Session 4 - Drugabetes Flashcards
What is a first line pharmacological treatment for diabetes?
Sulphonylureas (insulin release stimulants)
Give three examples of suphonylureas (include half lives and duration of action)
Tolbutamide (t½ ~ 4hrs, duration of action 6-12hrs)
Glibencamide (t½ ~ 10hrs, duration of action 18-24hrs)
Glipizide (t½ ~ 7hrs, duration of action 16-24hrs)
What are indications for sulphonylureas
Diabetes mellitus, in patients with residual β-cell activity
Give four contraindications for suphonylureas
Breastfeeding women, elderly, renal and hepatic insufficiency
What is the mechanism of action of sulphonylureas
Sulphonylureas antagonise β-cell K+/ATP activity, resulting in depolarisation. Voltage gated Ca2+ channels open, Ca2+ entry causes insulin vesicle fusion with cell membrane
What adverse reactions can sulphonylureas cause? (3)
Hypoglycaemia
GI disturbance
Weight gain
What drug-drug interactions can sulphonylureas cause?
Highly protein bound
What’s one of the most important second-line treatments for T2 diabetes?
Biguanides (metformin)
What are the indications for metformin?
Type II diabetes – Endogenous insulin presence required
What are the contraindications for metformin?
Compromised Kidney, lung and liver function
What is the mechanism of action for metformin?
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
What 2 adverse drug rections for metformin?
GI disturbances – ameliorated by slow dose titration
Lactic Acidosis
Give another two other types of insulin sensitiser, other than biguanide?
`Thiazolidinediones
Meglitidines
Give two examples of Thiazolidinediones
Rosiglitazone
Pioglitazone
What are the indications for Thiazolidinediones
Uncontrolled non insulin dependant diabetes
What is the mechanism of action for Thiazolidinediones
PPAR-γ agonist. Agonistically bind to a nuclear hormone receptor site.
Reduction in gluconeogenesis and an increased glucose uptake into muscles
What are the adversereactions to the glitazones? (2)
GI disturbance
Weight gain
What are the drug drug interactions of glitazones complicated by?
Very heavily protein bound (~99%)
Give two examples of meglitidines
Repaglinide
Nateglinide
What are the indications for meglitidines
Uncontrolled non insulin dependant diabetes
What is the mechanism of action for meglitidine?
K+/ATP channel antagonists on β-cells, resulting in depolarisation, calcium entry and fusion of insulin containing vesicles with membrane
What concerning adverse drug reactions mean it is good to treat with meglitidines? (2)
Relatively lower risk of hypoglycaemia than Sulphonylureas
Not associated with weight gain – useful in treating obese patients
Name four different types of insulins
Ultra Rapid
Short Acting
Intermediate
Intermediate/Long Acting
What are indications for short acting/rapid insulins
Meals/Acute Hyperglycaemia
What are indications for intermediate/long acting insulins
Basal Insulin/Overnight control
Give two different insulin regimes
Pre-mixed inssulin
Intermediate/long acting insulin + Fast or short acting insulin
What is involved in a pre-mixed insulin regime?
Pre-mixed insulin is given twice a day, with morning and evening meals.
What is involved in an intermediate/long acting insulin + Fast or short acting insulin regime
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.
What are indications for insulin treatment?
Insulin dependent diabetes mellitus
What is the mechanism of action of insulin?
Acts like endogenous insulin
Give three adverse drug reactions to insulin
Local reactions
Hypoglycaemia (coma) (overdose)
Rarely, immune resistance
Outline the process of T2 diabetes treatment
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
How is insulin dosing determined
Blood glucose monitoring several times a day
What is HbA1c?
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).
Give three anti-obesity agents
Orlistat
Sibutramine
Rimonabant
What is the mechanism of action of Orlistat
Gastric and pancreatic lipase inhibitor
Reduces the conversion of up to 30% of dietary fat to fatty acids and glycerol
What is the mechanism of action of Sibutramine
Noradrenaline and serotonin re-uptake inhibitor
Appetite suppression, increased thermogenesis
What is the mechanism of action of Rimonabant
Endocannabinoid antagonist
What are adverse drug reactions of Orlistat
Broad GI disturbances
(Soft fatty stools, flatus, faecal discharge/incontinence)
What are adverse drug reactions of sibutramine
Increased heart rate and blood pressure
What are adverse drug reactions of rimonabant
Depression – currently withdrawn in the UK by NICE
