Diabetes Management Flashcards
Sulphonylureas: mechanism of action?
Stimulates endogenous insulin secretion (from pancreatic B cells);
Act by binding K-ATP channels and reducing K+ efflux –> depolarisation –> Ca2+ entry –> insulin secretion.
What are the sulphonylureas?
- Gliclazide
- Glipizide
- Glibenclamide
- Glimepiride
- Chlorpropramide
What are the adverse effects of sulphonylureas?
- Hypoglycemia
- Weight gain (avoid in the obese)
- Renal excretion: do not give to those with renal impairment
What are the contraindications for sulphonylureas?
- Renal impairment (renal excretion)
- Pregnancy (crosses placenta)
- Type I DM
- Overweight people
What is the mechanism of action of the meglitinides?
Insulin secretagogues; secrete insulin rapidly and for short duration.
Bind K-ATP channels –> decrease K+ efflux –> depolarisation –> Ca2+ entry –> insulin secretion.
what are the meglitinides?
Repaglinide
Nateglinide
Which drugs have the same adverse effects as the meglitinides?
Sulphonylures; include hypoglycaemia and weight gain.
Meglitinides pharmacokinetics.
Rapid onset offset: T1/2 = 3h.
Administer pre-meal to anticipate post prandial rise in glucose
What is biguanide?
Metformin
Biguanides mechanism of action.
Sensitisation to insulin/decrease hepatic glucose production.
- Activate AMP-kinase
- Increase insulin mediated peripheral glucose uptake (via GLUT4)
- Increase hepatic insulin sensitivity and decrease hepatic glucose production
- small decrease in LDL and TGs.
What are the thiazoglitazones?
e.g. pioglitazone
What is the MoA of pioglitazone?
Like metformin: potentiate the action of endogenous or injected insulin.
- Interact with PPARa on adipose tissue;
- Alters transcription of genes involved in insulin signalling e.g. GLUT4
- Increase FFA uptake
- Improves HDL cholesterol and plasma TGs
- Activates AMP
Adverse effects of glitazones?
MANY!!
- Weight gain
- Oedema / fluid retention / CCF
- HA, fatigue, GI upset
- Bone fractures
-NO Hypoglycemia
Adverse effects of biguanides?
- No weight gain/?LoW
- No change to insulin secretion
- no hypoglycemia
- GI disturbances
- Lactic acidosis if improperly prescribed (in patients with hepatic or renal disease)
What are the alpha glucosidase inhibitors?
Acarbose
What is the MoA of acarbose?
Block gut a-glucosidase; enzyme that digests and absorbs starches.
AEx of acarbose?
- Flatulence/GI upset
- Loose stools
CI: IBD or cirrhosis
CIx biguanides?
Renal failure: risk of lactic acidosis.
What are the GLP-1 analogues?
- Exenatide
- liraglutide
Actions of GLP-1 analogues?
- Improve islet cell glucose sensing and insulin release
- Slow gastric emptying improving satiety ==> LoW (good for obese patients)
AEx GLP-1 analogues?
- N/V
- ?Pancreatitis
- Rarely = hypos
How are GLP-1 analogues used?
-S/C injection before meal
Liraglutide: OD
Exenatide: BD
What are the DPP-4 inhibitors?
-Sitagliptin
-alloglipitin
END IN GLIPTIN
MoA DPP-4 inhibitors?
Prolong GLP-1 action –> increased B cell sensing = increased insulin secretion / decreased glucagon secretion.
When are DPP-4 inhibitors used?
Second line after metformin if sulphonylureas CIx.
MoA SGLT2 inhibitors?
Inhibit SGLT2 (glucose transporter in renal tubule). -promote glycosuria -> decrease blood glucose
What are SGLT2 inhibitors?
- Dapagliflozin
- Canaglifozin
What was the outcome of the DCCT/EDIC study?
Early glycemic control reduces CVD complications many years later; “legacy effect”
What are the rapid acting insulins?
- Aspart (NovoRapid)
- Glulisine (Adipra)
- Lispro (Humalog)
Onset, peak and duration of rapid acting insulins?
ONSET: 10-20 mins
PEAK: 1-3h
DURATION: 3.5-4.0h
What are the long acting insulins?
- Detemir (levemir)
- Glargine (lantus)
Onset, peak and duration of long acting insulins?
-Detemir
ONSET: 2h
PEAK: 8-10h
DURATION: 14-16h (Det)
-Glargine
ONSET: 2-4h
PEAK: 8-16h
DURATION: 16-24h (Glar)
Escalation pattern in Mx TIIDM?
- Oral Monotherapy
- Oral dual therapy
- Oral triple therapy
- Insulin
When must care be taken with metformin? How should be managed?
Renal impairment; risk of lactic acidosis.
Reduce dose if eGFR
Which combination of diabetic therapeutics should be avoided to decrease risk of hypoglycaemia?
-SU and insulin
avoid if possible
Best oral therapy for overweight individuals with TIIDM? Which orals to be avoided?
- GLP1 and DPP4i an advantage
- Avoid glitazone
First line oral therapy?
Metformin in most pts.
What should be added if HbA1C above target on maximal tolerated metformin dose (up to 2000mg)?
Add sulphonylurea (SU). Gliclazide SU of choice.
Which occupations are Cix for SU therapy?
SU Cix or to be used with caution in pilots / professional drivers etc due to risk of hypoglycemia.
Mx of OHAs on initiation of insulin?
- Once daily insulin: pre mixed insulin pre dinner or glargine at bed time and continue orals
- Twice daily: BD premixed insulin and continue metformin
What are the regular acting insulins?
- ACtrapid
- Humulin R
Onset, peak and duration of long acting insulins?
ONSET: 30min
PEAK: 2-4h
DURATION: 5-8h
When are regular insulins used?
IV injections and infusions: rapid acting analogues have no advantage in IV use but cost more
What is medium acting insulin?
NPH ONSET: 2h PEAK: 6-10h DURATION: 12-16h Cloudy insulin, used in premixes.
What is insulin premix?
Mixture of regular (mixture) or short acting analogue (novomix, homolog mix) with NPH insulin.
Often used BD in TIIDM
Onset / peak / duration insulin premix?
ONSET: 10min
PEAK: double peak; 1-3h and 6-10h
DURATION: 12-16h
