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Pharmacology II > Diabetes mellitus medication > Flashcards

Diabetes mellitus medication Flashcards

1
Q

What is type 1 diabetes

A
  • absolute permanent insulin deficiency
  • autoimmune destruction
  • dogs
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2
Q

What is type 2 diabetes?

A
  • relative insulin deficiency
  • insulin resistance & beta cell dysfunction
  • sometimes reversible
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3
Q

What happens when animal has insulin resistance?

A

requires more insulin to get glucose uptake

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4
Q

What does endogenous insulin generally target?

A

liver, muscle & fat cells

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5
Q

function of endogenous insulin

A
  • decrease gluconeogenesis
  • promote storage of glucose. amino acids & fatty acids
  • stimulate lipid & protein synthesis
  • inhibit protein & lipid degradation
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6
Q

What happens during insulin deficiency?

A
  • reduced glucose into liver, muscle &fat
  • increase gluconeogenesis & glycogenolysis in liver
  • hyperglycemia
  • increase protein catabolism
  • deranged lipid metabolism & increase non-esterified fatty acids being transported to the liver
  • hepatic steatosis and hyperlipidemia
  • increased ketone production
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7
Q

What is the major risk factor for diabetes in cats?

A

obesity

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8
Q

How does obesity cause insulin resistance?

A
  • impaired insulin signaling
  • decrease concentration of adiponectin
  • increase secretion of leptin
  • decreased expression of GLUT4 in muscles and fat
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9
Q

How does amyloid deposition result in type 2 diabetes?

A
  • amylin is co-secreted with insulin from the pancreas
  • increased insulin secretion leads to increased amylin deposition in islet cells as amyloid
  • amyloid is toxic to beta cells and causes increased apoptosis & decreased insulin secretion
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10
Q

What does excess glucose and fatty acid cause?

A

apoptosis of beta cells and increased glycogen deposition

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11
Q

What are oral hypoglycemics?

A
  • liposoluble drugs that stimulate the release of insulin
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12
Q

Mechanism of action of oral hypoglycemics

A
  • block K+ channel to retain intracellular K+ in beta cells
  • depolarization of the islet beta cell and cause release of insulin
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13
Q

Why are oral hypoglycemics not effective in dogs?

A

do not have functional beta cells

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14
Q

How are insulin classified?

A
  • source
  • onset/ duration
  • formulation
  • potency
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15
Q

What can the source of insulin affect?

A

immunogenicity

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16
Q

How are human recombinant insulin created?

A

created by modifying the amino acid structure of human insulin

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17
Q

What determine the pharmacokinetics of insulin?

A

molecular structure

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18
Q

Why is insulin usually combined with zinc?

A
  • zinc binds insulin to make insulin hexamers for storage in the pancreas
  • keep the insulin in hexamers that converts to active insulin monomers slowly
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19
Q

What is the benefit of using U-40 insulin?

A

can be given in small amount accurately

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20
Q

What is a short-acting insulin?

A

Regular insulin

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21
Q

What is Regular insulin used for?

A
  • acute in-hospital management of diabetic ketoacidosis
  • 4-5 injections daily
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22
Q

What are the intermediate insulins?

A
  • NPH insulin
  • Porcine lente zinc insulin (caninsulin)
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23
Q

What is NPH insulin?

A

crystalline zinc insulin combined with protamine

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24
Q

What is protamine added in insulin for?

A

slow down absorption

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25
Q

General features of NPH insulin

A
  • U100
  • good first line treatment for dogs
  • may be beneficial in cats with insulin resistance & recurrent ketosis
  • good to stay with 1 brand
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26
Q

What is porcine lente zinc insulin?

A
  • the only remaining source of insulin
  • have biphasic activity: mixture of shorter-acting semi-lente amorphous insulin and longer-acting crystalline
  • insoluble because of the addition of zinc & acetate buffer
27
Q

General feature of porcine lenta zinc insulin

A
  • first-line for dogs
  • U40
  • more predictable onset & peak
28
Q

Name some long-acting insulin

A

-protamine zinc insulin
- Lantus
- Detemir

29
Q

What is the downside of using a long-acting insulin?

A

fine control of diabetes is not possible

30
Q

What does protamine zinc do in protamine zinc insulin?

A

slow down absorption

31
Q

Advantage & disadvantage of using protamine zinc insulin

A

Advantage:
- more accurate (U40)
- longer duration of action
Disadvantages:
- more variable glucose-lowering effect
- lower remission rate in cats

32
Q

What is Lantus/Glangine insulin?

A
  • long-acting human analogue
  • U-100
33
Q

What does alteration of the Glargine/ Lantus insulin do?

A
  • changes the pH and makes it microprecipitate at the site of SQ injection
  • longer duration
34
Q

Why can’t Lantus be diluted or mixed?

A

formation of microcrystals and slow absorption dependent on the acidity of the products

35
Q

Why is it inappropriate to change dose daily for glargine/Lantus insulin?

