insulins

Question 1

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

Answer 1

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

Question 2

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

Answer 2

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

Question 3

Insulin Aspart and Glulisine

Aspart (___), Glulisine (____)

___ ____-acting analogues

Profile of action and therapeutic benefits similar to ___

Onset: __-___ minutes

Peak: ___-___ minutes

Duration: __-__ hours

Answer 3

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

Question 4

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 ____

Answer 4

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

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

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

Answer 7

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

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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

Question 10

1. 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)

Answer 10

Five Main Side Effects

1. 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)

Question 11

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: ____)

Answer 11

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)

Question 12

Five Main Side Effects

2. 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 ____

Answer 12

Five Main Side Effects

2. 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

Question 13

Five Main Side Effects

3. Lipodystrophy - fat ___ at site of ___ injection

Answer 13

Five Main Side Effects

3. Lipodystrophy - fat atrophies at site of SQ injection

Question 14

Five Main Side Effects

4. Insulin Resistance
   - If patient requires > _)___ U insulin daily = “insulin resistance”
   - Acute insulin resistance is associated with ___ from ___/____
5. 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____

Answer 14

Five Main Side Effects

4. Insulin Resistance
   - If patient requires > 100 U insulin daily = “insulin resistance”
   - Acute insulin resistance is associated with trauma from infection/surgery
5. 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

Question 15

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)

Answer 15

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)

Question 16

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 ____

Answer 16

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

Question 17

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 _____

Answer 17

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

Question 18

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

Answer 18

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

Question 19

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

Answer 19

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

Question 20

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

Answer 20

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

Question 21

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

Answer 21

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

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

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 ____

Answer 24

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

Question 25

Glyburide Metabolism: \_\_\_\_ Metabolite excretion: Urine/feces One metabolite has \_\_\_% activity of parent compound Mild ___ effect Plasma clearance in ___ hours after discontinuation

Answer 25

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

Question 26

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 \_\_\_

Answer 26

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**

Question 27

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

Answer 27

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

Question 28

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

Answer 28

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

Question 29

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

Answer 29

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

Question 30

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 \_\_\_**

Answer 30

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**

Question 31

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 \_\_\_\_\_

Answer 31

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%**

Question 32

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**

Answer 32

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**

Question 33

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

Answer 33

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

Question 34

Thiazolidinediones (TZDs) Especially effective in ___ patients Decrease HbA1c by \_\_\_\_\_% Clinical effect takes \_\_\_-\_\_\_\_ weeks Can cause _____ (partly ECF - \_\_\_\_) Contraindicated: \_\_\_, ____ failure

Answer 34

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

Question 35

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

Answer 35

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

Question 36

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 \_\_\_\_

Answer 36

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

Question 37

Amylin Agonists **• \_\_\_\_\_\_which drug?** **• _______ alter insulin levels** * Suppress gastric emptying, inhibit glucagon release and reduce HbA1c levels * Side effects:nausea/vomiting

Answer 37

Amylin Agonists **• Pramlintide** **• Do not alter insulin levels** * Suppress gastric emptying, inhibit glucagon release and reduce HbA1c levels * Side effects:nausea/vomiting

Question 38

Other Medications - **Colesevalam** (\_\_\_\_sequestrant) and **bromocriptine mesylate** (\_\_\_ receptor agonist) lower glucose levels and decrease HbA1c (mechanism \_\_\_\_) - Not associated with hypoglycemia - May cause GI intolerance

Answer 38

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

Question 39

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

Answer 39

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

Question 40

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 \_\_\_\_

Answer 40

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

Question 41

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**

Answer 41

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**

Question 42

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

Answer 42

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

Question 43

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

Answer 43

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

Question 44

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**

Answer 44

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**

Question 45

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**

Answer 45

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**

Question 46

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

Answer 46

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