insulins Flashcards
Lispro (Humalog)
____-acting insulin
Closely parallels ____ insulin secretion and needs
Onset:within___minutes
Peak of action:__-___minutes
Duration: _-_hours
Must b eadministered ___-___ minutes before meal to limit postprandial hyperglycemia
Lispro (Humalog)
Short-acting insulin
Closely parallels physiologic insulin secretion and needs
Onset:within 15 minutes
Peak of action: 30-90 minutes
Duration:3-5hours
Must be administered 30-60 minutes before meal to limit postprandial hyperglycemia
Lispro has a lysine/proline switch that prevents hexamer formation and the ______ is rapidly absorbed
Administration just before eating provides similar profile to normal insulin secretion
**Benefit:decrease in ____ hyperglycemia and less risk of ____
___ may not decrease unless basal(NPH, detemir, glargine) doses are increased
Lispro has a lysine/proline switch that prevents hexamer formation and the monomer is rapidly absorbed
Administration just before eating provides similar profile to normal insulin secretion
**Benefit:decrease in postprandial hyperglycemia and less risk of hypoglycemia
HbA1c may not decrease unless basal(NPH, detemir, glargine) doses are increased
Insulin Aspart and Glulisine
Aspart (___), Glulisine (____)
___ ____-acting analogues
Profile of action and therapeutic benefits similar to ___
Onset: __-___ minutes
Peak: ___-___ minutes
Duration: __-__ hours
Insulin Aspart and Glulisine
Aspart (Novolog), Glulisine (Apidra)
Synthetic rapid-acting analogues
Profile of action and therapeutic benefits similar to lispro
Onset: 10-15 minutes
Peak: 45-75 minutes
Duration: 2-4 hours
Regular Insulin
___, ____, ____
_____ zinc insulin
___-acting preparation
ONLY preparation that can be given ___ and___
Can be mixed in ___ syringe as other insulin if ___ is similar
Preferred for treatment of ___ onset of ____ or ____
Regular Insulin
HumulinR, NovolinR, ReliOnR
Crystalline zinc insulin
Fast-acting preparation
ONLY preparation that can be given IV and SQ
Can be mixed in same syringe as other insulin if pH is similar
Preferred for treatment of abrupt onset of hyperglycemia or ketoacidosis
Regular Insulin
Perioperative: Single dose (___-_____ U) or infusion (___- ____ U/hr)
Onset: ____ minutes
Peak: __-____ hours after SQ injection because of inulin ____
Duration: ___-_____hours
Maximal effect when given ___-____ minutes before a meal
Regular Insulin
Perioperative: Single dose (1-5U) or infusion (0.5- 2.0 U/hr)
Onset: 30 minutes
Peak: 2-4 hours after SQ injection because of inulin hexamers
Duration: 6-8hours
Maximal effect when given 30-60 minutes before a meal
Neutral Protamine Hagedorn (NPH)
_____-acting
Absorption from SQ site is delayed due to ___ with ____
Preparation contains _____ protamine/U of insulin
Onset:___hour
Peak: ____ hours
Duration:_____ hours
Neutral Protamine Hagedorn (NPH)
Intermediate-acting
Absorption from SQ site is delayed due to conjugation with protamine
Preparation contains 0.005mg protamine/U of insulin
Onset:2 hour
Peak: 4-12 hours
Duration:18-28 hours
Detemir (Levemir)
_____-acting insulin: analogue for ____ replacement
Onset: ___hours
Peak: ___-____ hours
Duration: __-_____ hours
Can be administered as single ___ time injection to provide ___ insulin for ____ hours with less nocturnal _____
____ be mixed with ____-acting insulins
Detemir (Levemir)
Long-acting insulin: analogue for basal replacement
Onset: 2 hours
Peak: 3-9 hours
Duration: 6-24 hours
Can be administered as single bed time injection to provide basal insulin for 24 hours with less nocturnal hypoglycemia
Cannot be mixed with rapid-acting insulins
Glargine (Lantus)
_____-acting insulin analogue for ____ insulin replacement
____ onset of action and ____ peaks
Can bea dministered as a single ____ injection to provide ___ insulin for ___ hours with less nocturnal ____
Onset: ___ minutes
Peak: ___
Duration: _____ hours
