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Endocrine > DM medications > Flashcards

DM medications Flashcards

1
Q

What are the examples and the the MOA of biguanides?

A

Metformin 250-850mg OM-TDS

Activates ANP kinase, ↓ hepatic gluconeogenesis

↑insulin sensitivity for muscle glucose uptake

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2
Q

What are the advantages of metformin?

A

Cheap

Weight-neutral / loss

Min Hypogly Events Does not affect insulin production = no islet cell fatigue

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3
Q

What are the disadvantages of metformin?

A

GI S/E: diarrhoea, abdominal bloating, and nausea.

Metallic taste

B12 deficiency

Risk of lactic acidosis (very rare): Potentiates HAGMA if pt is alr acidotic /has renal impairment

  • eGFR <30: Avoid
  • eGFR 30-60: Max 1g/day
  • eGFR >60: Safe

C/I in pt w/ renal, hepatic or cardiac impairment 🡪 worsens lactic acidosis, Stop before giving contrast for imaging

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4
Q

What are the examples of sulfonylureas?

A

1st gen – tolbutamide, chlorpropamide

2nd gen – glibenclamide, gliclazide, glipizide

3rd gen – glimepiride

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5
Q

What are the MOAs of sulfonylureas?

A

Closes potassium ATP channels and opening calcium channels on beta-islet cell surface receptors, increasing insulin secretion

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6
Q

What are the advantages of sulfonylureas?

A

Thought to reduce microvascular risk

Elderly Friendly – tolbutamide (short T½)

CKD friendly – only gliclazide and glipizide, but gliclazide may require renal dose adjustment

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7
Q

What are the disadvantages of sulfonylureas?

A

Can cause significant hypoglycaemia and weight gain, especially long-acting sulfonylureas like glibenclamide

Not useful in patients with pancreatic insufficiency (late stage) or T1DM

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8
Q

What are the examples of GLP-1 mimetics (glucagon like peptide)

A

Activates GLP-1 receptors to enhance incretin effect:

1) ↑glucose-stimulated Insulin Release
2) Suppress Glucagon

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9
Q

What are the examples of GLP-1 mimetics?

A

exenatide, liraglutide

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10
Q

What are advantages of GLP-1 mimetics?

A

Induces weight loss (b/c ↑ Insulin, Inhibit glucagon, ↓ Appetite, Delay gastric emptying)

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11
Q

What are disadvantages of GLP-1 mimetics?

A

Must be given s/c

GI disturbances of nausea, vomiting, abdominal distension, diarrhoea

Headache, dizziness, diaphoresis

C/I in pregnancy, breastfeeding, FHx of MTC (medullary thyroid Dz) or MEN2

Not useful in patients with pancreatic insufficiency (late stage)

Small risk of pancreatitis – use w caution in pt with hx of pancreatitis

Not recommended in patients with moderate-severe renal impairment

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12
Q

What is the MOA of DPP4- inhibitors?

A

Inhibits DPP-4, an enzyme which breaks down GLP-1 and GIP (GI poplypeptide) incretins

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13
Q

What are examples of DPP4 inhibitors?

A

sitagliptin, linagliptin, vildagliptin

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14
Q

What are the advantages of DPP-4 inhibitors?

A

Weight neutral

GIT (diarrhea, constipation, nausea), nasopharyngitis

Good S/E profile, a/w minimal Hypogly events

CKD friendly 😊 – but sitagliptin require renal dose adjustment

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15
Q

What are the disadvantages of DPP-4 inhibitors?

A

Causes urticaria in some patients, and rarely angioedema

Not useful in patients with pancreatic insufficiency (late stage)

Small risk of pancreatitis – use w caution in pt with hx of pancreatitis

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16
Q

What are examples of Alpha-glucosidase inhibitors?

A

arbacabose

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17
Q

What is the MOA of Alpha-glucosidase inhibitors?

A

Inhibits α-glucosidase which breaks carbs into monosaccharide components, retarding glucose uptake in the intestine

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18
Q

What is the advantages of Alpha-glucosidase inhibitors?

A

Helps to reduce post-prandial glycaemic index

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19
Q

What is the disadvantages of Alpha-glucosidase inhibitors?

A
  • Needs to be taken thrice daily
  • SE a/w increased delivery of undigested starch to colon for fermentation: bloating, flatulence, and diarrhoea
  • Provides minimal A1c reduction. Being phased out
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20
Q

What are examples of SGLT-2 inhibitors?

A

dapagliflozin, canagliflozin, empaglifozin

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21
Q

What is the MOA of SGLT2 inhibitors?

A

Inhibits SGLT-2 in the proximal nephron, hence prevents glucose reabsorption and increases glycosuria

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22
Q

What is the advantages of SGLT2 inhibitors?

