Lecture 1: Drugs Affecting Glucose Metabolism Flashcards
1
Q
What is the normal glucose range for a dog
A
76-119
2
Q
What is the normal glucose range for cat
A
60-120
3
Q
What is normal glucose range for cow
A
40-100
4
Q
What is normal glucose range for horse
A
62-134
5
Q
What is the role of the liver in glucose regulation
A
Stores glucose as glycogen when BG high, releases glucose when BG low
6
Q
What are the 4 diabetogenic/glucose releasing hormones
A
- Glucagon
- Catecholamines
- Cortisol
- Growth hormone
7
Q
What is the 1 anti-diabetic hormone
A
Insulin
8
Q
What are some clinical signs of DM
A
PU/PD, weight loss, polyphasic, cataracts in dogs, neuropathy in cats
9
Q
What causes PU/PD in DM
A
Glucose in the urine- osmotic effect
10
Q
What is the value indicating glucosuria in dogs and cats
A
Dogs: 180-220mg/dL
Cats: 250-290 mg/dL
11
Q
What percent of dogs develop cataracts with type 1
A
80%
12
Q
What is the cause of type I DM
A
90% loss of functioning beta cells
13
Q
What are the 3 potential etiologies of type I DM
A
- Autoimmune
- Genetics
- Acute/severe pancreatitis
14
Q
What is the reason behind type II DM
A
Insulin resistant tissues
15
Q
What are some ways tissues become insulin resistant
A
- Anti-insulin antibodies- block receptor
- Anti-insulin receptor antibodies or down regulation
- Problems with downstream signaling
16
Q
What are some causes of mild or fluctuating insulin resistance
A
Obesity, hyperlipidemia, hyperthyroid cats, hypothyroid dogs, chronic inflammation, renal, hepatic or cardiac insufficiency
17
Q
What are some causes of severe persistent insulin resistance
A
- Diestrus induced increase in GH
- Cushing
- Diabetogenic drugs- progestins and glucocorticoids
- Acromegaly- pituitary tumor-releasing GH—> release glucose
18
Q
Is impaired insulin secretion reversible or irreversible
A
Irreversible
19
Q
Is insulin resistance reversible or irreversible
A
Reversible
20
Q
___is secreted every time insulin is secreted and is toxic to Beta cells, therefore reduces insulin secretion
A
Amyloids
21
Q
What does remission of type II DM in cats look like
A
- Return to euglycemia in absence of insulin tx
22
Q
How can acromegaly lead to type II DM
A
Pituitary tumor secreting GH which increases the amount of glucose released from liver
23
Q
What are the two methods to inhibit GH secretion
A
- Decrease levels of GH-RH (harder)
- Increase levels of GH-IH (easier)
24
Q
What is octreotide indicated for and how does it work
A
Indications: acromegaly-causing type II DM, insulinomas
PD:
- acromegaly human somatostatin analog (GH-IH) that decreases circulating GH and therefore glucose
- insulinomas: inhibit insulin gene expression
25
Which is more effective in cats: short acting octreotide or long acting
Long acting
26
What is a major concern in horses with type 2 DM
Laminitis
27
Which class of insulin is the endogenous molecule: short, intermediate or long acting
Short
28
When is short acting insulin used
For emergencies
29
How is short acting insulin administered
IV
30
How long does short acting insulin last
1-4hrs
31
What class of insulin is Novolin-R
Short acting
32
How long does intermediate acting insulin last
8-18hrs
33
How is intermediate acting insulin administered and what must you do for each administration
administered SQ, must rotate spots to avoid lipodystropic reactions
34
How long do long acting insulins last
12-24hrs
35
What is the dose for the veterinary use insulin
40U/mL
36
What are some adverse reactions for insulin use
Hypoglycemia, local or systemic immune reactions
37
What is the dose for the human use insulin
100U/mL
38
What species is porcine insulin zinc suspension used in and is it extra label or labeled
Labeled for cats and dogs
39
What class of insulin is porcine insulin zinc and what mechanism does it use to be so
Intermediate acting insulin- zinc slows absorption, allows for 2 peaks of activity
40
T or F: dogs have a high % chance of having an immune reaction to porcine insulin zinc
False, porcine insulin has the same amino acid sequence as dogs
41
What species is neutral protamine hagedorn insulin used in, and is it extra label or labeled
Extra-label for dogs
42
What class of insulin is neutral protamine hagedorn and what mechanism does it use for rate of absorption
Intermediate acting insulin- protamine slows absorption
43
How many peaks of activity does neutral protamine hagedorn insulin have
Single peak at 8.5hrs
44
T or F: dogs have no immune reaction to neutral protamine hagedorn insulin
False, human recombinant insulin so ~5% of dogs have immune reactions
45
What species is protamine zinc insulin used for and is it extra label or labeled
Labeled for cats
46
What class of insulin is protamine zinc and what is the mechanism of absorption
Long acting insulin- uses protamine to slow absorption
47
Which insulin drug is a mixed source insulin 90% beef and 10% pork and results in insulin antibody production in ~45% of dogs, also promotes insulin resistance
Protamine zinc insulin
48
What class of insulin is glargine insulin
Long acting insulin
49
What is the mechanism of action of glargine insulin
Acidic solution is neutralized when injected SQ which causes microprecipitates to form that dissolve at a constant rate- hence the long acting
50
Can you dilute an entire bottle of glargine insulin and store for later use
No! Precipitates will fall out of solution and then you won’t be injecting any insulin
51
What class of insulin is detemir insulin
Long acting insulin
52
What is the mechanism of action of detemir insulin
Forms microprecipitates following injection, has increased plasma protein binding which both contribute to long acting effect
53
Can you dilute an entire bottle of detemir solution and store for usage at later date
Yes, does not precipitate when dilated
54
Which insulins have the greatest likelihood of getting a cat into remission
1. Detemir
2. Glargine
55
What are the treatment goals of a diabetic patient
1. Eliminate clinical signs
2. Prevent short term complications- hypoglycemia, DKA
3. Good QOL
4, postpone/prevent cataracts in dogs
56
T or F: the biggest treatment goal for a diabetic patient is to maintain plasma glucose levels in a normal range
False!
