Test 2 Endocrine Pharm Of Diabetes

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goals of diabetes tx

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replcement, inhibition, stimulation, augmentation/mimickieng

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insulin stimuli

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glucose, fructose, amino acids, increase cAMP, glp1, secretin cholestikin, acetylcholine

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increased d cells in diavetes

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some evidence

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causes of insulin resistance

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HPL, HGH, decrease dreceptors (obesity down regulates), immune insulin resistance… new syndromes with ancothis nigricans decresased insulin receptor 9young women with amenorrhea and hirsuitism) antibodies to insulin receptors (older patients with sugessitoion of immunologic

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acanthosis nigrigans

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new sydnromes of insulin resistance.. Decreased # of insulin receptor (young women with amenorrhea nd hirsuit ism) and antibodies to insulin receptor (older people with suggessiton of immunoogic disease)

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lispro

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rapid insulin, can be mixed with longer acting, SC IM IV

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aspart

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fewer aggregates than reuglar insulin, absorbed more quickly (like lespro), shorter duration

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rapid insulin preps

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lispro, aspart, glulisine, exubera (regular) semilente (zinc)

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intermediate insulin

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NPH, Lente

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protamine

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slows, lispro aspart and NPH come in protamine suspension

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slow insulin preps

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ultralente, glargine, insulin detemir

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miristic acid

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promotes ablumin binding of detemir

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neutral ph long acting

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detemir

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ppt upon injection

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glargine acid ph

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generex oral lyn

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oral insulin… no pulmonary side effects

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adverse rx to insulin

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hypoglycemia most common, immune/allergic (includes humulin insulins; switich to another species may help) atrophy of subuctaneous fat (insulin lipoatrophy-rare)

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usual 1st dose of insulin

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10 units if nonketotic

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doses in insulin resitance… much higher, may be inexcess of 500 units

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DKA tx

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close motoring, insulin at 2-10 units/hr. Fluid therapy

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total dose of modified insulin is

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equal to 80% of the dose of regular insulin in a day

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maintsay of insulin regimens

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1 injection pre breakfast

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persistance of moring glycosuria

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fast acting insulin needed in am

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persistance of nocturnal glycosuria

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long acting insulin

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tight control of glucose achieved with

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combinations, dietary vigilance, insulin pumps/inhalers, multiple insulin injections (3 or more per day)

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sulfonylura

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inhibit atp sensitive k channel ad stimulate insulin secretion

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symlin

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meltime glucose control, analog of human amylin

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tolbutamide

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1st gen sulfonylurea inhibits atp k channel

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acetohexamine

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1st gen sulfonylurea inhibits atp k channel

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tolazamide

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1st gen sulfonylurea inhibits atp k channel

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chlorpropamide

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1st gen sulfonylurea inhibits atp k channel

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glipizide

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2nd gen sulfonylrurea

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glyburide

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2nd gen sulfonylrurea

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glymepiride

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2nd gen sulfonylrurea

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advantages of 2nd gen sulfonylureas

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high potency f ree water diures,s inactive emtabolites, non ionic binding, no alcohol flusing, more insulin sparing

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moa sulfonylureas

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primary… k channel blcok augmetnts glucose induced insulin secretion; increases glucose transporter in insulin adipocytes; increases intracellular soring of insulin recepto complex

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insulin sparing

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sulfonylureas… since glucose augments action of agents they are most effective after meals

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use of sulfonlureas

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monotherapy or with metformin or alpha glucosidease inhibitors that do not act on beta cells

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drugs that antagonize sulfonylureas

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corticosteroids, thiazide and furosemide diuteics, oral contraceptive

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corticosteroids

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inhibit insuline secretion and enhace glucose mobilizzation

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thiazide and fuorsemide digurets

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interfere with insulin response of tissue

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non hypoglycemia effects of sulfonylureas

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cardiovascular, ionotropic action, increased automatisity, hypertensive effects; antidiuretic effect- chlorpropamide especially in instancesof vasopresssin insufficiency or dehydration; not usually in helathy individual

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toxic reactions of sulfonylureas

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hematologic (leukopenia, hemolytic anemia) cutatneous, rashes photosensitive; gastro intestinal (nausea vomiting jaundice)

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alcohol and diabetis

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acute use enhances hypoglycemia by supressing gluconeogensis… chorin inhibits hypoglycemic effect due to enhaced metabolism of sulphureas in the liver

