Diabetes Flashcards
(64 cards)
1
Q
insulin synthesis
A
- cleave the C-peptide off proinsulin (presence of C-peptide indicates endogenous synthesis of insulin)
- stimulated by presence of glucose & amino acids (leucine, arginine) & acetylcholine -> acts on phospholipase C-IP3 pathway -> increase intracellular Ca2+
2
Q
insulin receptor
A
- insulin binds to the alpha receptor -> autophosphorylation and activation of tyrosine kinase in beta subunit
- phosphorylates IRS-1 protein
- activates PI3-kinase: PIP2 -> PIP3
- PIP3 binds to Akt -> recruitment of GLUT4
3
Q
insulin fn
A
maintains normal blood glucose levels - facilitate glucose uptake in cells - regulate carbs. lipid, protein metab increase glycolysis, decrease lipolysis, increase protein synthesis in muscle - promote cell division and growth
4
Q
insulin clearance
A
kidney: GFR and proximal tubular reabsorption
5
Q
types of DM
A
- type 1 DM: absolute insulin def - immune mediated beta-cell destruction so cannot produce insulin
- type 2 DM: insulin resistance
- gestational DM - glucose intolerance during pregnancy
6
Q
type 1 DM treatment
A
daily insulin injections
7
Q
type 2 DM treatment
A
lifestyle modification (diet, exercise)
8
Q
insulin therapy indications
A
type 1 DM
type 2 DM: only in severe hyperglycemia / OHAs not useful
9
Q
insulin therapy drugs
A
mimicks normal pancreatic insulin secretion
- basal insulin: suppresses hepatic production of glucose
- prandial: provides insulin to remove excess serum glucose after eating
10
Q
5 groups of insulin
A
- rapid-acting insulins
- short-acting insulins
- intermediate-acting
- long-acting
- premixed
11
Q
rapid acting insulin drugs
A
insulin analogues (has the letter s in it)
- lispro
- aspart
- glulisine
12
Q
rapid acting insulin analogues MOA
A
change to charge and conformation of the insulin molecule
reduce repulsion -> more rapid absorption = shorter duration of action
injected just before meals
13
Q
short acting insulin MOA
A
similar to regular human insulin - crystalline zinc insulin
injected 20-30min before meals
clear appearance
greater hypoglycemia risk than rapid acting insulin
14
Q
intermediate acting insulin drug
A
neutral protamine hagedorn (NPH)
15
Q
NPH MOA
A
protamine + human insulin
precipitated crystals of NPH insulin releases slowly -> slower onset
- high risk of hypoglycemia cause of the variability from the long onset of action
so must eat after medication
cloudy appearance
16
Q
long acting insulin drugs (2)
A
- glargine
- detemir - binds insulin to albumin: prolongs insulin action
acts for 18-24hrs
clear appearance
17
Q
insulin degludec
A
ultra long acting (U-LA) insulin - slow release of insulin
42hrs duration of action
because of the long duration, adjustments not easy -> esp for those that need dosage adjustment cause of renal/hepatic failure
18
Q
insulins that should NOT be mixed
A
- glargine (LA) -> incompatible pH
- detemir (LA)
- glulisine (RA) - exc that it can be mixed w/ NPH
19
Q
insulins that can be mixed
A
- most insulins can be mixed w/ NPH
- aspart (RA) + degludec (U-LA)
20
Q
factors affecting pk of insulin
A
- faster absorption through abdomen injection
- inject into muscles
- exercise increase rate of absorption
- heat
21
Q
DM caused by drugs
A
steroids: hyperglycemia
22
Q
ADR caused by insulin therapy
A
- risk of hypoglycemia if too much insulin is given
dizziness, tremor, weakness, hunger
esp in renal impaired pts/ elderly - lipodystrophy (abnormal fat distribution)
lipoatrophy: loss of fat at the site of the injection
lipohypertrophy: accumulation of fat due to repeated injections at the same - lipogenic effect of insulin
23
Q
methods to monitor blood glucose
A
- casual plasma glucose (>11.1mmol/l)
- fasting plasma glucose (>7mmol/l)
- 2 hour post challenge plasma glucose
- HbA1c - glycated haemoglobin (reflects 2-3mths blood glucose lvls)
24
Q
drugs to help maintain blood glucose levels in type 2 DM (insulin resistance) - MOA
A
- increase sensitivity of tissues to insulin
- reduce glucose release by liver
- slow down carbs digestion in intestines
- inhibit glucagon (glucagon inhibits insulin secretion)
- stimulate insulin release
- incretins ??
