Diabetes-Pharm

Front 1

types of Diabetes

Back 1

Type I: autoimmune destruction of Beta cells

Type 2: defects in insulin sensitivity

Front 2

diagnosis and screening

Back 2

-screening fasting plasma glucose levels every 3 yrs at age 45
- fasting glucose >/= 125 is diagnostic
-sx and random BGL >/= 200
-2 hr glucose >/= 200 during oral gluc tolerance test
-impaired gluc tol >/= 110 FBS

Front 3

diabtetes treatment goals

Back 3

1. reduce risk of complications
2. maintain BP <130/80
3. near nml glycemia
4. reduction of other CV risk factors
5. improve QOL
6. HbA1C target <7%
7. glycemic goals:
-preprandiol 80/90 - 120/130
-bedtime 11/110 - 140/150
-postprandial: <140-180

Front 4

therapy for DM

Back 4

1. insulin
2. sulfonylureas
3. short acting secretagogues
4. Biguanides
5. Thiazolidinecdiones
6. Alpha- glucosidase inhibitors

Front 5

Insulin

Back 5

-made from beta cells of pancreatic islets
-effects: anabolic and anticatabolic
-protein synthesis, glycogen synthesis, glucose uptake, lipogenesis, lipid synthesis, TG uptake into cells

Front 6

How does insulin lower blood glucose?

Back 6

-by inhibiting hepatic production and stimulating uptake and metabolism of glucose by muscle and adipose tissue

Front 7

regulation of insulin secretion

Back 7

-glucose, aa, fatty acids and ketone bodies --> stimulates insulin secretion
-stim of alpha 2 receptors --> inhibits insulin release
-Insulin binds to surface receptor causes intracellular cascade leading to tranlocation of glucose transporters and movement of glucose into cell

Front 8

Pharmacokinetics of insulin

Back 8

-onset, peak and duration of effects varies with type of insulin
-short, intermediate and long acting
-combo therapies

Front 9

Incretins

Back 9

-peptide hormones released from intestinal cells in response to a meal
-Glucagon-like peptide (GLP-1)
-MOA: binds to receptors on beta cells and
1. stimulate insuline synthesis and insulin release when glucose is high
2. suppresses glucagon release
3. slow rate of gastric empyting
4. triggers sense of satiety in brian

Front 10

Amylin

Back 10

-neuroendocrine hormone co-secreted with insulin postprandially
-effects:
1. slows release of food from stomach into SI
2. other glucose lowering effects
3. new amylin analog for insulin using DM is available

Front 11

Sulfonylureas

Back 11

-insulin secretagogues
-MOA: bind to and block K+ channels on beta cells --> less K+ leaks out of cells causing depol and opening of Ca++ channels --> insulin secretion
-liver metabolism, renal excretio

Front 12

first generation sulfonylureas

Back 12

not used anymore
-less potent, more DI, more variability in half lives

Front 13

second generation sulfonylureas

Back 13

-short half lives with extended hypoglycemic effects
-near nml wt. type 2 DM may start with this
-can be used as monotherapy but generally combined with metformin
1. Glimepiride
2. Glipizide (glucotrol)

Front 14

sulfonylureas AE

Back 14

1. hypoglycemia --> most common
2. wt gain
3. N/V
4. rash
5. BM suppression
6. hyponatremia
7. wearing off effect

Front 15

sulfonylureas DI

Back 15

1. displacement of SU from protein binding sites
-Salicylates, sulfonamides
2. Decreased urinary excretion of SU
-Allopurinol and probenecid

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short acting secretagogues

Back 16

1. Repaglinide (Prandin)
2. Nateglinide (Starlix)
-MOA: similar to sulfonylureas--> stimulates insulin release
-role: reduce postprandial blood glucose levels
-give a few min before meals
-short half life
-metabolized by liver
-less frequent hypoglycemia

Front 17

Biguanides

Back 17

-Metformin
-MOA: decrease hepatic glucose production and enhances insulin uptake and action in muscle and fat tissues
-DOES NOT affect insulin release
-role: FIRST LINE FOR OVERWT/OBESE TYPE 2 DM
-renal elimination so pts with renal impairment do NOT get metformin

