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Flashcards in Diabeetus Deck (44):
1

Type 1 diabetes

insulin-dependent, loss of beta cells. 5-10% of diabetics

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Type 2 diabetes

insulin-independent, decreased response to insulin, 85-90% of diabetics

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Type 3 diabetes

caused by gene mutations

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Type 4 diabetes

gestational diabetes (4% of all pregnancies)

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Central goal of DM therapy

correct hyperglycemia and maintain BGL near normal range. preventing, delaying, or reducing complications, minimizing side effects of therapy, and improving quality of life

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non-pharmological approaches to treatment

diet and exercise: large reduction in type 2 incidence

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what stimulates insulin release?

glucose, which stimulates depolarization of beta cells through closing K+ channels, causing the opening of Ca2+ channels

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what does insulin do?

stimulates the production of triglycerides in adipose tissue, stimulates the production of glycogen in liver cells, and stimulates the production of protein in muscles

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types of insulin

rapid acting, short acting, intermediate acting, and long acting

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rapid-acting

peak in 30 min-2 hrs, can be injected or inhaled

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inhaled insulin (Exubera)

used in combination with other insulin in Types 1 and 2 or alone in Type 2. contraindicated in smokers, not recommended for asthma or COPD patients. side effects are cough, shortness of breath, hypoglycemia

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oral hypoglycemic agents

Sulfonylureas and meglitinides; act to increase the levels of insulin

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sulfonylurea mechanism of action

block K+ channels, causing beta cell depolarization

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prototypical sulfonylureas

tolbutamide (1st gen,~8hr duration) and glyburide (2nd gen, ~12-24 hr duration)

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sulfonylurea contraindications

sulfa drug alerrgy, pregnancy, major stress (surgery, trauma, infection)

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sulfonylurea side effects

hypoglycemia, weight gain, rash, elevated liver enzymes, allergic reaction

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Meglitinides mechanism

inhibition of K+ channel at a different site from sulfonylureas

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prototypical meglitinides

repaglinide, nateglinide

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meglitinide pharmacokinetics

rapid onset and short duration, intended to be taken after meal

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meglitinide side effects

diarrhea, allergic reactions, headache. less chance of hypoglycemia than sulfonylureas

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antihyperglycemic agents

biguanides, alpha-glucosidase inhibitors, thiazolidinediones. act without changing insulin levels

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biguanide mechanism of action

inhibit production of glucose in liver, increase sensitivity to insulin, decrease GI glucose absorption. comparable to sulfonylureas in efficacy

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prototypical biguanide

metformin

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metformin side effects

metallic taste, nausea/diarrhea, reduced absorption of B12 and folic acid

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metformin pharmacokinetics

little binding to plasma proteins, no active metabolites

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advantages of metformin

no hypoglycemia or increased weight

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a-glucosidase inhibitor prototype

acarbose

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acarbose mechanism

competitive inhibition of intestinal alpha-glucosidase, reduction in starch digestion and glucose absorption

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acarbose side effects

bloating and flatulence. can cause hypoglycemia in combo with insulin, treatable with glucose

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acarbose contraindications

intestinal diseases exacerbated by gas (ulceration, inflammatory bowel disease)

31

thiazolidinediones prototypes

risigilitazone, pioglitazone

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thiazolidinedione mechanism of action

agonist for PPAR-gamma, increases insulin sensitivity in muscle, liver, and adipose tissue, and increases insulin's action on glucose and lipid metabolism. reduces A1c by 1.0-1.5%

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pharmacokinetics of thiazolidinediones

take 3-6 weeks to reach maximum effect

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thiazolidinediones side effects

weight gain, fluid retention, some liver toxicity

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thiazolidinedione contraindications

heart failure; rosigilitazone can cause MI (43% increase in MIs in one study) and CHF

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new drugs

sitagliptin, exenatide, pramlintide

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sitagliptin mechanism

inhibition of DPP4, an enzyme that leads to increased insulin production and decreased glucagon production

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sitagliptin pharmacokinetics

rapid absorption (PO), little metabolism (79% excreted whole in urine), hl of 11.8-14.4 hr. used as sole therapy or in combo with metformin or thiazolidinediones

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sitagliptin side effects

none, no hypoglycemia or weight gain

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exenatide mechanism

enhances glucose dependent insulin release, suppresses elevated glucagon secretion, slows gastric emptying
decreases HbA1c by .4-.8% and 2 hr PPG bt 63-71 mg/dl

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exenatide pharmacokinetics

subQ, used in combo with sulfonylureas and/or metformin

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exenatide side effects

indigestion, diarrhea, weight loss (1-3 kg)

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pramlintide mechanism

synthetic analog of amylin, a hormone co-secreted with insulin that slows gastric emptying, suppresses glucagon secretion after meals, and modulates appetite
decrease H1c by .5%, 1.5 kg weight loss

44

pramlintide pharmacowhatever

SubQ before meal