Insulin and & Oral Hypoglycemics Flashcards
(105 cards)
1
Q
Where is insulin synthesized?
A
β cells islets of Langerhans in pancreas
2
Q
Why is insulin needed?
A
Insulin needed for glucose transport across cell membranes
3
Q
What does insulin increase?
A
Insulin increases glucose uptake & use in fat and muscle
4
Q
What does insulin inhibit?
A
Insulin inhibits gluconeogenesis & glycogenolysis
5
Q
What happens in the state of Insulin deficiency & peripheral insulin resistance?
A
hyperglycemia results from impaired glucose utilization, increased glycogenolysis, & increased gluconeogenesis
6
Q
What happens in the absence of insulin?
A
- Absence of insulin
- increased lipolysis & circulating free fatty acids
- ketone production in liver
7
Q
What does hyperglycemia impair?
A
- vasodilation, proinflammatory, prothrombotic, and proatherogenic
- predisposes to vascular complications
8
Q
Define Type I DM.
A
Autoimmune mediated destruction of pancreatic β cells
9
Q
Define characteristiccs of Type I DM?
A
- Onset usually younger age
- sensitivity to insulin normal – require exogenous insulin administration
10
Q
Lack of insulin may precipitate ________
A
ketoacidosis
11
Q
Define components of Type II DM.
A
Failure to secrete insulin due to pancreatic β cells dysfunction coupled w/ peripheral insulin resistance
12
Q
What is the treatment of DM II?
A
Treatment w/ oral hypoglycemic agents or insulin
13
Q
What are the goals of DM tx?
A
prevent adverse consequences of hyperglycemia & hypoglycemia
14
Q
What is the components of HbA1c?
A
- Long-term glucose control best monitored with HbA1c levels
- glucose levels over 2-3 months
- <6-7% less associated w/ fewer microvascular complications
15
Q
Goal targeted for blood glucose ______
A
< 200 mg/dL intraoperatively
16
Q
What is the treatment of DM1?
A
DM require exogenous administration of insulin for survival
17
Q
What is the tx for DM2?
A
insulin also used in type 2 DM patients if oral hypoglycemics don’t achieve adequate glucose control
18
Q
What are the components of the insulin receptor?
A
Insulin receptors are tyrosine kinase receptors (2nd messenger receptors that work mainly via phosphorylation)
19
Q
What allows glucose into the cell?
A
upregulation of Glut 4
20
Q
What is the normal secretion of basal insulin?
A
Under normal condition, basal insulin is secreted into portal venous system at rate 1unit/hour
21
Q
total daily secretion of insulin is ________
A
approx. 40 units
22
Q
What stimulates a decrease in basal secretion insulin?
A
Sympathetic nervous system innervates islet cells of pancreas: α-adrenergic stim decreases basal secretion insulin
23
Q
What increases basal insulin secretion?
A
β-adrenergic stim & parasympathetic nervous system stim increases basal insulin secretion
24
Q
What is the pharmacological effects of insulin? Why?
A
Despite elimination ½ time of 5-10 min, pharmacologic effects last 30-60 min d/t insulin being tightly bound to tissue receptors
25
What is the administration of insulin?
SQ route produces a slower, sustained delivery
26
What is the prinicple of insulin replacement?
provide a slow, long-acting, continuous supply of insulin that mimics the nocturnal and between-meal basal secretion of normal pancreatic β cells
27
What are examples of principle of insulin replacement?
NPH, insulin glargine, insulin detemir, insulin degludec
28
What is rapid short acting insulin?
A rapid short-acting insulin administered before meals mimics normal meal-stimulated (prandial) release of insulin
29
What are examples of rapid short acting?
Insulin aspart, lispro, glulisine
30
What is the total exogenous insuling dose for type 1 DM?
Total daily exogenous insulin dose for tx of type 1 DM usually in range of 0.5 to 1 U/kg/day
31
What is true about the insulin requirements for DM 1?
this requirement may be increased by stress asso/w sepsis or trauma
32
Review components of insulin
33
What is the major side effect of diabetic medications?
* most serious side effect
* patients most susceptible if receive exogenous insulin administration in absence of carbohydrate intake (i.e., perioperative fasting period before surgery)
34
What are the first symptoms of hypoglycemia?
d/t increased epinephrine secretion to raise the blood glucose level (diaphoresis, tachycardia, HTN)
35
What is the somogyi effect?
