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3152 > DM - insulin > Flashcards

DM - insulin Flashcards

1
Q

when is insulin indicated?

A
  1. pregnant women (drug of choice)
  2. SYMPTOMATIC hyperglycemia (polyuria, polydipsia, polyphagia, blurring vision, weight loss, dehydration)
  3. HbA1c >/= 10% (despite optimised oral therapy?)
  4. BG > 16.7mmol/L
  5. ongoing catabolism (weight loss)
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2
Q

Therapeutic effect of insulin (on HbA1c)

A

*most effective in reducing HbA1c
reduces up to 2.5%

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3
Q

MOA of insulin

A

Regulation of Carbohydrates (CHO), fat, amino acids

Glucose: facilitates uptakes of glucose in muscle & adipose tissue; inhibits hepatic glucose output [glucogenolysis & gluconeogenesis]

Fat: enhances fat storage (lipogenesis); inhibits mobilization of fat for energy in adipose tissues (lipolysis & free fatty acid oxidation)

Protein: increase protein synthesis & inhibit proteolysis in muscle tissue

-> promote uptake of glucose, facilitate use of other sources of energy (fats, protein)

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4
Q

PK/PD of insulin

A

onset & duration of action
- response to insulin HIGHLY VARIABLE between individuals & within individual
- Route of administration: rapid, shorter for IV>IM>SC

Absorption: Activity after SC administration from injection site is RATE LIMITING STEP (SC depot formation)

Distribution: Blood stream directly after SC administration

Metabolism/ Elimination:
- EXOGENOUS insulin (injected): eliminated mainly via KIDNEYS
- endogenous insulin: eliminated mainly via liver

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5
Q

Range of insulin syringes & needles & which one to use

A

Needle length:
- Pen length (4mm - 12.7mm)
- Syringe needles (for vials) (6mm - 12.7mm)

Gauge size (thickness of needle): 28/ 29/ 30/ 31/ 32
*higher the gauge = FINER needle -> LESS PAIN (BUT more needle weakness, decreased speed of injection)

*WHICH SYRINGE SIZE TO USE: smallest size for the DOSE involved

*Longer needles NOT NECESSARILY NEEDED for patients with increased body fat (thicker skin(?))
- Average skin thickness at insulin injection sites: 2.4mm
- Difference in skin thickness not clinically different among different BMI, race or age
- “Third Injection Technique Workshop in Athens (TITAN)”: “no medical reason for recommending needles >8mm”

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6
Q

Sites of injection for insulin (& absorption rates + where to inject)

A

*from fastest to slowest rate of absorption:

  1. Abdomen (inject 2 inch circle around naval; rotate sites to prevent lipohypertrophy)
  2. outer upper arms: areas where fatty tissues are present
  3. top & outer thighs (avoid bony area above knees)
  4. buttocks
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7
Q

Common insulin vial sizes & stability

A

Common insulin vial size: U-100 = 100units of insulin per 1mL *usual vial size = 10mL -> each vial contains 1,000 units of insulin

eg. patient who uses 80units per day -> 2,240 to 2,400 units per month -> 3 vials needed each month (round up to 1000 units)
*NEVER ‘break’ vials; even if pt only needs 1.5 vials, give 2

Stability of insulin (rule of thumb):
- Unopened insulin vials; good until expiration date ONLY IF STORED IN REFRIGERATOR
-> if not refrigerated: good for 28 days
- Opened insulin vials: good for 28 days REGARDLESS OF REFRIGERATION
- Other insulin containing devices eg. pen, refill catridge: vary, see package insert

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8
Q

Insulin dose preparation steps

A
  1. Check insulin label for insulin type & expiration date
  2. Visually inspect insulin vial for contamination/ degradation (eg. white clumps, color change)
  3. FOR ALL CLOUDY INSULINS: roll vial gently back & forth between hands
  4. wipe top of vial & injection site with alcohol swabs
  5. remove protective covering over plunger & needle
  6. DRAW UP AIR EQUAL TO INSULIN DOSE TO BE ADMINISTERED IN THE SYRINGE
  7. inject the air into the insulin vial
  8. with the syringe still inserted, INVERT THE VIAL & withdraw the insulin dose
  9. if bubbles are present, gently tap the syringe & remove syringe from vial
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9
Q

