Diabetes Management Flashcards

1
Q

Sulphonylureas: mechanism of action?

A

Stimulates endogenous insulin secretion (from pancreatic B cells);

Act by binding K-ATP channels and reducing K+ efflux –> depolarisation –> Ca2+ entry –> insulin secretion.

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2
Q

What are the sulphonylureas?

A
  • Gliclazide
  • Glipizide
  • Glibenclamide
  • Glimepiride
  • Chlorpropramide
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3
Q

What are the adverse effects of sulphonylureas?

A
  • Hypoglycemia
  • Weight gain (avoid in the obese)
  • Renal excretion: do not give to those with renal impairment
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4
Q

What are the contraindications for sulphonylureas?

A
  • Renal impairment (renal excretion)
  • Pregnancy (crosses placenta)
  • Type I DM
  • Overweight people
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5
Q

What is the mechanism of action of the meglitinides?

A

Insulin secretagogues; secrete insulin rapidly and for short duration.

Bind K-ATP channels –> decrease K+ efflux –> depolarisation –> Ca2+ entry –> insulin secretion.

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6
Q

what are the meglitinides?

A

Repaglinide

Nateglinide

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7
Q

Which drugs have the same adverse effects as the meglitinides?

A

Sulphonylures; include hypoglycaemia and weight gain.

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8
Q

Meglitinides pharmacokinetics.

A

Rapid onset offset: T1/2 = 3h.

Administer pre-meal to anticipate post prandial rise in glucose

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9
Q

What is biguanide?

A

Metformin

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10
Q

Biguanides mechanism of action.

A

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.
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11
Q

What are the thiazoglitazones?

A

e.g. pioglitazone

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12
Q

What is the MoA of pioglitazone?

A

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
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13
Q

Adverse effects of glitazones?

A

MANY!!

  • Weight gain
  • Oedema / fluid retention / CCF
  • HA, fatigue, GI upset
  • Bone fractures

-NO Hypoglycemia

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14
Q

Adverse effects of biguanides?

A
  • 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)
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15
Q

What are the alpha glucosidase inhibitors?

A

Acarbose

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16
Q

What is the MoA of acarbose?

A

Block gut a-glucosidase; enzyme that digests and absorbs starches.

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17
Q

AEx of acarbose?

A
  • Flatulence/GI upset
  • Loose stools

CI: IBD or cirrhosis

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18
Q

CIx biguanides?

A

Renal failure: risk of lactic acidosis.

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19
Q

What are the GLP-1 analogues?

A
  • Exenatide

- liraglutide

20
Q

Actions of GLP-1 analogues?

A
  • Improve islet cell glucose sensing and insulin release

- Slow gastric emptying improving satiety ==> LoW (good for obese patients)

21
Q

AEx GLP-1 analogues?

A
  • N/V
  • ?Pancreatitis
  • Rarely = hypos
22
Q

How are GLP-1 analogues used?

A

-S/C injection before meal
Liraglutide: OD
Exenatide: BD

23
Q

What are the DPP-4 inhibitors?

A

-Sitagliptin
-alloglipitin
END IN GLIPTIN

24
Q

MoA DPP-4 inhibitors?

A

Prolong GLP-1 action –> increased B cell sensing = increased insulin secretion / decreased glucagon secretion.

25
Q

When are DPP-4 inhibitors used?

A

Second line after metformin if sulphonylureas CIx.

26
Q

MoA SGLT2 inhibitors?

A
Inhibit SGLT2 (glucose transporter in renal tubule).
-promote glycosuria -> decrease blood glucose
27
Q

What are SGLT2 inhibitors?

A
  • Dapagliflozin

- Canaglifozin

28
Q

What was the outcome of the DCCT/EDIC study?

A

Early glycemic control reduces CVD complications many years later; “legacy effect”

29
Q

What are the rapid acting insulins?

A
  • Aspart (NovoRapid)
  • Glulisine (Adipra)
  • Lispro (Humalog)
30
Q

Onset, peak and duration of rapid acting insulins?

A

ONSET: 10-20 mins
PEAK: 1-3h
DURATION: 3.5-4.0h

31
Q

What are the long acting insulins?

A
  • Detemir (levemir)

- Glargine (lantus)

32
Q

Onset, peak and duration of long acting insulins?

A

-Detemir
ONSET: 2h
PEAK: 8-10h
DURATION: 14-16h (Det)

-Glargine
ONSET: 2-4h
PEAK: 8-16h
DURATION: 16-24h (Glar)

33
Q

Escalation pattern in Mx TIIDM?

A
  • Oral Monotherapy
  • Oral dual therapy
  • Oral triple therapy
  • Insulin
34
Q

When must care be taken with metformin? How should be managed?

A

Renal impairment; risk of lactic acidosis.

Reduce dose if eGFR

35
Q

Which combination of diabetic therapeutics should be avoided to decrease risk of hypoglycaemia?

A

-SU and insulin

avoid if possible

36
Q

Best oral therapy for overweight individuals with TIIDM? Which orals to be avoided?

A
  • GLP1 and DPP4i an advantage

- Avoid glitazone

37
Q

First line oral therapy?

A

Metformin in most pts.

38
Q

What should be added if HbA1C above target on maximal tolerated metformin dose (up to 2000mg)?

A
Add sulphonylurea (SU).
Gliclazide SU of choice.
39
Q

Which occupations are Cix for SU therapy?

A

SU Cix or to be used with caution in pilots / professional drivers etc due to risk of hypoglycemia.

40
Q

Mx of OHAs on initiation of insulin?

A
  • Once daily insulin: pre mixed insulin pre dinner or glargine at bed time and continue orals
  • Twice daily: BD premixed insulin and continue metformin
41
Q

What are the regular acting insulins?

A
  • ACtrapid

- Humulin R

42
Q

Onset, peak and duration of long acting insulins?

A

ONSET: 30min
PEAK: 2-4h
DURATION: 5-8h

43
Q

When are regular insulins used?

A

IV injections and infusions: rapid acting analogues have no advantage in IV use but cost more

44
Q

What is medium acting insulin?

A
NPH
ONSET: 2h
PEAK: 6-10h
DURATION: 12-16h
Cloudy insulin, used in premixes.
45
Q

What is insulin premix?

A

Mixture of regular (mixture) or short acting analogue (novomix, homolog mix) with NPH insulin.
Often used BD in TIIDM

46
Q

Onset / peak / duration insulin premix?

A

ONSET: 10min
PEAK: double peak; 1-3h and 6-10h
DURATION: 12-16h