Insulin and Hypoglycaemics Flashcards Preview

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Flashcards in Insulin and Hypoglycaemics Deck (24):
1

What is glucosuria

elevated glucose levels saturate the glucose re-uptake mechanisms in the kidneys
diagnostic of underlying pathology = diabetes mellitus
leads to osmotic diuresis = thirst, dehydration, increased urine output, unconsciousness, death!

2

Homeostasis of hypergylcaemia

food intake/endogenous glucose production =
increase in plasma glucose =
insulin release from pancreatic B cells =
insulin action in liver, muscles, CNS =
decrease plasma glucose

3

Homeostasis of hypoglycaemia

fasting =
decrease in plasma glucose =
glucagon release by pancreatic A cells =
endogenous glucose production, action on liver, muscles, CNS =
increase in plasma glucose

4

Pancreatic Islets of Langerhans

approx. 1.5 mil per pancreas
contain different cell types:
- B cells that release insulin
- A cells that release glucagon
PP cells that release pancreatic polypeptide
E cells that release ghrelin

5

How does glucose stimulate insulin release?

food intake =
digestion =
glucose uptake by B cells =
inhibition of Katp channels (molecules which close K-channels mimic actions of glucose, used to treat hyperglycaemia - insulin secretagogues - . molecules which open K-channels inhibit the actions of glucose, used to treat hypoglycaemia - hypeglycaemia-inducing drugs) =
depolarization of the cell =
calcium influx =
insulin release.

6

Glucose homeostasis; integration with digestion

food intake =
digestion =
release of gut hormones =
rise in serum GLP-1 =
activation on the GLP-1 receptor (incretin effect)=
cell signalling =
insulin release.
oral glucose faster insulin response compared to i.v
- glucagon-like peptide 1 and gastric inhibitory peptide are incretin hormones

7

Functional effects of insulin

increases glucose - glycogen (stored in skeletal muscle, liver)
increases glucose - fat (stored as adipose tissue)
increases amino acids - proteins (muscle)
increases glucose and amino acid transport to cells
decreases glycogen breakdown
decreases glucose formation (gluceoneogenesis)

8

Insulin therapy

treatment for people with type 1 diabetes mellitus
3 preparations:
- short duration; rapid onset (30-60 mins)
soluble insulin and rapid onset insulin analogues: eg. insulin aspart, insulin glulisine, insulin lispro (s.c, i.v)
- intermediate action
eg. isophane insulin; can be porcine, human or bovine (s.c)
- longer lasting; slow onset and lasts for longer
eg. protamine zinc suspension - porcine, human or bovine (s.c)
insulin detemir, insulin glargine - recombinat human (s.c)

9

What are the 3 preparations in insulin therapy made up of?

short duration - insulin aspart, insulin glulisine, insulin lispro (s.c, i.v)
intermediate action - isophane insulin; can be porcine, human or bovine (s.c)
longer lasting - protamine zinc insulin, insulin zinc suspension - porcine, human or bovine (s.c)
insulin detemir, insulin glargine - recombinant human (s.c)

10

Short action insulin

peal action 2-4 hours
duration of 8 hours
injected just before or just after food, only lasts long enough for meal at which it was taken

11

Intermediate/longer acting insulin

onset 1-2 hours
peak action 4-12 hours
duration is 16-35 hours

12

Biphasic insulin preperations

mixture of intermediate and fast acting
rapid onset
longer-lasting actions
Eg. biphasic insulin aspart and lispro, biphasic isophane insulin

13

Other treatments for type 1 diabetes mellitus

islet/pancreas transplantation
prevention: immune-mediated destruction of B-cells

14

Insulin administration

subcut injection 3-4 times daily
- used needle/syringe pens
- portable infusion pump of continuous short acting insulin infusion

15

Glucagon therapy

for hyperglycaemia-inducing:
first treatment for severe hypoglycaemia when oral glucose is not possible
- given m=by i.m, i.v, s.c to increase plasma glucose levels
- SE = nausea, headaches
- glucagon promotes
> glycogenolysis
> gluconeogenesis
> lipolysis

16

Sulphonylureas

Secretagogues I
oral treatment for hypoglycaemia in type 2 diabetes mellitus
boosts insulin release
small molecule antagonist of the Katp channel receptor
oral agents: 1/2 doses daily before or with a meal
- short acting:
eg. Tolbutamide (Sulphonylureas)
longer lasting:
eg. Chlorpropamide, Glibenclamide (Sulphonylureas)
risk of hypoglycaemia with both

17

Prandial glucose regulators/ Meglitinides

Secretagogues I
oral treatment for hypoglycaemia in type 2 diabetes mellitus
boosts insulin release
eg. Nateglinide
decreased risk of hypoglycaemia

18

Diazoside

used to treat congenital hyperinsulism in infancy
small molecule antagonist of the Katp channel
SE = anorexia, nausea and vomiting, hypotension, tachycardia, arrhythmias

19

Exenatide/ Liraglutide

secretagogues II - incretin mimetic
injectable agent, s.c
combined with other therapies
reduced risk of hypoglycaemia
eg. Byetta
SE = GI disturbances, dizziness, headaches

20

DPP-4 inhibitors/ Gliptins

secretagogues III incretin mimetic
inhibitors of DPP-4
oral tablet
eg. Sitagliptin, Vildagliptin
can be combined with other medications
SE = GI disturbances, peripheral oedema, headache, upper respiratory infections

21

Biguanides

insulin sensitiser - improves sensitivity of target organs to insulin
2 modes of action:
- prevents hepatic production of glucose
- improves insulin sensitivity
eg. Metformin
- taken up to 3 times a day, immediately after a meal
- doesn't cause weight gain, best choice for patients who have heart failure
available in combination

22

Thiazolidinediones/ Glitazones

insulin sensitiser - improves sensitivity of target organs to insulin
oral; one/two times daily
activates a regulatory protein involved in transcription of insulin-sensitive genes which regulate glucose and fat metabolism
principle target = adipocytes
eg. Pioglitazone
history of concerns in aptients wth diabetes and ischaemic heart disease

23

Alpha glucosidase inhibitor

delay glucose absorption
eg. Acarbose
- a-glucosidase converts oligosaccharides to glucose
- acarbose inhibits this enzyme
absorption of starchy foods in slowed = slowing-down rises n plasma glucose following a meal
SE = flatulence, diarrhoea, nausea, indigestion, intestinal problems

24

SGLT2 inhibitors (flozins)

Sodium-coupled glucose transporter
promote glucose loss in the urine to reduce hyperglycaemia
potential advantages: weigh loss, insulin independent,
eg. Dapagliflozin, Canagliflozin