Glargine (Lantus)
Long-acting insulin analogue for basal insulin replacement
Later onset of action and less pronounced peaks
Can bea dministered as a single bedtime injection to provide basal insulin for 24 hours with less nocturnal hypoglycemia
Onset: 90 minutes
Peak: None
Duration: 20-24+ hours
Degludec (Tresiba)
____-acting insulin analogue for ____ insulin replacement
____ be mixed with rapid-acting insulins
Onset: ___ hours
Peak: ___
Duration: ___hours
SQ ___ daily administration
Can use in __/___ impairment
Degludec (Tresiba)
Long-acting insulin analogue for basal insulin replacement
Can be mixed with rapid-acting insulins
Onset: 2 hours
Peak: None
Duration: >40 hours
SQ once daily administration
Can use in hepatic/renal impairment
- Hypoglycemia
Most ____ side effect
At risk: Receiving exogenous insulin without ____ intake, ___ period (especially ____)
First symptoms are ____ effects of increased ____ secretion: ___, ____, ____, rebound ____ caused by SNS ___ may ____ diagnosis (___ effect)
CNS symptoms of hypoglycemia: mental ___, ___, ____ (severe effects because brain depends on glucose as a selective substrate for ____ metabolism)
Five Main Side Effects
- Hypoglycemia
Most serious side effect
At risk: Receiving exogenous insulin without carbohydrate intake, perioperative period (especially preop)
First symptoms are compensatory effects of increased epinephrine secretion: diaphoresis, tachycardia, HTN, rebound hyperglycemia caused by SNS activation may mask diagnosis (Somogyi effect)
CNS symptoms of hypoglycemia: mental confusion, seizures, coma (severe effects because brain depends on glucose as a selective substrate for oxidative metabolism)
Prolonged hypoglycemia==>___ brain damage
Difficult to diagnose under __ ____(____ symptoms are masked by anesthetic drugs)
Severe hypoglycemia treatment: ____ mL of ___% ____ IV
Glucagon_____mg IV/SQ
• (Side effect: ____)
Prolonged hypoglycemia==>irreversible brain damage
Difficult to diagnose under general anesthesia(SNS symptoms are masked by anesthetic drugs)
Severe hypoglycemia treatment: 50-100 mL of 50% glucose IV
Glucagon 0.5 – 1.0 mg IV/SQ
• (Side effect: N/V)
Five Main Side Effects
- Allergic Reactions
– ___ allergic rxns __x more frequent than ____ rxns
- Type I hypersensitivity rxn most frequent
– Chronic ____ exposure in NPH may stimulate production of ___ against ____->if large dose of ____ is administered IV to antagonize anticoagulant effects of heparin-> allergic reactions to ____
Five Main Side Effects
- Allergic Reactions
– Local allergic rxns 10X more frequent than systemic rxns
- Type I hypersensitivity rxn most frequent
– Chronic protamine exposure in NPH may stimulate production of antibodies against protamine->if large dose of protamine is administered IV to antagonize anticoagulant effects of heparin-> allergic reactions to protamine
Five Main Side Effects
- Lipodystrophy - fat ___ at site of ___ injection
Five Main Side Effects
- Lipodystrophy - fat atrophies at site of SQ injection
Five Main Side Effects
- Insulin Resistance
- If patient requires > _)___ U insulin daily = “insulin resistance”
- Acute insulin resistance is associated with ___ from ___/____ - Drug Interactions
- Hormones (administered as drugs) that ___ hypoglycemic effects of insulin: ___ hormone, ___ and ____
- ____ inhibits insulin secretion and stimulates ____
- ___, ___ and ____ increase duration of action of insulin (may have hypoglycemic effect)
- Hypoglycemia may be potentiated by____
Five Main Side Effects
- Insulin Resistance
- If patient requires > 100 U insulin daily = “insulin resistance”
- Acute insulin resistance is associated with trauma from infection/surgery - Drug Interactions
- Hormones (administered as drugs) that counter hypoglycemic effects of insulin: andrenocorticotrophic hormone, estrogen and glucagon