(insulin) Subcutaneous injection technique

A
  1. pinch the area to be injected (depends)
    **patients using 6-, 8-, 12.7-mm needles NEED to pinch a skinfold (medication can then reach intended absorption site)
    -> 4-/ 5-mm needles (only available in insulin pens) CAN BE USED BY ANY PATIENT (lean/ obese children & adults) -> DO NOT NEED TO PINCH A SKINFOLD (unless pts w lesser SC fat + use arms/thighs for injection - still need to pinch)
  2. insert the needle at 90 degree angle
    *if small children/ very thin adults/frail elderly: 45 degree angle to the skin (in the center of pinched area)
  3. release the pinch
  4. press the plunger to inject the insulin
  5. HOLD the syringe/ device in the area for 5-10s to ensure FULL DELIVERY OF INSULIN
  6. Remove device/ syringe
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10
Q

Common misconceptions of needle length required & tips regarding angle of injection + need for pinching skinfold

A

Needle length required:
- Skin thickness difference is not clinically different among different BMI/ race/ age
- average skin thickness at insulin injection sites: 2.4mm
- longer needles NOT needed for patients with increased body fat (common misconception)
- ‘Third Injection Technique Workshop in Athens (TITAN)’: no medical reason for recommending needles > 8mm

Angle of injection: most needles at 90 degrees angle
- 45 degrees advised for frail elderly/ cachexic adults/ children

Pinching skinfold:
- if using 4/5mm needles (can be used by any patient: lean/ obese children & adults) - DO NOT NEED to pinch a skinfold
*this length only available for insulin pens
**exception: pts with LESSER SC FAT who use ARMS/ THIGHS for injection STILL NEED TO PINCH

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11
Q

Factors altering insulin Absorption:

A

Temperature (higher temperature: more absorption)

Massage (increases absorption)

Exercise (increases absorption)

Jet injectors (increases absorption)
*via pressure rather than needle

Lipodystrophy:
- LipoAtrophy (concavity/ pitting of adipose tissue due to immune response due to pork/ beef insulin): INCREASES
- LipoHYPERtrophy (bulging of adipose tissue due to not rotating injection sites): DECREASES

Others: increases or decreases
- needle size/gauge, administration technique (IM: INCREASES as compared to SC), insulin preparation, mixtures, concentration, dose, insulin stability

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12
Q

Types of insulin (main classes)

A

Ultra-short acting
Rapid acting
Short acting
Intermediate-acting
Long-acting
Ultra-long acting
Others: mixed insulin

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13
Q

Rapid-acting insulin details (examples, PK/PD)

A

Examples: Aspart (novorapid), Glulisine (humalog), Lispro (apidra)

*Target BG: PPG

Onset of insulin: 5-15mins

Peak effects: 1-2h

Duration of action: 3-5h

*Use: one injection per meal (inject 5 mins BEFORE meals)

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14
Q

Short-acting insulin details (examples, PK/PD)

A

Example: Regular (Actrapid)

*Target BG: PPG

Onset of action: 30-60mins

Peak effects: 2-4h

Duration of action: 6-8h

*Use: one injection per meal (inject 10mins BEFORE meals)

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15
Q

Intermediate acting insulin details (examples, PK/PD)

A

Example: NPH (insulatard)

*Target BG: FASTING blood glucose

Onset of insulin: 1-2h

Peak effects: 6-12h

Duration of action: 10-16h

*Use: 2 injections for 24h coverage (inject REGARDLESS OF MEAL TIMINGS, AT THE SAME TIME EVERYDAY)

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16
Q

Long-acting insulin details (examples, PK/PD)

A

Examples: Detemir (Levemir), Glargine U-100 (Lantus)

