Insulin and & Oral Hypoglycemics Flashcards
Where is insulin synthesized?
β cells islets of Langerhans in pancreas
Why is insulin needed?
Insulin needed for glucose transport across cell membranes
What does insulin increase?
Insulin increases glucose uptake & use in fat and muscle
What does insulin inhibit?
Insulin inhibits gluconeogenesis & glycogenolysis
What happens in the state of Insulin deficiency & peripheral insulin resistance?
hyperglycemia results from impaired glucose utilization, increased glycogenolysis, & increased gluconeogenesis
What happens in the absence of insulin?
- Absence of insulin
- increased lipolysis & circulating free fatty acids
- ketone production in liver
What does hyperglycemia impair?
- vasodilation, proinflammatory, prothrombotic, and proatherogenic
- predisposes to vascular complications
Define Type I DM.
Autoimmune mediated destruction of pancreatic β cells
Define characteristiccs of Type I DM?
- Onset usually younger age
- sensitivity to insulin normal – require exogenous insulin administration
Lack of insulin may precipitate ________
ketoacidosis
Define components of Type II DM.
Failure to secrete insulin due to pancreatic β cells dysfunction coupled w/ peripheral insulin resistance
What is the treatment of DM II?
Treatment w/ oral hypoglycemic agents or insulin
What are the goals of DM tx?
prevent adverse consequences of hyperglycemia & hypoglycemia
What is the components of HbA1c?
- Long-term glucose control best monitored with HbA1c levels
- glucose levels over 2-3 months
- <6-7% less associated w/ fewer microvascular complications
Goal targeted for blood glucose ______
< 200 mg/dL intraoperatively
What is the treatment of DM1?
DM require exogenous administration of insulin for survival
What is the tx for DM2?
insulin also used in type 2 DM patients if oral hypoglycemics don’t achieve adequate glucose control
What are the components of the insulin receptor?
Insulin receptors are tyrosine kinase receptors (2nd messenger receptors that work mainly via phosphorylation)
What allows glucose into the cell?
upregulation of Glut 4
What is the normal secretion of basal insulin?
Under normal condition, basal insulin is secreted into portal venous system at rate 1unit/hour
total daily secretion of insulin is ________
approx. 40 units
What stimulates a decrease in basal secretion insulin?
Sympathetic nervous system innervates islet cells of pancreas: α-adrenergic stim decreases basal secretion insulin
What increases basal insulin secretion?
β-adrenergic stim & parasympathetic nervous system stim increases basal insulin secretion
What is the pharmacological effects of insulin? Why?
Despite elimination ½ time of 5-10 min, pharmacologic effects last 30-60 min d/t insulin being tightly bound to tissue receptors
What is the administration of insulin?
SQ route produces a slower, sustained delivery
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
What are examples of principle of insulin replacement?
NPH, insulin glargine, insulin detemir, insulin degludec
What is rapid short acting insulin?
A rapid short-acting insulin administered before meals mimics normal meal-stimulated (prandial) release of insulin
What are examples of rapid short acting?
Insulin aspart, lispro, glulisine
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
What is true about the insulin requirements for DM 1?
this requirement may be increased by stress asso/w sepsis or trauma
Review components of insulin
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)
What are the first symptoms of hypoglycemia?
d/t increased epinephrine secretion to raise the blood glucose level (diaphoresis, tachycardia, HTN)
What is the somogyi effect?
- rebound hyperglycemia caused by sympathetic nervous system activity response to hypoglycemia
- can mask actual diagnosis of hypoglycemia
What are the CNS effects of hypoglycemia?
- mental confusion progressing to seizures & coma
Prolonged hypoglycemia can result in _________
irreversible brain damage
What is the components of hypoglycemia and GA?
difficult b/c anesthetic drugs mask classic signs of sympathetic nervous system stimulation
What can hypoglycemia cause hemodynamically?
changes in HR & BP – likely to be confused w/evoked responses to painful surgical stimulation in anesthetized pt
What can also mask symptoms of hypoglycemia?
Nonselective β-adrenergic antagonists
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
What are allergic reaction components of insulin?
less common w/human insulins (no longer use animal-derived pork or beef)
What are the prinicple components of allergic reactions?
less common w/human insulins (no longer use animal-derived pork or beef)
Chronic exposure to low doses of protamine in NPH insulin may stimulate production of ______
antibodies against protamine
Patients who receive a large dose of protamine IV to antagonize anticoagulant effect of heparin may have ___________
allergic reaction
Define lipodystrophy.
fat atrophy at site of SC injections
What are hormone drugs that can interact with insulin?
Hormones (admin as drugs) that counter insulin hypoglycemic effect: ACTH, estrogens, glucagon
What are epinephrine’s interact with insulin?
inhibits insulin secretion & stim glycogenolysis
What drugs can increase insulin hypoglycemic effect?
tetracycline, chloramphenicol, salicylates, phenylbutazone, MAO inhibitors
Review oral hypoglyemics table.
