Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MD4001 WEEK 10 > Treatment of Diabetes > Flashcards

Treatment of Diabetes Flashcards

1
Q

What monitors blood glucose?

A

Pancreas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is central to controlling all glucose levels?

A

The liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where is glucagon released from and what is its purpose?

A

Glucagon is released from α cells + upper GI if blood glucose is low to stimulate glycogen breakdown + gluconeogenesis in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is insulin released from and what is its purpose?

A

Insulin is released from β cells if blood glucose is high to stimulates the liver, adipose and muscle to take up glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What occurs in diabetes?

A

Diabetes occurs when regulation of blood glucose is disrupted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the common differences between Type 1 and Type 2 diabetes.

A

TYPE 1:

  • Often diagnosed in childhood
  • Not associated with excess body weight
  • Often associated with higher than normal ketone levels at diagnosis
  • Treated with insulin injections or insulin pump
  • Cannot be controlled without taking insulin

TYPE 2:

  • Usually diagnosed in over 30 year olds
  • Often associated with excess body weight
  • Often associated with high blood pressure and/or cholesterol levels at diagnosis
  • Is usually treated initially without medication or with tablets
  • Sometimes possible to come off diabetes medication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why does the occur progressing from pre diabetes to diabetes occur?

A

This is due to a disruption of an individual’s ability to metabolise glucose.
Might not yet appear to have diabetes but may have hyperinsulinemia due to lower insulin sensitivity
Full diabetes progresses when beta-cell failure surpasses a critical threshold usually ~90%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the aim of insulin in treating Type 1 diabetes.

A

Aim in treating Type I diabetics - replacement therapy to normalize glucose levels 4-7 mM (pre- prandial/fasting).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are normal glucose levels two hours after a mean?

A

In normal individuals glucose level can rise higher but should be <7.8 mM two hours after a meal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When will glucose be detected in urine?

A

Blood glucose levels >10 mM will overload the renal capacity and be detected in the urine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How is insulin made?

A

human insulin is made by recombinant DNA technology, which allows an identical pure preparation, limiting allergic reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is insulin administered and why?

A

Insulin is administered parentally because it is a protein that would be destroyed/digested by the gut if taken orally.
For routine use it is given subcutaneously and by IV infusion in emergencies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are designer insulins?

A

Altering the amino acids in the insulin structure can usefully alter insulin kinetics – these modified human insulins are called designer insulins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe and name rapid-acting soluble insulin.

A

Insulin Lispro or Insulin Aspart, designer insulins that prevent dimer formation allowing more active monomers to be bioavailable and used rapidly.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe and name an intermediate-acting insulin.

A

Neutral Protamine Hagedorn/Isophane Insulin is an intermediate-acting insulin that precipitates insulin into suspensions which slowly dissolve.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe and name a longer acting designer insulin.

A

Insulin Glargine is a longer acting designer Insulin which has decreased solubility at neutral pH - forms aggregates that slowly dissolve.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe and name a long-acting designer insulin with a fatty acid.

A

Insulin Detemir is a long-acting designer insulin with a fatty acid – this confers albumin binding, which slowly dissociates prolonging circulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What type of insulin is often used in T1D?

A

T1Ds require insulin replacement so an intermediate-acting preparation or a more long-acting analogue is often combined with a short-acting analogue taken before meals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the duration of activity and formulation/structural changes of Insulin Lispro.

A

Rapid acting

Human insulin with penultimate lysine and proline reversed in beta chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What do structural changes in Insulin Lispro prevent?

A

Structural changes prevents insulin dimers and hexamers increasing availability of active monomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe the duration of activity and formulation/structural changes of Insulin Aspart.

A

Rapid acting

Human insulin with Proline 28 switched to Aspartic acid in beta chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do structural changes in Insulin Aspart prevent?

A

Structural changes prevents insulin dimers and hexamers increasing availability of active monomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe the duration of activity and formulation/structural changes of Neutral Protamine Hagedorn/ Isophane Insulin.