- Epinephrine inhibits insulin secretion and stimulates glycogenolysis
- Tetracycline, salicylates and phenylbutazone increase duration of action of insulin (may have hypoglycemic effect)
- Hypoglycemia may be potentiated by monoamine oxidase inhibitors
Oral Antidiabetic Drugs
Four major classes:
– Sec___gues (___ and ___) - increase ___ availability
• _____ are usually the treatment for ____
– Bi____ides (____) – suppress excessive ____ glucose release
– Thia___diones or glitazones (___, ___) - improve insulin ___
– Alpha-____ inhibitors (___, ____): delay ___ glucose ___ (used to maintain ___ control)
Oral Antidiabetic Drugs
Four major classes:
– Secretagogues (sulfonylureas and meglitinides) - increase insulin availability
• Sulfonylureas are usually the treatment for T2DM
– Biguanides (metformin) – suppress excessive hepatic glucose release
– Thiazolidinediones or glitazones (rosiglitazone, pioglitazone) - improve insulin sensitivity
– Alpha-glucosidase inhibitors (acarose, miglitol): delay GI glucose absorption (used to maintain glucose control)
Metformin
Oral ____
Often prescribed as ____ agent for T2DM
Decreases blood glucose concentrations in both ___ and ____ state
Rarely causes ___
Can be used in combination with ___ and ____
Metformin
Oral biguanide
Often prescribed as initial agent for T2DM
Decreases blood glucose concentrations in both fasting and postprandial state
Rarely causes hypoglycemia
Can be used in combination with insulin and sulfonylureas
Metformin
Contraindications: ____, ____, ____, acute ____ disease
Improves lipid profiles and fibrinolysis ,promotes mild to moderate weight loss
Other uses: ___ , ____ fatty liver, premature ____
Not bound to plasma proteins
Does not undergo _____
Metformin
Contraindications: lactic acidosis, AKI, GI intolerance, acute hepatic disease
Improves lipid profiles and fibrinolysis ,promotes mild to moderate weight loss
Other uses: PCOS (polycyptic ovary syndrome)__ , nonalcoholic fatty liver, premature puberty
Not bound to plasma proteins
Does not undergo metabolism
Metformin
Elimination via ____
90% oral dose is excreted in ___hours
Peak plasma concentration:___hours
Elimination half-time: __to ___ hours
Prescribed: __ID (____) with ___
Due to dependence on ___ clearance, caution in patients with renal dysfunction
Metformin
Elimination via kidneys
90% oral dose is excreted in12 hours
Peak plasma concentration:2 hours
Elimination half-time: 2 to 4 hours
Prescribed: TID (500-1000mg) with meals
Due to dependence on renal clearance, caution in patients with renal dysfunction
Metformin
MOA: blood glucose-lowering effect is ___ mediated through stimulation of endogenous ___ secretion
Activates ___ ___-activated ___ ___ase to suppress hepatic glucose production by decreasing ___ and ____ and to enhance postprandial insulin suppression of ___ glucose production
Also regulates glucose by decreasing GI absorption, increasing insulin sensitivity in peripheral tissues and enhancing synthesis of glucagon-like peptide-1 in ileum
Metformin
MOA: blood glucose-lowering effect is NOT mediated through stimulation of endogenous insulin secretion
Activates adenosine monophosphate-activated protein kinase to suppress hepatic glucose production by decreasing gluconeogenesis and glycogenolysis and to enhance postprandial insulin suppression of hepatic glucose production
Also regulates glucose by decreasing GI absorption, increasing insulin sensitivity in peripheral tissues and enhancing synthesis of glucagon-like peptide-1 in ileum
Metformin
Side Effects: anorexia, nausea, diarrhea
Does not cause ___\_
Associated with vitamin B12 deficiency
Lactic Acidosis
– Possible side effect of metformin therapy
– Discontinue ____hours before elective surgery
– Monitor for lactic acidosis (ABG, serum lactate, renal function)
– Anaerobic metabolism results in pyruvate==>reduced to lactate
