Term
| how does the structure/function of the pancreas break down? |
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Definition
| the pancreas has 2 kinds of tissue: acini (secrete digestive juices to the duo) and the islets of langerhans (secrete hormones directly into the blood). |
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Term
| what cells are found in the islets of langerhans? what do they produce? |
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Definition
| alpha cells produce glucagon, beta cells produce insulin, delta cells produce somatostatin, and PP cells secrete pancreatic polypeptide. |
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Term
| what characterizes insulin as a molecule? |
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Definition
| insulin is 2 amino acid chains connected by disulfide linkages, which if lost = loss of functional activity. when insulin binds, it has 2 alpha subunits outside the cell membrane and 2 beta subunits which penetrate the membrane and protrude into the cell cytoplasm. the beta subunits autophosphorylate and become activated enzymes which ultimately incur a decrease in blood glucose. |
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Term
| what are the 3 responses the body has to insulin binding? |
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Definition
| 1) initial, rapid cell membrane change to a higher permeability for glucose, AAs, K+, and phosphate. 2) slower response (10-15 min) of intracellular actions changing activity levels of various enzymes. 3) very slow process (hours-days) of transcription/translation rate changes. |
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Term
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Definition
| a hormone which increases blood glucose, the "hyperglycemic hormone", via increasing glycogenolysis/gluconeogenesis in the liver |
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Term
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Definition
| a stabilizing hormone which locally depresses release of both glucagon and insulin, decreases motility of the stomach/duodenum, and decreases secretion/absorption of food. somatostatin release is stimulated by increased blood glucose, AAs, FAs, and other GI hormones. |
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Term
| what are the glucose disorders? |
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Definition
| DM1: insulin dependent, DM2: insulin resistant, and hyperinsulinism |
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Term
| what are the different types of exogenous insulin available? |
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Definition
| human insulin (HUMULIN - from recombinant DNA), porcine (has 1 different AA at position 30), and bovine (has 2 different AA at 30 and 8/10) |
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Term
| what are the advantages to using recombinant human insulin? |
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Definition
| less antigenic, lower titers of insulin-binding Ab, and less allergenic (skin/immunologic resistance) |
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Term
| what are the different types of insulin available according to duration of action? |
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Definition
| 1) short/rapid action: regular crystalline zinc insulin injection or semilente insulin zinc suspension. 2) intermediate-acting: neutral protamine hagedorn (NPH), lente zinc suspension (mix of semi+ultra lente), and human insulin. 3) long-lasting: ultra lente zinc suspension and protamine zinc insulin. |
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Term
| what are the 2 popular mixtures of insulins with different durations of action? |
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Definition
| 1) 30% regular/70% NPH. 2) 50% regular/50% NPH. mixtures are becoming more common and are more accurate to the individual’s need. |
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Term
| what is the disadvantage of long-lasting insulin? |
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Definition
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Term
| what is the onset, duration, and peak for regular insulin injection? |
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Definition
| onset: IV 5 min/SC 15 min. peak: 2-4 hrs. duration: 4-6 hrs. |
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Term
| what is the onset, duration, and peak for semilente insulin? |
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Definition
| onset: 30-60 min. peak: 4-6 hrs. duration: 12-16 hrs. |
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Term
| what is the onset, duration, and peak for isophane/NPH insulin? |
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Definition
| onset: 2-4 hrs. peak: 6-10 hrs. duration: 24-48 hrs. |
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Term
| what is the onset, duration, and peak for lente insulin? |
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Definition
| onset: 2-4 hrs. peak: 6-10 hrs. duration: 12-24 hrs. |
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Term
| what is the onset, duration, and peak for protamine zinc insulin? |
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Definition
| onset: 4-6 hrs. peak: 14-20 hrs. duration: 24-36 hrs. |
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Term
| what is the onset, duration, and peak for ultralente insulin? |
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Definition
| onset: 4-6 hrs. peak: 16-18 hrs. duration: 20-36 hrs. |
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Term
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Definition
| a very rapid acting insulin - onset is about 5 minutes due to a slight AA chain reversal (pts should not take unless they are 5-10 min from eating). novolog is a similar drug. |
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Term
| what are the routes of administration used for insulin? |
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Definition
| subcutaneous injection (common), external infusion pump, and internal infusion pump. nasal/inhaled/oral are in various stages of development. |