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aspirin

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blocks gluconeogenis (uncouples oxhos in high doses) and enhances glucose uptake by the liver…. Interferse with uriniary excertion of chlorpropamide

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meglitide

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repaglinide

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repaglinide

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binds atp sensitive k channel different from sulfonylurea but same MOA

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advantavges of repaglinide

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LOW RATE OF HYPOGLYCEMIA, rapid onset short duration of action

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dephylalaine

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Nateglinide

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Nateglinide

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inhibits atp sensitive K channels (aa derivitive Dephellalanine)

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restores early insulin secretion and increase stotal insulin secretion

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nateglinide

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biguanide

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metromin

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metformin moa

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antihyperglycimic not hypoglycemic… activates AMP kinase, reducies hepatic gluconeogeniss, increases glucose uptake by muscle, mproves insulin sensitivity

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excessive alcohol intake and metformin

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causes lactic acidosis and hypoxemia and heart failure aand shock

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hepatic failure or surgery and metformin

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stop metformin

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thiazolidenodies

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oral hypoglcyimic sorta antihyper

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rosigltiazone

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thiazolidenedione

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pioglitaone

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thiazolidendione

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troglitazone

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thiazolidenedions (inducees P45O only thiaz to do so has hepatotoxic effects

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rosiglitazone side

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cardiovascular risk increased

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moa thiazolidenedionse

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reduces insulin resistance, increase insulin sensitivity (require insulin) potent PPAR gamma ligan that increasese gene for carb and lipid metabolism, induces adipocyte differentiation, inhibits cell growht and migration in vascular smooth muscle

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triple therapy

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metformin and sulfonylurea or glinide and pioglitazone

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thiazolinded precation

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not for pregnancy or breast feeding, hypoglycemia with other oral hypoglycemic agents, edema, anemia, ovulation, weight gain, fractures cardio vascular risk (rosiglitazone

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sulfonylurae

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greater risk of develpoing CHF

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increased risk of all cause death

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sulfonylurear montharpy

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lower risk of all cause mortality than metformin

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pioglitazone

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oral contraceptive not 99% effective

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pioglitazone/trogliaone (thiazolidenediones)

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alpha glucosides inhibitos

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antihyperglycimic acarbose and glyset

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acarbose

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alphaglucosidase inhibitor

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glyset

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alphaglucosidase inhibitor

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moa alpha glucosidase inhibitor

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delay and reduce uptake of carbohydrates… competitive and reversivle inhibition of enzymatic digestion of carbohydrates… since glucose absorption not affected drug is benifical in patients on a starch high fiber diet with restriced glucose and sucrose

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contraindicated in kidey dysfunction

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glyset

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flatulence/abdominal pain

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acarbose

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used in type 2DM ans mono or combo and in typ 1 with insulin

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acarbose

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dipeptidyl peptidase IV inhibitors

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sitagliptin, vildagliptin, saxagliptin (januvia is sitagliptin)

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sitaglipint

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oral drugs that inhibit dipeptidyl peptidase

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vildagliptin

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oral drugs that inhibit dipeptidyl peptidase

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saxagliptin

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oral drugs that inhibit dipeptidyl peptidase

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DPP IV

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membrane bound circulating serine protease… casuese early inactition of GLP-1 and GIP that potentiat glucse indused insulin secretion the dipeptyl petdiase inihibtors sitagliptin, vildagliptin… thus lenghten thes insulin secretion

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advantage of januvia/sitaglipitn

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patients do not gain weight or have water retention

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use of januvia

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initial therapy with metformin or add on to sulfonulureaor both

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emergency tx of hypglcymeia

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glucagon

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exenatide

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similar sequence to GLP1… stimulates insulin secretion by increase cAMP in B cell

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1st drug to lower LDL cholesterol while improving glycemic control

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colesevelam HCL a bile acid sequestrant polymer

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when to use colesevelam

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combo drug lowers FPG

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somatostatin

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lowers glucose in IDDM, investigational may supress glucagon

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vandates

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trace eliment with insulin like activity.. Investigational

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hyperglycemic agens

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sterptozotocin, diazoxide alloxan

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streptozotocin

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destroys islet beta cells by alkylating bases in dna

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diazoxide

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opens atp dependent K chanles

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alloxan

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inhibits glucose interaction with beta cel lglucokinase