– Do not administer in patients with ___ dysfunction, ____ insufficiency (creatinine > ___ mg/dL), IV ___, acute___, ___, arterial ___, ___\_
– Treatment: hemodialysis, bicarbonate administration
Metformin
Side Effects: anorexia, nausea, diarrhea
Does not cause hypoglycemia
Associated with vitamin B12 deficiency
Lactic Acidosis
– Possible side effect of metformin therapy
– Discontinue 48 hours before elective surgery
– Monitor for lactic acidosis (ABG, serum lactate, renal function)
– Anaerobic metabolism results in pyruvate==>reduced to lactate
– Do not administer in patients with hepatic dysfunction, renal insufficiency (creatinine > 1.5 mg/dL), IV contrast dye, acute MI, CHF, arterial hypoxemia, sepsis
– Treatment: hemodialysis, bicarbonate administration
Sulfonylureas
Can lower glucose levels to hypoglycemic levels
Improved blood glucose control, decreased hepatic production of very low-density lipoproteins, improved hypertriglyceridemia
Up to___% of patients do not have adequate _____response to maximal doses (primary failures) and another _____% of patients who initially respond will ______ to therapy each year (secondary failure)
Successful treatment requires some _____ function
Do not administer to patients with ____ allergy
Sulfonylureas
Can lower glucose levels to hypoglycemic levels
Improved blood glucose control, decreased hepatic production of very low-density lipoproteins, improved hypertriglyceridemia
Up to 20% of patients do not have adequate hypoglycemic response to maximal doses (primary failures) and another 10-15% of patients who initially respond will fail to respond to therapy each year (secondary failure)
Successful treatment requires some beta cell function
Do not administer to patients with sulfa allergy
Sulfonylurea Oral Hypoglycemics
MOA: act on ___ receptors on ___ and ____ cells; inhibit ___ ___ sensitive ____channels on pancreatic ___ cells resulting in ____ influx and simulation of ____ release
Decrease insulin resistance
Minor effect in decreasing blood glucose concentrations
Biological effects may be longer than plasma half-lives because of formation of ______metabolites
Weak____, circulate bound to protein (______%) and are eliminated by renal tubular secretion and in feces
Sulfonylurea Oral Hypoglycemics
MOA: act on sulfonylurea receptors on pancreatic and cardia cells; inhibit adenosine triphosphate sensitive K+ channels on pancreatic beta cells resulting in Ca2+ influx and simulation of insulin release
Decrease insulin resistance
Minor effect in decreasing blood glucose concentrations
Biological effects may be longer than plasma half-lives because of formation of active metabolites
Weak acids, circulate bound to protein (90-98%) and are eliminated by renal tubular secretion and in feces
Sulfonylurea Oral Hypoglycemics
____, while infrequent, is more often ___ and more ____ than hypoglycemia from insulin
Treat hypoglycemia with prolonged infusions of glucose- containing solutions
Renal disease decreases elimination of sulfonylureas and their active metabolites (greater risk for hypoglycemia)
Cross _____ (risk for ____ hypoglycemia)
Close _____ channels and inhibit ____ preconditioning (_____ mechanism)
May discontinue _____ hr preop for high-risk patients
Sulfonylurea Oral Hypoglycemics
Hypoglycemia, while infrequent, is more often prolonged and more dangerous than hypoglycemia from insulin
Treat hypoglycemia with prolonged infusions of glucose- containing solutions
Renal disease decreases elimination of sulfonylureas and their active metabolites (greater risk for hypoglycemia)
Cross placenta (risk for fetal hypoglycemia)
Close K-ATPase channels and inhibit ischemic preconditioning (cardioprotective mechanism)
May discontinue 24-48 hr preop for high-risk patients
Glyburide
Stimulates insulin secretion over___hrperiod
Dose: _____ daily (__D/___ID)
Peak plasma levels: __ hours
DOA:___-___ hours
