Diabetes and obesity Flashcards
Short-acting insulins
Lispro, Aspart, glulisine
- remain as monomers for rapid absorption
Intermediate-acting insulin
isophane (NPH-insulin), which is complexed with protamine
Long-acting insulins
Detemir- bound to a 14-C fatty acid, myristic acid, which promotes binding to albumin and slow dissociation
Glargine - less soluble, remains dimerised and is slowly absorbed
Metformin (Biguanide)
Enters the cell trough OCT1 and then inhibits mitochondrial electron complex 1.
This decreases ATP production and so increases AMP, which activates the kinase AMPK.
AMPK decreases gluconeogenesis and lipogenesis, increases glucose uptake into the muscles and liver, and reduces glucose absorption from the GIT.
First line treatment, except in renal impairment.
Sulphonylureas: Gliclazide, Tolbutamide and Glibenclamide
Bind to the SUR transporter, inhibiting K-ATP channels. This prevents efflux, depolarising the cell, opening VGCC and causing insulin release.
Action independent of plasma glucose levels - can cause hypoglycaemia and make insulin resistance worse.
Meglitinide analogues: Nateglinide and Repaglinide
Similar to sulphonylureas but bind to a different site on K-ATP channels.
Thiazolidinediones: Pioglitazone and Rosiglitazone
Activate PPAR-γ, which alters gene expression.
Reduce hepatic glucose release, increase GLUT-4 expression, increase glucose uptake in the liver and fatty acid uptake in adipose tissue, have anti-inflammatory action.
Insulin sensitisers
Incretin mimetics: exenatide, liraglutide, semaglutide
Mimics the action of GLP1 at β-cells and stimulates insulin secretion in a glucose-dependent manner.
Resistant to metabolism.
Also affect the hypothalamus, supressing appetite and affect reward pathways, so Saxenda (liraglutide) and Wegovy (semaglutide) are also used for obesity.
DPP4 inhibitors: sitagliptin, linagliptin, vildagliptin
Dipeptidyl peptidase-4 (DPP4) breaks down incretins, so these inhibitors enhance the action of endogenous GLP1.
Acarbose
Competitive inhibitor of α-glucosidase in the GIT - prevents the breakdown of carbohydrates, reducing the absorption of dietary sugars.
SGLT-2 inhibitors: Dapagliflozin and Canagliflozin
Inhibit SGLT-2 transporters in the kidney, preventing glucose reabsorption and so increasing excretion.
Orlistat (tetrahydrolipstatin)
Synthetic derivative of lipstatin, irreversibly inhibits gastric and pancreatic lipase.
Taken before meals, reduces absorption of dietary fat, reducing calorie intake.
Causes steatorrhea.
Mysimba
Combination of bupropion and naltrexone.
Bupropion is a dopamine and noradrenaline reuptake inhibitor, targeting reward pathways linked to appetite control and activating appetite supressing neurons.
Naltrexone is an opioid receptor antagonist, preventing negative feedback.
Setmelanotide
Melanocortin-4 receptor (MC4R) agonist used for some rare genetic related forms of obesity.
Genetic mutations cause a deficiency in POMC or leptin receptors involved in appetite supression. POMC is converted to melanocortin and acts on MC4R receptors.
Sibutramine - 5-HT system
NA and 5HT reuptake inhibitor.
5-HT controls the balance of release of appetite suppressing and appetite stimulating neurotransmitters in the brain, so the drug acts as an appetite suppressant.
No longer used as it increased BP and HR.