* rebound hyperglycemia caused by sympathetic nervous system activity response to hypoglycemia
* can mask actual diagnosis of hypoglycemia
36
What are the CNS effects of hypoglycemia?
* mental confusion progressing to seizures & coma
37
Prolonged hypoglycemia can result in \_\_\_\_\_\_\_\_\_
irreversible brain damage
38
What is the components of hypoglycemia and GA?
difficult b/c anesthetic drugs mask classic signs of sympathetic nervous system stimulation
39
What can hypoglycemia cause hemodynamically?
changes in HR & BP – likely to be confused w/evoked responses to painful surgical stimulation in anesthetized pt
40
What can also mask symptoms of hypoglycemia?
Nonselective β-adrenergic antagonists
41
What is the treatment of severe hypoglycemia?
* 50-100mL 50% glucose solution IV; glucagon 0.5-1mg IV or SC
* if no CNS depression, carbohydrate PO
42
What are allergic reaction components of insulin?
less common w/human insulins (no longer use animal-derived pork or beef)
43
What are the prinicple components of allergic reactions?
less common w/human insulins (no longer use animal-derived pork or beef)
44
Chronic exposure to low doses of protamine in NPH insulin may stimulate production of \_\_\_\_\_\_
antibodies against protamine
45
Patients who receive a large dose of protamine IV to antagonize anticoagulant effect of heparin may have \_\_\_\_\_\_\_\_\_\_\_
allergic reaction
46
Define lipodystrophy.
fat atrophy at site of SC injections
47
What are hormone drugs that can interact with insulin?
Hormones (admin as drugs) that counter insulin hypoglycemic effect: ACTH, estrogens, glucagon
48
What are epinephrine's interact with insulin?
inhibits insulin secretion & stim glycogenolysis
49
What drugs can increase insulin hypoglycemic effect?
tetracycline, chloramphenicol, salicylates, phenylbutazone, MAO inhibitors
50
Review oral hypoglyemics table.
51
What is the first line of tx for type 2 DM?
Metformin
52
What is the MOA of Metformin?
* suppresses hepatic glucose production
* decreases GI glucose absorption
* increases insulin sensitivity in peripheral tissues
53
What is not a risk with Metformin?
Hypoglycemia not a risk (as solo tx agent)
54
What can Metformin be used in combo with?
* Can be used in combination w/ insulin & sulfonylureas
* **+ risk of hypoglycemia in combo w/insulin and/or sulfonylureas**
55
What are other uses of Metformin?
weight loss, polycystic ovarian disease, nonalcoholic fatty liver disease, & premature puberty
56
What is a possible side effect of Metformin?
Lactic acidosis
57
What is the recommendation of Metformin and surgery?
DC metformin 48 hours or longer before elective surgery
58
What needs to be done if metformin can't be d/c before surgery?
must closely monitor patient for development of lactic acidosis
* ABG/pH
* serum lactate
* renal fnx
59
When should Metformin not be used?
* lactic acidosis
* acute kidney injury
* GI intolerance
* acute hepatic disease
60
What is tx of metformin-induced lactic acidosis?
* bicarbonate
* hemodialysis
* largely supportive
61
What is the MOA of metformin-induced lactic acidosis?
* b/c underlying pathologic change is blockade of mitrochondrial respiratory chain
* Metformin inhibits mitochondrial enzyme to suppress glucose production in liver
62
What is the use of Sulfonylureas?
Successful use in type 2 DM management requires some β cell function
63
What is Sulfonylureas ineffective in?
tx type 1 DM
64
Who should Sulfonylureas not be administered?
Should not be administered in patients w/sulfa drug allergy
65
What is the MOA of Sulfonylureas?
* exert their action on pancreatic sulfonylurea receptors by inhibiting ATP-sensitive K ion channels which cause influx of Ca
* release of insulin storage granules
66
What drugs are Sulfonylureas?
glyburide, glipizide, glimepiride
67
What is the most severe complication of Sulfonylureas?
Hypoglycemia
68
What are risk factors for sulfonylurea-induced hypoglycemia?
* Impaired nutrition
* age \> 60
* impaired renal function
* concomitant drug therapy that potentiates sulfonylureas (phenylbutazone, sulfonamide antibiotics, warfarin)
* interaction w/alcohol or salicylates
69
What is the greatest risk of for sulfonylurea-induced hypoglycemia?
drugs w/long elimination half-life (glyburide, chlorpropamide)
70
What is true about the hypoglycemia associated with Sulfonylureas?
