Week 10 Lecture Slides on Medications for Metabolic & Renal Conditions PDF

EHR522 EXERCISE FOR METABOLIC & RENAL CONDITIONS WEEK 10 – MEDICATIONS IN METABOLIC AND RENAL CONDITIONS ORAL GLUCOSE-LOWERING MEDICATIONS 2 BIGUANIDES • Metformin − Fortamet − Glumetza − Glucophage • Primarily decrease hepatic glucose production • May also improve insulin resistance in...

EHR522 EXERCISE FOR METABOLIC & RENAL CONDITIONS WEEK 10 – MEDICATIONS IN METABOLIC AND RENAL CONDITIONS ORAL GLUCOSE-LOWERING MEDICATIONS 2 BIGUANIDES • Metformin − Fortamet − Glumetza − Glucophage • Primarily decrease hepatic glucose production • May also improve insulin resistance in muscles • Very low risk of hypoglycaemia (possibly after prolonged strenuous exercise) • Not used in patients with abnormal creatinine clearance (CHF and CKD) 3 SULFONYLUREAS (1ST GENERATION) • Rarely used in current clinical practice. Examples include − Tolbutamide (Orinase) − Tolazamide (Tolinase) − Chlorpropamide (Diabenese) • Increase insulin production in the pancreas • Carry a significant risk of hypoglycaemia • Many have a very long half-life and are typically now only used in patients with a well-established history of taking them 4 SULFONYLUREAS (2ND GENERATION) • Examples include − Glyburide (Micronase, Diabeta, Glynase) − Glipizide (Glucotrol, Glucotrol XL) − Glimepiride (Amaryl) • Increase insulin production in the pancreas • Carry a risk of hypoglycaemia (but less than that of 1st generation sulfonylureas) • 2nd generation sulfonylureas provide more predictable results with fewer side effects and more convenient dosing when compared with 1st generation sulfonylureas 5 THIAZOLIDINEDIONES • • • Examples include − Pioglitazone (Actos) − Rosiglitazone (Avandia, Avandamet, Avandaryl) Works via multiple mechanisms − Decrease insulin resistance, increasing glucose uptake − Redistribution of fat − Minor decrease in hepatic glucose output − Preserve beta cell function − Decrease vascular inflammation No significant risks with exercise, but can cause mild to moderate oedema 6 ALPHA-GLUCOSIDASE INHIBITORS • Examples include − Acarbose (Precose) − Miglitol (Glyset) • Slows the absorption of starch, disaccharides and polysaccharides from the GI tract • No significant risks with exercise, but can cause gas, bloating and occasionally diarrhoea 7 DIPEPTIDYL PEPTIDASE 4 (DPP-4) INHIBITORS • Examples include − Sitagliptin (Januvia) − Saxagliptin (Onglyza) − Vildagliptin (Glavus) − Linagliptin (Tradjenta) • Inhibits the DPP-4 enzyme that is responsible for degrading the incretins, glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) • The increasing incretin levels inhibit glucagon release, which in turn increases insulin secretion and decreases BGLs 8 DIPEPTIDYL PEPTIDASE 4 (DPP-4) INHIBITORS • DPP-4 inhibitors carry a low risk of hypoglycaemia with exercise • DPP-4 inhibitors are not used in T1DM 9 SODIUM-GLUCOSE CO-TRANSPORTER 2 (SGLT2) INHIBITORS • • Also known as gliflozins, examples include − Canagliflozin (Invokana) − Dapaglifozin (Farxiga) − Empagliflozin (Jardiance) − Erugliflozin (Steglatro) Inhibit the reabsorption of glucose in the kidneys, therefore lowering BGLs • Can increase the risk of ketoacidosis and UTI • Can cause dehydration, so ensure patients are wellhydrated with exercise 10 INJECTED (NON-INSULIN) MEDICATIONS 11 GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS • Examples include − Exenatide (Byetta) − Dulaglutide (Trulicity) − Liraglutide (Victoza) − Semaglutide (Ozempic) − Lixisenatide (Adlyxin) • Works via multiple mechanisms − Decreases post-meal glucagon production − Delays gastric emptying − Increase satiety, leading to decreased caloric intake 12 GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS • Not suitable for T1DM • May reduce the rate of absorption of