Front 18

Metformin AE and DI

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1. N/V/D and flatulence
2. anorexia
3. start low and take with meals
4. lactic acidosis* (avoid in pts with renal failure, unstable CHF, hypoxemia, sepsis or shock)

DI: Cimetidine; withhold for 48hrs after IV contrast

Front 19

Metformin combo products

Back 19

1. Glucovance: glyburide + metformin
2. Actoplus Met: metformin + pioglitazone

Front 20

Thiazolininediones (glitazones or TZDs)

Back 20

1. Rosiglitazone (Avandia)
2. Pioglitazone (Actos)*
-MOA: insulin sensitizers; bind to receptor which activates insulin sensitive genes --> reduce peripheral insulin resistance and may lower liver glucose production
-delayed clinical effects 6-12wks
-metabolized by the liver
-regular LFT monitoring
-used in combo!

Front 21

glitazones AE

Back 21

1. edema
2. wt gain
3. liver toxicity
4. dec bone density
5. black box warning --> HF!

Front 22

Alpha-glucosidase inhibitors

Back 22

1. Acarbose (Precose)
2. Miglitol (Glyset)
-MOA: reduce intestinal absorption of starch and disaccarides by inhibiting the intestinal brush border alpha glucosidase
-role:
1. reduction of postprandial bl gluc
2. modest effect on overall glycemic control
3. good add on therapy

Front 23

Alpha-glucosidase inhibitors- AE

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1. flatulence, malabsorption, diarrhea, abd cramps
-give once daily with meals and inc as tolerated

Front 24

Januvia (sitagliptin)

Back 24

-new drug
-inhibits enzyme that breaks down incretins
-add to metformin or glitazone in poorly controlled DM type 2
-reducing postprandial bl glucose

AE: URI, HA, sore throat
-cat B

Front 25

Onglyza (saxagliptin)

Back 25

-MOA: DPP IV inhibitor --> increase in incretins
-reduction in postprandial/FBS

-AE: URI, HA, UTI

Front 26

Increyin analog

Back 26

1. Byetta: subQ
-MOA: incretin analog; enhances meal-related insulin release, moderates meal related glucogon release, delays gastric emptying and reduces food intake

AE: hypoglycemia**, N/V/D and jittery feeling

Front 27

Liraglutide (Victoza)

Back 27

-glucagon-like peptide-1 receptor agonist
-once daily injection
-not recommended for first line tx
-AE: HA, N/D, wt loss, association with pancreatitis

Front 28

Amylin analog

Back 28

-Symlin
-role: type 2 and tpe 1 DM without adequate glucose control
-given with meals
-NO MIXING
-AE: hypoglycemia*, must lower bolus insulin dose, N/V/D

Front 29

Diabetic Ketoacidosis mgmt

Back 29

1. correct fluid deficit with NS then 1/2 NS infusion
2. insulin IV when BGL <250
3. Potassium replacement once urine output established and level is <5.0
4. Correct PO4 and Mg deficiencies

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Hyperglycemic hyperosmolar state

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-severe hyperglycemia and dehydraiton
1. NA then 1/2 NS to correct fluid deficits
2. correct potassium, Mg and PO4 deficits
3. add insulin
4. monitor vs, lytes and BGL

Front 31

Preperations of insulin

Back 31

1. Generated by human recombinant DNA
-subQ, IV
2. Short acting: rapid onset, injected 30 min or directly before meals
-rapid acting: lispro and aspart
3. Intermediate: NPH
4. Long: Glargine, Detemir
-onset of action, peak, duration

Front 32

rapid acting insulines

Back 32

1. Lispro - onset <25 min, peak .5-1.5 hrs, duration 3-4 hrs
2. Apart - same
3. Glulisine - onset 10-15 min, peak 1-1.5 hrs, duration 3-5 hrs (dosed right when they are going to start eating)

