The other drugs Flashcards
Statins (-statin)
Eg. Simvastatin, Atorvastatin, Mevastatin
Inhibits 3 hydroxymethylglutaryl (HMG) CoA-reductase which is the rate limiting step in the synthesis of cholesterol
Lowers LDL (less LDL receptors) slightly increases HDL
Fungal (T1): Prava/simvastatin
Synthetic (T2): Atorva/rosuva/fluvastatin
Risk of myopathy with high dose simvastatin and grapefruit juice increases availability of lova/simva/atorvastatin as both metab’d by CYP3A4
Ezetimibe
Inhibits Niemann-Pick C1 like 1 (NPC1L1) membrane transport proteins. This inhibits cholesterol absorption in gut
Reduces LDL but reduces plant stanol (part of cholesterol lowering diet)
Used with statin or on own when statin contraindicated
Fibrates
Eg.Fenofibrate, gemfibrozil
Bind and activates PPARalpha which dimerises with RXR
This PPARalpha/RXR complex activates transciption of LPL and increases expression of apo A1 and A2 (HDL lipoproteins)
Decreases VLDL, increase HDL, LDL uptake and oxidation of FA
Not to be used in pregnancy
Bile acid binding resins (Coles-)
Eg. Colestyramine, colestipol, colesevelam
Binds bile acids in gut to reduce reabsorption of cholesterol via enterohepatic circulation
Decrease LDL, no effect on HDL but increase TG
Can be used in pregnancy
Nicotinic acid
Eg. Niacin, Vit B3
Activates HCA2 receptor in adipocytes which inhibits lipolysis. Therefore less VLDL so less LDL
Increases apo-A1 therefore increased HDL
Causes facial/skin flashes due to increase in PGD2
Lots of ADR’s mean risks outweigh benefits
Fish oil derivatives (Omega 3 FA’s)
Causes reduction in TG and LDL
Anti-PCSK9 antibodies
Eg. Evolocumab, alirocumab
Used in patients who have not responded to other treatments
Sulfonylureas (-ide)
Eg. Tolbutamide, glicazide, glibenclamide
Increases insulin secretion via blocking ATP sensitive K channel causing +ve charge to build up within the cell causing influx of Ca2+ which causes exocytosis of insulin vesicles.
Can cause hypoglycaemia and weight gain esp. with longer acting sulfonylureas as well as B cell failure
Do not use in pregnancy and cation in hepatic/renal failure
Meglitanides
Eg. Repaglinide, nateglinide
Act in the same way as sulfonylureas but are non sulfonylureas
More rapidly absorbed
Biguanides
Metformin is the only one
Decreases glucose production via inhibition of gluconeogenesis via reducing ADP to ATP conversion
Increases expression of tyrosine kinase (insulin sensitisation)
Increases glucose uptake/use in skeletal muscle
Can cause GI effects and lactic acidosis (caused by lactic acid build due to mitochondrial action blockade)
alpha Glucosidase inhibitors
Eg. Acarbose
Reduces carb digestion by slowing absorption in GI tract (causes 30-35% reduction in glucose)
Causes flatulence and diarrhoea so high discontinuation
Does not cause hypoglycaemia or weight gain
Thiazolidinediones (TZD’s) (-glitazones)
Eg Pioglitazone, rosiglitazone
They are PPAR agonist and so increase the beta-oxidation of fatty acids and causes a net increase in insulin sensitivity
It also represses gene transcription and has anti-inflammatory properties
Causes a lot of weight gain but SC fat not visceral
Excreted unchanged so renal impairment not an issue
Incretins (GLP-1 analogues) (-tide)
Eg. Exanatide, liraglutide
They inhibit glucagon release and increases insulin synthesis and secretion under hyperglycaemic conditions
It also signals satiety but can cause nausea
DPP4 inhibitors (-gliptin)
Eg. Sitagliptin, vildagliptin
Dipeptidyl peptidase IV (DPP-4) is an enzyme which degrades GLP-1
Blocking it increases action of GLP-1 which means increased insulin secretion, glucagon inhibition and slowed gastric emptying due to satiety
SGLT2 inhibitors (-flozin)
Eg. Canagaflozin, Dapagliflozin
Inhibits sodium glucose transporter 2 (SGLT2) in the renal PCT stopping reabsorption of glucose
Does not cause hypoglycaemia but could cause UTI’s
