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Diabetes Flashcards

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1
Q

What is the structure of active insulin

A

consists of 2 peptide chain connected by disulphide bond

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2
Q

How does proinsulin become insulin

A

enzyme cleave off C peptide to release active insulin, and C peptide arises only from endogenous insulin

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3
Q

Where is insulin stored

A

in pancreatic B cells packed into densely clustered granules consisting of insoluble crystalline hexameric insulin

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4
Q

What stimulates insulin release, and how does it work

A

glucose, amino acid like arginine, leucine and parasympathetic release of ACH.

acts via phospholipase C-lP3 pathway to increase intracellular Ca2+ in pancreatic beta cell

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5
Q

What supresses insulin release

A

adrenaline

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6
Q

how does the insulin receptor look like

A

2 heterodimers each containing an extracelular a subunit and transmembrane B subunit, containing tyrosine kinase

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7
Q

What is Glut 2 Km

A

15-20mM. considered high Km, low substrate affinity

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8
Q

what is the function of insulin

A

maintain normal blood glucose through
- facilitating cellular glucose uptake, regulate carb, lipid and protein metabolism, promote cell division and growth

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9
Q

Where is insulin cleared

A

major site is the kidney, removes about 50% of peripheral insulin via glomerular filtration and proximal tubular reabsorption and degradation

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10
Q

What causes type 1 diabetes

A

immune mediated B cell destuction leading to absolute insulin deficiency

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11
Q

What level of insulin does insulin therapy need to achieve

A

basal insulin level and prandial insulin level

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12
Q

In what situation do type 2 diabetes also need insulin therapy

A

when they have sever hyperglycemia, or glycemic targets were not reached with 2 or more oral hypogycemic agents. Insulin can be given alone or in combination with OHA

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13
Q

What are the types of insulin analogues

A

rapid acting insulin analogues: insulin lispro, insulin aspart, insulin glulisin

short acting insulin: regular human insulin

intermediate acting insulin: neutral protamine hagedorn

long acting insulin: insulin glargine and insulin detemir

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14
Q

What is good about rapid acting insulin anlogue

A
  1. they demonstrate faster absorption kinetics, can be injected just before meals
  2. they attain higher concentration after subcutaneous injection compared to conventional human insulin and reduce post prandial glucose to a greater extenet
  3. they have shorter duration of action, can lead to lower incidence of hypoglycemia
  4. dose can be adjusted proportionate to fod consumed
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15
Q

What are short acting insulin consisted of

A

dissolved zinc-insulin crystals

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16
Q

Why is there a delayed onset of action of 30-60 mins for short acting insulin

A

because they aggregate in subcutaneous tissue

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17
Q

What determines the hypoglycemic risk of insulin therapy

A

the duration of action, the longer the more risk

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18
Q

What is Neutral Protamine Hagedorn comprised of

A

combination of human insulin with protamine

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19
Q

what is the dosing regime for Neutral Protamine Hagedorn

A

typically twice a day

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20
Q

What is the potential adverse effect of using NPH

A

High risk of hypoglycemia, due to high intra and inter patient variability of NPH action and

Long peak effect. NPH insulin acts as a basal and prandial insulin, necessitating that patients eat a meal at the time the insulin is peaking

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21
Q

at what pH is insulin glargine formulated?? At what Ph will it be activate

A

formulated at ph4. At ph7 is when it forms aggregate that slowly release insulin over time

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22
Q

What should glargine not be mixed with

A

any other insulins

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23
Q

What is the only insulin that can be mixed with glulisin

A

NPH

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24
Q

Where should you not administer insulin and why

A

intramuscularly, beacause hard to predict onset and duration of action and the peak of action