A

Intermediate acting

Human insulin complexed with positively charged polypeptide (protamine) and zinc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe the slow dissolving of Neutral Protamine Hagedorn/ Isophane Insulin.

A

Aggregates in suspension that slowly dissolve from injections site; “Isophane” insulins were (initially made with porcine insulin but now use recombinant human insulin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe the duration of activity and formulation/structural changes of Insulin Detemir.

A 
Long acting “peakless"
Fatty acid (myristic acid) added to Lys29 of beta chain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe the features of absorption and dissociation of Insulin Detemir.

A

Rapidly absorbed but FA side-chain confers binding to albumin. Slowly dissociates from complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Describe the duration of activity and formulation/structural changes of Insulin Glargine.

A

Long acting “peakless” basal analogue

Glycine for Asparagine substitution at N21 and 2 arginine amino acids added to the end of beta chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What makes Insulin Glargine less soluble, what is the purpose?

A

Shift isoelectric point making it less soluble at neutral pH creating aggregates which slowly dissolve into active monomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Why is fixed dose therapy useful?

A

A fixed dose therapy can help to simplify the understanding of blood glucose results but does not offer the flexibility of how much carbohydrate patients choose to consume at each meal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

When is flexible insulin therapy used?

A

Flexible insulin therapy is used for patients that really understand glucose metabolism and gives patients more control of what they eat and how they balance their blood glucose levels but will take time and commitment to learn how best to adjust insulin doses.
On a flexible insulin therapy patients choose how much insulin to inject at each meal and also allows doses to be varied in response to different carbohydrate quantities in meals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q 
Once daily regimen:
Number of injections?
Time of injections?
Suitability?
Meal time and content:
Required patient understanding?
A

Number of injections: 1

Time of injections: Morning

Suitability: T2D

Meal time and content: Less flexible

Required patient understanding: Basic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Describe the formulations used in the once daily insulin regimen.

A

long acting (Glargine) or Intermediate (e.g. NPH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q 
Twice daily regimen:
Number of injections?
Time of injections?
Suitability?
Meal time and content:
Required patient understanding?
A

Number of injections: 2

Time of injections: Morning + Evening

Suitability: T1D and T2D

Meal time and content: Less flexible

Required patient understanding: Basic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Describe the formulations used in the twice daily insulin regimen.

A

Short acting mixed with intermediate formulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q 
Basal-Bolus regimen:
Number of injections?
Time of injections?
Suitability?
Meal time and content:
Required patient understanding?
A

Number of injections: Multiple

Time of injections: Throughout day

Suitability: T1D, some T2D

Meal time and content: Flexible

Required patient understanding: High

36
Q

Describe the formulations used in the Basal-Bolus insulin regimen.

A

Intermediate or long acting with short acting formulation

37
Q 
Insulin Pump regimen:
Number of injections?
Time of injections?
Suitability?
Meal time and content:
Required patient understanding?
A

Number of injections: Semi-automated: as needed

Time of injections: Throughout day

Suitability: T1D

Meal time and content: Flexible

Required patient understanding: Medium/High

38
Q

Describe the formulations used in the Insulin Pump insulin regimen.

A

Short acting insulin formulation

39
Q

What is the principal oral hypoglycemic agent.

A

Metformin (a biguanide drug)

40
Q

When are oral hypoglycemic tablets used?

A
  • used to alter glucose metabolism in T2Ds
  • T2Ds have some residual insulin and insulin sensitivity: metformin can potentiate residual insulin by increasing insulin sensitivity
41
Q

What is the aim of metformin?

A

Acts to reduce gluconeogenesis in the liver, which is markedly increased in type 2 diabetes and opposes the action of glucagon.

42
Q

What does metformin do?

