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Diabetic medications Flashcards

1
Q

What is the process that ends up with DMII?

A

Normal
Hyperinsulinaemia (normal glucose w/ raised insulin)
Hyperglycaemia (high both)
DMII (falling insulin levels as beta cells fail)

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2
Q

First line treatment for diabetes?

A

Diet control, and then metformin 500mg/day for 1 week, raising to 500mg BD. Max dose is 2g/day.

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3
Q

What type of drug is metformin?

A

Biguanide

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4
Q

MOA of biguanides?

A

AMPK (liver enzyme) activation:

  • decreased hepatic gluconeogenesis
  • decreased hepatic fatty acid and cholesterol synthesis
  • increased peripheral insulin sensitivity (skeletal muscle)
  • Increased peripheral insulin sensitivity is by AMPK-mediated GLUT4 transporter upregulation in skeletal muscle which increases insulin dependent glucose uptake, and stabilisation of the insulin:insulin receptor interaction

ALL RESULTS IN WEIGHT LOSS, IMPROVED GLYCAEMIC CONTROL, IMPROVED LIPID PROFILE, IMPROVED VASCULAR FUNCTION

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5
Q

Limitation of metformin?

A

Requires beta cell function

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6
Q

Indications of metformin?

A

First line oral agent if diet control fails

Primarily for those with a BMI of over 25 but basically everyone goes onto it

ALSO PCOS

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7
Q

Caution with metformin

A
  • NO hypoglycaemia risk.
  • SAFE in pregnancy.
  • Iodine contrast: suspend before and 48h after and normal renal function returned.
  • GA: suspend before and until normal renal function.
  • Monitor renal function: before commencing and at least twice a year
  • Lactic acidosis: usually secondary to CKD/AKI on CKD
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8
Q

Contraindications of metformin

A

eGFR below 30
GA
Iodine contrast

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9
Q

AEs of metformin

A

GI: (a,n,v,d) - take with food
Quite significant diarrhoea
Metallic taste
Lactic acidosis - withdraw

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10
Q

When would you stop metformin?

A

eGFR below 30
Iodine contrast/GA
Lactic acidosis

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11
Q

Sulfonylureas examples?

A

Glubenclamide (LA)
Gliclazide (SA)
Tolbutamide (SA)

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12
Q

Which SU is not suitable in the elderly?

A

Glubenclamide as LA so high risk of hypos

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13
Q

MOA of gliclazide?

A

It is a SU (what are the other SUs?); so it binds to the SUR1 receptor on the pancreatic beta cell, causing closure of the ATP-dependent K+ channel, which prevents K+ induced hyperpolarisation of the cell, and therefore causes depolarisation and induces calcium influx, which increases insulin vesicle release

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14
Q

Limitations of gliclazide?

A

SU

Insulin release augmentation only, so requires some beta cell function

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15
Q

Indications of SUs?

A

When metformin not tolerated/contraindicated (E.g. CKD stage 4 patient), or in combination with metformin.

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16
Q

A/Es of SUs?

A

Weight gain*
Hypoglycaemia**

  • Weight gain obvious as increased insulin and decreased glycosuria

** Hypoglycaemia worse with long-acting e.g. glubenclamide; can persist for hours so needs hospital treatment

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17
Q

Cautions with SUs?

A
  • THERE IS A hypoglycaemia risk.
  • AVOID in pregnancy (nn hypoglycaemia)
  • Weight gain (avoid in obese)
  • Surgery: omit in AM and replace with insulin
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18
Q

AEs of SUs

A

Weight gain
GI
Hypo

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19
Q

Contraindications of SUs

A

Porphyria

Ketoacidosis

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20
Q

MOA of acarbose?

A

Intestinal alpha-glucosidase inhibitor

  • decreased breakdown of polysaccharides = decreased production/absorption of monosaccharides
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21
Q

Indications of acarbose?

A

3rd line - rarely used

Note useful for weight loss!

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22
Q

AEs of acarbose?

A

Flatulence
Diarrhoea
Abdo cramps

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23
Q

Thiazolidinediones examples

A

Pioglitazone

Rosi but banned due to ?CV effects

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24
Q

Pioglitazone MOA?

