Pharmacology 1 - Final Exam

insulin physiology

• biosynthesis

  • in pancreas by beta cells

• secretion

  • blood sugar increases → beta 2 receptors in pancreas are activated → inhibits alpha receptors

• metabolic actions

  • anabolic

• metabolic consequences of insulin deficiency

  • catabolic mode → contributes to signs and symptoms of DM, breakdown of complex molecules into their simpler constituents (glycogen into glucose, proteins into amino acids)

  • 3 mechanisms that promote hyperglycemia

    • increased glycogenolysis → breakdown of glycogen to glucose

    • increase gluconeogenesis → formation of glucose from amino acids and fatty acids

    • reduced glucose utilization → insulin deficiency decreases cellular uptake of glucose and decreases conversion of glucose to glycogen

types of insulin

• short duration (rapid acting)

  • insulin lispro (Humalog)

  • insulin aspart (Novolog)

  • insulin glulisine (Apidra)

• short duration (slower acting)

  • regular insulin (Humalin R, Novolin R)

• intermediate duration

  • neutral protamine hagedorn (NPH) insuling

• long duration (24+ hours)

  • insulin glargine

  • insulin determir (Levemir)

insulin aspart

• Novolog → analog of human insuling

• rapid onset (15-30 minutes)

• short duration (3-6 hours)

• administer immediately before eating or even after eating

insulin lispro

• Humalog → rapid acting analog of regular insulin

• rapid onset (15-30 minutes after subcutaneous injection)

• short duration (3-6 hours)

• usual route is subcutaneous via injection or use of an insulin pump

• acts faster than regular insulin but has a shorter duration of action

• should be injected minutes before meals

inslulin glulisine

• Apidra → synthetic analog of natural human insulin

• rapid onset (15-30 minutes)

• short duration (3-6 hours)

• should be administered close to the time of eating

regular insulin

• Humalin R, Novolin R → unmodified human insulin

• slower acting insulin

• 4 approved routes → subcutaneous injection, subcutaneous infusion, IM injection, oral inhalation (approved but not currently used)

• effects begin in 30 to 60 minutes

• peak in 1 to 4 hours

• duration up to 6-10 hours

• clear solution

• available → U-100 (most common), U-500

NPH insulin

• Humalin N, Novolin N

• intermediate duration insulin

• drug is injected 2-3 times daily to provide glycemic control between meals and during the night → not given with meals

• this is the only suitable insulin for mixing with short-acting insulins

• allergic reactions are possible

• cloudy → must be agitated before administration (but do not shake)

• administered via subcutaneous injection only

• onset 1-2 hours

• peak 4-12 hours

• duration 18-24 hours

insulin glargine

• Lantus → modified human insulin

• long-duration insulin

• onset 1-2 hours

• no peak

• prolonged duration (20-24 hours)

• once daily subcutaneous dosing to treat adults and children with DMI or DMII

• given at the same time each day

• clear solution

insulin detemir

• Levemir → human insulin analog

• long duration insulin

• slow onset and dose-dependent duration of action

• used to provide basal glycemic control

• clear, colorless solution

• dosed once or twice daily by subcutaneous injection

• do NOT mix with other insulins

• must not be given IV

how to mix insulin

put air into NPH vial → put air into short acting vial → draw up short acting → draw up NPH

(clear → cloudy)

insulin dosing considerations

• decreased insulin dose → missed meals, increased exercise, low carbs

• increased insulin dose → infection, stress, obesity, growth spurt, pregnancy

biguinides

• ex. Metfomin

• uses → DMII, gestational DM, PCOS

• MOA → decreased hepatic glucose production

• notes → dc with eGFR <46

• side effects → GI, no risk for hypoglycemia

sulfonylureas

• ex. Glipzide, Glyburdie, Tolazamide, Tolbutamide, Glimepride

• uses → DMII

• MOA → increased insulin secretion in beta cells of pancreas

• notes → adjust dose with changes in activity or caloric intake

• side effects → hypoglycemia, GI, rash, weight gain

meglintinides

• ex. Repaglinide, Nateglinide

• uses → DMII

• MOA → increased insulin secretion after meal

• notes → MUST be taken with a meal

• side effects → hypoglycemia

thiazolidinediones

• ex. Pioglitazone

• uses → DMII

• MOA → increased insulin sensitivity (decreased insulin resistance)

• notes → may improve lipid levels

• side effects → fluid retention, HF, upper respiratory infection, headache, sinusitis, hepatotoxicity, myalgia

thyrotoxic crisis

• also known as thyroid storm and is life-threatening

• cause

  • significant stress (surgery, illness), not triggered by a rise in thyroid hormones, cannon be identified by laboratory testing

• signs

  • hyperthermia (105 degrees F or higher)