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Term
| what are the 2 kinds of oral hypoglycemics (used for DM2)? |
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Definition
| sulfonylureas and biguanide derivatives |
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Term
| what is the MOA for the sulfonylureas? |
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Definition
| stimulation of insulin release from beta cells (requires some level of blood glucose to work) via binding receptors that *increase Ca2+ intracellular influx (insulin release is Ca2+ dependent). this ultimately enhances the effects of insulin by producing more insulin for a better chance of binding receptors (faulty or good receptors). |
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Term
| what are the 1st gen sulfonylureas? |
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Definition
| tolbutamide, tolazamide, acetohexamide, and chlorpropamide (disulfiram rxn) |
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Term
| what are the 2nd gen sulfonylureas? |
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Definition
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Term
| what ADRs are associated w/the sulfonylureas? |
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Definition
| hypoglycemia (if the drug is displaced from carrier proteins by other drugs), GI disturbances, allergic rxns, dermatological problems, transient leukopenia (usually upon initiation of therapy), and a disulfiram rxn w/chlorpropamide (also causes fluid retention). |
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Term
| what is the MOA for the biguanides/metformin? |
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Definition
| this DOC for DM2 makes insulin that is present more effective and reduces glucose levels via *reduction of glucose production in the liver, *stimulation of glycolysis in peripheral tissues, *decrease in glucose absorption in the intestines, and *increased insulin binding. since biguanides don't affect insulin itself, it *rarely causes hypoglycemia. biguanides can also *reduce LDLs and increase HDLs. |
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Term
| when are biguanides/metformin contraindicated? |
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Definition
| in renal and hepatic insufficiency |
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Term
| what ADRs are associated w/biguanides/metformin? |
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Definition
| metallic taste, lactic acidosis (rare), impaired vit B12 absorption (supplemental B12 in anemic pts), n/v, anorexia, abdominal discomfort, and diarrhea |
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Term
| what drugs facilitate the action of insulin? |
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Definition
| acarbose, linogliride, pioglitazone, and rosiglitazone |
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Term
| what is the MOA for acarbose? |
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Definition
| acarbose *prevents the hydrolysis of complex dietary carbohydrates (does not stimulate insulin release/increase its action/cause hypoglycemia). ADRs: GI |
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Term
| what is the MOA for linogliride? |
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Definition
| this is in a different molecular class but essentially functions like sulfonylureas and appears to act as an *insulin secretagogue. |
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Term
| what is the MOA for pioglitazone? |
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Definition
| this *decreases insulin resistance in periphery (not a secretagogue) as an agonist at the proliferator-activated receptor gamma (PPAR gamma) which upregulates transcription of insulin responsive genes involved in glucose/lipid metabolism. rosiglitazone is basically the same thing, but has been taken off the market as it is associated w/an increased heart attack rate. |
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Term
| what is the major hyperglycemic and when is it used? |
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Definition
| glucagon, which stimulates gluconeogenesis, glycogenolysis and ketogenolysis. it is used to counter severe hypoglycemia (can raise plasma concentration of glucose w/in 15 min). |
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Term
| what is the onset, half-life, and duration for tolbutamide? |
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Definition
| onset: 1-4 hrs. half-life: 3-5 hrs. duration: 6-10 hrs. |
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Term
| what is the onset, half-life, and duration for chlorpropamide? |
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Definition
| onset: 1-3 hrs. half-life: 24-48 hrs. duration: 24-72 hrs. |
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Term
| what is the onset, half-life, and duration for tolazamide? |
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Definition
| onset: 4-6 hrs. half-life: 4-7 hrs. duration: 16-24 hrs. |
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Term
| what is the onset, half-life, and duration for acetohexamide? |
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Definition
| onset: 1-2 hrs. half-life: 3-11 hrs. duration: 12-18 hrs. |
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Term
| what is the onset, half-life, and duration for glyburide? |
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Definition
| onset: 2-4 hrs. half-life: 10-16 hrs. duration: 18-24 hrs. |
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Term
| what is the onset, half-life, and duration for glipizide? |
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Definition
| onset: 1-2 hrs. half-life: 1-5 hrs. duration: 16-24 hrs. |
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Term
| what is the onset, half-life, and duration for metformin? |
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Definition
| onset: 1-2 hrs. half-life: 2-6 hrs. duration: 18-24 hrs. |
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