Front 33

Short acting insulin

Back 33

1. Regular insulin
onset = .5-1hr
peak = 2-3 hrs
duration = 3-6 hrs
-30 min before eating
-booster

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intermediate acting insulin

Back 34

1. NPH:
onset = 2-4 hrs
peak = 6-10
duration = 10-16
-dosed 2 times per day
-mimic a basal
-often combined with a regular or rapid acting insulin (premixed)

Front 35

long acting insulin

Back 35

1. Ultralente: onset 6-10, peak 10-16, duration 18-20
2. Glargine (lantus):onset 1 hr, peak -, duration 24hr
3. Detemir (Levemir): onset .8-2 hrs, peak-, duration dose dependent (12 hrs for lower dose, 20 hrs for higher dose)

Front 36

Novolog mix

Back 36

-30% insulin aspart and
-70% insulin aspart protamine (analoge of NPH)
-once with breakfast, once with dinner

Front 37

Humalog mix

Back 37

-25% insulin lispro
-75% insulin lispro protamine
-onset = 10-30 min
-dual peaks = 2-6 hrs
-duration = 10-16 hrs max to 24 hrs

Front 38

Insulin Regimens

Back 38

-type 1 DM = need insulin right away; .5-1 U/kg per day divided into doses
-type 2 DM = .3-.4U/kg per day
-regimens: NPH mixed with short acting before the morning meal and evening meal or short acting at dinner and NPH at bedtime

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Most physiologic (Intensive therapy)

Back 39

-short acting insulin with every meal with long acting basal insulin at bedtime such as glargine
-flexible with meal times but requires self blood glucose monitoring 4-8x per day

Front 40

Most commonly prescribed insulin regimens

Back 40

-continuous insulin infusion with insulin pump or
-multiple subQ injections
1. NPH or lente BID or
2. Lantus at bedtime as basal insulin
AND
3. regular insulin 30 min before each meal OR
4. lispro or aspart 5-10 min before meals as bolus/booster insulin

Front 41

mixing NPH and regular insulin

Back 41

-mix regular first then NPH
(Lantis has to be injected separatly)

Front 42

continuous subq insulin infusion

Back 42

-pump provides continuous basal infusion of short acting insulin
-programmable changes in short acting insulin bolus dosages based on meals and exercise (inc or dec)
-constant infusion of short acting insulin with boluses for meals

Front 43

Adjustments of insulin

Back 43

1. based on BGL readings
-patterns >3 days
-adjust for hypoglycemia first
-correct highest readings next
2. based on grams of CHO intake
-15 g of CHO = 1 unit of insulin
-add 1 unit of insulin for every 50 mg/dL above the targeted glucose level (which is around 100mg/dl)

Front 44

adjust units based on current dose

Back 44

1. if <10 units/dose than adjust by 1 unit
2. if dose is 10-20 units than +/- 2 units
3/ > 20 units than +/- 10%

Front 45

When to check BGL

Back 45

-intensive therapy at least 4 times each day (before each meal and at bedtime)
-may need early morning BGL (3am)
-Somogyi phenomenon- hypogycemia at 3am
-Dawn phenomenon- hyperglycemia at 3am

Front 46

adjustments of basal insulin should be based on..

Back 46

-fasting self blood glucose monitoring
-increase 2 U if FPB = 120-140
-inc 4 U if FPG > 140
-inc 6 U if FPG > 160

Front 47

Insulin adverse rxns

Back 47

1. Hypoglycemia - MOST COMMON
-initially hunger, parasthesias, hynger, sweating, tremor, anxiety, then difficulty concentrating, blurred vision
-manage with good, glucose tabs, milk possible IV dextrose

Front 48

insulin issues

Back 48

1. insulin allergy and resistance
2. insulin edema: wt gain due to Na+ retention
3. lipoatrophy and lipohypertrophy

Front 49

times when insulin demands change

Back 49

1. obesity
2. severe illness
3. dietary changes
4. burns
5. labor
6. fever and infx
7. wt gain/loss
8. decrease in exercise/increase in exercise

Front 50

common errors with insulin

Back 50

-randome roation of injection sites
-failure to account for peaks
-improper dosing
-delay use for type 2 DM
-Lantus must NOT be diluted or mixed!