Elimination half-time: ___-___hours
MOA:increases insulin ____ and inhibits liver production of ____
Glyburide
Stimulates insulin secretion over 24-hrperiod
Dose: 2.5–20mg daily (QD/BID)
Peak plasma levels: 3 hours
DOA:18-24 hours
Elimination half-time: 4.6-12 hours
MOA: increases insulin sensitivity and inhibits liver production of glucose
Glyburide
Metabolism: ____
Metabolite excretion: Urine/feces
One metabolite has ___% activity of parent compound
Mild ___ effect
Plasma clearance in ___ hours after discontinuation
Glyburide
Metabolism:Liver
Metabolite excretion: Urine/feces
One metabolite has 15% activity of parent compound
Mild diuretic effect
Plasma clearance in 36 hours after discontinuation
Glipizide
Dose: ____mg daily
QD/BID dosing
DOA: ____ hours
Elimination half-time: ___ hours
Peak plasma levels: 1 hour after PO administration
Stimulates insulin secretion over 12-hour period
MOA: increases glucose uptake and suppresses liver glucose output – effects persist for prolonged periods without tolerance
Metabolism: Liver -> ___ substances (urine)
____ plasma clearance minimizes risk for ___
Glipizide
Dose: 5-40 mg daily
QD/BID dosing
DOA: 12-24 hours
Elimination half-time: 4-7 hours
Peak plasma levels: 1 hour after PO administration
Stimulates insulin secretion over 12-hour period
MOA: increases glucose uptake and suppresses liver glucose output – effects persist for prolonged periods without tolerance
Metabolism: Liver -> inactive substances (urine)
Rapid plasma clearance minimizes risk for hypoglycemia
Glimepiride
Dose:____mg daily
QD/BID dosing
DOA:___hours
Elimination half-time: ____hour
MOA:Decreases blood glucose by ___ release of __ from ___ and may decrease ___ glucose production
Combined with insulin therapy when ____ are not effective
Glimepiride
Dose: 2-4mg daily
QD/BID dosing
DOA:24+ hours
Elimination half-time: 5-8 hour
MOA:Decreases blood glucose by stimulating release of insulin from pancreas and may decrease hepatic glucose production
Combined with insulin therapy when sulfonylureas are not effective
Meglitinides
____ and ____
Exert effects on beta cells (similar to sulfonylurea)
Peak effect in 1 hour
DOA about 4 hours
Beta cell stimulation lowers HbA1c by 1%
Administer 15-30 minutes before meal
Never ingest while ___
____ DOA in the presence of glucose should lower risk of prolonged ___
Metabolism: Liver
Meglitinides
Repaglinide and Nateglinide
Exert effects on beta cells (similar to sulfonylurea)
Peak effect in 1 hour
DOA about 4 hours
Beta cell stimulation lowers HbA1c by 1%
Administer 15-30 minutes before meal
Never ingest while fasting
Short DOA in the presence of glucose should lower risk of prolonged hypoglycemia
Metabolism: Liver
Repaglinide (Prandin)
class ____
MOA: stimulates release of ___ from beta islet cells of pancreas
Protein binding > 98%
Excretion by kidneys is ____ – no need to dose adjust for renal insufficiency
Metabolism: Liver oxidation and glucuronidation (CYP3A4)
Elimination half-life: 1 hour
Excretion: Fecal, urine
Repaglinide (Prandin)
Meglitinide
MOA: stimulates release of insulin from beta islet cells of pancreas
Protein binding > 98%
Excretion by kidneys is minimal – no need to dose adjust for renal insufficiency
Metabolism: Liver oxidation and glucuronidation (CYP3A4)
Elimination half-life: 1 hour
Excretion: Fecal, urine
Nateglinide (Starlix)
class: _____
MOA: lowers blood glucose by stimulating release of insulin from pancreas
Metabolism: Liver
Metabolites excreted by kidney
Protein binding: 98%
Elimination half-life: 1.5 hours
Accumulation of ___ metabolites may cause ___
Nateglinide (Starlix)
Meglitinide
MOA: lowers blood glucose by stimulating release of insulin from pancreas
Metabolism: Liver
Metabolites excreted by kidney
Protein binding: 98%
Elimination half-life: 1.5 hours
Accumulation of active metabolites may cause hypoglycemia
Alpha-Glucosidase Inhibitors
