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pharm
diabetes mellitus part 2
| Question | Answer |
|---|---|
| Biguanide | aka metformin (Glucophage) |
| Biguanide MOA primary | decreases hepatic glucose production |
| Biguanide MOA secondary | improves insulin sensitivity (increases peripheral glucose uptake and utilization) |
| Biguanide side effects | GI: diarrhea, abd discomfort, stomach upset metallic taste vitamin b12 deficiency (w long term use-check annually) rare: lactic acidosis (50% fatal) |
| Biguanide clinical pearls | take w the first bite of food to prevent GI upset (can lead to metabolic acidosis) |
| Biguanide hold when: | hold metformin at the time of iodinated contrast procedure if eGFR 30-60 or if liver disease, alcoholism, or heart failure; or if intra-arterial contrast. Recheck eGFR 48 hours after procedure and only restart if renal function stable |
| Biguanide does NOT... | cause renal failure, however, renally excreted and accumulated in pts with renal insufficiency |
| Sulfonylureas | Glipizide Glyburide Glimepiride |
| All Sulfonylureas MOA | stimulates pancreatic beta cells to secrete insulin |
| All Sulfonylureas A1C lowering | 1-2% |
| Glipizide usual dose | 2.5-40 mg daily- 30 minutes before 1st meal XL: 2.5-20mg once daily |
| Glyburide usual dose | 1.25-20mg once daily PresTabs 0.75-12mg once daily |
| Glimepiride usual dose | 1-8mg once daily |
| All Sulfonylureas major side effects | hypoglycemia weight gain tachyphylaxis: reduced effect over time (long term durability is poor) |
| All Sulfonylureas advantages | extensive track record of safety and effectiveness low cost |
| All Sulfonylureas clinical pearls | hypoglycemia risk higher in patients who skip meals, exercise vigorously, have renal disease, or lose substantial amounts of weight. should be avoided or used w extreme caution in older adults. |
| Meglitinides (Glinides) | repaglinide, nateglinide |
| Meglitinides (Glinides) MOA | stimulated pancreatic beta cells to secrete insulin |
| Meglitinides (Glinides) A1C lowering | 0.8-1% |
| repaglinide usual dose | 0.5-4mg x3 daily 15-30 minutes before meals |
| nateglinide usual dose | 60-120 x3 daily 1-30 minutes before meals |
| Meglitinides (Glinides) major side effects | hypoglycemia weight gain |
| Meglitinides (Glinides) clinical pearls | -can be used in renal insufficiency -only lowers post-meal blood glucose -skip dose if skipping the meal -reduced effect over time (requires pancreatic insulin production) |
| Meglitinides (Glinides) co-administration | Co-administration of clopidogrel, cyclosporine, gemfibrozil, and ketoconazole may increase repaglinide levels increasing risk of hypoglycemia |
| Thiazolidinediones (TZDs) | pioglitazone, rosiglitazone |
| Thiazolidinediones (TZDs) MOA | insulin "Sensitizers": improves glucose uptake in muscle and fat; also decreases hepatic glucose output, inhibits lipolysis, and preserves beta cell function |
| Thiazolidinediones (TZDs) A1C lowering | 1-2% |
| pioglitazone usual dose | 15-45mg once daily |
| rosiglitazone usual dose | 2-8mg once daily |
| Thiazolidinediones (TZDs) major side effects | -weight gain -edema due to NA and water retention -new onset or worsening heart failure -inc risk of fractures in upper and lower limbs of postmenopausal women -may increase risk of bladder cancer -rare: increased risk of macular edema |
| Thiazolidinediones (TZDs) clinical pearls | takes up to 12 weeks to see full benefit check liver enzymes prior to initiate and use caution if increased contraindicated in NYHA class III or IV heart failure |
| role of incretins in glucose homeostasis | body's natural way of managing BGL after eating |
| the incretin response | the "go" signal when you eat food, smI releases incretin hormones (GLP1 and GIP), they act on Beta cells and Alpha cells |
| the incretin response on beta cells | they trigger a glucose dependent increase in insulin, this helps muscles take up glucose for energy |
