Flashcards in Session 3 Deck (18):
Describe how biguanides are used to manage diabetes, and give an example of a drug.
E.g. Metformin. Increase sensitivity to insulin. Increased insulin receptor sensitivity and enhances skeletal and adipose glucose uptake. Also inhibits gluconeogenesis.
Give examples of ADRs and contraindications associated with Biguanides.
Contraindications include patients with renal failure and respiratory disease.
Describe how Thiazolidinediones are used to manage diabetes, and give an example of a drug.
E.g. Pioglitazone. Reduce gluconeogenesis and increase glucose uptake into muscle. Also decrease hepatic glucose output. Upregulates genes involved in insulin signalling and glucose/lipid metabolism.
Give examples of ADRs and contraindications associated with Thiazolidinediones.
CVS concerns, oedema, weight gain, effects on bone metabolism and increased risk of bladder cancer.
Contraindicated in heart failure.
Describe how Sulphonylureas are used to manage diabetes, and give an example of a drug.
E.g. Tolbutamide, Gliclazide. Bind to and antagonise beta-cell ATP channel activity. Causes increased calcium entry, which governs the fusion rate of insulin vesicles and their release into circulation.
Give examples of ADRs and contraindications associated with Sulphonylureas.
Greater incidence of hypoglycaemia, GI disturbance and weight gain.
Gliclazide is hepatically metabolised, hence can be used in renal impairment.
Describe how Meglitidine is used to manage diabetes, and give an example of a drug.
E.g. Repaglinide and Nateglinide. Similar mechanisms of action to Sulphonylureas.
Low risk of causing hypoglycaemia and not associated with weight gain.
Describe how Acarbose is used to manage diabetes, and give an example of a drug.
E.g. Acarboseis. Inhibits breakdown of carbohydrates to glucose by blocking the enzyme alpha-glucosidase.
Side-effects include flatulence, loose stools and diarrhoea.
Describe how GLP-1 receptor agonists are used to manage diabetes, and give an example of a drug.
E.g. Exenatide. Increases insulin secretion, decreases glucagon secretion and increases insulin biosynthesis.
ADRs include nausea, loose stools, diarrhoea, gastro-oesophageal reflux.
Describe how DPP-4 inhibitors are used to manage diabetes, and give an example of a drug.
E.g. Sitagliptin, Saxagliptin. Inhibit DPP-4 activity, hence reduced breakdown of GLP-1. This therefore decreases glucose levels.
ADRs include GI symptoms, hypoglycaemia, weight neutral.
Describe how sodium-glucose co-transporter 2 inhibitors are used to manage diabetes, and give an example of a drug.
E.g. Dapagliflozin. Selectively inhibits SGLT2 channels in the PCT. Hence reduced glucose in reabsorbed so it leaves in the urine.
ADRs include increased risk of lower urinary tract symptoms, polyuria and low risk of hypoglycaemia.
Describe the role of insulin.
-Stimulates uptake of glucose into liver, muscle and adipose tissue
-Decreases hepatic glucose output via inhibition of gluconeogenesis
-Promotes uptake of fats
Describe the main 5 insulin categories
1) short acting - works 30-60 mins after injection. Injected before eating. Lasts 8-10 hours.
2) Rapid acting - works 5-15 mins and injected just prior to eating. Lasts 4-6 hours.
3) Intermediate acting - works after 2-4 hours, and lasts 12-24 hours. Tends to peak during the night.
4) Long acting - works after 2-6 hours and lasts up to 24 hours
5) Very long acting - can last up to 50+ hours.
Describe the adverse effects of insulin.
How is treatment for type 2 diabetes usually started?
Initially no drug therapy, start with diet and lifestyle changes.
Then start with Metformin.
If HbA1c above 7%, add a Sulphonylurea.
If still no reduction in HbA1c, add a Thiazolidinediones or start insulin therapy.
What does HbA1c show?
Acts as an integral measure of overall glucose levels and provides a stable clinical marker. It is usually about 6%, and when it rises above 7% the risk of vascular complications rises exponentially.
What are anti-obesity drugs?
Orlistat is a gastric and pancreatic lipase inhibitor, so reduces up to 30% of dietary fat conversion to fatty acids and glycerol.
Broad GI disturbance, soft fatty stools and flatus.