A

Induces LOW b/c does not drive glucose into tissue

Good S/E profile, a/w Min Hypogly events

Cardioprotective (against HF dev)

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23
Q

What is the disadvantages of SGLT2 inhibitors?

A

Increased risk of UTI

Increased risk of genital mycotic infections

Polyuria

Dose-related risk of volume depletion, dehydration

LDL increase

Risk of euglycemic DKA
C/I if CrCl <45 🡪 inc risk of pre-renal impairment because of dehydration

Will not recommend in BPH patients / bedbound / diapers 🡪 impaired urine clearance and worse genital hygiene

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24
Q

What do you need to counsel patients on when they are on SGLT2 inhibitors?

A

Empty bladder regularly 🡪 the longer they hold the higher the risk of infection (because urine very sweet), and important for proper

Hygiene 🡪 clean perineal region after urination

Need to stop 2 days before any elective procedure

Need to stop on day of acute hospital admission

When severely sick w/ vomiting high fever 🡪 need to stop SGLT2 inhibitor (no need to stop for mild illnesses / mild URTI)

Ramadan 🡪 body in stressed state hence must stop SGLT2 inhibitors as well

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25
Q

What are examples of Thiazolidinediones? How are they usually given?

A

pioglitazone, rosiglitazone

In view of side effects, usually only considered if patient

  • Does not tolerate Metformin
  • Severely insulin resistant / refuses insulin
  • Not at risk of heart failure / bladder CA / osteoporosis
26
Q

What is the MOA of Thiazolidinediones?

A

Activates PPAR 🡪 ↑ transcription of GLUT1/4 🡪 ↑ glucose uptake
↑ insulin sensitivity

27
Q

What are the advantages of Thiazolidinediones?

A

Min Hypogly events

May be used synergistically with metformin

28
Q

What are the disadvantages of Thiazolidinediones?

A

There can be significant weight gain, fluid retention leading to oedema, and heart failure

C/I in ANY form of heart failure

We generally avoid in renal failure, because counterproductive to give drug that causes fluid overload in renal failure

29
Q

Which oral hyperglycemic agent to prescribe?

A

The main classes of drugs that are most commonly used: Metformin, Sulfonylureas, DPP4 Inhibitors, SGLT2 Inhibitors

2nd line – either Metformin / Sulfonylureas; or DPP4 / SGLT2 inhibitors if the former are C/I

  • In obese pt on sulfonylureas, we will want to add on SGLT2 inhibitors to promote weight loss
  • In pt w/ normal weight 🡪 we can consider both metformin and sulfonylureas 😊

3rd line – either DPP4 / SGLT2 inhibitors

30
Q

What is the MOA of meglitinides?

A

Both the meglitinide analog repaglinide and the D-phenylalanine derivative nateglinide inhibit KATP channels in pancreatic β cells to stimulate insulin production.

Administer 15min before meals

31
Q

What are the advantages of meglitinides?

A
  • Used in renal failure – 100% cleared hepatically

- For Prandial Glycaemic control

32
Q

What are examples of meglitinides?

A

Repaglinide; Nateglinide

33
Q

What are the disadvantages of meglitinides?

A
  • Hypoglycemia

- Weight gain

34
Q

What are the insulin adjustments in a patient with kidney problems?

A
  • GFR > 50: no dose adjustments
  • GFR 10-50: reduce by up to 25%
  • GFR < 10: reduce by up to 50%
35
Q

What are the glucose levels during haemodialysis?

A

Both glucose and insulin are removed during dialysis

  • Risk of hypoglycemia during dialysis
  • Risk of hyperglycemia after dialysis

Insulin resistance improves on post HD days due to removal of urea!

36
Q

What are the glucose levels during peritoneal dialysis?

A
  • PD: Insulin resistance improves with dialysis; HOWEVER:
  • Use of Icodextrin: can lead to spuriously high glycaemic index, should change to newer blood glucose monitor device
  • Use of Dextrose: lead to elevated glycaemic index and poorer control
37
Q

What are rapid acting SC insulin to inject immediately before food?

What is the onset, peak and duration of action?

A

Analogs

Aspart (Novorapid)

  • Onset: 10-20 min
  • Peak: 1-3 hours
  • Duration of action: 3-5 hours

Glulisine (Apidra)

  • Onset: 10-20 min
  • Peak: 0.5 -1.5 hours
  • Duration of action: 2-4 hours

Lisopro (Humalog)

38
Q

What are short acting SC insulin to inject 30 minutes before food?

What is the onset, peak and duration of action?