A
  • takes up to 72 hours for the full effects to occur
  • dose increase is not repeated until at least 3 days have passed
36
Q

Special features of Glrdine/Lantus insulin

A
  • first-line treatment for most feline diabetic patients
  • have fewer troughs and a slower, smoother glycemic effect
  • can be given SQ, IM or IV (van be used to treat ketoacidosis)
37
Q

What are the advantages/ disadvantages of using Glardine/ Lantus insulin?

A

Advantage:
- reduced frequency & severity of clinical hypoglycemia
- high remission rate
Disadvantage:
- U-100 and decreased accuracy

38
Q

What is Detemir insulin?

A
  • long-acting human insulin analogue
  • U-100
  • has added fatty acid side chain, making it bind to albumin reversibly
39
Q

What does Detemir insulin reversible albumin binding do?

A
  • gives more rapid & consistent absorption with a prolonged duration of action due to slow release from the albumin into plasma
40
Q

How does protamine/ zinc combination differ from Detemir in prolonged duration of action?

A
  • Hexamer dissociation is the rate-limiting step of absorption
  • causes greater variability in the rate absorption &increases risk of hypoglycemic events
41
Q

Detemir insulin effect in cats

A
  • remission rate similar to Glargine insulin
  • longer duration & less variability
42
Q

What to do when switching dogs from NPH insulin to Determir?

A
  • due to Detemir’s increased potency, require dose reduction
  • used in dogs with difficult control of diabetes
43
Q

Disadvantage of using Detemir

A
  • poor choice for small dogs
    cannot be given IM for ketoacidosis
44
Q

Adverse effects of insulin

A
  • hypoglycemia ( tachycardia or hunger due to epinephrine release)
  • insulin shock (CNS disturbance)
  • insulin resistance due to insulin antibodies
  • stress causing the secretion of epinephrine/ cortisol, causing down-regulation of insulin receptors
45
Q

What is Bexacat?

A

sodium-glucose cotransporter 2 inhibitor

46
Q

Where are sodium-glucose cotransporter 2 located?

A

kidneys

47
Q

What are sodium-glucose cotransporter 2?

A
  • responsible for most of the glucose reabsorption from the urine into the body
48
Q

How are glucose normally reabsorbed into the body from the kidneys?

A
  • Na/K+ATPase on basolateral membrane create down hill gradient with more Na+ in the urine
  • SGLT2 cotransporter use energy to transport Na+ and glucose from urine into the proximal tubule cell
  • Na+ & glucose then transported out of the cell and into the peritubular capillaries
49
Q

What happens when glucose are too high in the plasma?

A

glucose lost in urine due to saturation of SGLT2 transporter

50
Q

What does Bexacat do?

A
  • inhibition of the SGLT2 cotransporter causing glucose loss in urine
  • improves glycemic control without providing additional insulin
51
Q

What are the suitable candidates for Bexacats?

A

Otherwise healthy cats with no insulin treatment ( sick cats increase risk of ketoacidosis)

52
Q

What is feline diabetic diet?

A
  • high-protein & high fat diet
  • help with weight loss & induction of remission
53
Q

How does incretin impact diet of diabetic cats?

A

Incretin warns the liver & pancreas of nutrient’s arrival and markedly impact numerous metabolic processes:
- GLP-1 inhibits hepatic gluconeogenesis & stimulates insulin release before nutrient enter the circulation
- GLP-1 trophic for pancreatic beta cells

54
Q

What are incretin?

A

hormones (glucose-dependent insulinotropic peptide/ glucagon-like peptide-1) released by specialized enterocytes in response to arrival of nutrientsin the small intestine

55
Q

What triggers incretin release in cats?

A

protein & fat

56
Q

What does incretin analogue do?

A
  • improves insulin sensitivity & promote growth of new islet cells (can result in remission)
  • suppress food intake & support gradual weight loss
57
Q

What is the maximum dose of insulin in diabetic dogs?

A

dose that the animal requires to resolve clinical sign

58
Q

Diabetes drug protocol for dogs

A
  • 1st option: BID intermediate products (NPH/ porcine-origin lente)
  • Detemir next choice if the previous does not work
59
Q

What does dogs with a post-pranadial glucose spike benefit from?

A

additional rapid-acting insulin as a bolus/meal time treatment with slightly reduced insulin dosage

60
Q

What type of insulin is preferred in cats & why

A
  • long-acting
  • better control & higher remission rate
61
Q

Insulin therapy protocol in cats

A
  • Insulins routinely used in cats: Lantus, Prozinc, Detemir
  • BID best
62
Q

What is the preclinical diabetic period in cats?

A

clinically normal with higher-than-normal serum glucose despite insulin release

63
Q

How does preclinical diabetes progress to clinical diabetes in cats?

A
  • hormone amylin is co-secreted with insulin from the pancreas
  • increased insulin secretion leads to increased amylin deposition in islet cells as amyloid—> toxic to islet cells & increase apoptosis
  • glucose level slowly rises and causes glucose toxicity, which leads to neuropathy & apoptosis of the islet cells

Pharmacology II (8 decks)

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