Walters-Insulin and Oral Hypoglycemic Agents-karsi

8/8/2019 Walters-Insulin and Oral Hypoglycemic Agents-karsi

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INSULIN AND ORALINSULIN AND ORAL

HYPOGLYCEMIC AGENTSHYPOGLYCEMIC AGENTSCitation: Dr. Walters note packet Citation: Dr. Walters note packet



What is the cause of IDDM?What is the cause of IDDM? A. Degeneration of beta cells in islets from A. Degeneration of beta cells in islets fromautoauto--antibodies to beta cells, insulin, or enzymesantibodies to beta cells, insulin, or enzymesin insulin synthesisin insulin synthesisB. Genetic deficiency in enzymes in theB. Genetic deficiency in enzymes in thesynthesis of insulinsynthesis of insulinWhat is the cause of NIDDM?What is the cause of NIDDM?Insulin resistance due to one of the following:Insulin resistance due to one of the following:1. decr number of receptors in target tissue1. decr number of receptors in target tissue

2. post receptor resistance/dysfunction2. post receptor resistance/dysfunction3. incr IgG against insulin or receptor3. incr IgG against insulin or receptorWhat is acanthosis nigricans?What is acanthosis nigricans?IgG against receptorIgG against receptor



What is the mech of action of insulin?What is the mech of action of insulin?

1. translocation of glut 1. translocation of glut- -4 glucose4 glucosetransportertransporter2. activate glycogen synthase2. activate glycogen synthase3. inhibit glycogen phosphorylase3. inhibit glycogen phosphorylaseWhat are 5 other effects of insulin?What are 5 other effects of insulin?1. decr gluconeogenesis1. decr gluconeogenesis2. incr fatty acid uptake2. incr fatty acid uptake3. decr lipolysis3. decr lipolysis4. incr protein synthesis4. incr protein synthesis5. decr proteolysis5. decr proteolysis



Insulin Products (human):Insulin Products (human):What is the rapid acting insulin, and the only one that What is the rapid acting insulin, and the only one that can be given IV?can be given IV?Regular InsulinRegular InsulinWhat Rx is used in tx insulin resistance?What Rx is used in tx insulin resistance?Humulin R Regular UHumulin R Regular U- -500500

Ultra Rapid Acting:Ultra Rapid Acting:What Rx has the lysine & proline positions reversed onWhat Rx has the lysine & proline positions reversed onthe beta chainthe beta chain what is the purpose of this?what is the purpose of this?

Insulin LisproInsulin Lispro decr formation of insulin complexesdecr formation of insulin complexesspeeds onset speeds onset What Rx is the shortest acting and has an aspratic acidWhat Rx is the shortest acting and has an aspratic acidin place of a proline?in place of a proline?Insulin Aspart Insulin Aspart



Intermediate Acting:Intermediate Acting:What does NPH stand for, and what is its other name?What does NPH stand for, and what is its other name?

Neutral (neutral pH)Neutral (neutral pH)Protamine (basic protein, binds insulin, releases insulinProtamine (basic protein, binds insulin, releases insulinslowly, extended duration of action)slowly, extended duration of action)Hagedorn (inventor)Hagedorn (inventor)Other name = Isophane Insulin SuspensionOther name = Isophane Insulin Suspension

Isophane = all binding sites on protamine are takenIsophane = all binding sites on protamine are takenWhat Rx is AKA Insulin Zinc Suspension?What Rx is AKA Insulin Zinc Suspension?LenteLente

Lente: slow onset of actionLente: slow onset of actionZinc: to stabilizeZinc: to stabilize

Semilente: few small particlesSemilente: few small particles rapid onset rapid onset Ultralente: lot of large crystalsUltralente: lot of large crystals slower onset, but slower onset, but longer actinglonger acting



Long Acting:Long Acting:What Rx has a glycine in place of asparagine in theWhat Rx has a glycine in place of asparagine in thealpha chain, as well as 2 arginines added to the Calpha chain, as well as 2 arginines added to the Cterminus of the beta chain?terminus of the beta chain?Insulin GlargineInsulin GlargineWhat Rx is extended insulin zinc?What Rx is extended insulin zinc?UltralenteUltralente

What are side effects of insulin?What are side effects of insulin?1. hypoglycemia1. hypoglycemia LOC, convulsions, brain damage,LOC, convulsions, brain damage,deathdeath2. Somogyi effect = morning hyperglycemia following2. Somogyi effect = morning hyperglycemia followingnocturnal hypoglycemianocturnal hypoglycemia3. insulin coma3. insulin coma what is the cause and tx?what is the cause and tx?