A

Recombinant human

Actrapid (s/c injection)

  • Onset: 30 min
  • Peak: 1-3 hours
  • Duration of action: 7-8 hours
39
Q

What is the difference between Recombinant human (Actrapid) and Analogs (Glulisine, Lispro, Aspart)? In terms of

  • onset
  • administration
  • prandial glucose
  • hypoglycemia
  • dose adjustment
A

Actrapid

  • Slow onset (30mins)
  • administered 30- 45min before meals
  • prandial glucose: Mismatch between injection and postprandial peak
  • Hypoglycaemia: Risk of inter-prandial hypoglycemia
  • Dose adjustment: Renal adjustment

Analogs (Glulisine, Lispro, Aspart)

  • Rapid onset (5 mins)
  • administered immediate before/ after
  • prandial glucose: improved post prandial glucose control
  • Hypoglycaemia: reduces night time hypoglycemia
  • Dose adjustment: no renal adjustment
40
Q

What is the intermediate acting SC insulin to be injected once or twice a day?

A

Recombinant:

- Isophane Insulin (Insulatard)

41
Q

What is the long acting SC insulin to be injected once or twice a day?

A

Detemir (Levemir) - injected once or twice a day

Glargine (Lantus) - inject once a day

42
Q

Insulatard (NPH)

  • Onset
  • Administration
  • Fasting glucose
  • hypoglycemia
A
  • 2 hours
  • BD
  • fasting glucose good
  • hypogly mid morning/ night time hypo (especially mix tard)
43
Q

Detemir (Levemir)

  • Onset
  • Administration
  • Fasting glucose
  • hypoglycemia
A
  • Immediate
  • BD (sometimes OM)
  • fasting glucose good (may be suboptimal OM)
  • lower risk of hypogly
44
Q

Glargine (Lantus)

  • Onset
  • Administration
  • Fasting glucose
  • hypoglycemia
A
  • Immediate
  • OM/ON
  • fasting glucose good
  • lower risk of hypogly

Specifically, glargine is advantageous in that it provides peakless insulin lasting up to 24 hours but is very, very expensive!

45
Q

Who is premixed insulin not appropriate for?

A

Comprises a fixed ratio of rapid/fast-acting & intermediate/long-acting insulin

Not Appropriate for T1DM

Not Appropriate for newly Dx T2DM due to need for tight control

MAY be considered for some T2DM pt, but in general should be avoided

46
Q

What are the cons pf premixed insulin?

A

Unable to adjust in terms of dosage (wrt food) and timing, which is especially important for poorly controlled diabetics / newly diagnosed diabetics / diabetics with erratic schedules and unable to follow a normal meal times

No advantage wrt glycaemic control compared to non-pre-mixed insulin

47
Q

What are the pros of premixed insulin?

A

Cheaper (since 1 pen instead of 2) and less painful (minimize by 1 injection) for diabetics that is well controlled at a fixed ratio 😊

48
Q

What is the premixed insulin that contains (short + immediate acting) SC insulin to be injected 30 min before food?

What is the onset, peak, and duration?

A

Mixtard: 30% actrapid, 70% Isophane insulin (NPH insulin).

Onset: 30 min
Peak: 2-8 hours
Duration: Up to 24 hours

49
Q

What is the premixed insulin that contains (rapid+ immediate acting) SC insulin to be injected immediately before food?

What is the onset, peak, and duration?

A

Novomix: 30% Aspart, 70% Aspart protamine

  • Onset: 10-20min
  • Peak: 1- 4 hours
  • Duration of action: up to 24 hours

Humalong mix: 50% lispro, 50% lispro protamine

  • Onset: 10-15min
  • Peak: 0.5- 1.5 hours
  • Duration of action: up to 24 hours
50
Q

Mixtard 30/70

  • onset
  • administration
  • fasting glucose
  • prandial glucose
  • hypoglycemia
A

Onset

  • 30min: actrapid
  • 2 hours: insulatard

Admin: BD, 2 injections per day

Fasting glucose good

Prandial glucose good but requires regular meals

Hypogly

  • mid morning/ night time hypogly
  • compulsory to eat lunch
  • may need bed time snack
51
Q

Glulisine + Glargine

  • onset
  • administration
  • fasting glucose
  • prandial glucose
  • hypoglycemia
A

Onset

  • 5min: glulisine
  • immedate: glargine

Admin:

  • TDS pre-meal – Glulisine
  • OM – Glargine
  • 4 injections per day

Fasting glucose good

Prandial glucose good

Hypogly

  • Lower risk
  • Flexible: erratic hours, shift work, travelling across time zones, regular sports
52
Q

What are the different types of insulin regimens?