• ___ and ___
• Decrease ____ digestion and absorption of ___ by interfering with intestinal ___ activity
- Slower release of glucose from food anda bsorption from GI tract
- HbA1c decreases _____
Alpha-Glucosidase Inhibitors
• Acarbose and Miglitol
• Decrease carbohydrate digestion and absorption of disaccharides by interfering with intestinal glucosidase activity
- Slower release of glucose from food anda bsorption from GI tract
- HbA1c decreases 0.5-0.8%
Alpha-Glucosidase Inhibitors
Useful as _____ when ____ hyperglycemia is the problem
Side effects:flatulence, abdominal __ and ___, increases in liver ___
– Due to undigested ___ that reach ___ in the lower colon
No __ with monotherapy
Alpha-Glucosidase Inhibitors
Useful as monotherapy when postprandial hyperglycemia is the problem
Side effects:flatulence, abdominal cramping and diarrhea, increases in liver transaminases
– Due to undigested carbohydrates that reach bacteria in the lower colon
No hypoglycemia with monotherapy
Thiazolidinediones (TZDs)
____ and _____
Act at ___ muscle, ___ and ___ tissue via _____ proliferator activator receptor-gamma to decrease insulin ____ and hepatic glucose ___, and to increase use of ____ by liver
Insulin ____
Decrease insulin ___
Act in the _____ of insulin
Thiazolidinediones (TZDs)
Rosiglitazone and Pioglitazone
Act at skeletal muscle, liver and adipose tissue via peroxisome proliferator activator receptor-gamma to decrease insulin resistance and hepatic glucose production, and to increase use of glucose by liver
Insulin sensitizers
Decrease insulin resistance
Act in the presence of insulin
Thiazolidinediones (TZDs)
Especially effective in ___ patients
Decrease HbA1c by _____%
Clinical effect takes ___-____ weeks
Can cause _____ (partly ECF - ____)
Contraindicated: ___, ____ failure
Thiazolidinediones (TZDs)
Especially effective in obese patients
Decrease HbA1c by 1-1.5%
Clinical effect takes 4-12 weeks
Can cause weight gain (partly ECF - ____)
Contraindicated: CHF, liver failure
Glucagon-like Peptide-1 Receptor Agonists
GLP-1 receptor agonists
Long-acting and short-acting
[list of drugs]
Injectable agents that bind to receptors in pancreas, GI tract and brain to increase ___ secretion from ____ cells (glucose dependent), decrease ____ production from ____ cells and reduce gastric ___
Reduced ___ and ____ loss
Side effects:nausea/vomiting
Risk of hypoglycemia increases if combined w/ sulfonylurea
Exenatide – short and long-acting formulations, ____ weekly injections
Liraglutide – half life 8-14 hours; injected QD
Glucagon-like Peptide-1 Receptor Agonists
GLP-1 receptor agonists
Long-acting and short-acting
Exenatide, Lixisenatide, Liraglutide, Dulaglutide, Semaglutide
Injectable agents that bind to receptors in pancreas, GI tract and brain to increase insulin secretion from beta cells (glucose dependent), decrease glucagon production from alpha cells and reduce gastric emptying
Reduced appetite and weight loss
Side effects:nausea/vomiting
Risk of hypoglycemia increases if combined w/ sulfonylurea
Exenatide – short and long-acting formulations, once weekly injections
Liraglutide – half life 8-14 hours; injected QD
Dipeptidyl-Peptidase-4 Inhibitors
DDP-4 Inhibitors enhance the ___ effect via inhibition of native GLP-1 degradation
___liptin, ____liptin, ___liptin, ___liptin, ___liptin
Increase insulin ___ from ___ cells(glucose dependent) and reduce pancreatic alpha cell secretion of ___
DOA:12-24 hours
Reduce dose for renal ____
Dipeptidyl-Peptidase-4 Inhibitors
DDP-4 Inhibitors enhance the incretin effect via inhibition of native GLP-1 degradation
Saxagliptin, Sitagliptin, Linagliptin,Alogliptin, Vildagliptin
Increase insulin secretion from beta cells(glucose dependent) and reduce pancreatic alpha cell secretion of glucagon
DOA:12-24 hours
Reduce dose for renal insufficiency
Amylin Agonists
• ______which drug?