A
  • Increases glucose uptake and utilisation in skeletal muscle
  • Slightly delays carbohydrate absorption in the gut.
  • Increases fatty acid oxidation - reducing circulating LDL and VLDL., which can help in obesity associated diabetes and atherosclerosis development
  • Can encourage weight loss by suppressing appetite but can cause anorexia in rare cases.
  • Can be combined with drugs that stimulate insulin release.
43
Q

Describe the mechanism of action of Metformin.

A
  • Metformin alters energy metabolism
  • It acts on the mitochondria to change the ratio of AMP to ATP
  • ↑ AMP:ATP ratios activate AMP- activated protein kinase (cells metabolic master switch) - Inhibits glucagon signaling and gluconeogenic pathways
  • AMPK increases transcription of genes important for glucose transport fatty oxidatin and inhibits fatty acid synthesis
  • Takes time due to regulating gene networks
44
Q

What are insulin secretagogues?

A

Sulphonylureas/Meglitinides:
Sulphonylureas are an older class of orally-active hypoglycemic drugs
Meglitinides are next gen secretagogues

45
Q

What do Sulphonylureas do?

A

interfere with beta cell ion channels to potentiate insulin secretion

46
Q

Give examples of Sulphonylureas.

A

Tolbutamide
Chlorpropamide
Glibenclamide
Glipizide

47
Q

Describe the tolerance of Sulphonylureas.

A

Well tolerated but can lead to weight gain by stimulating appetite.

48
Q

When are Sulphonylureas used?

A

Used in early stages of type 2 diabetes – as they require functional b cells

49
Q

What can Sulphonylureas be combined with?

A

Metformin and Glitazones

50
Q

Describe drug interactions of Sulphonylureas.

A

But can interact with other drugs to produce severe hypoglycaemia due to competition for metabolising enzymes, plasma binding proteins, and excretory pathways.

51
Q

Give examples of meglitinides.

A

Repaglinide and Nateglinide

52
Q

Describe the mechanism of action of meglitinides.

A

similar mechanism of action (blocking KATP channels to ↑insulin release) – short duration of activity leads to lower risk of hypoglycaemia

53
Q

Describe the mechanism of action of Sulphonylureas.

A
  • High affinity receptors for these drugs are present in b- cell membranes.
  • Block ATP-sensitive potassium channels in b- cells.
  • Causes beta cell depolarisation, which leads to insulin secretion.
  • Only work if b cells of the pancreas are functional
54
Q

What does Pioglitazone do?

A

It is a Thiazolidinediones (glitazones):

increases insulin sensitivity and lowers blood glucose in type 2 diabetics.

55
Q

What do Thiazolidinediones (glitazones) do?

A
  • Reduces the amount of exogenous insulin needed by about 30%.
  • Increases glucose uptake into muscle in response to insulin.
  • Reduces blood glucose and free fatty acid concentrations.
  • Are peroxisome proliferator activated receptor – g ( PPARg - a nuclear receptor) agonists – PPARg expressed in adipose tissue, muscle and liver.
  • Promote transcription of several genes with products that are important in insulin signalling but take months to work.
56
Q

What are the side effects of Thiazolidinediones (glitazones) ?

A

Can cause weight gain and fluid retention.
Has been linked to bladder cancer, heart failure, and osteoporotic
fractures - withdrawn from Germany, France and India

57
Q

What is Rosiglitazone?

A

another PPARy agonist recently withdrawn from UK

58
Q

What is the mechanism of action of Pioglitazone?

A
  • PPAR-γ ligands promote transcription of genes important in insulin signalling: lipoprotein lipase, fatty acid transporters, Glut-4 and others.
  • Pioglitazone is used in the clinic as an additive to other oral hypoglycaemic drugs such as metformin and Sulphonylureas
59
Q

What is Acarbose?

A

inhibitor of intestinal a-glucosidase

60
Q

What does acarbose do?

A

Delays carbohydrate absorption in the small intestine reducing the postprandial spike in glucose.

61
Q

When is acarbose used?

