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Endocrine > Diabetic Drugs > Flashcards

Diabetic Drugs Flashcards

1
Q

Name the 6 classes of drugs commonly used in treatment of T2DM. Provide an example of each.

A

Biguanide - Metformin
Sulphonylureas - (gliclaz)ide
Thiazolidinediones - (Pio)glitazone
SGLT2i - (Dapa)gliflazon
DPP4i - (Sita)gliptin
GLP-1RA - (Sema)glutide

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2
Q

Metformin MOA

A

Inhibits complex 1 in respiratory chain =>
Decrease in cellular ATP =>
Increased AMP:ATP ratio =>
Activation of AMP kinase =>
Decreased gluconeogenesis in the liver &
Increased gut glucose utilisation & metabolism

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3
Q

Metformin target organs

A

Kidneys, LIVER, intestine

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4
Q

Metformin class drug

A

Biguanide

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5
Q

Metformin non-glucose benefit

A

Cardiovascular benefit

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6
Q

Metformin effect on weight

A

Weight neutral

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7
Q

Metformin contraindications

A

Heart failure
Renal failure (does should be lowered in renal impairment)
Liver failure

… as Metformin increases lactate production & the liver & kidneys are responsible for clearing Metformin, meaning if they are impaired, lactic acidosis risk is increased

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8
Q

If a patient develops renal impairment, what should happen to their Metformin

A

Dose should be lowered

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9
Q

Metformin side effects

A

GI - anorexia, nausea, pain, bloating, dyspepsia, diarrhoea
Risk of lactic acidosis

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10
Q

Sulphonylureas MOA

A

Binds to sulphonylurea receptor (SUR1) =>
Closure of Kate channels =>
Rise in membrane potential =>
Ca influx =>
Insulin exocytosis

I.e. Glucose independent insulin secretion

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11
Q

Sulphonylurea medication example

A

Gliclazide

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12
Q

Sulphonylurea target organ/cell

A

Pancreatic beta cells

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13
Q

Sulphonylureas benefits

A

Cheap
Potent glucose lowering

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14
Q

Sulphonylureas side effects

A

Weight gain
Hypoglycaemia

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15
Q

Why does Sulphonylureas cause weight gain

A

They increase insulin
Insulin is anabolic & increases fat, glucose & protein uptake
Insulin also stimulates appetite

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16
Q

Why do Sulphonylureas cause hypoglycaemia

A

They cause glucose-independent insulin release

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17
Q

What increases an individuals risk of hypoglycaemia due to Sulphonylureas

A

Increased age
Long time since diabetes diagnosis
Impaired renal function
Lower HbA1c

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18
Q

Sulphonylureas contraindications/cautions

A

Use with care in people with liver or RENAL disease

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19
Q

TZDs MOA

A

Binds to PPAR-𝛾 - nuclear receptor =>
Increases pre-adipocyte to adipocyte conversion =>
Increases fat mass =>
‘Lipid steal’ & reduced fat in liver & muscles =>
Decreased lipotoxicity =>
Increased adipocetin =>
Increased liver insulin sensitivity

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20
Q

TZDs example

A

Pioglitazone

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21
Q

TZDs benefits

A

Cheap
True insulin sensitiser

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22
Q

TZDs contraindications

A

Avoid in HF & in elderly (>65yrs) due to risk fluid retention

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23
Q

TZDs side effects

A

Weight gain
Fluid retention
Increased fracture risk
Mild anaemia

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24
Q

SGLT2i MOA

A

Sodium-glucose transporter 2 inhibitor =>
Reduced renal afferent dilatation & filtration pressure => Increased urinary glucose excretion =>

25
SGLT2i drug example
empagliflozin, Dapagliflozin, canagliflozin
26
SGLT2i benefits
Weight loss Mild diuretic & so benefit to HF Increased urate excretion & so benefit to gout & CVD Renal protection Increased FFA & ketones (cardiac fuel) & so cardiac benefit
27
Why are SGLT2i’s beneficial in patients with episodes of gout
It increases urate excretion
28
Why are SGLT2i’s beneficial in HF
It also reduces Na reabsorption & so is a mild diuretic
29
Why are SGLT2i’s beneficial in CVD
Glucose reduction → decreased insulin and increased glucagon → increase in lipolysis → increase in FFA which also increases ketone body production → FFA & ketones are a fuel to cardiac myocytes → cardiac benefit
30
SGLT2i contraindications
Reduced eGFR (as causes afferent renal vasoconstriction) Diuretics (as mild diuretic) Prolonged fasting/acute illness (as increases urinary glucose excretion regardless of blood glucose levels)
31
SGLT2i side effects
- Genital candiasis - secondary to glycosuria - Fournier gangrene - rare but severe - Hypovolaemia, hypotension & dehydration - diuretic effect - DKA - Slight increase in LDL and HDL cholesterol
32
Why do SGLT2i’s increase the risk of DKA
Glucose reduction → decreased insulin and increased glucagon → increase in lipolysis → increase in FFA which also increases ketone body production → ketocosis → increased ketoacidosis risk
33
What medication increases the risk of Fournier gangrene
SGLT2i’s
34
TZDs target cell/ receptor
Adipocytes (PPAR-𝛾 - nuclear receptor)
35
SGLT2i target cell/ receptor
sodium glucose transporter 2 in the proximal convoluted tubules in the kidneys
36
Describe the incretin effect
Intestine releases GLP1 & GIP in response to nutrients These hormones bind to receptors on pancreatic beta cells & amplify insulin release upon presence of glucose GLP-1 has a very short half life and is broken down by the enzyme DPP4
37
GLP-1RA MOA
GLP-1 receptor agonist that avoids breakdown by DPP4 This promotes insulin secretion & lowers glucose It also reduces appetite (hypothalamus) It also reduces gastric emptying (intestine)
38
GLP-1RA drug example
Semaglutide
39
GLP-1RA benefits
Weight loss (by reducing appetite) Lowers blood pressure & so CV benefit Avoids hypoglycaemia (as insulin only enhanced in presence of glucose)
40
GLP-1RA side effects
N&V, bloating from gastroperesis (delayed gastric emptying) Gallstones
41
Why does GLP-1RA benefit the kidneys
It reduces new onset macroalbuminuria (But no impact on eGFR)
42
GLP-1RA contraindications
Acute pancreatitis
43
GLP-1RA formulation
SC injections
44
DPP4 inhibitors
Inhibit DPP4 enzyme => Inhibit GLP & GIP breakdown => Increased insulin & decreased glucagon & lower bp
45
DPP4i benefits
Weight neutral Lowers blood pressure Avoids hypoglycaemia (as insulin only enhanced in presence of glucose)
46
DPP4i side effects
N&V Increased risk of pancreatitis May increase HF risk
47
DPP4i formulation
Oral
48
DPP4i & GLP-1RA target organ/cell
Intestine
49
What is first line T2DM treatment
Metformin
50
What extra medication would you add in patients with atherosclerotic disease (e.g. previous MI) & T2DM
GLP-1RA (Or SLGT2i if eGFR okay & GLP-1RA not tolerated)
51
What extra medication would you add in patients with heart failure or chronic kidney disease & T2DM
SLGT2i (Or GLP-1RA if eGFR not okay)
52
What medication would you avoid if you want to reduce the risk of hypoglycaemia in a patient with T2DM
Sulphonylureas
53
What medication would you add in patients with T2DM who need to lose weight
SGLT2i or GLP-1RA
54
What medication would you add in patients with T2DM where cost is a problem
Sulphonylureas or TZDs
55
What insulin regime are most T1DM patients on & why
Basal-bolus regime - Long-acting 1-2/day & rapid-acting insulin before each meal - mimics normal physiological insulin secretion
56
Name 3 rapid acting insulins (bolus insulin analogues)
- Insulin aspart (NovoRapid), - lispro (Humalog), - glulisine (Apidra)
57
Name 2 long acting insulins (basal insulin analogues)
- lantus (glargine), - levemir (dertermir)
58
Summarise the different insulins available
Rapid acting (analogue) - preferred bolus insulin - Humalog, NovoRapid, Apidra - 60-90mins peak Short acting (soluble) - Humulin S (human insulin), Actrapid, Insuman Rapid - 2-4hr peak Intermediate acting (isophane) - Insulatard, Humulin I (human isophane), insuman basal - 4-6hr peak Long acting (analogue) - preferred basal insulin - Lantus (glargine), levemir (dertermir) - less peak activity
59
Insulin injection site should be rotated to prevent…
Lipohypertrophy

Endocrine (23 decks)

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