• _______ alter insulin levels
- Suppress gastric emptying, inhibit glucagon release and reduce HbA1c levels
- Side effects:nausea/vomiting
Amylin Agonists
• Pramlintide
• Do not alter insulin levels
- Suppress gastric emptying, inhibit glucagon release and reduce HbA1c levels
- Side effects:nausea/vomiting
Other Medications
- Colesevalam (____sequestrant) and bromocriptine mesylate (___ receptor agonist) lower glucose levels and decrease HbA1c (mechanism ____)
- Not associated with hypoglycemia
- May cause GI intolerance
Other Medications
- Colesevalam (bile acid sequestrant) and bromocriptine mesylate (dopamine receptor agonist) lower glucose levels and decrease HbA1c (mechanism unclear)
- Not associated with hypoglycemia
- May cause GI intolerance
Combination Therapy
Target two or more causes of hyperglycemia simultaneously
Metformin (decrease ____ in liver)+ sulfonylurea (increased insulin ___)
Exogenous insulin may also be apartof combination therapy
Primary aim:decrease ___
Secondary aim:decrease in ____dose
Combination Therapy
Target two or more causes of hyperglycemia simultaneously
Metformin (decrease insulin resistance in liver)+ sulfonylurea (increased insulin secretion)
Exogenous insulin may also be apartof combination therapy
Primary aim:decrease HbA1c
Secondary aim:decrease in daily insulin dose
Anesthetic Implications
• DM+HTN=___% likelihood of diabetic ___ ___ (decreased ability to compensate/risk of CV ___/sudden cardiac death)
Incidence of periop CV instability is increased by concomitant use of ____ inhibitors or angiotensin receptor blockers
Autonomic dysfunction->delayed gastric emptying (gastroparesis)->premed with nonparticulate ___ and ____
Anesthetic Implications
• DM+HTN=50% likelihood of diabetic autonomic neuropathy (decreased ability to compensate/risk of CV instability/sudden cardiac death)
Incidence of periop CV instability is increased by concomitant use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
Autonomic dysfunction->delayed gastric emptying (gastroparesis)->premed with nonparticulate antacid and metoclopramide
Anesthetic Implications
Diabetic renal dysfunction – elevated serum creatinine – Most T1DM have kidney disease by ___years of age
Glycosylation of tissue proteins and limited mobility of joints
– ___ joint and ___ spine mobility should be assessed preoperatively in diabetic patients to assess for risk for ____
– Difficult intubation ~ ____% of T1DM
Intraoperative blood glucose management to avoid hypoglycemia
– Keep glucose < ____mg/dL
Anesthetic Implications
Diabetic renal dysfunction – elevated serum creatinine – Most T1DM have kidney disease by 30 years of age
Glycosylation of tissue proteins and limited mobility of joints
– Temporomandibular joint and cervical spine mobility should be assessed preoperatively in diabetic patients to assess for risk for difficult intubation
– Difficult intubation ~ 30% of T1DM
Intraoperative blood glucose management to avoid hypoglycemia
– Keep glucose < 180 mg/dL
Anesthetic Implications
Hyperglycemia associated with:hyperosmolarity, ____, poor wound ___, increased mortality
Sever hyperglycemia->worse ___ outcomes following ischemia (CV surgery/acute MI)
Keep glucose
Control blood glucose levels important in ___ diabetic patients to improve ___ outcomes
Anesthetic Implications
Hyperglycemia associated with:hyperosmolarity, infection, poor wound healing, increased mortality
Sever hyperglycemia->worse neurological outcomes following ischemia (CV surgery/acute MI)
Keep glucose<180mg/dL during CPB