oral medications • Can increase the risk of hypoglycaemia when combined with a sulfonylurea 13 AMYLIN ANALOGUE • Pramlintide (Symlin) • Amylin is a peptide hormone that is co-secreted with insulin from the pancreatic beta cells and is therefore deficient in diabetics • Works via multiple mechanisms − Decreases post-meal glucagon production − Delays gastric emptying − Increase satiety, leading to decreased caloric intake • The degree of response is dependent upon plasma glucose levels 14 AMYLIN ANALOGUE • Indicated for insulin-treated T2DM and T1DM • Contraindicated in patients with hypoglycaemia unawareness • Should not be mixed with insulin (must be injected separately) • Can increase the risk of hypoglycaemia when combined with insulin. Insulin dose is typically reduced by 50% when initiating treatment with an amylin analogue 15 INSULIN MEDICATIONS 16 RAPID ACTING INSULIN 17 RAPID ACTING INSULIN Do not allow patients to exercise at the peak insulin dose of a rapid acting insulin 18 SHORT ACTING INSULIN 19 INTERMEDIATE ACTING INSULIN 20 LONG ACTING AND ULTRA LONG ACTING INSULIN 21 NON-DIABETES MEDICATIONS 22 OVERWEIGHT AND OBESITY - PHARMACOTHERAPY 23 STATINS - EFFECTS OF GRAPEFRUIT • The chemicals in grapefruit do not interact directly with statin medications. Rather these chemicals bind to an intestinal enzyme, blocking its action and making the passage of the medication easier from gut to bloodstream • As a result, blood medication levels may rise faster and remain at higher than normal levels, and in some cases abnormally high levels are dangerous • Regarding statins and grapefruit use, some statins are affected more than others. For example, atorvastatin (Lipitor), simvastatin (Zocor) and lovastatin (Mevacor), blood levels are boosted more than when fluvastatin (Lescol), pravastatin (Pravachol) or rosuvastatin (Crestor) is the prescribed medication. • As a recommendation, any grapefruit product should be avoided when taking a statin 24 LIPID-LOWERING MEDICATIONS 25 LIPID-LOWERING MEDICATIONS • A longstanding limitation for niacin has been that it is not well tolerated, although extended-release forms have improved tolerance • Niacin therapy often results in flushing, skin rashes, gastrointestinal problems and pruritus • Niacin is not recommended for individuals with hypotension, liver dysfunction or peptic ulcers or for those with diabetes mellitus, as it often causes increases in blood glucose concentrations • You should remind patients to take niacin before going to sleep at night to avoid these unwanted side effects during the day and especially with exercise • You should also make patients aware of these side effects to distinguish between the effect of the drug and what might be experienced during exercise 26 LIPID-LOWERING MEDICATIONS • Up to 25% of patients taking lipid-lowering medications, particularly statins and fibric acid derivatives, may experience some form of medication intolerance that includes muscle inflammation or muscle damage • Rhabdomyolysis – A severe side effect arising from medication-induced muscle damage, is characterised by the presence of myoglobin in the blood, reduced and dark urine output and a general feeling of weakness. • Since kidney damage may result, a patient experiencing these symptoms should immediately contact their Physician 27 PCOS – PHARMACEUTICAL INTERVENTION • Pharmaceutical treatment for PCOS focuses primarily on addressing reproductive dysfunction and insulin resistance • Oral contraceptives are used to treat menstrual irregularity, hirsutism and acne. Long-term use of oral contraceptives, however, remain controversial from a cardiometabolic standpoint • Spironolactone (aldosterone antagonist) and finasteride (5-alpha reductase inhibitor) are used to treat symptoms of androgen excess 28 29 29