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Endocrine > Insulin and Diabetes > Flashcards

Insulin and Diabetes Flashcards

1
Q

Insulin not orally bioavailable. What is the physiological problem with insulin injections?

A

Pancreatic insulin brought directly to liver to inhibit glucose production. Much higher concentration than is achieved via injection

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2
Q

Physiologic basal insulin release

A

~50 pM

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3
Q

Physiologic prandial insulin release

A

~500 pM

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4
Q

PHSL fasting glucose level

A

70-100 mg/dL

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5
Q

PHSL fasting glucagon

A

High glucagon –>glycogenolysis and gluconeogenesis

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6
Q

PHSL post-prandial glucose level

A

130 mg/dL

  • promotes insulin secretion
  • Glc uptake in liver, skeletal muscle, and adipose
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7
Q

Insulin secretion stimulated by____(5x)

A
  1. Glucose
  2. Glucagon-like peptide (GLP-1)
  3. Glucose-dependent insulinotropic polypeptide (GIP)
  4. Cholinergic nerves
  5. Medications
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8
Q

How does insulin promote Glc uptake

A

stimulates phosphorylation to Glc-6-p

–>glycogen storage, etc

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9
Q

Rapid acting AA substitutions

A

Aspart
GluLisine
LisPro

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10
Q

Short acting substitution

A

N/a

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11
Q

Intermediate -acting formulation

A

NPH (Neutral protamine hagedorn)

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12
Q

Long acting substitutions

A

Detemir

Glargine

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13
Q

Regular insulin

A

(Humulin R, Novolin R)

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14
Q

Humulin-R/Novolin-R
Effect
Peak
Duration

A

30 min
2-3 h
5-8 h

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15
Q

How are humulin-R and novolin-R release slowed?

A

high concentration w/ Zn center –> aggregation

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16
Q

Humulin-R and novolin-R administration time?

A

30-45 min pre-meal

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17
Q

Primary differences between Regular and NPH

A

NPH - Lower peak but longer duration.

Still lower incidence of hypoglycemia (near basal)

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18
Q

Rapid acting administration time

LisPro, Aspart, GluLisine

A

15 min or less pre meal

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19
Q

Lispro (humalog) structural difference and effect

A

pro/lys 28/29 swapped.

Does not self associate –> dissociates into monomers and absorbed faster and to completeness faster

20
Q

which insulin formulation is best for continuous SC infusion pumps?

A

Rapid acting

21
Q

Rapid acting duration

A

Max ~5 h

22
Q

Intermediate Acting Insulins

A

Humulin-N
Novolin-N
Neutral protamine hagedorn (NPH)

23
Q

NPH formulation

A

Suspension of native insulin complexed w/ zinc and protamine

24
Q

How is NPH insulin delayed

A

complexed with (+) charged protamine, proteolytic tissue enzyme must degrade protamine

25
Q

NPH
onset
Duration

A

2-5 h

4-12 h

26
Q

NPH dose and activity profile

A

small doses have earlier peaks and shorter duration

27
Q

NPH and variability

A

HIGH up to 50%

28
Q

Rapid acting variability

A

LOW ~5%

29
Q

Long-acting Insulin

A

Glargine (Lantus)

Detemir (Levemir)

30
Q

Glargine (Lantus)

Formulation

A

pH4 stabilizes hexamer

neutral pH on injection –>aggregation

31
Q

Glargine(Lantus)

PK PD

A

Prolonged, peakless, predictable absorption
Better Q24h coverage
lower risk of hypoglycemia
Absorption not changed by site or exercise

32
Q

Detemir (Levemir)

Formulation

A

Removed threonine added myristic acid

Myristoylation increases self-aggregation and albumim binding

33
Q

Detemir (Levemir) PK/PD

A

slow absorption and reduced hypoglycemia compared to NPH
Duration (high dose) ~23h
Duration (Low dose)

34
Q

Detemir’s friends

A

Cannot mix Detemir (Levemir) with other insulins

35
Q

HumuLIN 70/30

A

70% NPH

30% Humulin-R

36
Q

General Insulin Absorption

A

More rapid if IM than SC
SC variable w/ temp/exercise
Site variation: faster in arm

37
Q

Average insulin dose in T1DM

A

0.7 u/kg/d

38
Q

T1DM Initial dose

*w/ketosis, during illness

A
  1. 3-0.5 u/kg/d

* 1-1.5 u/kg

39
Q

T2DM with insulin resistance

A

0.7-1.5 u/kg

40
Q

Most common adverse effect with insulin therapy

A

Hypoglycemia

  • Inappropriately large dose
  • temporal mismatch, tpeak and food intake
  • increased sensitivity: adrenal or pituitary insufficiency
  • Increased insulin-independent glucose uptake (exercise)
41
Q

Mild Hypoglycemia symptoms

60-80 mg/dL

A

60-80 mg/dL:

  • SNS; sweating, palpations, tremor, anxiety
  • PNS; Nausea, hunger
42
Q

Severe Hypoglycemia

A

Neuroglypenic; difficulty concentrating, confusion, weakness, drowsiness, dizziness, blurred vision, loss of conciousness
-If untreated: Convulsions, coma, death

43
Q

Hypoglycemia Treatment

A

-Glc Admin
Mild: Dex tabs, Glc gel, Sugary bev/food
Severe: 20-50 no IV, 1 mg glucagon SC or IM restores conciousness w/in 15 min

44
Q

Insulin treatment of DKA

A

Insulin IV - prevents lipolysis and AA catabolism

  • IV fluid and electrolyte replacement,
  • careful monitoring
45
Q

Insulin Treatment Hyperglycemic Hyperosmolar State
>600 mg/dL
Osmotic diuresis
Hemo-conentration

A
  • Insulin admin IV (regular w/ rapid acting)
  • IV fluid and electrolyte replacement
  • Careful monitoring of clinical status

Endocrine (6 decks)

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