57
Keeping insulin levels <300mg/dL requires >___ insulin in dogs or cats
1.5U/mL
58
When adjusting insulin levels you must be conservative because of ____
Hypoglycemia-can be fatal
Hyperglycemia- rarely fatal
59
What is the polyol pathway useful at indicating
Hyperglycemia
60
Describe the polyol pathway
Glucose in blood—> sorbitol—> fructuose
Sorbitol—> glycation of protein NH2 groups—> fructosamine and HbA1C
Fructose—> glycolysis
61
What symptoms are found in patients with increase polyol pathway/hyperglycemic
1. Decrease BF
2. Neuropathy
3. Cataracts- decrease glycogen
62
What causes DKA
Prolonged, uncontrolled hyperglycemia
63
In DKA if the body is unable to utilize glucose, what forms and what is the result
Ketone bodies, resulting in metabolic acidosis
64
What are some signs of DKA
Lethargy, depression, coma, dehydration, unkempt, muscle wasting, hepatomegaly, plantigrade cats, cataracts in dogs, acetone on breath
65
What is the treatment protocol for DKA
1. Hydrate-0.9% saline, add glucose to prevent hypoglycemia post insulin
2. Administer short acting insulin (CRI-preferred or IM)
3. Correct electrolyte imbalances
4. Correct acidosis
66
Are DKA patients at risk of become hypokalemia or hyperkalemic and why
Hypokalemic because prolonged PU leads to wasting of K+ by renal tubules
67
How does insulin affect the Na+/K+ pump
Increases activity leading to uptake of K+
68
In DKA patients what must you monitor their heart for and why
Arrhythmias due to mass movement of K+ from the blood into the cell
69
What is bexagliflozin and velagliflozin labeled for
Type II DM cats that have never been given insulin
70
How does bexagliflozin and velaglifozin work
Inhibit SGLA2 which resorbs glucose from proximal tubule—> decreases circulating glucose levels
71
What are the adverse effects of bexagliflozin and velagliflozin
Hypoglycemia, DKA, UTI, anorexia, increased USG and fPL, PU/PD, vomiting, diarrhea, lethargy, anorexia, death
72
What are some contraindications of bexagliflozin and velagliflozin
Anorexia, lethargy, dehydration, liver or kidney insufficiency, pancreatitis
73
What is kinostat indicated for
Prevention of cataracts in diabetic dogs
74
How does kinostat work
Kinostat blocks aldose reductase which is responsible for converting glucose to sorbitol in polyol pathway so blocks glycation of NH2 proteins which is what leads to glycation of collagen in the lens that causes cataracts
75
What is glipizide indicated for
Extra label for type II cats, especially if owners don’t want to given injections
76
What is the mechanism of action of glipizide
Blocks ATP dependent K+ channels, therefore convincing cell it is in high glucose state, so it will increase beta cell secretion of insulin
77
What are some adverse effects of glipizide
Promotes formation of toxin amyloid fibers that kill beta cells, reduces remission likelihood, hypoglycemia
78
What is metformin indicated for
Type II DM in cats (not great), horses
Extra label
79
How does metformin work
Reduces glucose by increasing glucose uptake by the liver and inhibiting gluconeogenesis by opposing glucagon
80
What are some adverse effects of metformin
Overdose can cause lactic acidosis, one trial showed 20% of cats died
81
What is one benefit of metformin/what adverse effect does it not cause that most insulins do cause
Hypoglycemia
82
What is considered hypoglycemic in dogs
<70mg/dL
<60mg/dL- indicating of underlying pathology
83
What can cause hypoglycemia
1. Insulin overdose
2. Diabetogenic hormones- catecholamines secondary to Addison
3. Sepsis- bacteria like glucose
4. Malnutrition in neonates or toy breeds
5. Liver pathologies
6. Cancer- hepatic, leiomyosarcomes, insulinomas
84
What are some signs of hypoglycemia
Lethargy, depression, head tilt, seizures, coma
85
What are some treatment options at home for hypoglycemia
1. D/c insulin until hyperglycemia, add karo syrup to gums
86
What are some treatment options at hospital for hypoglycemia
IV fluids containing dextrose and adjust insulin
87
T or F: dogs can become refractory to octreotide
True (can move to diazoxide)
88
What is diazoxide indicated for
Insulinomas in dogs and ferrets
89
What is the mechanism of action of diazoxide
Opens K+ channels in beta cells, causing hyperpolarization, inhibits insulin release
