Diabetes Drugs Flashcards
What is the normal range for blood glucose levels?
3.5 - 8 mmol/L
What are some of insulins actions?
Increased: - glucose uptake - glycogenesis - glycolysis - lipogenesis - esterification of FAs - lipoprotein lipase activity - amino acid uptake and protein synthesis Decreased: - gluconeogenesis - lipolysis - ketogenesis - proteolysis
What are some of the actions of glucagon?
Increased: - glycogenolysis - gluconeogenesis - ketogenesis - lipolysis Decreased glygogenesis
How does insulin bring about action?
Circulates free in the blood plasma and binds to surface receptors which stimulates enzymes and proteins inside the cell to act.
How does glucagon bring about action?
Binds to glucagon receptors in cell membranes and stimulates adenylate cyclase, increase cAMP. This activates protein kinase A which phosphorylates and activates enzymes inside the target cell.
How can you describe diabetes mellitus?
An inability to regulate plasma glucose withing normal range.
Give some characteristics of diabetes mellitus
- absolute/relative insulin deficiency
- hyperglycaemia
- glycosuria
- polyuria- polydipsia
What is the first line of treatment when someone is diagnosed with type 2 diabetes?
Use diet and exercise to try and maintain adequate glucose control.
- limit fat intake
- increase intake of complex carbohydrates
- reduce alcohol
- stop smoking
- increase amount of exercise
Give some of the major groups of oral hyperglycaemics
Sulphonureas Biguanides Thiazolidinediones/glitazones Gliptins/DPP-4 inhibitors SGLT2 Inhibitors/Gliflozins
Describe the mechanism of action of sulphonylureas
They antagonise K+/ATPase activity of beta cells, causing depolarisation. VOCCs open and increase Ca2+ causes insulin vesicles to fuse with the membrane and release increased amounts of insulin.
Why can you only prescribe sulphonylureas in certain patients?
Patients need to have residual beta cell activity- helps to enhance the remaining activity.
What are some ADRs that can arise from taking oral suphonureas?
Hypoglycaemia
GI disturbance
Weight gain
Give some examples of some sulphonureas
Tolbutamide
Glibencamide
Glipizide
When would you not prescribe sulphonureas?
Breastfeeding women
Elderly
Patients with renal or hepatic insufficiency
Describe the mechanism of action of biguanides
Unclear mostly
- increase insulin receptor sensitivity
- enhances skeletal muscle and adipose uptake of glucose- inhibits hepatic gluconeogenesis
- does not induce hypoglycaemia
Give an example of a biguanide
Metformin
When would you prescribe a biguanide?
In type 2 diabetes when there is endogenous insulin presence
When would you not prescribe a biguanide?
With compromised:
- Heart function
- Renal function
- Hepatic function
Give some ADRs of biguanides
GI disturbances (slow titration limits this) Lactic acidosis
Give the mechanism of action of Thiazolidinediones
PPAR-gamma agonist
- binds to a nuclear hormone receptor site
- reduces gluconeogenesis
- increases glucose uptake into muscles(PPARG regulates FA storage and glucose metabolism)
Give some examples of thiazolidinediones
RosiglitazonePioglitazone
When would you prescribe a thiazolidinediones?
In uncontrolled, non-insulin dependent diabetes
Give some ADRs for thiazolineinediones
GI disturbance
Weight gain
Give a drug-druf interation for thiazolineinediones
Are heavily protein bound so could potentially be displaced
Give the mechanism of action for meglitidines
K+/ATP antagonists on beta cells, causing depolarisation, calcium entry and fusion of insulin containing vesicles with the cell membrane
Give some examples of meglitidines
Repaglinide
Nateglinide
Why have insulin analogues been developed?
- Do not have to rely on extraction of insulin from animals- can give an injection containing different types of insulin with varying characteristics e.g. rapid acting + intermediate acting + long acting. This helps to give the best control of blood glucose levels as possible.
When would you use ultra rapid and short acting insulin?
Afters mealsWith acute hyperglycaemia
When would you use intermediate and long acting insulin?
Basal insulinOvernight control
What are the different types of insulin regimes?
Pre-mixed insulin - given twice a day with mealsIntermediate/long acting insulin + Fast or short acting insulin- intermediate insulin provides a basal level that acts overnight and short acting insulin is given with meals for an acute response.
Which insulin regimen gives a better level of glycaemic control?
The mix of different insulins
Describe the monitoring that must occur with acute treatment
- Need to monitor several times a day with advanced diabetes- Helps to initially determine the dosing levels of insulin
Describe the monitoring in chronic diabetes treatment
Glucose reacts with the terminal valine on Hb to produce glycosylated Hb (HbA1c). The HbA1c is a good indicator of how effective blood glucose control has been.
How often do you need to measure HbA1c levels?
3 months - this is how long RBCs stay in the circulation
What HbA1c percentage would be indicative of poorly controlled diabetes?
10% and above
What are the main types of anti-obesity agents?
Orlistat
Sibutramine
Rimonabant
Describe the mechanism of action of orlistat
Is an inhibitor of gastric and pancreatic lipase. This means there is a reduction in conversion of dietary fat to FAs and glycerol by 30%.
Give some ADRs for orlistat
Soft fatty stools
Flatus
Faecal discharge/ incontinence
Describe the mechanism of action for sibutramine
Is a noradrenaline and seratonin re-uptake inhibitor which causes appetite suppression and increased thermogenesis
Give some ADRs for sibutramine
Increased heart rateIncreased blood pressure
Describe the mechanism of action for rimonbant
Is an endocannabinoid antagonist- decreases body weight- helps regulate body-weight gain
Give some ADRs for rimonabant
Depression – has been withdrawn from use by NICE
Describe the mechanism of action for gliptins
DPP-4 inhibitors
- block action of DPP-4, an enzyme which breaks down incretin
- Increased incretin levels acts to stimulate insulin release
Give some examples of glilptins
Sitagliptin
Anagliptin
Give the mechanism of action of SGLT2 inhibitors
Inhibit SGLT2 channel in kidney, so there is less glucose reabsorption, causing a reduction in blood glucose levels.
- increase insulin sensitivity
- increase glucose uptake in muscles
- decreased gluconeogenesis
- improved first phase insulin release
