Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

brs (phase 1b) > (pharm) pharmacology of diabetes > Flashcards

(pharm) pharmacology of diabetes Flashcards

1
Q

what are four commonly prescribed drugs for diabetes?

A

metformin

DPP-4 inhibitors (dipeptidyl-peptidase 4)

sulphonylurea

SGLT2 inhibitors (sodium-glucose cotransporter inhibitors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

explain the primary mechanism of action of metformin

A

1 - metformin activates AMPK in hepatocyte mitochondria

= inhibits ATP production + blocks hepatic gluconeogenesis and subsequent hepatic glucose output

2 - blocks adenylate cyclase which in turn promotes fatty acid oxidation (reduces accumulation of FAs and lipids)

both mechanism help to restore insulin sensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the drug target for metformin?

A

5′-AMP-activated protein kinase (AMPK)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the main side effects of metformin?

A

(mainly GI side effects in 20-30% of patients)

abdominal pain

diarrhoea

vomiting

decreased appetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the primary site of action of metformin?

A

hepatic mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is AMPK?

A

adenosine monophosphate-activated protein kinase

an enzyme that switches on an off to regulate energy intake and expenditure and control energy metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is the function of AMPK?

A

switches on and off to regulate control energy metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is AMPK an effective drug target in diabetes?

A

once activated by metformin, AMPK inhibits hepatic gluconeogenesis, reducing hepatic glucose output AND increases insulin sensitivity

= reduces the further exacerbation of the hyperglycaemia in T2DM patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how is insulin sensitivity restored using metformin?

A

1 - activation of AMPK will inhibit hepatic gluconeogenesis and reduce subsequent hepatic glucose output

2 - blocking of adenylyl cyclase increases fatty acid oxidation (reduced accumulation of FAs and lipids)

= both restore insulin sensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how many people who take metformin experience GI side effects?

A

approx 20-30% of people

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how can dosage monitoring improve outcomes for metformin patients and why?

A

high doses of metformin tend to lead to GI side effects and so a slow increase in dose may improve tolerability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

how does metformin access tissues?

A

via the OCT-1 transporter (organic cation transporter)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

why is OCT-1 important for metformin?

A

to enable uptake into hepatocytes

as metformin is an organic cation (i.e. polar) and cannot cross the non-polar lipid bilayer of hepatocytes unless the carrier protein OCT-1 is present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

where is metformin most likely to accumulate?

A

liver and GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

why does metformin accumulate in the liver?

A

the metformin-specific transporter OCT-1 is found predominantly in the liver and GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

why does metformin accumulate in the GI tract?

A

the metformin-specific transporter OCT-1 is found predominantly in the liver and GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

when is metformin most effective?

A

in the presence of endogenous insulin so when there are some residual functioning pancreatic beta islet cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

why must be present for maximal metformin efficiency?

A

endogenous insulin (so there must be some residual functioning pancreatic beta islet cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how can the tolerability of metformin be improved?

A

a slow increase in the dose (especially if high doses are prescribed) = prevent GI side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are DPP-4 inhibitors?

A

dipeptidyl peptidase - 4 inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

give an example of a DPP-4 inhibitor

A

sitagliptin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

explain the primary mechanism of action of DPP-4 inhibitors

A

bind to and inhibit the enzyme DPP-4 in the vascular endothelium so incretin levels are increased

increased incretin levels will work to increase insulin production, reduce glucagon secretion, decrease appetite and slow down digestion = decrease blood glucose levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is the drug target for DPP-4 inhibitors?

A

the DPP-4 enzyme found in the vascular endothelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the primary site of action of DPP-4 inhibitor action?

A

vascular endothelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what are the most common side effects of DPP-4 inhibitors?

A

upper respiratory tract infections

flu-like symptoms = headache, runny nose, sore throat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are the less common side effects of DPP-4 inhibitors?

A

serious allergic reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

in whom is the administration of DPP-4 inhibitors contraindicated?

A

patients w pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

give one reason why are DPP-4 inhibitors preferred to other anti-diabetic drugs

A

do not appear to cause weight gain (like metformin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what are incretins?

A

gut hormones that are secreted by enteroendocrine cells that stimulate a decrease in blood glucose by augmenting the secretion of insulin from pancreatic beta cells from the islets of Langerhans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

give an example of an incretin

A

GLP-1

31
Q

where is incretin secreted from?

A

enteroendocrine cells

32
Q

why must be present for maximal DPP-4 inhibitor efficiency and why?

A

some functional residual pancreatic beta cells must be present as DPP-4 inhibitors work by augmenting incretin function to stimulate insulin secretion

33
Q

what are sulphonylureas?

A

a class of drugs that lower blood sugar levels by stimulating insulin production but run the risk of causing hypoglycaemia

34
Q

give an example of a sulphonylurea

A

gliclazide

35
Q

explain the primary mechanism of action of sulphonylureas

A

bind to the ATP-sensitive potassium channels on pancreatic beta cells inhibiting them and inducing depolarisation and the subsequent calcium influx causes vesicular exocytosis of insulin into the bloodstream

36
Q

what is the drug target for sulphonylureas?

A

the ATP-sensitive potassium channels on the pancreatic beta cell membrane

37
Q

what is the primary site of action for sulphonylureas?

A

pancreatic beta cells

38
Q

what are the main side effects of sulphonylureas?

A

weight gain

hypoglycaemia

39
Q

why must be present for maximal sulphonylurea efficiency and why?