What is the first line of tx for type 2 DM?
Metformin
What is the MOA of Metformin?
- suppresses hepatic glucose production
- decreases GI glucose absorption
- increases insulin sensitivity in peripheral tissues
What is not a risk with Metformin?
Hypoglycemia not a risk (as solo tx agent)
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
What are other uses of Metformin?
weight loss, polycystic ovarian disease, nonalcoholic fatty liver disease, & premature puberty
What is a possible side effect of Metformin?
Lactic acidosis
What is the recommendation of Metformin and surgery?
DC metformin 48 hours or longer before elective surgery
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
When should Metformin not be used?
- lactic acidosis
- acute kidney injury
- GI intolerance
- acute hepatic disease
What is tx of metformin-induced lactic acidosis?
- bicarbonate
- hemodialysis
- largely supportive
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
What is the use of Sulfonylureas?
Successful use in type 2 DM management requires some β cell function
What is Sulfonylureas ineffective in?
tx type 1 DM
Who should Sulfonylureas not be administered?
Should not be administered in patients w/sulfa drug allergy
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
What drugs are Sulfonylureas?
glyburide, glipizide, glimepiride
What is the most severe complication of Sulfonylureas?
Hypoglycemia
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
What is the greatest risk of for sulfonylurea-induced hypoglycemia?
drugs w/long elimination half-life (glyburide, chlorpropamide)
What is true about the hypoglycemia associated with Sulfonylureas?
Hypoglycemia often more prolonged & more dangerous than hypoglycemia from insulin
Where are Sulfonylureas metabolites excreted?
renally excreted
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)
What Sulfonylureas has longer duration of action?
glyburide or Chlorpropamide
When are Sulfonylureas not recommended?
patients w/ hepatic dysfunction (prolongs elim half-life & enhances hypoglycemic effect)
What is associated with Chlorpropamide?
Sulfonylureas
- disulfiram-like reaction & inapprop secretion of arginine vasopressin hormone resulting in hyponatremia
What drugs are Thiazolidinediones
(TZDs)?
rosiglitazone, pioglitazone
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
What do Thiazolidinediones (TZDs) result in?
decrease in HgbA1c
When are Thiazolidinediones (TZDs) contraindicated?
These drugs contraindicated in patients w/liver failure
What should be monitored with Thiazolidinediones (TZDs)?
Must monitor plasma hepatic transaminases d/t possibility of drug-induced liver dysfunction
What are Glucagon-Like Peptide-1 Receptor Agonists (GLP-1) drugs?
liraglutide, semaglutide
What are the characteristics of GLP-1 agonists?
are injectable agents that bind to receptors in pancreas, GI tract, & brain
What does binding of GLP-1 agonists result in?
increased insulin secretion from β cells, decreasing glucagon production from α cells in pancreas
What is the result of GLP-1 agonists?
These drugs result in slowing of gastric emptying, reducing appetite, weight loss
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)
Where is Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2) present?
SGLT2 is a transport protein present in proximal tubule
What is SGLT2 responsible for?
responsible for approx. 90% glucose reabsorption in the kidneys
What do SGLT2 inhibitors cause?
These drugs lower serum glucose levels by increasing glucose excretion in the kidneys via osmotic diuresis
What are examples of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2)?
empagliflozin, canagliflozin, dapagliflozin, ertugliflozin
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
What is the PO Dipeptidyl-Peptidase-4 (DPP-4) Inhibitors?
saxagliptin, sitagliptin, linagliptin, alogliptin, vildagliptin
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
What is the side effects of Dipeptidyl-Peptidase-4 (DPP-4) Inhibitors?
musculoskeletal pain, pancreatitis
What is the recommendation for herbal medications?
General recommendation is two stop 2-3 weeks before surgery
Review herbal medications.
How many people use St. John’s Wart?
7.5 million Americans take regularly
What is the use for St. John’s Wart?
Used for anxiety, depression, sleep disorders
What effect can St. John’s Wart have on anesthesia?
May intensify or prolong the effects of opioids and thus the anesthetic
How many individuals take Ginkgo Biloba?
11 million Americans take regularly
What is the use for Ginkgo Biloba?
Used to improve memory, enhance blood circulation
What is the effect of Ginkgo Biloba on anesthesic?
- May reduce platelet function and clotting formation
- Acts as an anticoagulant
What are 4G’s are increased bleeding risk?
garlic, ginseng, gingko, ginger (and Vit E)
What is the most popular herbal preparation?
Ginseng
What is the use of Ginseng?
Used for vitality, fatigue, and cancer prevention
What are the properities of Ginseng?
- May cause episodes of tachycardia and hypertension
- May have anticoagulant properties
