Exam (elaborations) PHARMACOLO N5334 Exam 3 Study Questions and answers

Exam 3 Study Questions  What drugs are used to treat gestational diabetes? o Metformin and Insulin  What A1C value indicates diabetes mellitus? Pre-DM? o 6.5% or greater is considered diabetes o 5.7-6.4% pre-diabetes  What fasting and random values indicate DM? o Fasting plasma glucose—126 or greater is diabetes o Random (casual) plasma glucose—anything greater than 200 is diabetes  What are complications of insulin therapy? o Hypoglycemia o Can develop lipohypertrophy  Accumulation of subcutaneous fat that occurs when it is injected too frequently at the same site o Allergic reactions  Characterized by red and intensely itchy welts, breathing becomes difficult  If severe allergy develops:  Desensitization procedure (small doses to larger doses) o Hypokalemia  Promotes the uptake of potassium cells and insulin activates a membrane-bound enzyme with sodium potassium and ATPase that pumps potassium into the cells and sodium out  Drug interactions? o Hypoglycemic agents  Can intensify the hypoglycemia included by insulin  Examples: sulfonylureas, glinides, alcohol o Use with caution with hyperglycemic agents  Examples: thiazide and glucocorticoids and sympathomimetics  What effect do beta blockers have on insulin? o delay awareness of and response to hypoglycemia by masking the signs that are associated with stimulation of sympathetic nervous system o Impair glycogenolysis o Prevent the bodies counter-regulatory response  What are other therapeutic uses besides DM? o Hyperkalemia o Aids in diagnosis of GH deficiency o Diabetic ketoacidosis  Insulin dosage must be coordinated with what? o Carbohydrate intake  What is B/P goal in diabetic? o To be controlled, within normal 120/80  What medication can be given to decrease risk of diabetic nephropathy? o ACE inhibitor or ARB 1  What role does exercise play in treatment of both type 1 and type 2 DM? o Exercise increases cellular responsiveness to insulin and increases glucose tolerance o 150 minute per week of moderate intensity exercise is recommended  What are the 4 steps in the 4-step approach? o Step 1—diagnosis  Lifestyle changes plus metformin o Step 2  Lifestyle changes plus metformin and a second drug (sulfonylurea, TZD or a DPP4 inhibitor, a sodium glucose cotransporter or SGLT-2 inhibitor, a glucagon-like peptide 1, or a GLP-1 receptor agonist or basal insulin  Second drug choice made considering efficacy, the hypoglycemia risk of the patient, the patient tolerability, and weight-related considerations (some help weight loss, some cause weight gain), cost o Step 3  Three drug combination  Metformin  Plus 2 other drugs from step 2 o Decided based on a drug and patient specific considerations o Step 4  If 3 drug combination that includes basal insulin fails after 3-6 months, more complex insulin regimen  Usually in combination with one or more non-insulin medications  When a patient is on insulin therapy what are the blood glucose goals before meals? At bedtime? o Before meals—70-130 o Bedtime—100-140  What is the A1C goal? When is goal below 7 not appropriate? o 7% or below o Those with severe hypoglycemia risk, limited life expectancy, advanced microvascular or macrovascular complications—not below 7  What are the short acting insulins? Intermediate? Long acting? o Short duration: Rapid acting  Insulin lispro [Humalog]  Insulin aspart [NovoLog]  Insulin glulisine [Apidra] o Short duration: Slower acting  Regular insulin [Humulin R, Novolin R] o Intermediate duration  Neutral protamine Hagedorn (NPH) insulin  Insulin detemir [Levemir] o Long duration  Insulin glargine  When are short duration insulins used? 2 o Administered in association with meals to control the post-prandial rise in blood glucose between meals and at night  When are intermediate insulins needed? o Administer 2-3 times daily to provide glycemic control between meals and during the night  How long is duration of glargine? Levemir? Degludec? o Glargine—up to 24 hours o Levemir  Low dose (0.2 units/kg)—12 hours  High doses (0.4 units/kg)—20-24 hours o Degludec—up to 42 hours  What are routes of administration? Which can be inhaled? o SQ injection o IV infusion o Inhalation—Afrezza, mealtime insulin  What is typical dosing for type 1? Type 2? o Total doses may range from 0.1 unit/kg body weight to more than 2.5 units/kg o Type 1  Initial doses typically range from 0.5-0.6 units/kg per day o Type 2  Initial doses range from 0.2-0.6 units/kg per day  Dosage increased or decreased according to carb intake, activity  What are the 3 dosing schedules? o Twice daily dosing o Intensive basal/bolus strategy o Continued subcutaneous insulin  How does metformin work? o Inhibits glucose production in the liver o Reduces glucose absorption in the gut o Sensitizes insulin receptors in target tissues (fat and skeletal muscle) thus increase glucose uptake and response to whatever insulin is available  What are side effects? BB warning? o GI effects—diarrhea o Lactic acidosis  How does alcohol effect? o Inhibits the breakdown of lactic acid  What are the therapeutic uses other than DM? o Gestational diabetes o PCOS  Sulfonylureas o First generation  Chlorpropamide [Diabinese]  Tolazamide [Tolinase] 3  Tolbutamine [Orinase] o Second Generation:  Glyburide [Diabeta, Glynase, Micronase] with metformin [Glucovance]  Glypizide (Glucotrol, Glucotrol XL); with metformin [metaglip])  Glimepiride (Amaryl; with metformin [Amaryl M], with pioglitazone [Duetact] with rosiglitazone [Avandaryl] o MOA?  