A

sulphonylureas work by augmenting insulin release and so a baseline residual level of pancreatic beta cell function is required

40
Q

how is the side effect weight gain due to gliclazide administration mitigated?

A

administer metformin

41
Q

what must be discussed when prescribing a patient gliclazide?

A

the side effect of hypotension (especially if concomitant glucose-lowering drugs are also being taken)

42
Q

why must the side effect of hypoglycaemia be discussed especially in patients taking gliclazide?

A

in case they also take concomitant glucose-lowering drugs

43
Q

what are SGLT2 inhibitors?

A

sodium-glucose transport protein 2 inhibitors that are used to treat reduce blood glucose levels

44
Q

give an example of an SGLT2 inhibitor

A

dapagliflozin

45
Q

explain the primary mechanism of action of dapagliflozin

A

reversibly inhibits the sodium-glucose cotransporter (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion

46
Q

what is the drug target for dapagliflozin?

A

SGLT2 in the renal proximal convoluted tubule

47
Q

what is the primary site of action of dapagliflozin?

A

proximal convoluted tubule in the kidney

48
Q

what are the main side effects of dapagliflozin?

A

urogenital infections

slight decrease in bone formation

can worsen diabetic ketoacidosis

49
Q

in how many patients do dapagliflozin cause urogenital infections?

A

around 5% of patients

50
Q

why does dapagliflozin affect bone formation?

A

linked to suppression of serum calcitonin and excretion of calcium

51
Q

how can dapagliflozin cause urogenital infection?

A

increases glucose load of urine which can attract pathogenic organisma

52
Q

what happens if dapagliflozin worsens diabetic ketoacidosis?

A

daptafliflozin administration must be stopped

53
Q

how can dapagliflozin lead to diabetic ketoacidosis?

A

decreases blood glucose levels by decreasing endogenous insulin secretion

= subsequent increase in glucagon secretion causes ketogenesis that can potentially lead to ketoacidosis

54
Q

what must be present for maximal SGLT2 inhibitor function?

A

depends on normal renal function and so cannot be given to patients with renal impairment

55
Q

in whom is the administration of SGLT2 inhibitors contraindicated?

A

patients with renal impairment (as SGLT2 inhibitors have to act on the renal proximal convoluted tubule)

56
Q

what commonly is the therapeutic objective for patients with diabetes?

A

normalise HbA1c, hypertension, HDL and LDL cholesterol levels and reduce BMI

57
Q

why is it important to reduce HbA1c levels in patients with diabetes?

A

reduce the microvascular and macrovascular complications of diabetes

58
Q

why is it important to reduce hypertension levels in patients with diabetes?

A

reduces the risk of cardiovascular disease

59
Q

why is it important to regulate HDL and LDL levels in patients with diabetes?

A

linked to the formation of atherosclerotic plaques which increase the risk of an infarction and CVD

60
Q

why is it important to reduce obesity in patients with diabetes?

A

reduces cardiovascular complications and insulin resistance

61
Q

what are the indications for metformin administration?

A

lifestyle should be reviewed before every treatment escalation

if HbA1c rises still = metformin

if HbA1c rises to 58mmol/mol = dual therapy in the form of metformin AND either SU, DPP-4 inhibitor, SGLT2 inhibitor, or pioglitazone

if HbA1c continues to rise = insulin-based treatment OR triple therapy

62
Q

how does the molecular structure of metformin influence its absorption into the blood and distribution to body tissues?

A

metformin is an organic cation and so is polar = cannot cross the non-polar lipid membranes of cells and so must be transported using the OCT1 transporter

63
Q

in which tissues is the expression of OCT1 highest?

A 
liver hepatocytes (highest)
small intestinal enterocytes
renal proximal tubules
64
Q

in which tissues is the expression of OCT1 highest?

A

liver hepatocytes (highest)

small intestinal enterocytes

renal proximal tubules

65
Q

why is OCT1 expression high in hepatocytes?

A

determines distribution to the site of action

66
Q

why is OCT1 expression high in small intestine enterocytes?

A

site of absorption of metformin

67
Q

why is OCT1 expression high in the renal proximal tubule?

A

site of excretion of metformin

68
Q

what must you do in patents on metformin that show signs of renal impairment?

A

clinically essential that you monitor kidney function in any patient on metformin that shows signs of renal impairment (eGFR)

69
Q

why can renal impairment cause problems for diabetic patients on metformin?

A

metformin is primarily excreted unchanged by the kidneys SO if there is renal impairment = metformin accumulates in the blood and the elevated serum metformin can lead to lactic acidosis + more extreme side effects

70
Q

how is metformin administration altered in patients with renal impairment like CKD?

A

the dose is not usually halved as NICE guidelines suggest and so monitor eGFR regularly to ensure it does not fall below 30

(if it does, stop metformin immediately)

71
Q

why is it important to ensure hypoglycaemia does not occur in older patients on metformin?

A

can risk falls and hip fractures and other injuries

72
Q

what is the biggest problem for metformin adherence?

A

the GI side effects

73
Q

what measures can someone take to tolerate the GI side effects of metformin?

A

practical measures such as take it after NOT before food, switch to a better tolerated preparation or sustained release metformin can be taken

74
Q

how is sustained release metformin different?

A

absorbed more slowly (so less GI side effects) but it is more expensive

brs (phase 1b) (71 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions