Session 4 - Drugabetes Flashcards

1
Q

What is a first line pharmacological treatment for diabetes?

A

Sulphonylureas (insulin release stimulants)

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2
Q

Give three examples of suphonylureas (include half lives and duration of action)

A

 Tolbutamide (t½ ~ 4hrs, duration of action 6-12hrs)
 Glibencamide (t½ ~ 10hrs, duration of action 18-24hrs)
 Glipizide (t½ ~ 7hrs, duration of action 16-24hrs)

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3
Q

What are indications for sulphonylureas

A

 Diabetes mellitus, in patients with residual β-cell activity

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4
Q

Give four contraindications for suphonylureas

A

 Breastfeeding women, elderly, renal and hepatic insufficiency

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5
Q

What is the mechanism of action of sulphonylureas

A

 Sulphonylureas antagonise β-cell K+/ATP activity, resulting in depolarisation. Voltage gated Ca2+ channels open, Ca2+ entry causes insulin vesicle fusion with cell membrane

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6
Q

What adverse reactions can sulphonylureas cause? (3)

A

 Hypoglycaemia
 GI disturbance
 Weight gain

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7
Q

What drug-drug interactions can sulphonylureas cause?

A

Highly protein bound

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8
Q

What’s one of the most important second-line treatments for T2 diabetes?

A

Biguanides (metformin)

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9
Q

What are the indications for metformin?

A

 Type II diabetes – Endogenous insulin presence required

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10
Q

What are the contraindications for metformin?

A

 Compromised Kidney, lung and liver function

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11
Q

What is the mechanism of action for metformin?

A

 Unclear – Precise actions under current study
 Increases insulin receptor sensitivity, enhancing skeletal and adipose glucose uptake
 Inhibits hepatic gluconeogenesis
 Reduces hyperglycaemia, but does not induce hypoglycaemia

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12
Q

What 2 adverse drug rections for metformin?

A

 GI disturbances – ameliorated by slow dose titration

 Lactic Acidosis

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13
Q

Give another two other types of insulin sensitiser, other than biguanide?

A

`Thiazolidinediones

Meglitidines

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14
Q

Give two examples of Thiazolidinediones

A

 Rosiglitazone

 Pioglitazone

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15
Q

What are the indications for Thiazolidinediones

A

 Uncontrolled non insulin dependant diabetes

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16
Q

What is the mechanism of action for Thiazolidinediones

A

 PPAR-γ agonist. Agonistically bind to a nuclear hormone receptor site.
 Reduction in gluconeogenesis and an increased glucose uptake into muscles

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17
Q

What are the adversereactions to the glitazones? (2)

A

 GI disturbance

 Weight gain

18
Q

What are the drug drug interactions of glitazones complicated by?

A

 Very heavily protein bound (~99%)

19
Q

Give two examples of meglitidines

A

 Repaglinide

 Nateglinide

20
Q

What are the indications for meglitidines

A

 Uncontrolled non insulin dependant diabetes

21
Q

What is the mechanism of action for meglitidine?

A

 K+/ATP channel antagonists on β-cells, resulting in depolarisation, calcium entry and fusion of insulin containing vesicles with membrane

22
Q

What concerning adverse drug reactions mean it is good to treat with meglitidines? (2)

A

 Relatively lower risk of hypoglycaemia than Sulphonylureas

 Not associated with weight gain – useful in treating obese patients

23
Q

Name four different types of insulins

A

Ultra Rapid
Short Acting
Intermediate
Intermediate/Long Acting

24
Q

What are indications for short acting/rapid insulins

A

Meals/Acute Hyperglycaemia

25
Q

What are indications for intermediate/long acting insulins

A

Basal Insulin/Overnight control

26
Q

Give two different insulin regimes

A

Pre-mixed inssulin

Intermediate/long acting insulin + Fast or short acting insulin

27
Q

What is involved in a pre-mixed insulin regime?

A

Pre-mixed insulin is given twice a day, with morning and evening meals.

28
Q

What is involved in an intermediate/long acting insulin + Fast or short acting insulin regime

A

Intermediate/long lasting insulin provides a basal level that extends overnight, fast or short acting insulin is injected with meals to provide an acute response. This gives a better level of glycaemic control.

29
Q

What are indications for insulin treatment?

A

Insulin dependent diabetes mellitus

30
Q

What is the mechanism of action of insulin?

A

Acts like endogenous insulin

31
Q

Give three adverse drug reactions to insulin

A

 Local reactions
 Hypoglycaemia (coma) (overdose)
 Rarely, immune resistance

32
Q

Outline the process of T2 diabetes treatment

A

o Begin with no pharmacological intervention, therapy starting with Diet, Exercise and Lifestyle changes
o A Biguanide (Metformin) started when necessary
o Over time if HbA1c levels go above 7%, a Sulphonylurea (e.g. Tolbutamide) is added to therapy
o Over time if HbA1c levels go about 7.5% a Thiazolidinedione (e.g. Rosiglitazone) may be added, or a newer hypoglycaemic, or start insulin therapy
o If on this regime if HbA1c levels go above 7.5%, doses will be titrated upwards to regain adequate glycaemic control

33
Q

How is insulin dosing determined

A

Blood glucose monitoring several times a day

34
Q

What is HbA1c?

A

Glucose in the blood will react with the terminal valine of the haemoglobin molecule to produce glycosylated haemoglobin (HbA1c). The percentage of HBA1c is a good indicator of how effective blood glucose control has been.
As RBCs normally spend ~3 months in the circulation the %HbA1c is related to the average blood glucose concentration over the preceding 2-3 months.
Poorly controlled diabetics can have a HbA1c value above 10%. In combination therapy, new medications are added at HbA1c values of 7 or 7.5% (see above).

35
Q

Give three anti-obesity agents

A

Orlistat
Sibutramine
Rimonabant

36
Q

What is the mechanism of action of Orlistat

A

 Gastric and pancreatic lipase inhibitor

 Reduces the conversion of up to 30% of dietary fat to fatty acids and glycerol

37
Q

What is the mechanism of action of Sibutramine

A

 Noradrenaline and serotonin re-uptake inhibitor

 Appetite suppression, increased thermogenesis

38
Q

What is the mechanism of action of Rimonabant

A

 Endocannabinoid antagonist

39
Q

What are adverse drug reactions of Orlistat

A

 Broad GI disturbances

 (Soft fatty stools, flatus, faecal discharge/incontinence)

40
Q

What are adverse drug reactions of sibutramine

A

 Increased heart rate and blood pressure

41
Q

What are adverse drug reactions of rimonabant

A

 Depression – currently withdrawn in the UK by NICE