Control blood glucose levels important in pregnant diabetic patients to improve fetal outcomes
Anesthesia Management
“Time-honored” approach– patient takes 2/3 nighttime insulin (NPH/regular) and 1⁄2 total morning insulin dose in form of intermediate- acting insulin (NPH)
AM dose of regulari nsulin should _____
• For pump: decrease overnight rate by ____% and keep at basal rate for ____
• If patient takes glargine and lispro/aspart daily,t ake2/3 glargine dose and entire lispro/aspart the night before; hold all ___ dosing
Anesthesia Management
“Time-honored” approach– patient takes 2/3 nighttime insulin (NPH/regular) and 1⁄2 total morning insulin dose in form of intermediate- acting insulin (NPH)
AM dose of regulari nsulin should be held
• For pump: decrease overnight rate by 30% and keep at basal rate for DOS
• If patient takes glargine and lispro/aspart daily,t ake2/3 glargine dose and entire lispro/aspart the night before; hold all AM dosing
Anesthesia Management
Insulin is then administered after IV access and blood glucose level checked
Alternatively, administer regular insulin via infusion
Add regular insulin to NS in concentration of ____ and begin at ___(wt based dose) (Target: glucose < ___ mg/dL)
Regular insulin – Units per hour = plasma glucose/____
One unit of regular insulin usually lowers plasma glucose by ___-____ mg/dL
Anesthesia Management
Insulin is then administered after IV access and blood glucose level checked
Alternatively, administer regular insulin via infusion
Add regular insulin to NS in concentration of 1 unit/mL and begin at 0.02 -0.1 unit/kg/hr (Target: glucose < 180 mg/dL)
Regular insulin – Units per hour = plasma glucose/150
One unit of regular insulin usually lowers plasma glucose by 25-30 mg/dL
Anesthesia Management
Oral medications – can continue drugs until ____
Sulfonylureas and metformin have long half-lives, discontinue ____hours before surgery
Can restart postop when patient resumes PO intake
Stress causes increased catecholamines, glucocorticoids and growth hormones->stress hyperglycemia and ___ insulin requirements
Monitor plasma glucose levels frequently (insulin infusions – monitor ___ minutes or ____)
Pumps: continue ____ infusion settings
Anesthesia Management
Oral medications – can continue drugs until day of surgery
Sulfonylureas and metformin have long half-lives, discontinue 24-48 hours before surgery
Can restart postop when patient resumes PO intake
Stress causes increased catecholamines, glucocorticoids and growth hormones->stress hyperglycemia and increased insulin requirements
Monitor plasma glucose levels frequently (insulin infusions – monitor q30 minutes or hourly)
Pumps: continue basal infusion settings
Sodium-Glucose Cotransporter 2 Inhibitors
____2 – transport protein in proximal tubule responsible for 90% of _____ in kidneys
Gliflozins – orally administered agents
Empagli____ and Canagli____
MOA: rely on normal renal function to lower serum glucose levels by increasing glucose excretion in kidneys
Weight loss and reduced blood pressure
Side effects: hypotension, AKI, urinary tract infection, reduced bone mineral density
Sodium-Glucose Cotransporter 2 Inhibitors
SGLT2 – transport protein in proximal tubule responsible for 90% of glucose reabsorption in kidneys
Gliflozins – orally administered agents
Empagliflozin and Canagliflozin
MOA: rely on normal renal function to lower serum glucose levels by increasing glucose excretion in kidneys
Weight loss and reduced blood pressure
Side effects: hypotension, AKI, urinary tract infection, reduced bone mineral density