OD, glucoseOD, glucose4. diabetic coma4. diabetic coma ketoacidosis, electrolyte imbalance,ketoacidosis, electrolyte imbalance,dehydrationdehydration cause and tx?cause and tx?

Insulin deficit, insulinInsulin deficit, insulin



What Rx enhances the effects of insulin (hypoglycemicWhat Rx enhances the effects of insulin (hypoglycemiceffects) and how?effects) and how?Beta blockersBeta blockers block effects of catecholamines onblock effects of catecholamines onglycogenolysis and gluconeogenesisglycogenolysis and gluconeogenesis hypoglycemiahypoglycemiaRxs that antagonize effects of insulin (hyperglycemicRxs that antagonize effects of insulin (hyperglycemiceffects):effects):What Rx stimulates alpha 2 receptors in the islets,What Rx stimulates alpha 2 receptors in the islets,

therefore inhibits insulin release?therefore inhibits insulin release?ClonidineClonidineWhat Rx decr insulin secretion by depleting K+?What Rx decr insulin secretion by depleting K+?Diuretics (thiazides): deplete K+Diuretics (thiazides): deplete K+ hyperpol beta cellshyperpol beta cellsinhibit Ca++ influxinhibit Ca++ influx inhibit insulin releaseinhibit insulin releaseWhat Rx increases gluconeogenesis?What Rx increases gluconeogenesis?GlucocorticoidsGlucocorticoidsTwo other Rxs that antagonize insulin effects?Two other Rxs that antagonize insulin effects?Beta 2 agonists, Ca++ channel blockersBeta 2 agonists, Ca++ channel blockers



Sulfonylureas:Sulfonylureas:Mech?Mech?

A. Block K+ channels A. Block K+ channels depoldepol Ca++ channelsCa++ channelsopenopen insulin (this effect is glucose dependent)insulin (this effect is glucose dependent)B. Release somatostatin (inhibits insulin release,B. Release somatostatin (inhibits insulin release,auto off mech)auto off mech)What can happen in hepatic/renal insufficiency?What can happen in hepatic/renal insufficiency?Hypoglycemia b/c metabolized by liver, excretedHypoglycemia b/c metabolized by liver, excretedby kidney, therefore insufficiencyby kidney, therefore insufficiency accumulationaccumulation

hypoglycemiahypoglycemiaDo they cross the placenta?Do they cross the placenta?

Yes, and they are teratogenic Yes, and they are teratogenicWell absorbed orally, food decr absorptionWell absorbed orally, food decr absorptionHighly protein bound, Rx interactions based onHighly protein bound, Rx interactions based ondisplacement displacement



How can sulfonylureas cause a disulfiram reaction?How can sulfonylureas cause a disulfiram reaction?By inhibiting aldehyde dehydrogenaseBy inhibiting aldehyde dehydrogenase incr acetaldehydeincr acetaldehydeflushing, tachy, hyperventilationflushing, tachy, hyperventilationCan cause Syndrome of Inappropriate ADH secretionCan cause Syndrome of Inappropriate ADH secretion H2OH2Oretention, dilutional hyponatremiaretention, dilutional hyponatremia

11st st generation sulfonlyureas:generation sulfonlyureas:What Rx is avoided in elderly?What Rx is avoided in elderly?ChlorpropamideChlorpropamide

What Rx has metabolite more active than parent?What Rx has metabolite more active than parent? Acetohexamide AcetohexamideWhat Rx has metabolite less potent than parent?What Rx has metabolite less potent than parent?TolazamideTolazamideWhat Rx is safest for elderly, why?What Rx is safest for elderly, why?TolbutamideTolbutamide shortest actingshortest actingWhat Rx has highest incidence of disulfiram reaction & SIADH?What Rx has highest incidence of disulfiram reaction & SIADH?ChlorpropamideChlorpropamideWhat Rx has an incr in number of deaths from CV dz compared toWhat Rx has an incr in number of deaths from CV dz compared toinsulin or placebo?insulin or placebo?TolbutamideTolbutamide



22ndnd generation sulfonylureas (more potent thangeneration sulfonylureas (more potent than11st st generation):generation):

What Rxs make Glucovance?What Rxs make Glucovance?Glyburide + metforminGlyburide + metforminWhat Rxs make Metaglip?What Rxs make Metaglip?Glipizide + metforminGlipizide + metforminWhat Rx is most potent and long acting?What Rx is most potent and long acting?GlimepirideGlimepirideWhat Rx is less likely to cause hypoglycemia?What Rx is less likely to cause hypoglycemia?

