:
o Genetics, inactivity, obesity, diet
o Drugs: corticosteroids, progestins
in type 2 diabetes mellitus, is diabetic control helpful? possible outcomes with and without control?
Diabetic control may ameliorate glucose toxicity and suppressed
insulin secretion
o Remission possible
o b-cell loss occurs with longer standing hyperglycemia
ways to control type 2 diabetes mellitus? are they commonly used?
Oral hypoglycemics & dietary manipulation may be very effective
o Insulin may be required initially to gain glycemic control
o To date, there has been limited veterinary use of oral hypoglycemics
Oral Hypoglycemics, drug categories and options, when they are useful
- Insulin Secretagogues
- Assumes some β-cell function present !!
- General caution regarding potential for hypoglycemia
- eg. Sulfonylureas
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- Require insulin, but do not promote release !!
- eg. biguanides
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- eg. acarbose
what is Glipizide? how does it work?
how to administer? adverse possibilities?
-oral hypoglycemic, insulin secretagogue, sulfonylureas
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- Increase release of insulin by blocking ATP-sensitive-K+ channel on β-cells
- Administered in conjunction with a meal; short-lived response
- Clinical response in cats variable
- May accelerate NIDDM to IDDM; potentially harmful
Metformin - what is this drug? what does it do? how is it used? adverse effects vs other similar drugs?
- oral hypoglycemic, insulin sensitizer, biguanide
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o Reduces hepatic gluconeogenesis
o Increase insulin utilization by peripheral target cells (muscle, fat)
o Used alone or in combination with the secretagogues
o Also used with insulin therapy in humans
o Less likely to produce hypoglycemia
what is acarbose? how does it work? what is it used with? adverse effects?
- oral hypoglycemic, a-glucosidase Inhibitors
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o Inhibits intestinal alpha-glucosidases and post-prandial digestion and absorption of starches and disaccharides
o Generally used in combination with sulfonylureas or insulin
o Adverse effects include abdominal pain, flatulence, diarrhea
SGLT2-Sodium-Glucose Cotransporter Inhibitors
- what drugs are in this category?
- availability?
- how do they work? for what animal and what condition?
- Bexagliflozin, velaglifozin
o Currently available in US, EU (pending), but not Canada
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o Both are SGLT2 sodium-glucose co-transporter inhibitors
o Transporters are found on the proximal convoluted tubules where they prevent glucose from being excreted in the urine
o Blockage of the transporter results in glucose being removed in the urine (reduces renal threshold for reuptake of glucose by blood)
o Both products are available as tablets
o Licensed for use in cats with Type 2 diabetes mellitus
most common complication of insulin therapy
Hypoglycemia
causes of complications of insulin therapy
o Insulin overdose
o Failure to feed or reduced appetite
o Change in exercise schedule
o Other disease/conditions:
o Porto-systemic shunts
o Hepatic failure
o Hypoadrenocorticism
o Beta-cell tumor (insulinomas)
o Sepsis/bacteremia
concurrent diseases that can contribute to complications from insulin therapy
o Porto-systemic shunts
o Hepatic failure
o Hypoadrenocorticism
o Beta-cell tumor (insulinomas)
o Sepsis/bacteremia
clinical signs hypoglycemia as a complications from insulin therapy
o Polyphagia
o Bizarre behaviour o Lethargy
o Weakness
o Ataxia
o Collapse
o Coma/seizure
how do we treat an animal that is hypoglycemic as a complication of insulin therapy
mild vs severe
o Mild: oral - dextrose/glucose better than sucrose
o Severe: IV glucose
o Glucagon; maybe used if glucose ineffective !
> injectable preparations available
> good for short acting response
Problems with regulation of insulin therapy
o Administration problems
o Antibodies to insulin or other foreign proteins in the preparation
o Other hormones can be diabetogenic
> corticosteroids, progestins
o Stress, infections, obesity
o Rapid metabolism of insulin (short duration of action)
> Variability in duration of insulin in individuals is subject to differences in metabolic rate
o Somogyi effect—rebound hyperglycemia
> hypoglycemia induces counterregulatory hormones that increase blood glucose
> epinephrine, glucagon, cortisol, growth hormone
what is the somogyi effect?
—rebound hyperglycemia
o hypoglycemia induces counterregulatory hormones that increase blood glucose
o epinephrine, glucagon, cortisol, growth hormone
> often noted in the morning, people will falsely think that they need to give more insulin, making things worse