| the incretin response on alpha cells | they suppress the release of glucagon, less glucagon tells the liver to stop producing unnecessary glucose |
| result of incretins in glucose homeostasis | blood glucose levels drop to a healthy range |
| DPP-4 enzyme | the "stop" signal the natural off switch for these incretin hormones causes rapid degradation of GLP1 and GIP into inactive form causes endogenous incretins to have a short half life |
| GLP1 also | inhibits gastric emptying promotes feeling of satiety |
| GLP1 receptor antagonists | Semaglutide, Dulaglutide, Exenatide (ER or IR), Liraglutide |
| GLP1 receptor antagonists MOA | increases glucose dependent insulin secretion, slows gastric emptying, promotes satiety, decreases glucagon secretion (resulting in decreased hepatic glucose output) |
| GLP1 receptor antagonists A1C lowering | 1-2% |
| GLP1 receptor antagonists major side effects | N/V diarrhea dec appetite risk of thyroid C-cell tumors (in rodents) associated w cases of acute pancreatitis and GB disease case reports of AKI or worsening renal func |
| GLP1 receptor antagonists clinical pearls | weight loss, lipid and BP reductions avoid in pts w PMH or fam Hx of medullary thyroid carcinoma follow slow dose titration recs to prevent GI effects stop long-acting GLP1, 1 week before surgery oral semaglutide taken 30 mins before food/drink/meds |
| GLP1 receptor antagonists NOT recommended for | pts w gastroparesis pts on DPP-4 inhibitors (similar MOA) |
| brand name for semaglutide: | Wegovy: approved for obesity comes SubQ and oral |
| GIP and GLP1 receptor agonist | Tirzepatide (mounjaro) |
| GIP and GLP1 receptor agonist MOA | selectively binds and activates BOTH GIP and GLP1 receptors same side effects and contraindictions as GLP1 RA class |
| brand name for Tirzepatide | Zepbound: approved for obesity |
| Dipeptidyl peptidase (DPP4) inhibitors | sitagliptin, saxagliptin, linagliptin, alogliptin |
| Dipeptidyl peptidase (DPP4) inhibitors MOA | by inhibiting DPP4, enhances levels of GLP1 and other incretin hormones. this stimulates glucose-dependent insulin secretions and suppresses glucagon |
| Dipeptidyl peptidase (DPP4) inhibitors A1C lowering | 0.5-0.8% |
| Dipeptidyl peptidase (DPP4) inhibitors major side effects | generally well tolerated assoc. w acute pancreatitis INC hospitalizations for HF (agoliptin, saxagliptin) bullous pemphigoid requiring hospitalization arthralgias |
| Dipeptidyl peptidase (DPP4) inhibitors clinical pearls | well tolerated but the glucose lowering effects are not as robust as the other classes of agents |
| Where are Sodium-Glucose Cotransporters (SGLTs) specifically located within the kidney? | In the brush border of the proximal tubules. |
| What is the primary physiological function of SGLTs? | To reabsorb filtered glucose from the nephron back into the blood to prevent energy loss (glucosuria) |
| Under normal physiological conditions, how much glucose is typically excreted in the urine? | None or minimal glucose excretion |
| Which transporter is responsible for the majority (~90%) of glucose reabsorption? | SGLT2 |
| In which specific segment of the proximal tubule is SGLT2 located? | The S1 (first) segment |
| What percentage of glucose is reabsorbed in the S3 segment of the proximal tubule? | approximately 10% |
| At what blood glucose concentration does the "renal threshold" typically occur (exceeding SGLT capacity)? | 180–200 mg/dL |
| What happens to glucose in a patient with uncontrolled diabetes when blood sugar rises above 200 mg/dL? | The capacity of the SGLTs is exceeded (saturated), and glucose is excreted in the urine |
| Sodium Glucose Cotransporter 2 (SGLT2) inhibitors | canagliflozin, empagliflozin, dapagliflozin, ertigliflozin |
| SGLT2 inhibitors MOA | reduces urinary glucose reabsorption and increases urinary glucose excretion |
| SGLT2 inhibitors | 0.7-1% |
