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59 Cards in this Set
- Front
- Back
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Regulation of insulin:
-Substances that stimulate release |
-glucose in food, also amino acids and lipids have some effect
-GI hormones (CCK, GI glucagon) -GI incretins in response to food glucose: GLP-1, GIP -muscarinic PNS receptors control basal levels of insulin -Beta2 agonists increase insulin secretion |
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Insulin regulation:
-Substances that inhibit release |
-Alpha2 agonists inhibit release
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Insulin regulation:
-t 1/2 of insulin |
-3-5 minutes; degraded by insulinase and proteases in liver and kidney
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Insulin regulation:
-Cellular mechanism of release in Beta pancreatic cells |
1. Glucose is transpoted into Beta cell by GLUT2 transporter
2. Glucose metabolism generates ATP 3. Increased levels of ATP close potassium channels 4. Built up intracellular potassium depolarizes cell 5. Voltage dependent calcium channels open 6. Ca influx causes vesicle fusion with PM and release (of insulin + C peptide) |
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Drugs that can cause hyperglycemia
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1. Thyroid hormones
2. Thiazides (decreases K+ levels, which then inhibits insulin release) 3. Estrogens 4. Glucocorticoids |
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Mechanism of action on insulin target cells
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1. Insulin binds alpha subunits of insulin receptor
2. Beta subunits of insulin receptor=tyrosine kinases that autophosphorylate each other 3. Phosphorylated tyr kinases then phosphorylate IRS 4. IRS activates MAP kinase pathways and PI-3 Kinase pathways 5. Cell translocates glucose transporter proteins (i.e. GLUT4 in skeletal muscle and adipose) to plasma membrane; also activates trascription factors of over 100 genes 6. Insulin:receptor complex is internalized and insulin degraded |
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Effects of insulin on:
-Skeletal muscle -Adipse tissue -Liver |
-Skeletal muscle: increases uptake of glucose and glycogen synthesis; increases uptake of amino acids and protein synthesis
-Adipose tissue: increases uptake of glucose and fatty acids and triglyceride synthesis; inhibits lipolysis; increases plasma lipoprotein lipase activity -Liver: Increases glucose uptake and glycogen synthesis; Increases triglyceride synthesis; inhibits glycogenolysis, poduction of keto acids, and gluconeogenesis |
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Symptoms of insulin deficiency
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hyperglycemia, glycosuria, tissue wasting, musle weakness, hyperlipemia, polyuria, pruritis, vascular complications, peripheral neuropathy, ketoacidosis if severe
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Indications of insulin injections
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-Type I DM
-Uncontrolled type II DM -Gestational diabetes -Emergency diabetic ketoacidosis |
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Conditions that require an increase in insulin dosage
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Anything that can cause hyperglycemia
1. Hyperthyroidism 2. Stress (metal, surgery, or injury) 3. Cessation of exercise 4. Increased food intake 5. Drug therapy: estrogens, thiazides, glucocorticoids |
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Insulin aspart
-Onset -Peak -Duration |
-Onset: 15 min.
-Peak: 1-3 hours -Duration: 3-5 hours Rapid and short acting |
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Insulin Glulisine
-Onset -Peak -Duration |
-Onset: less than 15 min.
-Peak: 0.5-2 hours -Duration: 3-5 hours Rapid and short acting |
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Lispro Insulin (Humalog)
-Onset -Peak -Duration |
-Onset: 15 min.
-Peak: 1hour -Duration: 3-6 hours Rapid and short acting |
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Crystalline zinc (Regular)
-Onset -Peak -Duration |
-Onset: 30 min.
-Peak: 1-3 hours -Duration: 6-8 hours Rapid and short acting |
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Characteristics of rapid and short acting insulin preps
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-All clear solutions
-Can use with insulin pump and IV (won't form precipatates) -Insulin aspart, Insulin Glulisine, and Lispro insulin have more rapid onsets and shorter durations, which is more like endogenous insulin release |
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NPH and Lente Insulin
-Onset -Peak -Duration |
-Onset: 1-2 hours
-Peak: 8-10 hours -Duration: 12-16 hours Intermediate acting |
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-Insulin Glargine
-Onset -Peak -Duration |
-Onset: 1-1.5 hours
-Duration: 11-24 hours or longer Long acting |
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Insulin Detemir
-Onset -Peak -Duration |
-Onset: 1-2 hours
-Duration: 12-24 hours Long acting |
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Characteristics of intermediate and long acting preparations
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-Come in suspensions where insulin precipitates out of solution and stays around longer (ex. Insulin Glargine is a soln. at pH4, but when injected, it crystallizes in muscle and causes long lasting effect)
-Can't use with insulin pumps |
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Side effects of injectable insulin preps
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-Hypoglycemia (tired, musle ache, tremor, tachycardia)
-Allergic reactiong (esp. if contains protamine) |
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Premixture injections
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1. 50/50 NPH Insulin and Lispro insulin
2. 75/25 NPH and Lispro insulin 3. 70/30 NPH and insulin aspart |
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Why shouldn't you give Beta blockers to diabetics?