A

Used in type 2 diabetes often in combination with other hypoglycemics

62
Q

What are the side effects of acarbose?

A

Side effects can include flatulence and diarrhoea

63
Q

Give examples of Selective sodium glucose cotransporter 2 (SGLT2) inhibitors.

A

Canagliflozin
Dapagliflozin
Empagliflozin

64
Q

When are Selective sodium glucose cotransporter 2 (SGLT2) inhibitors used?

A

Used in T2D as monotherapy when diet & exercise alone is not adequate for whom metformin is contraindicated or inappropriate.

65
Q

What do Selective sodium glucose cotransporter 2 (SGLT2) inhibitors do?

A
  • Block glucose reabsorption by the proximal tubule leading to therapeutic glucosuria
  • Controls glycaemia independently of insulin pathways
  • Lead to reduced HbA1c up to 1.17% compared to placebo – Well tolerated, reduce weight and reduce systolic blood pressure
  • Do not cause hypoglycaemia but associated with increased risk of urinary tract infections
66
Q

Give examples of incretins?

A

Glucagon-like peptide-1 (GLP-1) is secreted by L-cells in the gut
Gastric inhibitory peptide (GIP) secreted by K-cells in gut

67
Q

What do incretins do?

A
  • Incretins directly stimulate insulin biosynthesis and secretion, inhibit glucagon secretion in the pancreas, delay gastric emptying, increase cardiac output and increase satiety signals in the brain.
  • Incretins also indirectly increase insulin sensitivity in the muscle and decrease gluconeogenesis in the liver
68
Q

How are incretins degraded?

A

Incretins are rapidly degraded by an enzyme called dipeptidyl peptidase-4 (DPP-4).

69
Q

Give examples of incretin mimetic - analogs of exendin-4/GLP-1.

A

Exenatide
Exenatide LAR
Liraglutide

70
Q

Describe Exenatide.

A

given twice daily, but can cause nausea

71
Q

Describe Exenatide LAR.

A

a long-acting release formulation that is administered weekly and induces less nausea

72
Q

Describe Liraglutide.

A

has an additional fatty side-chain that confers albumin binding and slows renal clearance

73
Q

What do incretin analoges do?

A

Incretin analogs lowers blood glucose after a meal by increasing insulin secretion and suppressing glucagon secretion.

74
Q

When are incretin analoges used?

A

Used for type 2 diabetes in addition to oral agents to improve control and aid weight loss.

75
Q

How are incretin analoges given?

A

Given subcutaneously (SC) as peptide analogs.

76
Q

What are the side effects of incretin analoges?

A

Can cause hypoglycemia and a range of gastrointestinal effects

77
Q

Give examples of DPP-4 Inhibitors - Gliptins.

A

Sitagliptin and vildagliptin

78
Q

What do DPP-4 Inhibitors - Gliptins do?

A

Enhance endogenous incretin effects
by blocking DPP-4
Lowers blood glucose by increasing first phase of insulin response after meals.

79
Q

When are DPP-4 Inhibitors - Gliptins used?

A

Used in type 2 diabetes in addition to other oral hypoglycaemic drugs.

80
Q

Describe Sitagliptin.

A

well tolerated and weight neutral

81
Q

Describe Vildagliptin.

A

is not available in the USA - found associated with respiratory tract infections, headache and on occasion serious pancreatitis.

82
Q

What are the symptoms of diabetes?

A
  • Always tired
  • Frequent urination
  • Sudden weight loss
  • Wounds that won’t heal
  • Always hungry
  • Sexual problems
  • Blurry vision
  • Vaginal infections
  • Numb or tingling hands or feet
  • Always thirsty
83
Q

What is a normal FPG?

A

< 6.1 mmol/L

84
Q

What is a pre-diabetes FPG?

A

6.1 - 6.9 mmol/L

85
Q

What is a diabetes FPG?

A

> 7.0 mmol/L

MD4001 WEEK 10 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions