Pharmacology of Oral Hypoglycaemic Agents Flashcards
1
Q
What is blood glucose rises in diabetes due to?
A
- An inability to produce insulin due to beta cell failure
- Insulin resistance preventing insulin from working effectively, despite adequate insulin production
2
Q
Why is diabetes considered to be a progressive disoder?
A
Beta cell function declines and there is a deteroration of glycaemic control
3
Q
What effect does diabetes have on the risk of cardiovascular disease?
A
It increases it
4
Q
What has caused the diabetes epidemic?
A
Environment, not genetics
5
Q
What is the net change in glucose per day under normal glucose homeostasis?
A
0g/day
6
Q
What is the average daily glucose input?
A
250g/day
7
Q
What contributes to the net glucose input?
A
- Dietary intake
- Glucose production
8
Q
How much glucose is taken in in the diet per day?
A
About 180g/day
9
Q
How much glucose is produced by the body per day?
A
70g
10
Q
By what processes does the body produce glucose?
A
- Gluconeogenesis
- Glycogenolysis
11
Q
How much glucose does the body take up for its use per day?
A
250g
12
Q
How much glucose does the brain take up for its use per day?
A
125g
13
Q
How much glucose does the kidney filter per day?
A
About 180g
14
Q
What happens to the glucose filtered by the kidney?
A
It reabsorbs and refilters it
15
Q
How is glucose reabsorbed by the kidney?
A
- 90% by SGLT2
- Remaining glucose by SGLT1
16
Q
How is type 1 diabetes treated?
A
- Lifestyle
- Insulin
17
Q
How is type 2 diabetes treated?
A
- Lifestyle
- Non-insulin therapies
- Insulin
18
Q
What are the non-insulin therapies used in the treatment of type 2 diabetes?
A
- Biguanides
- Sulphonylureas
- Thiazolidinediones
- DPP4 inhibitors
- alpha-Glucosidase inhibitors
- SGLT2s
- GLP1
- Analogues
19
Q
What do both type 1 and 2 diabetes require in their management?
A
- Patient education
- Ability to monitor results of therapy
20
Q
Why is patient education required in diabetes?
A
Need to know how to self manage with regard to diet, exercise, and healthy living
21
Q
Why is it important to consider the key challenges for patients with type 2 diabetes?
A
Because they are important in patient adherence and quality of life
22
Q
What are the key challenges for patients with type 2 diabetes?
A
- Weight gain, or fear of
- Hypoglycaemia, or fear of
23
Q
Why is weight gain a key challenge for patients with type 2 diabetes?
A
Insulin is an anabolic hormone, and so builds up protein and lays down fat
24
Q
How are newer drugs reducing the problem of weight gain in patients with diabetes?
A
Newer drugs are weight neutral, or promote weight loss
25
What is the result of patients fearing hypoglycaemia?
Patients often run a little higher to prevent hypoglycaemic episodes
26
Why is hypoglycaemia a potential problem for patients with type 2 diabetes?
Excessive stimulation of beta-cells can cause increased insulin, and so reduced blood glucose
27
When is insulin-induced hypoglycaemia especially common?
* Between meals and overnight
* In elderly
28
What is the NICE HbA1c target in type 2 diabetes?
6.5-7.5%
29
What % of type 2 diabetics achieve the NICE HbA1c target?
\<50%
30
How should diabetes be treated if the HbA1c is 6.5%?
Using diet and first 2 treatment steps
31
What should be done if the HbA1c is above 7.5% in patients with diabetes?
Go beyond the first 2 treatment steps, *unless at risk of severe hypoglycaemia*
32
What is the action of metformin?
* Decreases insulin resistance, leading to increased glucose utilisation by tissues
* Decreases hepatic glucose production
33
What are the advantages of metformin?
* Limits weight gain
* Decreases incidence of CVS events
* Can be combined with all other diabetes medications
* Cheap
34
Who is offered metformin?
All patients presenting with type II diabetes without contraindications
35
What should be done if control of diabetes is not sufficient on metformin?
The patient should be left on metformin, and other medications should be added
36
What effect does metformin have when it is given with insulin?
It allows better control with lower doses of insulin when used in conjunction with metformin
37
What are the problems with metformin?
* Side effects
* Rarely, lactic acidosis
* Uncommonly, vitamin B12 deficiency
38
What are the side effects of metformin?
* Nausea
* Vomiting
39
What should be done when a patient on metformin develops side effects?
Should stop the medication, and try modified release preperation
40
How can metformin cause vitamin B12 deficiency?
It can interfere with B12 absorption at the terminal ileum
41
What are the contraindications for metformin?
* Renal failure
* Cardiac failure
* Respiratory failure
* Liver failure
42
At what GFR should metformin not be given?
\<30ml/min
43
Why should metformin not be given in renal failure?
Risk of accumulation and lactoacidosis
44
What is the action of sulphonylureas?
Stimulate beta cells to release insulin by attaching to a receptor on the beta cell
45
What are the advantages of sulphonylureas?
* Decreased microvascular risk
* Low cost
46
What are the problems with sulphonylureas?
* Weight gain
* Hypoglycaemia
47
What are the two most commonly used sulphonylureas?
* Gliclazide
* Glimepiride
48
What are the possible formations of gliclazide?
Standard or slow release
49
In what special situation can gliclazide be used?
In renal impairment
50
Why can gliclazide be used in renal impairment?
As it is metabolised hepatically
51
How is acarbose unique?
It is the only alpha-glucosidase inhibitor available
52
What is the action of acarbose?
It inhibits the breakdown of carbohydrates to glucose in the bowel by blocking the action of the enzyme alpha-Glucosidase
53
What are the side effects of acarbose?
* Flatulence
* Loose stools
* Diarrhoea
54
Why is acarbose rarely, if ever, used nowadays?
It is not very effective
55
By how much can acarbose reduce HbA1c?
0.5%
56
What is the mechanism of action of glitazones?
Binds to and activates one or more peroxisome proliferator activated receptors, which increases insulin sensitivity in muscle and adipose tissue, and decreases hepatic glucose output
57
What are the advantages of glitazones?
Can be used in combination with other oral agents
58
Give two examples of glitazones
* Rosiglitazone
* Pioglitazone
59
Why is rosiglitazone no longer used?
Due to cardiovascular concerns
60
Is pioglitazone still used?
Yes, but there are concerns
61
What are the concerns regarding pioglitazone?
* Weight gain
* Fluid retention
* Heart failure
* Bone metabolism
* Bladder cancer
62
What are the concerns regarding pioglitazone and bone metabolism?
Increased risk of fractures due to exacerbation of oesteoporosis, especially in elderly women
63
What is high glucose in type 2 diabtes due to?
Insufficient insulin release, and over production of glucagon
64
What does GLP-1 therapy do?
It increases insulin secretion from beta cells, and decreases production of glucagon from alpha cells
65
What is GLP-1 released from?
Intestinal L cells
66
What does GLP-1 act on physiologically?
* Brain
* Stomach
* Pancreas
* Liver
* Muscle
67
What effect does GLP-1 have on the brain?
It increases satiety, *and therefore decreases food intake*
68
What is the end effect of GLP-1 action on the brain?
Causes patients to loose weight
69
What effect does GLP-1 have on the stomach?
Decreases gastric emptying
70
What effect does GLP-1 have on the pancreas?
* Increases inuslin secretion
* Decreases glucagon secretin
* Increases insulin biosynthesis
71
What effect does GLP-1 have on liver?
Indirectly decreases glucose production
72
What effect does GLP-1 have on muscles?
It indirectly increases glucose uptake
73
What are the types of GLP-1 therapies?
* Oral preparations
* Injectables
74
What are the oral preparations of GLP-1 therapies known as?
DDP-4 inhibitors, or gliptins
75
What is the mechanism of action of gliptins?
Protect the native GLP-1 from inactivation by DPP-4, and therefore increases postprandial active GLP-1 concentrations
76
Give 4 examples of gliptins
* Sitagliptin
* Vildagliptin
* Saxagliptin
* Linagliptin
77
What are the advantages of gliptins?
* Low risk of hypoglycaemia
* Weight neutral, or promote weight loss
78
What are the problems with gliptin therapy?
* GI symptoms
* Possible increased risk of pancreatitis
* Only a modest HbA1c reduction
* High cost
79
How much does gliptin therapy cost?
£30 a month
80
What are the injectable GLP-1 therapies known as?
GLP-1 receptor agonists
81
What is the mechanism of action of GLP-1 receptor agonists?
They mimic the nature of native GLP-1
82
What are the advantages of GLP-1 receptor agonists?
* Low risk of hypoglycaemia
* Generally perceived to be safe and well tolerated agents
83
Do GLP-1 receptor agonists cause pancreatitis?
*Despite concerns,* NICE and the FDA found no evidence of pancreatitis in reported studies
84
What are the problems with GLP-1 receptor agonists?
* Side effects
Ocassionally painful to inject
85
What are the side effects of GLP-1 receptor agonists?
* Nausea
* Loose stools/diarrhoea
* Gastro-oesophageal reflux
86
Why are GLP-1 receptor agonists ocasionally painful to inject?
Because it is an acidic solution
87
What are the contraindiciations for treatment with GLP-1 receptor agonists?
* eGFR \<30ml/min
* Organ failure
88
What should be used instead of GLP-1 receptor agonists in organ failure?
An agent with a more predictable metabolism, *e.g. insulin*
89
Give two examples of GLP-1 receptor agonists
* Exanatide
* Liraglutide
90
How often is exanatide taken?
Twice daily, or once weekly
91
Give an example of a sodium-glucose co-transporter 2 inhibitor
Glifozin
92
What approach does glifozin take to remove excess glucose?
A novel insulin-independant approach
93
Who can glifozin be used in?
Patients with type 2 diabetes, as an add on therapy
*Not currently prescribed for type 1, but trials ongoing*
94
What are the side effects of glifozin?
* Increased risk of lower urinary tract symptoms
* Polyuria
95
In what % of men and women on glifozin do genital or urinary tract infections occur?
* 5% of women
* 1% of men
96
What action should be taken if a patient on glifozin presents with a genital or urinary tract infection?
If it happens once, treat the condition. If it happens again, stop the drug
97
How much extra urine is produced due to glifozin treatment?
Up to 350ml/day
98
Give three examples of glifozins?
* Dapagliflozin
* Canaglifozin
* Empaglifozin