*Target BG: FBG

Onset of action: 0.8-2h (detemir), 1.5h (glargine)

Peak effects: hill (detemir), peakless (glargine)

Duration of action:
Detemir - 12h for 0.2units/kg; 20-24h for 0.4units/kg
Glargine - ~24h

*Use:
Detemir: 2 injections per 24h for better coverage
Glargine: 1 injection for 24h
**INJECT REGARDLESS OF MEAL TIMINGS, AT THE SAME TIME EVERYDAY

17
Q

Features of ultra-short acting insulin

A
  1. Insulin aspart (Fiasp)
    - 2 additional excipients:
    1) Vitamin B3 - INCREASES SPEED of inital absorption
    2) L-arginine - stabilises formulation
  2. Insulin lispro-aabc (Lyumjev)
    - 2 additional excipients:
    1) Treprostinil - enchances absorption via VASODILATION
    2) Citrate - enhances VASCULAR PERMEABILITY
18
Q

ultra-long acting insulin details (examples, PK/PD)

A
  1. Insulin degludec
    - Peakless w duration of action: 42h
    - Inject subcutaneously OD at ANY TIME OF DAY
  2. Insulin Glargine U-300
    - Peakless w duration of action: 36h
    - inject ONCE DAILY AT SAME TIME EVERY DAY
    *not the same + NOT bioequivalent to gargline U-100!!!

**BOTH appears to have LOWER RATES OF HYPOGLYCEMIA than glargine (U-100)

19
Q

Compatibility of insulin mixes (self-mixed)

A

Stable mixes:
1. NPH + regular
2. NPH + rapid-acting

UNSTABLE mixes:
1. Glargine + ANY other insulin
*incompatible pH
2. Glulisine (rapid) + other insulins (other than NPH)
3. Detemir + ANY OTHER INSULIN
(not recommended by manufacture)

-> LONG-ACTING INSULINS NOT COMPATIBLE WITH ANY OTHER INSULINS

-> when self-mixing, draw up CLEAR insulin first, then CLOUDY (NPH)

20
Q

Examples of pre-mixed insulin products

A
  1. Novomix 30: 30% insulin aspart, 70% insulin aspart protamine (long-acting)
  2. Humalog Mix 75/25: 25% insulin lispro, 75% lispro protatmine (long-acting)
  3. Humalog Mix 50/50: 50% insulin lispro, 50% insulin lispro protamine

*1-3: give within 30mins of a meal

  1. Mixtard 70/30: 70% NPH, 30% regular
    *give 30mins before meals

**NPH/ NPH-like component -> give 2x a day

21
Q

Use of pre-mixed insulin products

A

*for meal/snack AND basal coverage

Benefits:
- Beneficial for pts who have difficulty measuring & mixing insulins
- Retains individual PD profile
- Less injections
- multiple peaks expected

Limitations:
Challenging to titrate & adjust dose
-> BOTH basal & prandial coverage adjusted TOGETHER
*not impossible if know pts & their lifestyle
**Easier to optimise if pts perform self monitored blood glucose (SMBG) at home

22
Q

Considerations for oral therapies when injectables are started

A

Metformin - CONTINUE

TZDs - DISCONTINUE when initiating insulin OR REDUCE TZD dose

SUs
-> DISCONTINUE or REDUCE dose by 50% when BASAL insulin is initiated (if PT AT RISK OF HYPOGLYCEMIA)
->IF MEALTIME INSULIN INITIATIED/ ON PREMIX REGIMEN: DISCONTINUE SU
**effectiveness will gradually wear off; might have to completely rely on insulin

SGLT-2i: CONTINUE

DPP-4i: IF GLP-1 agonist initiated: DISCONTINUE

23
Q

Insulin Dosing Conversion principles

A

General: most insulin conversions at 1:1 units
eg. Mixtard 30 (70% NPH, 30% regular)/ Insulatard (NPH) 16 units AM, 8 units PM <-> Novomix 30 (30% insulin aspart, 70% insulin aspart protamine) 16 units AM, 8 units PM
- REDUCE DOSE BY 10-20% if pt is at HIGH RISK OF HYPOGLYCEMIA