A

Insulin sensitisation

  • decreased insulin resistance and increased biological response of liver and muscle cells
  • PPARy activation = liver / muscle cell increased insulin signalling (e.g. increased glucose uptake into muscle and decreased glucose production in liver)
  • PPARa activation = increased lipogenesis of adipocytes -> decreased FFA/TG levels and decreased visceral fat but increased S/C fat
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25
Cautions of pioglitazone?
Do not prescribe to this with bladder cancer If less than 0.5% Hba1c drop in 6 months, discontinue
26
AEs of pioglitazone
Peripheral oedema CHF Anaemia Fractures
27
Indications of pioglitazone
- Combination with metformin - Combination with SU if metformin not tolerated (e.g. CKD4) - Combination with metformin + SU
28
Where are the incretin hormones produced and what is their effect?
L and K endocrine cells of the intestine following food ingestion Stimulate insulin secretion from beta cells of islets of Langerhans in the pancreas
29
What is the secretory insulin response relevant to the action of exenatide?
Plasma insulin response following oral glucose load is significantly higher (50-70%) than an IV bolus of glucose of the same size. This is due to the release of GLP-1 (and GIP in non-diabetics) by K and L cells of the intestine when food is in the intestine.
30
Examples of GLP-1 agonists?
Liraglutide | Exenatide
31
MOA of GLP-1 agonists?
Mimic native GLP1. Enhance insulin secretion in glucose-dependent manner (which means increased glucose uptake by muscles) Suppress glucagon secretion in pancreas = decreased gluconeogenesis Restore first phase plasma insulin response Also delays gastric emptying which decreases food intake. ALL OF THIS LEADS TO DECREASED GLUCOSE + WEIGHT LOSS :)
32
Examples of DPP-4 inhibitors?
Sitagliptin Saxagliptin etc
33
DPP4 inhibitor MOA?
Prevent breakdown of GLP-1 and GIP in the blood by DPP-IV enzyme (which is usually very fast) This leas to increased GLP1 and GIP = 1. Increased insulin secretion by beta cells (which means increased glucose uptake from muscles) 2. Suppresses glucagon secretion by alpha cells = decreased gluconeogenesis 3. Restores first phase insulin response 4. Delays gastric emptying = early satiety = decreased food intake
34
Why might GLP-1 agonists be particularly useful in a diabetic patient?
1. Lowers BP 2. Lowers lipids 3. Improved beta cell function 4. Weight loss
35
GLP-1 agonist A/Es
GI effects: N&V Acute pancreatitis Hypoglycaemia (minor)
36
Which drug may cause acute pancreatitis?
GLP-1 agonists (e.g. exenatide, liraglutide)
37
Which drug is linked with thyroid carcinoma in mice?
GLP-1 agonists
38
Cautions with GLP-1 agonists?
MILD hypoglycaemia risk AVOID in pregnancy Previous acute pancreatitis; discontinue if pancreatitis diagnosed
39
A/Es with DPP-IV inhibitors?
GI disturbances Peripheral oedema URTI Pancreatitis
40
Cautions with DPP-IV inhibitors?
Pancreatitis risk | Reduce dose in CKD
41
Indications of incretin drugs?
Monotherapy or combo therapy
42
SGLT-2 inhibitor examples?
-Flozins e.g. cana, dapa
43
SGLT2 MOA?
90% of glucose reabsorption is via SGLT2 transporters in the proximal tubule. This lowers blood glucose. (The transporters reach capacity and at that point glycosuria ensues (around 10). With SGLT2i's, the level of capacity is lowered and glycosuria occurs earlier which means more glucose excreted in urine.)
44
SGLT2 indications?
Combo treatment e.g. with SUs, biguanide
45
A/Es of SGLT2s
Genital infections / UTIs Hypotension* Euglycaemia DKA AKI Fractures Amputations Due to osmotic effect of glucose; average drop around 4mmHg
46
Which drug has association with hypotension?
SGLT-2 inhibitors e.g. -flozins
47
Which drugs are asssociated with increased fractures?
SGLT-2 inhibitors e.g. -flozins Pioglitazone (thiazolidinedione)
48
Which drugs are associated with euglycaemic DKA?
SGLT-2 inhibitors e.g. -flozins
49
Which drugs are associated with amputations?
SGLT-2 inhibitors e.g. -flozins
50
Which drugs are associated with diarrhoea?
Metformin++
51
Which drugs are associated with metallic taste?
Metformin Clarithromycin Metronidazole
52
Which drugs are safe in pregnancy?
Metformin
53
Which drugs should be stopped with IV contrast?
Metformin
54
Which drugs are associated with lactic acidosis?
Metformin
55
Which drug is unsuitable for elderly living alone?
Glubenclamide; long acting SU which can cause hypos
56
Which drugs activate AMPK to cause insulin sensitisation?
Metformin AMPK (liver enzyme) activation: - decreased hepatic gluconeogenesis e.g. decreased fatty acid and cholesterol synthesis - increased peripheral insulin sensitivity* * Increased peripheral insulin sensitivity is by AMPK-mediated GLUT4 transporter upregulation in skeletal muscle which increases insulin dependent glucose uptake, and stabilisation of the insulin:insulin receptor interaction
57
Which drugs close the ATP-dependent K+ channel to increase beta cell secretion of insulin?
SUs E.g. Gliclazide, gubenclamide
58
Which drugs are associated with weight gain?
SUs e.g. gliclazide Insulin!!
59
Which drug has an effect on starch absorption? What is its MOA?
Acarbose Alpha glucosidase inhibitor = decreased monosacharride production and absorption
60
Which drugs are associated with flatulence / diarrhoea? Its MOA?
Acarbose - alpha glucosidase inhibitor
61
Which drug is associated with increased S/C fat?
Pioglitazone (thiazolidinedione); activates PPAR receptors - PPARy activation = liver / muscle cell increased insulin signalling (e.g. increased glucose uptake into muscle and decreased glucose production in liver) - PPARa activation = increased lipogenesis of adipocytes -> decreased FFA/TG levels and decreased visceral fat but increased S/C fat
62
Which drug is associated with bladder cancer?
Pioglitazone
63
Which drugs cause peripheral oedema?
Pioglitazone
64
Which drugs are associated with anaemia?
Pioglitazone
65
Which drugs have particular protective effects on the heart?
GLP-1 agonists (exenatide) and DPP-IV inhibitors (sitagliptin) (lower BP, lower lipids) Metformin (lowers lipids, improves vascular)
66
Which drugs are associated with acute pancreatitis?
DPPIVi (gliptins) and GLP-1 agonists (-tides)
67
Which drugs are associated with UTIs?
SGLT2 inhibitors e.g. -flozin's
68
Which øf the drug class _____ are most associated with fractures?
Canagliflozin (SGLT2i)
69
Which drugs are associated with AKI?
Metformin SGLT2-inhibitors Monitor renal function prior to initiation; above 60

Billy week 142 (1 decks)

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