Diabetes mellitus medication Flashcards
(63 cards)
1
Q
What is type 1 diabetes
A
- absolute permanent insulin deficiency
- autoimmune destruction
- dogs
2
Q
What is type 2 diabetes?
A
- relative insulin deficiency
- insulin resistance & beta cell dysfunction
- sometimes reversible
3
Q
What happens when animal has insulin resistance?
A
requires more insulin to get glucose uptake
4
Q
What does endogenous insulin generally target?
A
liver, muscle & fat cells
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
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
7
Q
What is the major risk factor for diabetes in cats?
A
obesity
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
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
10
Q
What does excess glucose and fatty acid cause?
A
apoptosis of beta cells and increased glycogen deposition
11
Q
What are oral hypoglycemics?
A
- liposoluble drugs that stimulate the release of insulin
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
13
Q
Why are oral hypoglycemics not effective in dogs?
A
do not have functional beta cells
14
Q
How are insulin classified?
A
- source
- onset/ duration
- formulation
- potency
15
Q
What can the source of insulin affect?
A
immunogenicity
16
Q
How are human recombinant insulin created?
A
created by modifying the amino acid structure of human insulin
17
Q
What determine the pharmacokinetics of insulin?
A
molecular structure
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
19
Q
What is the benefit of using U-40 insulin?
A
can be given in small amount accurately
20
Q
What is a short-acting insulin?
A
Regular insulin
21
Q
What is Regular insulin used for?
A
- acute in-hospital management of diabetic ketoacidosis
- 4-5 injections daily
22
Q
What are the intermediate insulins?
A
- NPH insulin
- Porcine lente zinc insulin (caninsulin)
23
Q
What is NPH insulin?
A
crystalline zinc insulin combined with protamine
24
Q
What is protamine added in insulin for?
A
slow down absorption
25
General features of NPH insulin
- U100
- good first line treatment for dogs
- may be beneficial in cats with insulin resistance & recurrent ketosis
- good to stay with 1 brand
26
What is porcine lente zinc insulin?
- 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
General feature of porcine lenta zinc insulin
- first-line for dogs
- U40
- more predictable onset & peak
28
Name some long-acting insulin
-protamine zinc insulin
- Lantus
- Detemir
29
What is the downside of using a long-acting insulin?
fine control of diabetes is not possible
30
What does protamine zinc do in protamine zinc insulin?
slow down absorption
31
Advantage & disadvantage of using protamine zinc insulin
Advantage:
- more accurate (U40)
- longer duration of action
Disadvantages:
- more variable glucose-lowering effect
- lower remission rate in cats
32
What is Lantus/Glangine insulin?
- long-acting human analogue
- U-100
33
What does alteration of the Glargine/ Lantus insulin do?
- changes the pH and makes it microprecipitate at the site of SQ injection
- longer duration
34
Why can't Lantus be diluted or mixed?
formation of microcrystals and slow absorption dependent on the acidity of the products
35
Why is it inappropriate to change dose daily for glargine/Lantus insulin?
- takes up to 72 hours for the full effects to occur
- dose increase is not repeated until at least 3 days have passed
36
Special features of Glrdine/Lantus insulin
- 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
What are the advantages/ disadvantages of using Glardine/ Lantus insulin?
Advantage:
- reduced frequency & severity of clinical hypoglycemia
- high remission rate
Disadvantage:
- U-100 and decreased accuracy
38
What is Detemir insulin?
- long-acting human insulin analogue
- U-100
- has added fatty acid side chain, making it bind to albumin reversibly
39
What does Detemir insulin reversible albumin binding do?
- gives more rapid & consistent absorption with a prolonged duration of action due to slow release from the albumin into plasma
40
How does protamine/ zinc combination differ from Detemir in prolonged duration of action?
- Hexamer dissociation is the rate-limiting step of absorption
- causes greater variability in the rate absorption &increases risk of hypoglycemic events
41
Detemir insulin effect in cats
- remission rate similar to Glargine insulin
- longer duration & less variability
42
What to do when switching dogs from NPH insulin to Determir?
- due to Detemir's increased potency, require dose reduction
- used in dogs with difficult control of diabetes
43
Disadvantage of using Detemir
- poor choice for small dogs
cannot be given IM for ketoacidosis
44
Adverse effects of insulin
- 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
What is Bexacat?
sodium-glucose cotransporter 2 inhibitor
46
Where are sodium-glucose cotransporter 2 located?
kidneys
47
What are sodium-glucose cotransporter 2?
- responsible for most of the glucose reabsorption from the urine into the body
48
How are glucose normally reabsorbed into the body from the kidneys?
- 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
What happens when glucose are too high in the plasma?
glucose lost in urine due to saturation of SGLT2 transporter
50
What does Bexacat do?
- inhibition of the SGLT2 cotransporter causing glucose loss in urine
- improves glycemic control without providing additional insulin
51
What are the suitable candidates for Bexacats?
Otherwise healthy cats with no insulin treatment ( sick cats increase risk of ketoacidosis)
52
What is feline diabetic diet?
- high-protein & high fat diet
- help with weight loss & induction of remission
53
How does incretin impact diet of diabetic cats?
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
What are incretin?
hormones (glucose-dependent insulinotropic peptide/ glucagon-like peptide-1) released by specialized enterocytes in response to arrival of nutrientsin the small intestine
55
What triggers incretin release in cats?
protein & fat
56
What does incretin analogue do?
- improves insulin sensitivity & promote growth of new islet cells (can result in remission)
- suppress food intake & support gradual weight loss
57
What is the maximum dose of insulin in diabetic dogs?
dose that the animal requires to resolve clinical sign
58
Diabetes drug protocol for dogs
- 1st option: BID intermediate products (NPH/ porcine-origin lente)
- Detemir next choice if the previous does not work
59
What does dogs with a post-pranadial glucose spike benefit from?
additional rapid-acting insulin as a bolus/meal time treatment with slightly reduced insulin dosage
60
What type of insulin is preferred in cats & why
- long-acting
- better control & higher remission rate
61
Insulin therapy protocol in cats
- Insulins routinely used in cats: Lantus, Prozinc, Detemir
- BID best
62
What is the preclinical diabetic period in cats?
clinically normal with higher-than-normal serum glucose despite insulin release
63
How does preclinical diabetes progress to clinical diabetes in cats?
- 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