- block glucose reabsorption at kidneys
25
groups of drugs to increase sensitivity of tissues to insulin (2)
- biguanide
| - thiazolidinediones
26
group of drugs to reduce glucose release by liver
biguanides
27
group of drugs to slow down carbs digestion in intestines
a-glucosidase inhibitors
28
groups of drugs to inhibit glucagon (2)
- biguanide
| - glucagon-like peptide-1 agonist
29
groups of drugs to stimulate insulin release (3)
- sulfonylureas
- meglitinide
- glucagon-like peptide-1 agonist
30
groups of drugs to increase incretins
- dipeptidyl peptidase-4 (DPP-4) inhibitor
| - bile acid sequestrants
31
groups of drugs to block glucose reabsorption at kidneys
SGLT2 inhibitors (sodium glucose co-transporter 2)
32
biguanide drug + MOA
| [insulin sensitizer]
metformin
- decreases hepatic glucose production
- increase sensitivity of insulin receptors by increasing density of insulin receptors at tissues
- decrease intestinal glucose absorption
- improve muscle glucose absorption
DOES NOT affect amount of insulin secreted
*first line T2DM treatment: does not cause hyperinsulinemia/ hypoglycemia
33
metformin ADR + CI
GI: diarrhea, vomiting, indigestion, flatulence -> eat after meals
cause it affects glucose absorption in intestines -> may also cause vit B12 malabsorption
(CI/ just be cautious): renal problems; lactic acidosis
34
```
thiazolidinediones drugs (2)
[insulin sensitizer]
```
```
(-glitazone)
- pioglitazone*
oral, high absorption, hepatic metab
duration of action: 1 day
fecal excretion
- rosiglitazone
```
35
thiazolidinediones MOA
- increase insulin-dependent glucose disposal
- decrease insulin resistance in the periphery + liver
activates PPAR-y (regulate glucose metab, adipogenesis + improve insulin sensitivity) -> increase production of GLUT1 &4
36
pioglitazone ADR
fluid retention
- weight gain
- peripheral edema
- increased risk of HF
- bone fractures
induce CYP450 - increase metab of other drugs - careful of DDIs
37
sulfonylureas drugs
| [insulin secretagogues]
(-amide)
- tolbutamide
- gibenclamide: risk for hypoglycemia
(-zide/-ride)
- glipizide
- gliclazide* preferred
- glimepiride
38
sulfonylureas MOA
stimulate release of insulin from pancreas (beta cells in pancreatic islets)
- bind to sulfonylurea (SU) receptor proteins -> inhibit Katp channel mediated K+ efflux -> so Ca2+ exocytose instead -> exocytosis of insulin granules tgt
39
recommended sulfonylurea drug
gliclazide: 80mg tablet, 0.5h before food
| hepartic metab, excreted in urine
40
sulfonylurea ADR + CI
weight gain
gibenclamide: risk for hypoglycemia (esp elderly, renal/hepatic impairment)
CI: allergy
41
meglitinides drugs
```
(-glinide)
- repaglinide
hepatic metab
half life: 1h
short duration of action
mainly excreted in feces
- nateglinide
hepatic metab
half life: 1.5h
duration of action: 4h
mainly excreted in urine
```
both have rapid onset + short duration of action - good choice - take before meal
42
meglitinides MOA
bind and close Katp channels - glucose dependent
since it is glucose dept, and original insulin lvls are supposed to be so, low risk of hypoglycemia - cause it will auto off when glucose levels are low
43
meglitinides caution
caution in pts with hepatic impairment - hepatic metab
44
a-glucosidase inhibitor drugs
- acarbose*
| - miglitol
45
a-glucosidase inhibitor MOA
irreversibly inhibit a-glucosidase in brush border