| SGLT2 inhibitors major side effects | genital mycotic infections increased rick of necrotizing fasciitis of perineum hypotension dehydration euglycemia DKA increases risk of bone fracture |
| SGLT2 inhibitors major side effects- genital mycotic infections | UTIs becuase of the glucose in urine and increased urination |
| SGLT2 inhibitors major side effects- hypotension | due to osmotic diuresis |
| SGLT2 inhibitors major side effects- dehydration | increased risk of AKI, syncope, falls |
| SGLT2 inhibitors clinical pearls | glucose lowering efficacy reduced in renal impairment drink plenty of water and stay hydrated good hygiene practices to reduce risk of genitial infections stop SGLT2i 72 hours before scheduled surgeries |
| hypoglycemia | not a complication of diabetes itself but a side effect of some meds used to treat diabetes!!! (insulin or insulin secretagogues) |
| level 1 hypoglycemia | (mild) initial threshold for the release of counter-regulatory hormones |
| level 1 hypoglycemia criteria | BGL 54-69 |
| level 1 hypoglycemia symptoms | sweating, shaking, hunger, anxious, weakness, tachycardia, pallor |
| level 2 hypoglycemia | (moderate) threshold for neuroglycopenia symptoms |
| level 2 hypoglycemia criteria | BGL <54 |
| level 2 hypoglycemia symptoms | confusion, poor coordination, loss of concentrations, glassy eyes, slurred speech |
| level 3 hypoglycemia | (severe) requires assistance from another person for recovery |
| level 3 hypoglycemia criteria | any |
| level 3 hypoglycemia | altered mental status/physical status, unresponsiveness, agitation, convulsions, unconsciousness |
| Tx of hypoglycemia | rule of 15: eat 15 grams of fast-acting carbs to raise BGL |
| 15 grams of fast-acting carbs | 3-4 glucose tabs tube of glucose gels 4 oz of juice or soda (not diet) 1 tbsp of sugar, honey, or corn syrup hard candies, jellybeans, or gumdrops- look at "total carb grams" |
| Tx of hypoglycemia- recheck | recheck blood sugar after 15 minutes, if still <70mg/dL, have another serving. repeat until BGL is atleast 70 |
| Tx of hypoglycemia- after blood sugar is normal | eat a meal or snack (carb + protein) to make sure it doesn't lower again |
| what route is best for hypoglycemia Tx | treat hypoglycemia BY MOUTH, if pt is alert and can swallow safely |
| Tx of severe hypoglycemia | do not tx by mouth is pt cannot swallow |
| Tx of severe hypoglycemia- IV dextrose | IV dextrose is best Tx for inpatient/pts found by EMTs available in different concentrations |
| different concentrations of IV dextrose | concentrated IV dextrose 50% (D50) provides 25g of dextrose in a standard 50 mL dose |
| Tx of severe hypoglycemia- AFTER IV dextrose | administer continuous infusion of IV dextrose 5% or 10% in water to prevent recurrent hypoglycemia |
| Glucagon | for severe hypoglycemia in the community or when pt doesn't have IV access |
| Glucagon route and dose | SubQ or IM: 0.5mg in kids <45kg and 1mg in older kids/adults Intranasal: 3mg in kids (>4 yo) and adults |
| Glucagon MOA | stimulates hepatic glycogenolysis activates hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver |
| when is glucagon ineffective? | pts w liver failure glycogen-depleted pts (binge drinkers or critically ill) |
| glucagon common side effects | VOMITING lay pt on side |
| what needs to follow glucagon? | oral carbs (if pt can eat) OR obtain IV access and start dextrose-containing fluids as soon as possible |
| traditional glucagon emergency kit | includes vial of med, syringe, and needle needs to be mixed prior to use |
| traditional glucagon emergency kit- pt education: | instruct pt fam/friends on proper reconstitution and administration. turn pt on its side (vomiting). injection site: large muscle (buttocks, thigh, arm) |
| Glucagon- alternative products | Gvoke HypoPen Baqsimi (glucagon) nasal powder |
| Gvoke HypoPen | premixed autoinjector 0.5mg for pediatric pts <45kg 1mg if >45kg |
| Baqsimi (glucagon) nasal powder | 3mg for adults and kids over 4 |
Created by:
ago24