DM Drugs PDF

Chronic systemic disease characterized by metabolic and vascular abnormalities Disorder of carbohydrate metabolism Hyperglycemia occurs and can experience vascular changes that can lead to organs failing Monosaccharide: glucose is the only sugar that the body is able to break down for...

Chronic systemic disease characterized by metabolic and vascular abnormalities Disorder of carbohydrate metabolism Hyperglycemia occurs and can experience vascular changes that can lead to organs failing Monosaccharide: glucose is the only sugar that the body is able to break down for energy In DM, insulin promotes movement of glucose to organs ○ Brain does not rely on glucose transport mediated by insulin Results from inadequate production or underutilization of insulin Endogenous Insulin Protein composed of 2 polypeptides linked by a disulfide bond Produced by the pancreatic B cells as the precursor protein known as pro-insulin When secreted it is cleavage into insulin and protein C (both are secreted) Glucose is the major stimulus of secretion Factors that inhibit insulin secretion ○ Hypoxia ○ Hypothermia ○ Stimulation of alpha adrenergic 2 receptors Physiology Secreted by beta cells Binds to cells of organ that are insulin dependent for glucose utilization Liver, muscle, and fat cells  Supports glucose transport Must be present for muscle and fat tissues to use glucose for energy Regulates glucose metabolism to produce energy for cellular function Fat metabolism Insulin promotes glucose into fat cells where it is broken down to A-glycerophosphate which combines w/ fatty acids to form triglycerides Cholesterol and phospholipids are also increased Insulin is lipogenic Protein metabolism Insulin increases body protein by increasing transport of amino acids into cells and synthesizing protein Lack of insulin causes protein breakdown into amino acid Signs, symptoms, types Weight loss, weakness Hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia, and possibly itching Fasting blood glucose is higher than 126 ○ hypolipid substance ? PVD, cardiovascular disease such as CAD, neuropathies, retinopathies Type 1– patient secretes NO insulin, needs exogenous insulin to live ○ AI disorder that destroys pancreatic beta cells ○ Usually has sudden onset ○ Requires exogenous insulin ○ 10% of DM ○ Elevated levels glutamic acid decarboxylase (GAD) antibodies (enzyme requires for regulation of insulin production) ○ No orals rx to type 1– insulin TOC* Type 2– patient secretes insufficient amounts of insulin and insulin receptors are resistant to existent circulating insulin, may require insulin to control hyperglycemia ○ Cause of type 2: Obesity* ○ Characterized by hyperglycemia due to insulin resistance ○ Decreased uptake of glucose in liver, muscle, and fat cells ○ Insulin resistance— hyper insulin emit Insulin being overworked If lifestyle doesn’t change, can get hyperglycemia ○ Occurs @ any age, multi factorial ○ 7% of HbA1c will be linked to sugar, will give normal glycosylated levels Every 3 months, our RBCs disintegrate by the pigment serum bilirubin goes into liver to form bilirubin along w/ cholesterol for the emulsification of fat  A1c: the average of how much sugar is attached to the RBCs in 3 mo. & does not need to be done fasting ○ Gradual onset ○ Less severe symptoms initially ○ Easier to control ○ More MIs and strokes ○ 90% of those with diabetes, ○ Drugs to treat DM Classified by onset and duration of action ○ Exogenous insulin ○ Now days is identical to endogenous insulin, but it is produced by recombinant DNA technology— human cadaveric and animal hardly used Used to take DNA from dead people and animals ○ Primarily administered SC, cannot be given orally Only one type of insulin that can be given IV ○ Increases glucose uptake*** ○ Indicated for type 1 DM ○ Also used for: Type 2 DM (not TOC but can be used), chronic pancreatitis, those on TPN, treat hyperkalemia (infusion w/ dextrose and insulin)- it stimulates the Na+/K+ ATPase pump Rapid Acting ○ Insulin Lispro (Humalog) or Insulin Aspart (Novalog) (SC) ○ *Insulin analogs— modified forms of insulin engineered to have specific properties, such as altered onset and duration of action ○ More effective in decreasing post-prandial hyperglycemia ○ Less likely to cause hypoglycemia before the next meal ○ Onset is 15’, peaks in 1-3 hrs., duration is 3-5 hrs. ○ Must not be diluted or mixed w/ any other insulin or solutions ○ Check sugar first, inject, then check sugar (TID) ○ Infusion pumps are used w/ rapid acting Short-acting: Regular (R) ○ Humulin R, Novolin R ○ May be given sub Q or IV (cont. drip) In cases of diabetic ketoacidosis in ER: hydrate first and then IV insulin; then cont. drip  ○ Only that may be given IV ○ Onset is ½ - 1 hr., peak is 2-3 hrs. And duration is 5-7 hrs ○ Also used post-prandial hyperglycemia Can be administered in the same fashion as rapid acting Intermediate-acting ○ Neutral Protamine Hagedorn (NPH)* ○ AKA Isophane Insulin Suspension ○ Humulin N, Novolin N ○ Onset is 1-1.5 hrs., peaks in 8-12 hrs. And duration is 18-24 hrs. ○ Takes a lot longer to wear off vs. rapid-acting, short-acting regular Long-acting Insulin ○ Newer versions are insulin analogs ○ Onset is 4-8 hrs., peaks in 10-30 hrs. And duration is 36+ hours ○ Never peaks, and maintains the same fashion Only mixture you can do is NPH form of the medication w/ the same R form in a 70/30 fashion Mixtures ○ Humulin 70/30– NPH/R ○ Novolin 70/30– NPH/R ○ Humalog 75/25– Lispro protamine (Intermediate)/Lispro Intensive tx ○ Seeks glucose