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1. Inhibit B2 stimulation of insulin release
2. Masks symptoms of hypoglycemia by preventing tremors and tachycardia 3. Inhibit Beta effect of increasing gluconeogenesis, which is important in hypoglycemia |
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Sulfonylureas
-MOA |
-Require at least 30% of normal insulin release to work
-Increase the secretion of insulin by binding to receptors near the potassium channel, reducing potassium efflux, and causing greater depolarization and calcium influx. -If taken chronically, reduce serum glucagon and potentiate the effects of insulin |
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Sulfonylureas
-side effects |
-cause more hypoglycemia than other oral agents, esp. in elderly, kidney patients, and liver patients
-Can accumulate in patients with decreased renal function -GI symptoms -muscle weakness -mental confusion |
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Sulfonylurea durations:
1. Tolubutamide (Orinase) 2. Tolazamide (Tolinase) 3. Chlorpropamide (Diabinese) 4. Glyburide (Diabeta) 5. Glipizide (Glucotrol) 6. Glimepiride (Amaryl) |
1. 6-12 hours
2. 10-14 hours 3. up to 60 hours 4. 10-24 hours 5. 10-24 hours 6. 10-24 hours |
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Metformin (Glucaphage)
-MOA |
-Reuqires the presence of insulin to be effective
-Inhibits liver glucose production and increases glucose uptake in insulin sensitive cells -does not effect insulin secretion |
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Metformin
-side effects |
-Does not cause hypoglycemia, and can be taken with sulfonylureas
-metallic taste -GI upset and diarrhea, reduced if take with food -anorexia -Can cause lactic acidosis, esp. if have renal dysfunction |
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Metformin
-contraindications |
-Renal dysfunction of failure
-If have CHF and are on pharmological treatment for it -Hypoxemia -sepsis [because can cause lactic acidosis] |
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Acarbose (Precose)
-MOA |
-inhibit alpha glucosidase, which inhibits hydrolysis of dietary dissacharides and complex carbs
-if taken at the beginning of a meal, delays absorption of glucose and other monosacharrides |
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Acarbose (Precose)
-side effects |
-flatulence, cramp, and diarrhea
-may reduce Fe absorption -does not cause hypoglycemia |
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Miglitol (Glyset)
-MOA |
-inhibit alpha glucosidase, which inhibits hydrolysis of dietary dissacharides and complex carbs
-if taken at the beginning of a meal, delays absorption of glucose and other monosacharrides |
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Miglitol (Glyset)
-side effects |
-flatulence, cramp, and diarrhea
-may reduce Fe absorption -does not cause hypoglycemia |
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Rosiglitazone (Avandia)
-MOA |
-Thiazolidenedione
-Binds PPAR-y receptor and increases trascription of insulin-responsive genes -When given with insulin, or in presence of endogenous insulin, reduses gluconeogenesis and increases glucose uptake |
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Rosiglitazone (Avandia)
-adverse effects |
-Causes fluid retention
-Black box warning: don't give to CHF patients, can cause and worsen CHF -Don't use with liver disease patients; should monitor patient's liver function -Increased risk of hypoglycemia -Causes weight gain |
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Pioglitazone (Actos)
-MOA |
-Thiazolidenedione
-Binds PPAR-y receptor and increases trascription of insulin-responsive genes -When given with insulin, or in presence of endogenous insulin, reduses gluconeogenesis and increases glucose uptake |
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Pioglitazone (Actos)
-adverse effects |
-Causes fluid retention
-Black box warning: don't give to CHF patients, can cause and worsen CHF -Don't use with liver disease patients; should monitor patient's liver function -Increased risk of hypoglycemia -Causes weight gain |
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Repaglinide (Prandin)
-MOA |
-Meglitinide
-similar MOA as sulfonylureas, but more rapid onset and faster acting -Close K+ channels, causing increased Beta cell depolarization |
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Repaglinide (Prandin)
-Side effects |
-less likely to cause hypoglycemia than sulfonylureas
-safer in renal patients |
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Nateglinide (Starlix)
-MOA |
-Meglitinide
-similar MOA as sulfonylureas, but more rapid onset and faster acting -Close K+ channels, causing increased Beta cell depolarization |
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Nateglinide (Starlix)
-side effects |
-less likely to cause hypoglycemia than sulfonylureas
-safer in renal patients |
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Exenatide (Byetta)
-MOA |
-GLP1 agonist injected twice a day with meals
