Diabetes Drugs Flashcards by Luke Wilkins

What type of substance is Insulin?

Hormone

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Where in the body is Insulin made?

pancreatic beta cells

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How does insulin effect blood glucose levels?

facilitates uptake of glucose into skeletal muscle and adipose tissue by increasing nbr of glucose transporters (GLUT 1 & GLUT 4)

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What is the molecular structure of insulin?

2 amino acid chains (A&B) - 51 amino acids, 3 disulfide bonds

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Disease: not enough insulin

Type I / IDDM / Juvenile Onset Diabetes

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Disease: response to insulin not adequate

Type II / NIDDM / Adult Onset Diabetes

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what condition does insulin treat other than diabetes?

hyperkalemia

(IV-Insulin –> dose-dependent decline in serum potassium

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Treatment for Hyperkalemia

10 units IV insulin  +
25g dextrose
lowers serum potassium by 
1 meq/L (mmol/L) w/in 10-20 min
lasts 4-6 hours

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ECG changes from hyperkalemia

peaked T-waves (think peaked, potassium, Paris - Eiffel Tower)

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Insulin production - basal rate

1 U/hr … up to 40 U/day

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Insulin (endogenous) duration of action

30-60 min

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Insulin - mechanisms of action

increase number of glucose transporters (GLUT 4) so facilitates uptake of glucose into skeletal muscle and adipose tissue

(GLUT 1 transporters respond to blood glucose levels)

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Insulin - metabolism

kidney and liver - 50% 1st pass

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IV Insulin - elimination half-time

5-10 min

but sustained effect b/c tightly bound to tissue receptors

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What is the relationship between plasma insulin concentration and number of insulin receptors?

inverse
(e.g., high glucose levels -> high insulin levels -> down regulation of insulin receptors -> insulin resistance -> need even more insulin to overcome)

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What is insulin made from?

Now: manufactured by recombinant DNA technology

Before: extracted from beef & pork (good not any more –> reduces chance of allergy)

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Categories of insulin (by duration of action)

Rapid-acting (Lispro)
Short-acting (regular - CZI - crystalline zinc insulin)
Intermediate-acting (Isophane: NPH)
Long-acting (Ultralente)

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What type of insulin do we use in the OR?

Short-acting (regular)
(e.g., Humulin or Novolin)

Only IV insulin (can also be given subQ)
From pork, beef, human, or genetically engineered w/ E. coli

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Short-acting Insulin onset/duration

Onset 30-60 min

Duration 6-8 hours

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Names for Intermediate-acting Insulin

Isophane Insulin Suspension =

Neutral Protamine Hagedorn (Humulin-N and Novolin-N)

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Where does the protamine in NPH come from?

Salmon sperm

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Intermediate-Acting Insulin onset/duration

Onset 1-2 hours

Duration 10-16 hours

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Name(s) for long-acting insulin

Ultralente

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Why is Ultralente Insulin long-acting?

Large particle size and crystalline form

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Basic approach to taking insulin daily

maintain basal level, plus rapid-acting at meal times if necessary

1 U Insulin - effect on blood glucose

1 U insulin lowers blood glucose 25-30 mg/dL

Formula for insulin dosage in OR

Units/hr = (glucose/150)

After giving insulin in the OR, how long to wait before testing blood glucose?

30 min

Most common basal insulins patients take

Lantus (glargine ~24 hrs) | Levemir (detemir ~18 hrs)

Side effects of insulin

``` Hypoglycemia Allergic reactions Lipodystrophy Resistance Drug Interactions ```

Most serious side effect of hypoglycemia

Irreversible brain damage

Initial symptoms of hypoglycemia Other symptoms

Initial: diaphoresis, tachycardia, hypertension Other: Rebound hyperglycemia CNS symptoms Treatment options

Insulin - drug interactions

Epinephrine (inhib. secretion of insulin) MAO Inhibitors (potentiate hypoglycemic effects) Antibiotics (Tetracycline) (increase duration and can cause hypoglycemia) Salicylates

Categories of oral drugs for treatment of NIDDM

Sulfonylureas Meglitinides Biguanides Aloha-Glucosidaise Inhibitors

Sulfonylureas (oral hypoglycemic) - mechanism

stimulate release of endogenous insulin | so only for Type II - Type I can't be stimulated

Sulfonylureas - risk

hypoglycemia

Sulfonylureas - example

Glyburide

Meglitinides - mechanism

stimulate insulin secretion

Meglitinides - risk

hypoglycemia

Meglitinides - example

Repaglinide

Biguanides - mechanism

inhibit glucose production by liver

Biguanides - example

Metformin

Metformin - what type of rug

Biguanide

Glyburide - what type of drug

Sulfonylurea

Alpha-Glucosidase Inhibitors - mechanism

slow digestion and absorption of carbohydrates

Alpha-Glucosidase Inhibitors - example

Arcabose

Glyburide - don't give to patient allergic to:

sulfa drugs | it's a Sulfonylurea, derivative of sulfonamide.

Sulfonylureas - Pharmacokinets

GI absorption Protein binding (90-95%) Metabolism: Liver (renal excretion)

Side effects of sulfonylureas

hypoglycemia, esp. w/long acting

Fetal effects of sulfonylureas

cross placenta - can cause fetal hypoglycemia

Glyburide (Micronase) - which generation sulfonylurea - duration

2nd generation stimulates insulin over 24 hours

Glipizide (Glucotrol) - which generation sulfonylurea - duration

2nd generation stimulates insulin over 12 hours

When to use Metformin

When sulfonylurea treatment has failed

Advantage of biguanides in treatment of NIDDM

- decrease in blood glucose with very low risk of hypoglycemia - positive effect on blood lipids - may lead to some weight loss

Risk w/biguanides in treatment of NIDDM

severe lactic acidosis

Metformin (Glucophage) - metabolism

100% renal clearance (unchanged - no hepatic metabolism) Use cautiously (or not at all) with renal failure)

Metformin (Glucophage) - mechanism of action

lowers blood glucose (inhibits hepatic gluconeogenesis, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization)

Arcabose - type of drug

Intestinal glycosidase inhibitor

Arcabose - mechanism

decreases carbohydrate digestion and absorption

Arcabose - benefits

- NO hypoglycemia | - can be used with insulin

Blood glucose level for surgery

180 (closer to 120 if possible)

How much insulin should patient take morning of surgery?

Half dose

Infusion level for Insulin

BG/150 = Units/hr

Add what when administering insulin?

10 - 20 meq KCL to each liter of IV fluid (to avoid hypokalemia)

Should patients take oral hypoglycemic agents morning of surgery?

When to discontinue oral hypoglycemics before surgery?

24-48 hours

Target blood glucose to maintain during surgery

150-180 mg/dL

Cardiac risk w/diabetic patients

occult cardiac disease (don't get angina because of de-innervation around heart)

Test to determine long-term blood glucose control (and therefore cardiomyopathy and heart failure)

Hb A1C Normal 5 7 or below = good 8-10 poor control

Diabetes Drugs Flashcards

(69 cards)