Anti Diabetic Drugs/pharm

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insulin secretion is stimulated by

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glucose
amino acids
GI hormones

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rapid acting insulins are(don't form hexamers)

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insulin Lispro
insulin Aspart
insulin Glulisine

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native insulin monomers are

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associated as hexamers

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short acting insulins are

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regular insulin (soulble crytalline zinc insulin)

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intermediate acting insulins are

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semilente insulin
isophane insulin
lente insulin

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also called as neutral protamine hagedorn(NPH)

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isophane insulin suspension.

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long acting insulins

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ultralente insulin
protamine zinc insulin suspension
insulin glargine
insulin detemir

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what does insulin regemins use

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long acting insulins to provide basal levels and rapid acting to meet the meal time requirements.

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insulin regimens

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two shots of intermediate acting insulin(NPH or lente) and short acting insulin(Lispro, aspart or regular)

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multiple component regimen

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one shot of GLARGINE at bedtime and three shots of LISPRO or ASPART to cover meal times

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countinous SC insulin infusion

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lispro or aspart

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Adverse reactions of insulin

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hypoglycemia
allergic reactions
lipodystrophy

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safest sulfonylurea for use in elderly diabeteics

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tolbutamide

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what are the first generation sulfonylurea

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tolbutamide
chlorpropamide

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containdicated in elderly patinetrs

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chlorpropamide

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second generation sulfonylureas: should be used caution in patients with CV disease or in elderly patinets in whome hypoglycemia would be dangerous

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glyburide
glipizide
glimepride

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meglitinides

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repaglinide
nateglinide

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post prandial glucose regulators

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meglitinides:repaglinide
nateglinide

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biguanides

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metformin

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unlike insulin secretagogues decreases body weight

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metformin

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only hypoglycemic agent ashown to reduce macrovascular events in DM tyoe 2

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metformin

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first line of agent in type 2 DM

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metformin

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pot fetal risk of lactic acidosis

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metformin

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thiazolidinediones

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pioglitazone
rosiglitazone

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CI in parinets with class III or IV heart failure

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thiazolidinediones

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ligands of peroxisome proliferation activated receptors

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thiazolidinediones

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alpha glucosidase inhibitors

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acarbose
miglitol

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analog of glucagon like polypeptide1 (GLP-1)

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exenatide: from the salivary gland og glia monster

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resistent to dipeptidyl peptidase IV

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exenatide

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full agonists at human GLP1 receptors

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exenatide

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selective inhibitor of DPP-IV

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sitagliptin

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analog of amylin

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pramlintide

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bile acid used to lower LDL and is approved for DM type IV

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colesvelan

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insulin is inactivated by

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insulinase: found in liver (60% clears blood) and kidney(35-40% clears insulin). But in patients with SC injections this ration is reversed.

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insulin receptors

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mainly in liver
muscle
adipose tissue

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differs from regular insulin at lysine and proline at 28 and 29 in the B chain are reversed. Also has a low propensity to form hexamers

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insulin Lispro

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sunstitution of the B 28 proline by an aspartate

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insulin aspart

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replacement of asparagine by lysine at B3 anod lysine by glutamate at B29

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insulin Glulisine

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safely used in pregnancy

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regular insulin : souble crystalline zinc insulin

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Two arginine residues are added to the C terminus of the B chain and an asparagien residue in position A21 of the A chain is replaced by glycine

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insulin Glargine

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soulble in acidic PH but PPT in neutral PH after SC injection.

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insulin Glargine

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terminal threonine is removed from the B30 position and myristate is attached to terminal B29 lysine

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insulin Detemir

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other drugs that cause hypoglycemia

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ethanol(inhibits gluconeogenisis)
B blockers (block effect of catecholamines on gluconeogenesis and block the symphatatic symptoms of hypoglycemia)
salicylates(enhances pancreatic B cell sensitivity to glucose and potentiates insul;in secreation)

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dosage excess of 500 mg daily increase the risk of jaundice

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chlorpropamide

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noncompetitive inhiobitor of aldehyde dehydrogenase and results in hyperemic flush with alcoho;l

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chlorpropamide

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causes hyponatremia

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chlorpropamide

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approved as a monotherapy or in combination with metformin and thiazolidinediones

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repaglinide

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decreases glucose production by inhibiting gluconeogeneisis and increases insulin action in muscle and fat

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metformin

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assocaited with decrease in weight

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metformin

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also used in PCOS

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metformin

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best treatment for PCOS

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clomiphene

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use of rosiglitazone with ehat is nogt recommended

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nitrates, they can aslo aggrevate cingestive heart failure in soem patients

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severe hepatic toxicity

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troglitazone

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alpah glucosidases are

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sucrases, maltase, glycoamylase, and dextranase

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most common initial combination used in management of type II diabetes

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sulfony;urea and metformin

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insulin lispro and aspart

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category B drugs in preg

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metformin

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cata B

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sulfonylureas

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catagory C except glyburide which is category B

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glucagon causes

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insulin release fromB cells
catecholamines from phechromocytoma
calcitonin from medullary carcinoam cells

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indicate B cell s secretion

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mesurnment of C peptide

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glucagon is also useful for reversing cardiac effects

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of an overdose B blocekrs as it increases cAMP in the heart.

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half life of circulating insulin

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3-5 min

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insulin receptors bind insulin with

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high specificity and affinity in a picomolar range

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insulin receptor

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2 covalently linked hetrodimers(alpha (extracellular)) and Beta which spans the membrane.

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caontain tyrosine kinase

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beta subunit

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first proteins needs to be phosphorelated are

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insulin receptor substrate proteins(IRS)

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insulin increases what in muscle and adipose tissue

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GLUT4 glucose transporters in the cell membrane thus helping them to take more glucose.

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how does insulin increase glucose in the liver

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by induces the biosynthesis of glucokinase and thus increases the phosphorylation of glucose as that the intacellular glucose is low in con and thus faciolitates the entry of glucose into the cells of liver.

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insulin innibits

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hormone sensitive lipase in adipoose tissue and thus decreases the level of circulating fatty acids. But it increases the syn of fatty acids and TAGS and their storage in the in the adipose tissue.

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insulin when taken orally

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is degraded so SC injections are given

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use of lispro, aspart and glulisine in pregnancy

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is advised only if clearly needed.

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it achieves the blood glucose lowering with the lowest dose of any sulfonlyurea compound.

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gimepiride: 2nd generation sulfonylureas

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causes hypoglycemia in only 2-4% in 2nd generation sulfonlyurea compound

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gimepiride: 2nd generation sulfonylureas

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shortest half life in 2nd generation sulfonylureasn

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glipizide

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hypoglycemia in 20-30% of patients in2nd generation sulfonylureas

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glyburide

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co adminstration of rosiglitazone(thiazolidinediones)insulin sensitizers and insulin

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not recommended as it increases incidence of edema.

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in the absence of contraindication which is choice of antidiabetic drug

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metformin

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weight gain and hypoglycemia

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sulfonylurea