slows down the increase in glucose lvls after a meal
to be taken with food
46
acarbose
- route
- metabolism
- half life
- duration of action
- excretion
- route: oral
- metabolism: by intestinal bacteria and digestive enzymes
- half life: 2hrs
- duration of action: 2-4hrs
- excretion: fecal
47
acarbose SEs + CIs
cause glucose is not absorbed -> more in colon
gaseous distention and flatulence (pass more gas)
poor tolerance -> not preferred
CI: pts w/ GI diseases (IBD)/ renal/hepatic disease
48
incretin based therapy (IBT)
- dipeptidyl peptidase 4 inhibitors
| - GLP-1 receptor agonists
49
IBT MOA
incretins (hormones) released augment secretion of insulin by b cells in pancreas
2 incretins:
GIP (glucose dependent insulinotrophic polypeptide);
GLP-1 (glucagon-like peptide-1)
50
dipeptidyl peptidase (DPP-4) inhibitors MOA
DPP-4 degrades incretin
- > inhibit DPP-4 will increase incretin lvls
- > incretin stimulates insulin secretion in b-pancreatic cells + suppress a-cell mediated glucagon release & hepatic glucose production
51
DPP-4 inhibitors drugs
(-gliptin)
- sitagliptin
- vildagliptin: hepatic metab - cannot be used in pts w/ hepatic impairment
- linagliptin*: fecal elimination (rest are renal) - no dose adjustment needed for renal impairment
oral
52
DPP-4 inhibitors SEs
```
GI: nausea, diarrhoea, stomach flu
Flu-like: headache, runny nose, sore throat
skin reactions
careful if pt has pancreatitis
expensive
```
53
GLP-1 receptor agonists MOA
activates GLP-1 receptor (membrane bound receptor in pancreatic b-cells)
- > increase insulin release when glucose conc increases [GLUCOSE DEPENDENT - WILL ONLY HAVE EFFECT IF IT IS IN THE ORIGINAL HYPERGLYCEMIC STATE]
- > glucose-dept: no effect if glucose conc decreases and are normal
54
GLP-1 receptor agonists drugs (2)
- exenatide - does not metabolise, shorter half-life
- liraglutide
subcutaneous injection
55
GLP-1 receptor agonists SEs
GI: nausea, vomiting, diarrhoea
exenatide CI: pancreatitis
VERY expensive
56
GLP-1 receptor agonists clinical use
- obesity
| - reduce CVS diseases, + reduce hospitalisation for HF
57
SGLT-2 inhibitors drugs (3)
```
(-gliflozin)
- empagliflozin
- canagliflozin
- dapaglifozin
oral
```
58
SGLT-2 inhibitors MOA
SGLT2: reabsorption of glucose from tubules
| inhibit SGLT2 = decrease reabsorption - more glucose excreted
59
SGLT2 inhibitors clinical use
atherosclerotic CHD
reduce hospitalisation for HF
reduce progression of renal disease
60
SGLT2 inhibitors ADR
```
UTI - glucose in urine = bacteria!
increased urination
genital mycotic (fungal) infection
diabetic ketoacidosis
canagliflozin: risk of LL amputation
```
61
types of hypoglycemic drugs (5)
- insulin sensitizers
- insulin secretagogues
- a-glucosidase inhibitors
- sglt2 transporter inhibitor
- incretin therapy
62
chronic DM complications**
- micro: retinopathy, neuropathy, nephropathy
- macro: CVS related - atherosclerosis
- decrease leukocyte function -> increased risk of infections
63
prevent/minimise chronic DM complications**
retinopathy - laser treatment
nephropathy - renal transplant/ dialysis
atherosclerosis/thrombosis: aspirin
64
classification of drugs
- insulin sensitisers: biguanide (metformin), thiazoldinediones
- insulin secretagogues: sulfonylureas, meglitinides
- a-glucosidase inhibitors: acarbose
- incretin based: DPP4 inhibitors, GLP1 agonist
- SGLT2 inhibitors