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25
What are the factors affecting the pharmacokinetics of insulin
1. site of injection, abdomen faster and more reproducible absorption due to difference in blood flow 2. depth of injection, make sure it is into subcutaneous tissue. 3. larger volume can delay absorption 4. exercising the muscle group before injecting insulin into the area can increase absorption of insulin 5.massage of injection area
26
What are some adverse effect of insulin therapy
1. hypoglycemia 2.lipodystrophy 3. lipohypertrophy
27
what are some symptoms of hypoglycemia
dizziness, tremor, confusion weakness
28
What are ways to regulate blood glucose level
1. insulin sensitisers 2. a- glucosidase inhibitor 3. Insulin secretagogues 4. incretin based therapy 5. SGLT-2 inhibitors
29
what is an example of an insulin sensitiser
metformin( a biguanide), thiazoldinediones like pioglitazone and rosiglitazone
30
What is the duration of action and half life of metformin
8-12 hours duration of action, half life 1.5-3hrs
31
what does metformin achieve
1. decrease hepatic glucose production 2. increase density of insulin receptors at tissues 3. decrease intestinal glucose absorption 4. improve muscular glucose absorption
32
why are some good side effects of metformin
potential or some modest weight loss, does not result in hypoglycemia or hyperinsulinemia
33
what are some cons of metformin
GI issues like diarrhea, vomitting, indigestion increase risk of vit b12 malabsorption, can worsen neuropathy symptoms Patients with renal problems may increase risk of lactic acidosis at high concentration
34
What does thiazoldinediones do
increase insulin dependent glucose disposal, decrease insulin resistance in periphery and liver
35
What are some side effects of thiazodinediones
1. weight gain 2. peripheral edema 3. increase risk of heart failure and bone fracture
36
What is a side effect of pioglitazone
can induce cyp450 activity, reduces serum concentration of drugs metabolised by these enzymes
37
What does insulin secretagogues do
get pancreatic B cell to secrete more insulin
38
What are some examples of insulin secretagogues
1. sulfonylureas: glibenclamide, glipizide, gliaclazide, glimepiride 2. meglitinides: nateglinide, repaglinide
39
which sulfonylurea has the highest risk of hypoglycemia
glibenclamide, highest risk due to longest duration of action
40
which sulfonylurea has the quickest onset of action
glipizide
41
what is the main target of sulfonylurea
the ATP sensitive potassium channel which controls B cell membrane potential
42
How does sulfonylurea act
binds to SU receptor protein, a subunit of the Katp channel. Drug binding inhibits Katp channel mediated K+ efflux, triggering calcium-dependent exocytosis of insulin granules from pancreatic B cells
43
When is gliclazide take
0.5 hr before food to improve absorption
44
What are the side effects of sulfonylurea
hypoglycemia, weight gain
45
What are the contraindication for sulfoylurea
those with sulfa allergy
46
how does meglitinides work
binds and close atp dependent potassium channel on pancreatic B cell in a glucose dependent manner stimulating insulin release. Action mediates through a unique binding site on the SUR1 of the beta cell, different from sulfonylurea site of binding
47
What is the difference between how meglitinide and sulfonylurea work
meglitinide work in a glucose dependent manner, and binds at a different site of binding as compared to sulfonylurea
48
What is meglitinide good for
useful for administration just before a meal to control post prandial glucose level as it has a rapidonset and short duration of action
49
What are some examples of a-glucosidase inhibitors
acarbose and miglitol
50
What is the mechanism of action of a-glucosidase inhibitors
reversibly inhibit membrane bound a-glucosidase in intestinal brush borders, slowing down rise in glucose level after a meal
51
What must a-glucosidase inhibitor be administered with
food
52
What are the side effects of a-glucosidase inhibitor
gastric distention, flatulence
53
What are some contraindications for a-glucosidase inhibitors
patients with GI disease like IBD, and in severe renal or hepatic disease
54
What is incretin
is a group of metabolic hormones that is released after eating
55
What does incretin do
augment secretion of insulin released from pancreatic B cell of the islet of langerhans in a glucose dependent manner
56
What are the two naturally occurring hormones of incretin
Glucose dependent Insulinotropic polypeptide (GIP) and Glucagon like peptide 1(GLP)
57
What is incretin rapidly inactivated by
dipeptidyl peptidase- 4, have a short half life
58
How does incretin- base therapy work
dipeptidyl peptidase-4 inhibitor and glucagon like peptide 1 receptor
59
What are some examples of dipeptidyl peptidase 4 inhibitor
Sitagliptin, vildagliptin, linagliptin
60
What are some examples of glucagon like peptide 1 receptor drug
liraglutde, semaglutide
61
How is GLP-1 receptor taken
Via subcutaneous injection except semaglutide which is available as oral tablet
62
What are the mechanism of action of dipeptidylpeptidase-4 inhibitor
binds and inhibit DPP4, prolonging action of endogenous incretins, stimulate pancreatic B cells to increase glucose stimulated insulin release
63
What are some side effects of DPP4- inhibitors
Gi problems like nausea, diarrhoea, stomach pain, flu like symptoms like headache, runny nose, sore throat skin reactions
64
What is the contraindications for DPP-4 inhibitor
patients with history of pancreatitis
65
Is DPP-4 inhibitor expensive
yes
66
How does GLP-1 receptor drugs work
It activates the GLP1 receptor, a membrane bound cell surface receptor in pancreatic B cells. This increases insulin release in the presence of elevated glucose concentration, and insulin secretion subsides as blood glucose concentration decrease and approach euglycemia
67
What are some side effects of GLP-1 receptor drugs
Gi problems like nausea, vomiting, diarrhea low risk of hypoglycemia
68
What are some otheradvantages of GLP-1 receptor drugs
can result in weight loss as it reduces appetite Cardioprotective
69
Is GLP-1 receptors drugs very expensive
ya no shit
70
What are some examples of SGLT-2 inhibitors
empagliflozin, canagliflozin, dapagliflozin
71
what is an SGLT2 transporter
it is a low affinity, high capacity glucose transporter. Responsible for 90% of reabsorption of filtered glucose from tubular lumen.
72
What does SGLT2 inhibitor do
reduces the reabsorption of filtered glucose, lowers the renal threshold for glucose, increasing urinary glucose excretion
73
What are some good stuff about SGLT-2 inhibitor
have some cardiaorenal protective effect
74
What are some adverse effect of SGLT-2 inhibitor
UTI, female genital mycotic infection, increased risk of lower limb amputation for canagliflozin, diabetic ketoacidosis

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