Hypoglycemia often more prolonged & more dangerous than hypoglycemia from insulin
71
Where are Sulfonylureas metabolites excreted?
renally excreted
72
What are the short acting Sulfonylureas? When are these prefered?
* Shorter-acting sulfonylureas (glipizide, glimepiride) have short half-lives & inactive metabolites
* are preferable to use in patients w/renal insufficiency to those w/longer duration of action (glyburide)
73
What Sulfonylureas has longer duration of action?
glyburide or Chlorpropamide
74
When are Sulfonylureas not recommended?
patients w/ hepatic dysfunction (prolongs elim half-life & enhances hypoglycemic effect)
75
What is associated with Chlorpropamide?
Sulfonylureas
* disulfiram-like reaction & inapprop secretion of arginine vasopressin hormone resulting in hyponatremia
76
What drugs are Thiazolidinediones
(TZDs)?
rosiglitazone, pioglitazone
77
Where do Thiazolidinediones (TZDs) act?
**rosiglitazone, pioglitazone**
Act at skeletal muscle, liver, & adipose tissue to decrease insulin resistance & hepatic glucose production, increase glucose use by the liver
78
What do Thiazolidinediones (TZDs) result in?
decrease in HgbA1c
79
When are Thiazolidinediones (TZDs) contraindicated?
These drugs contraindicated in patients w/liver failure
80
What should be monitored with Thiazolidinediones (TZDs)?
Must monitor plasma hepatic transaminases d/t possibility of drug-induced liver dysfunction
81
What are Glucagon-Like Peptide-1 Receptor Agonists (GLP-1) drugs?
liraglutide, semaglutide
82
What are the characteristics of GLP-1 agonists?
are injectable agents that bind to receptors in pancreas, GI tract, & brain
83
What does binding of GLP-1 agonists result in?
increased insulin secretion from β cells, decreasing glucagon production from α cells in pancreas
84
What is the result of GLP-1 agonists?
These drugs result in slowing of gastric emptying, reducing appetite, weight loss
85
What is the relationship between hypoglyecmia and GLP-1 agonists?
Do not cause hypoglycemia unless combined w/other medications known to cause hypoglycemia (sulfonylureas & insulin)
86
Where is Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2) present?
SGLT2 is a transport protein present in proximal tubule
87
What is SGLT2 responsible for?
responsible for approx. 90% glucose reabsorption in the kidneys
88
What do SGLT2 inhibitors cause?
These drugs lower serum glucose levels by increasing glucose excretion in the kidneys via osmotic diuresis
89
What are examples of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2)?
empagliflozin, canagliflozin, dapagliflozin, ertugliflozin
90
What is the side effects of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2)?
* volume loss d/t osmotic diuresis may cause hypotension or acute kidney injury (esp in patients taking diuretics, ACE-I or ARB drugs)
* renal function assessment recommended
91
What is the PO Dipeptidyl-Peptidase-4 (DPP-4) Inhibitors?
saxagliptin, sitagliptin, linagliptin, alogliptin, vildagliptin
92
What is the effect of Dipeptidyl-Peptidase-4 (DPP-4) Inhibitors?
Lower blood glucose by increasing insulin secretion from β pancreatic cells & reduce α pancreatic cell secretion of glucagon
93
What is the side effects of Dipeptidyl-Peptidase-4 (DPP-4) Inhibitors?
musculoskeletal pain, pancreatitis
94
What is the recommendation for herbal medications?
General recommendation is two stop 2-3 weeks before surgery
95
Review herbal medications.
96
How many people use St. John’s Wart?
7.5 million Americans take regularly
97
What is the use for St. John’s Wart?
Used for anxiety, depression, sleep disorders
98
What effect can St. John’s Wart have on anesthesia?
May intensify or prolong the effects of opioids and thus the anesthetic
99
How many individuals take Ginkgo Biloba?
11 million Americans take regularly
100
What is the use for Ginkgo Biloba?
Used to improve memory, enhance blood circulation
101
What is the effect of Ginkgo Biloba on anesthesic?
* May reduce platelet function and clotting formation
* Acts as an anticoagulant
102
What are 4G's are increased bleeding risk?
garlic, ginseng, gingko, ginger (and Vit E)
103
What is the most popular herbal preparation?
Ginseng
104
What is the use of Ginseng?
Used for vitality, fatigue, and cancer prevention
105
What are the properities of Ginseng?
* May cause episodes of tachycardia and hypertension
* May have anticoagulant properties