Exceptions (MUST DECREASE DOSE)
1. Switching from 2x daily NPH (alone/ in pre-mixed) to 1x daily GLARGINE/ DETEMIR: DECREASE BY 20%
eg. 20u NPH twice daily (total 40u daily) -> 32u glargine once daily
2. Switching from Glargine U-300 to OTHER ALTERNATIVE BASAL INSULIN ANALOG: DECREASE BY 20%
eg. 40units of U-300 glargine -> 32 units of U-100 glargine/ detemir

24
Q

Insulin adverse effects

A
  1. HYPOGLYCEMIA (BG < 4.0mmol/L (70mg/dL)
    - S/Sx: blurry vision, sweating, tremor, hunger, confusion, anxiety, shaking, rapid heart beat, dizziness, headache, weakness & fatigue, irritability etc.
    *nocturnal: nightmares, restless sleep, profuse sweating, morning headache
    -> MANAGEMENT: 15-15-15 -> 15g of fast-acting carbs (1/2 cup fruit juice/ soft drinks *not sugar-free, 3cubes/1tbsp sugar, 5-6pc hard candy, 1 tbsp honey // glucose tablets/gel), then wait 15 mins, then check BG - if still <4.0mmol/L then another 15g of fast-acting carbs
  2. Weight gain (> SU) [~4kg more than conventional treatment @ 5y (T1DM) or 10y (T2DM)]
    *benefits of glycemic control > weight gain -> remind pts on diet, exercise & losing weight
  3. Lipodistrophy
    - Lipoatrophy: concavity/ pitting of adipose tissue due to immune response due to pork/beef insulin (less common due to phasing out)
    - LipoHYPERtrophy: bulging of adipose tissue due to not rotating injection sites
  4. Local allergic reaction: redness, swelling, itching at injection site (more common with beef/pork insulin)
  5. *RARE: Systemic allergic reaction
  6. *RARE: Insulin resistance (immune phenomenon)
25
Q

Insulin Dosing (initial initiation, titration, MAX )

A

Normally: initial with BASAL control (FBG) ** higher HbA1c levels -> major contributor is FBG

Intiation: NPH 10 units/ 0.1-0.2units/kg/day
(glargine, detemir possible BUT costly)

If A1c UNCONTROLLed (target FBG range: 5-7mmol/L), continue to act on FBG
-> INCREASE insulin 2 units EVERY 3 DAYS until FBG at goal
(may increase by 4 units every 3 days if FBG consistently >10mmol/L)
-> may decrease by 10-20% if no clear reason for HYPOglycemia

MAX: 0.5units/kg/day

26
Q

When to adjust insulin dosing (from 1 dose -> add prandial coverage etc)?

A

*when A1c still ABOVE goal, DESPITE
1. basal dose >0.5units/kg
OR
2. FBG at goal

-> Add Prandial coverage (rapid/ regular insulin)
- start with 1 dose with LARGEST meal
- 4 units OR 10% of basal
*if A1c <8%: ALSO DECREASE basal dose by 4units/ 10%

OR

-> if on BEDTIME NPH: consider splitting doses into 2: 2/3 in AM, 1/3 in evening

27
Q

Insulin regimens & populations suitable for each regimen

A
  1. Full basal-bolus regimen (total: 4 injections)
    - one basal (detemir/ glargine) + THRE injections of rapid/ regular for each meal
    -> T1DM w SEVERE insulin deficiency
    -> LONG duration of T2DM (insulin deficiency)
    -> Specific situations that require TIGHT control (pts undergoing Coronary Artery Bypass Grafting CABG// Gestational Diabetes with inadequate glycemic control on medical nutritional therapy)
  2. Twice daily pre-mixed regimen (total: 2 injections)
    - NPH + rapid (Novomix)/ regular (Mixtard)
    *2/3 in AM, 1/3 in PM

*BASAL DOSE: 50% OR MORE of total daily dose

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