A

Basal Insulin only – To use long / Intermediate acting insulin to keep blood glucose constant during fasting

Bolus Insulin only – To use short / rapid acting insulin to keep blood glucose under control after meals

Basal Plus – essentially Basal + single bolus for the largest meal of the day

Basal Bolus – Combination of both Basal & Bolus regimes to emulate normal physiological insulin patterns

  • Basal Bolus is the Gold Standard for T1DM
  • T2DM can afford simpler alternatives such as Basal / Bolus only
53
Q

What is the basal insulin regimen like?

A
  1. Start a long-acting insulin at 0.15 units/kg/day (e.g. 70kg ~ 10 units)
    - Glargine 10 units OM
    - Insulatard 5 units BD – lower cost!
  2. Monitor fasting CBG daily pre-breakfast
  3. Titrate dose (+2 units) every 3 days until target of ≤6 mmol/L is reached
  4. Continue OHGAs
  5. Hypoglycemia advice!
54
Q

What is the basal plus insulin regimen like?

A
  1. Start a short-acting insulin at the LARGEST meal of the day (e.g. Dinner)
    - Actrapid 4 units ON 30 min pre-meal
    - Glulisine 4 units ON immediately pre-meal
  2. Monitor pre- and post-meal blood glucose on top of fasting glucose
  3. Titrate dose until target of ±2 mmol/L between pre- and post-meal blood glucose is reached
  4. Continue long-acting insulin (Glargine 12 units OM) and OHGAs
  5. Hypoglycemia advice!
55
Q

What is the basal bolus insulin regimen like?

A
  1. Start a short-acting insulin at the LARGEST meal of the day (e.g. Dinner)
    - Actrapid 4 units ON 30 min pre-meal
    - Glulisine 4 units ON immediately pre-meal
  2. Monitor pre- and post-meal blood glucose on top of fasting glucose
  3. Titrate dose until target of ±2 mmol/L between pre- and post-meal blood glucose is reached
  4. Continue long-acting insulin (Glargine 12 units OM) and STOP OHGAs
  5. Hypoglycemia advice!
56
Q

What is the preixed bolus insulin regimen like?

A
  1. Start pre-mixed insulin twice daily at breakfast and dinner (0.5 units/kg/day)
    - Mixtard 10 units BD
    - Novomix 10 units BD
    - Humalog 10 units BD
    (Pre-breakfast and pre-dinner dose can be adjusted independently)
  2. Monitor pre- and post-meal blood glucose on top of fasting glucose (ideally)
  3. Titrate dose until target of ±2 mmol/L between pre- and post-meal blood glucose is reached
  4. ± Continue OHGAs
  5. Hypoglycemia advice!
57
Q

When do we start insulin?

A 
When do we start insulin?
- T1DM
- LADA (Latent autoimmune diabetes of adults – a type of T1 DM in adulthood)
- T2DM with below features
o Pregnancy
o DKA
o Pancreatic Insufficiency

When do we start Insulin for T2DM?

  • Failure of OHGA to control CBG (e.g. ≥2 OHGA at optimal doses, or contraindications to multiple OHGAs)
  • Symptomatic hyperglycaemia e.g. weight loss, polyuria, polydipsia
  • Severe hyperglycaemia (e.g. pre-meal CBG > 20 mmol/L for 2 consecutive episodes)
58
Q

What do you counsel a diabeticpatient on during ramadan?

A

1st ask about opinions and perceptions and if patient has complications + what the control is like

If severely complicated – explain why it will be beneficial to not fast! Because good sugar control is important

Important medications to change

  • SULFONYLUREA –give at night instead of OM
  • INSULIN: insulatard (intermediate acting) – stop morning dose, and give NIGHT dose instead (to compensate breaking fast)
  • Glargine / long acting – to reduce dose by 20%
  • SGLT2 INHIBITORS – STOP!

Other medications

  • Can give other meds, but avoid giving during the fasting period: if OM, then change to ON (eg: GLP1 mimetics)
  • Can continue metformin, but change TDS to OM: so that don’t need take during fasting time
59
Q

How do you know if Glargine dose is sufficient?

A
  • We look at 7am glucose (pre-breakfast – as good as fasting glucose test)
  • If sufficient glargine –> 7am glucose normal
  • If too much glargine –> 7am glucose LOW –> will probably wake up in middle of night to look for snacks due to HypoG
60
Q

How do you know if Actrapid dose is sufficient?

A
  • If Actrapid is given for 30min before breakfast –> look at glucose level PRE-LUNCH / POST-BREAKFAST
  • If Actrapid is sufficient the post-meal should be +/- 2 away from the pre-meal
  • However, don’t confuse Actrapid effectiveness VS good control ↓ Actrapid can work but control still be bad!
61
Q

What is the ideal glucose control for CBG monitoring?

A
  • Pre-Breakfast Hypocount <7
  • Pre-meal Hypocount 4-6
  • Post Meal Hypocount <8

Endocrine (18 decks)

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