GlipizideGlipizide b/c shortest t ½b/c shortest t ½What Rx is not used in liver dz?What Rx is not used in liver dz?GlipizideGlipizide b/c 90% metabolized by liverb/c 90% metabolized by liver



Biguanide:Biguanide:What Rx is a euglycemic agent?What Rx is a euglycemic agent?MetforminMetformin does not stimulate insulin release or causedoes not stimulate insulin release or causehypoglycemiahypoglycemiaMech?Mech?1. inhibits gluconeogenesis1. inhibits gluconeogenesis2. stimulates glycolysis2. stimulates glycolysis3. decr LDL, incr HDL3. decr LDL, incr HDL

Advantage? Advantage?Does not cause wt gainDoes not cause wt gainS.E.?S.E.?

Fatal lactic acidosis, N, diarrhea, abdominal discomfort,Fatal lactic acidosis, N, diarrhea, abdominal discomfort,metallic taste, anorexiametallic taste, anorexiaChronic use leads toChronic use leads toDecr abs of vitamin B12Decr abs of vitamin B12



Meglitinides:Meglitinides:Mech?Mech?

A. Block K+ channels A. Block K+ channels depoldepol Ca++ channels openCa++ channels openinsulininsulinB. Release somatostatinB. Release somatostatinWhat Rx can be taken immediately before meals?What Rx can be taken immediately before meals?NateglinideNateglinide

What Rx is taken 15What Rx is taken 15- -30 min before meals?30 min before meals?RepaglinideRepaglinide Alpha Alpha--glucosidase inhibitors:glucosidase inhibitors: Acarbose, Miglitol Acarbose, MiglitolMech?Mech?

Inhibits alphaInhibits alpha- -glucosidaseglucosidase slow incr in glucose afterslow incr in glucose aftermealmealS.E.?S.E.?Flatulence, diarrhea, abdominal crampsFlatulence, diarrhea, abdominal cramps



Thiazolidinediones:Thiazolidinediones:Euglycemic agentsEuglycemic agentsMonitor liver fxn, do not use of decr liver fxnMonitor liver fxn, do not use of decr liver fxnRosiglitazone,Rosiglitazone,PioglitazonePioglitazoneMech?Mech?

Stimulate peroxisome proliferator activatedStimulate peroxisome proliferator activatedreceptorc(PPAR) gamma, which regulates transcriptionreceptorc(PPAR) gamma, which regulates transcriptionof genes that code for enzymes in carbohydrate and lipidof genes that code for enzymes in carbohydrate and lipidmetabolismmetabolismResult?Result?

A. Incr glycolysis A. Incr glycolysisB. Decr gluconeogenesisB. Decr gluconeogenesis

Advantage, disadvantage: Advantage, disadvantage:Incr HDL, incr LDLIncr HDL, incr LDL



Rxs to elevate blood glucose:Rxs to elevate blood glucose:What Rx is normally released from alpha cells of What Rx is normally released from alpha cells of pancreas in response to low blood sugar?pancreas in response to low blood sugar?GlucagonGlucagon stimulates gluconeogenesis & glycogenolysisstimulates gluconeogenesis & glycogenolysisUses:Uses:

A. Decr GI motility for radiological exams A. Decr GI motility for radiological examsB. Tx severe hypoglycemiaB. Tx severe hypoglycemiaC. Tx OD of betaC. Tx OD of beta--blockerblockerWhat Rx is also used to tx hypertensive emergencies?What Rx is also used to tx hypertensive emergencies?DiazoxideDiazoxide mech?mech?

Prevents closing of K+ channels in beta cellsPrevents closing of K+ channels in beta cells K+ effluxK+ effluxhyperpolhyperpol decr insulin releasedecr insulin release incr plasma glucoseincr plasma glucoseS.E.?S.E.?Na+/H2O retentionNa+/H2O retention

What is the other Rx that elevates blood glucose?What is the other Rx that elevates blood glucose?glucoseglucose

Walters-Insulin and Oral Hypoglycemic Agents-karsi

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