level normalization w/ more frequent insulin injections ○ Goal is to achieve glucose levels of 175 mg/dl w/ total HbA1c of 7% of total hemoglobin ○ This intensive tx shows 60% reduction of long term complications if diabetes compared with those using standard tx Standard tx ○ Relies on insulin BID maintaining glucose levels b/w 225-275 mg/dl w/ total HbA1c of 8-9% of total hemoglobin Intensive tx & standard insulin tx ○ Intensive Multiple daily injections (MDI) Frequent blood glucose monitoring Tight glycemic control- reducing A1c levels typically to below 7% (or as individualized) ○ Standard Less frequent injections Routine monitoring— once or twice a day Looser glycemic control targets- typically resulting in A1c levels higher than 7% Complications of insulin tx (all b/c too much insulin) ○ Coma, seizures, hypoglycemia, tachycardia, confusion, vertigo, diaphoresis, lipodystrophy, hypersensitivity Oral diabetic drugs (Only for Type 2) Sulfonylureas ○ Increase release of insulin (for patients that need to produce insulin) ○ Decrease production of glucose in the liver ○ Increase the # of insulin receptors and increase peripheral use of glucose Too much fat = lack of insulin receptors ○ Effective only if have functioning beta cells This medication cannot work if no functioning beta cells b/c this med. works based off the beta cell process ○ Primary SE is hypoglycemia ○ 1st gen. are essentially obsolete ○ Use 2nd generation agents Glipizide (Glucotrol) Glyburide (Diabeta) Glimepiride (Amaryl) ○ Can be used w/ metformin, glitazones, insulin or acarbones ○ Caution w/ renal or hepatic impairment If pt has kidney disease type III, stay away from these med. Glomerular rate below 60, chronic kidney disease (stage III) Below ~45 is stage 3A ○ Not used in pregnancy or allergic to sulfas Alpha glucosidase inhibitors ○ Acarbose (Precose) and Miglitol (Glyset) ○ Inhibit alpha-glucosidase enzymes (Maltese, amylase, sucrose) in GI tract ○ Delays absorption of complex CHO (carbohydrates) and simple sugars ○ Can be combined therapy w/ insulin or w/ sulfonylurea but it has a problem w/ patients w/ renal or liver impairment ○ Contraindicated in cirrhosis, malabsorption, severe renal impairment ○ Take @ beginning of each meal ○ Can cause bloating, gas, and diarrhea ○ Not used as often anymore Biguanides ○ Metformin (Glucophage) increases the use of glucose by muscle and fat cells Cheapest drug around, gain muscle mass, lose weight ○ Decreases hepatic glucose production Decreases intestinal absorption of glucose ○ Does not cause hypoglycemia Does not peak ○ May be used alone or in combo. ○ Contraindicated in liver and renal impairment ○ Must check renal function and liver function before beginning this medication ○ Caution w/ parenteral radiographic contrast media containing iodine— may cause renal failure and has been associated w/ lactic acidosis  If CT w/ iodine media ordered, order patient to stay off of metformin for a while before testing as lactic acidosis can happen and shut down liver Glitazones ○ AKA thiazolidinediones or TZDs ○ Pioglitazone (Actos) and Rosiglitazone (Avandia) ○ Are insulin sensitizers ○ Decrease insulin resistance ○ Stimulate receptors on muscle, fat, and liver cells ○ Results in increased uptake of glucose in periphery and decreased production by the liver ○ Contraindicated in patients w/ liver disease or who have high ALT levels ○ May be used as mono therapy or in combination w/ insulin, metformin (Glucophage) or a sulfonylurea ○ Caution in patients w/ heart failure Be careful in using insulin w/ glitazones as it may cause fluid retention (lower extremities can get swollen) ○ Ensure baseline LFTs are performed (liver enzymes) ○ Not a favorite drug by endocrinologists DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors) ○ Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta) ○ SE Nausea, diarrhea, or abdominal pain URI- sinusitis, pharyngitis Pancreatitis Joint pain ○  DPP-4 inactivate GLP-1, so this medication inhibits DDP-4 (as it says in the name) GLP-1 stimulates insulin release + inhibit glucagon release = lowering blood glucose ○ Endocrinologists like this medication for type 2 diabetics GLP-1 agonists (glucagon-like peptide-1 receptor agonists) ○ Mimic the action of the hormone GLP-1, which is involved in glucose metabolism ○ Increase insulin secretion, decreased glucagon secretion, slow gastric emptying (reduce the rate of glucose absorption from the intestines), increased satiety (acting on centers in the brain that regulate appetite) For satiety: 2 hormones that control our appetite which is relin (gives us the hunger feelings) and ghrelin (gives the full feeling) ○ Liraglutide (Victoza), Exenatide (Byetta), Dulaglutide (Trulicity), Semaglutide (Ozempic) ○ SE Nausea, diarrhea, or abdominal pain URI- sinusitis, pharyngitis Pancreatitis ○ Thyroid tumors: certain GLP-1 agonists (liraglutide and semaglutide) have been associated w/ thyroid C-cell tumors in rodent studies, not been definitively established in humans ○ DJ uses this to teach patients “how to eat” ○ Administered subcutaneous once a week ○ GLP1 & GLP2: Tirzepatide (Mounjaro)  ○ SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors) ○ Prevent the re absorption of glucose in the kidneys, leading to increased glucose excretion in urine Increased urine so they do need to hydrate a lot ○ Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), Ertugliflozin (Steglatro), ○ SE Genital and UTIs- due to increased glucose Dehydration and hypotension Type 2 DM Pharmacology Treatment Paradigm