-GLP-1=incretin, released by GI cells to increase glucose dependent insulin secretion -slows gastric emptying -inhibits food intake and weight gain -supresses inappropriate prandial glucagon secretion -Induces Beta cell neogenesis and proliferation while inhibiting apoptosis |
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Exenatide (Byetta)
-side effects |
-nausea
-Increased risk of hypoglycemia when used with sulfonylureas -May redue the absoprtion of other medications (can't take exenatide with meds that need to be taken with food) |
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Sitagliptan (Januvia)
-MOA |
-inhibits dipeptidyl-peptidase 4, which metabolizes GLP-1 and GIP incretins
-increases glucose dependent insulin secretion -slows gastric emptying -decreases inappropriate glucagon release -decrease weight gain and food intake |
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Sitagliptan (Januvia)
-side effects |
-can cause hypoglycemia
-stomach upset |
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Pramlinatide
-MOA |
-injectable amylin analog
-amylin=slows gastric emptying, inhibits food intake and weight gain |
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Pramlinatide
-side effects |
-Hypoglycemia
-GI distress -Need to decrease meal time insulin by 50% |
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non-thyroid related Drugs that induce hypoparathyroidism
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1. Amiodarone and I containing drugs: block 5' deiodinase (and hepatic 5'-iodothyronine monodeiodinase), decreasing the deiodination of T4 to the active T3
2. Lithium: blocks TH synthesis 3. Phenytoin, Rifampin, and Carbamazepine induce the metabolism of TH |
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t1/2 of T3 and T4
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-T3 t1/2=1.5 days
-T4 t1/2=7 days |
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Levothyroxine
-MOA |
-Thyroxine (T4)
-Used to treat hypothyroid |
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Levothyroxine
-Administration |
-Given once a day by pill
-Takes 6-8 weeks to reach steady state levels, so start with low dose and then increase slowly |
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Levothyroxine
-Adverse effects |
-can cause hyperthyroidism
-Enhances oral anticoagulants by increasing the catabolism of Vitamin K-dependent coagulation factors -Reduces serum levels of digitalis glycosides and decreases their therapeutic effect -Amiodarone inhibits levothyroxine's conversion to T3 -Phenytoin, carbamazepine, and rifampin accelerate TH metabolism, requiring larger thyroxine doses |
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Propylthiouracil
-MOA |
-inhibits thyroid peroxidase, preventing organification (attachment of iodide to thyroglobulin molecule)
-also inhibits peripheral deiodinase activity, reducing conversion of T4 to T3 - thiourea used for hyperthyroidism |
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Methimazole
-MOA |
-Inhibits thryoid peroxidase organification
-thiourea used for hyperthyroidism |
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What happens if you miss a dose of methimazole and propylthiouracil?
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-Thioureas don't effect the amount of thyroid hormone already synthesized, and takes 4-6 weeks before stores of T4 are depleted
-If skip one dose, thyroid stores quickly are reformed and will take another 4-6 weeks for the drug to work again |
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Thiourea adverse effects
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-Development of skin rash
-Lupus like symptoms -Agranulocytosis -Prolonged use may cause goiter formation, because decreased T3 and T4 levels increases TSH secretion -May develop resistance and therapeutic failure (can do thyroidectomy or radioidine treatment) |
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Should thioureas be used to treat hyperthyroid in pregnancy?
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-Use only at the minimally effective dose because can cross the placenta and cause fetal hypothyroidism
-Use propylthiouracil because is more strongly protein bound and less readily crosses placenta -Thyroidectomy (not radioiodine treatment) preferred |
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Perchlorate
Pertechnetate Thiocyanate |
-Anion inhibitors, previously used for hyperthyroid
-Inhibit the transport of iodide into the follicular cells because have molecular radii nearly equal to iodide's -Not used anymore because cause fatal aplastic anemia |
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Iodides
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-Inhibit the release of T3 and T4 from thyroid
-Not used for hyperthyroid anymore; instead used to block the accumulation of radioactive iodide by the thyroid followng nuclear power plant accidents and stuff |
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How are Beta blockers used in hyperthyroidism?
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-Useful in first 4-6 weeks of thiourea treatment before they kick in to reduce thyrotoxicosis
-Propanolol |