Promote insulin release o Main side effect?  Hypoglycemia  Weight gain o How does cimetidine effect? Beta blocker?  Cimetidine—intensifies the response  Beta blockers—diminish the benefits by suppressing the insulin release  Meglitinides (Repaglinide and Nateglinide) o MOA—stimulate pancreatic insulin release o Drug/Drug interaction—gemfibrozil  Thiazolidinediones (glitazones) o Reduce glucose levels primarily by decreasing insulin resistance o Only indication is type 2 diabetes, mainly as an add-on to metformin o Rosiglitazone [Avandia]: Restricted use o Pioglitazone [Actos] o Can they be used in patient with CHF?  No  Alpha-glucosidase inhibitors (Acarbose or Precose; Miglitol (glyset)) o What races are these more effective in?  Latinos and African Americans  DPP-4 inhibitors (gliptins) o MOA—promote glycemic control by enhancing the actions of the incretin hormones and they stimulate glucose dependent release of insulin  Suppress your post-prandial release of glucagon o What is the % of A1C reduction?  0.5%  Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (Canagliflozin, Dapagliflozin)  How does colesevelam work in treatment of DM? Bromocriptine? o Colesevelam—bile acid sequestrant used to lower cholesterol and helps lower blood glucose  Many with diabetes also have high cholesterol so 2 birds-1 stone o Bromocriptine—adjunct to diet and exercise (0.5% reduction)  Injectables o Amylin memetics?  Pramlintide  Side effects—hypoglycemia when used with insulin  Drug/Drug—insulin 4 o GLP-1 receptor agonists (or incretin mimetics)  Can cause medullary thyroid cancer  What is treatment of diabetic ketoacidosis (DKA)? Hypoglycemia? o Insulin replacement, reverse acidosis with bicarbonate, replace water, sodium, potassium, normalize glucose levels o Hypoglycemia—IV glucose, glucagon is glucose not available  What is hyperosmolar hyperglycemia state (HHS)? o Large amount of glucose excreted in the urine and results in dehydration and loss of blood volume o Increases blood concentration of electrolytes and nonelectrolytes, particularly glucose and hematocrit o When does this occur?  Most frequently with type 2 diabetics with acute infection or illness or other stressors o Treatment?  Correcting hyperglycemia and dehydration with IV insulin, fluids, and electrolytes  What effect does iodine have on thyroid? o When iodine availability is low production of thyroid hormones decrease  Why is normal thyroid function important in first trimester of pregnancy? How much does requirement unusually increase in pregnant women taking thyroid supplements? o Fetus is unable to produce its own hormones, without can result in permanent neuropsychologic deficits o Usually increases as much as 50%  When is fetal thyroid gland full functional? o 16 weeks  If not treated, what does hypothyroidism cause in an infant? o Large protruding tongue, potbelly, and dwarfish stature o The development of the nervous system, bones, and teeth is impaired  When should treatment be stopped? How long? o At 3 years of age for 4 weeks, then TSH is checked o If rise—deficiency is permanent, thyroid replacement needed o If normalize—transient deficiency, no further replacement required  How is Graves’ Disease treated? o Surgical removal, destruction of the thyroid tissue, suppression of the thyroid hormone synthesis and/or beta blockers o Non-radioactive iodine can be used to distract the thyroid tissue  Thyroid Storm? o Hyperthermia, severe tachycardia, restlessness, agitation, tremor o Unconscious, hypotensive, heart failure o Cannot be identified by lab testing, not triggered by a rise in thyroid hormones o Treatment—methimazole, beta blocker, sedation, cooling, glucocorticoids, IV fluids  Levothyroxine 5 o T4 o Long half life o How should this be taken?  In the morning, at least 30 to 60 minutes before breakfast o Side effects—tachycardia, angina tremors o Drug/Drug  Warfarin—intensify effects  Drugs that reduce absorption  H2 receptor blockers, PPIs, cholestyramine, colestipol, Maalox, Mylanta, calcium supplements, iron, magnesium, orlistat  Accelerate metabolism  Phenytoin, carbamazepine, rifampin, sertraline, phenobarbital  Catecholamines—increase cardiac responses  Increase requirements of insulin and digoxin o How is this dosed? How does dosage differ for someone over 50? 65 and older? Someone with heart disease? Overweight? Underweight?  1.6-1.8 mcg/kg/day  Obese—go by ideal body weight  Underweight—actual weight  Older patients with CAD—start with 12.5-25 mcg  Elderly—start low and go slow  Younger than 3 months—10 to 15 mcg/kg/day  Children (3-5 months)—8 to 10 mcg/kg/day  Children (6-11 months)—6 to 8 mcg/kg/day  Children 1-5 years—5 to 6 mcg/kg/day  Children 6-12—4 to 5 mcg/kg/day  Liotrix—a mixture of synthetic T4 plus synthetic T3 in a 4:1 fixed ratio o Because levothyroxine alone produces the same ratio of T4 to T3, Liotrix offers no advantage over levothyroxine for most indications  Armour—consists of desiccated animal thyroid glands. o Standardization is based on content of iodine, levothyroxine, and liothyronine. o The ratio of levothyroxine to lipthyronine is not less than 5:1 o Thyroid is available in tablets (15-300 mg)  Methimazole—used in hyperthyroidism o Cell form of therapy for Graves’ disease o Adjunct to radiation therapy until the effects of radiation become manifested o Suppresses the thyroid hormone synthesis in preparation for thyroid gland surgery o Thyrotoxic crisis  Propylthiouracil o Inhibits thyroid hormone synthesis o Second line for graves o Short half-life o Full benefits—6 to 12 month