Drugs in diabetes

BYDr.V.Padma,

Associate professor of Medicine,Shree Balaji Medical College,Chrompet,Chennai.

OBJECTIVESAt the end of the class the student should be

able to identify which antidiabetic drug is indicated in different type of diabetes.

Common side effects of antidiabetic drugs.

CLASSIFICATIONType 1 DMType 2 DMOther specific types of diabetes Genetic defects Exocrine pancreatic diseases Endocrinopathies Drug or chemical induced,Infections.Gestational diabetes mellitus

TREATMENTType 1 DM → InsulinGDM → Insulin

Type 2 DM -Diet -Exercise -Medication -Oral hypoglycemic

drugs,Insulin.

GLUCOSE LOWERING THERAPIES FOR TYPE 2 DIABETES

ORAL: -BIGUANIDES -ALPHA GLUCOSIDASE INHIBITORS -DIPEPTIDYL PEPTIDASE 4 INHIBITORS -INSULIN SECRETAGOGUES-

Sulphonylureas,non sulphonylureas -THIZOLIDINE DIONESPARENTERAL-INSULIN,GLP-1 agonists, Amylin

agonists. MEDICAL NUTRITIONAL THERAPY

MEDICAL NUTRITION THERAPY AND PHYSICAL ACTIVITY Mechanism of action Decreased insulin resistance,increased insulin secretion

EXAMPLE Low calorie,low fat diet,exercise

A1C Reduction 1-2%

Specific advantages Other health benefits

Specific disadvantages

Compliance difficult,long term success low

Contra indications

DOSAGE

BIGUANIDESMECHANISM OF ACTION

Decreased hepatic glucose production,weight loss,improves peripheral glucose utilization,insulin resistance

EXAMPLE Metformin

A1C Reduction 1-2%

Specific advantages Weight loss


Lactic acidosis,nausea,diarrhoea.

Contra indications Sr. creatinine>1.5mg/dl,CHF,radiographic contrast studies,seriously ill patients,acidosis.

DOSAGE 500-1000MG BID

ALPHA GLUCOSIDASE INHIBITORSMechanism of action Decreased glucose absorption-by inhibiting the enzyme that

cleaves oligosaccharides into simple sugars in intestinal lumen. EXAMPLE Acarbose,miglitol,voglibose

A1C Reduction 0.5-0.8%

Specific advantages Reduces post prandial glycemia.


GI flatulence,diarrhoea,abdominal distension-increased delivery of oligosaccharides to large bowel

Contra indications Renal or liver disease,pt with inflamatory bowel disease,gastroparesis,cr>2 mg%,avoid cotreatment with antacids,bile acid resins.

DOSAGE Acarbose,Miglitol-25-50mg,Voglibose-0.2-0.3mg.

THIAZOLIDINEDIONESMechanism of action Increased glucose utilization,decreased insulin resistance

Binds to PPAR G nuclear receptor,-promote adiposite differentiation,reduces hepatic fat,reduces insulin resistance-increases FA storage and increases adiponectin levels,induces ovulation in premenopausal with PCOS.

EXAMPLE pioglitazone


Specific advantages Lower insulin requirements


Weight gain,peripheral edema,CHF,fractures,macular edema,rosi increases risk of MI.

Contra indications CHF,liver failure

DOSAGE PIO-15-45MG,

DIPEPTIDYL PEPTIDASE 4 INHIBITORSMechanism of action Prolongs endogenous GLP-1 action

EXAMPLE Sitagliptin,vildagliptin

A1C Reduction 0.5-1%

Specific advantages No hypoglycemia

Specific disadvantagesContra indications Reduce dose with renal disease

DOSAGE 100 mg daily

SULFONYLUREASMechanism of action Increases insulin secretion by interacting with ATP- sensitive

potassium channel on the beta cellEXAMPLE Glimepride,gliclazide,glibenclamide

A1C Reduction 1-2 %

Specific advantages Lower fasting blood glucose


Hypoglycemia,weight gain

Contra indications Renal/liver disease

DOSAGE Glibenclamide,glipizide-2.5-10mg,glimepride-1-4mg,gliclazide-40-120mg

NON SULFONYL UREAS

Mechanism of action Increases insulin secretion by interacting with ATP-sensitive K channel

EXAMPLE Repaglinide,nateglinide

A1C Reduction 1-2%

Specific advantages Short onset of action,lowers PP glucose


hypoglycemia

Contra indications Renal/liver disease

DOSAGE Repa-0.5-16mg,nate-180-360mg

GLP-1 AGONISTSMechanism of action Increase insulin,decreased glucagon,slow gastric emptying

EXAMPLE exenatide

A1C Reduction 0.5-1mg%

Specific advantages Weight loss


Injection,nausea,increased risk of hypoglycemia with secretogogues

Contra indications Renal disease,agents that slow GI motility

DOSAGE 5microgm sc bid-10 microgm bid

AMYLIN AGONISTMechanism of action Slow gastric emptying,decreased glucagon,does not alter

insulin levelEXAMPLE pramlintide


Specific advantages Reduced postprandial glycemia,weight loss


Injection,nausea,increased hypoglycemia with insulin

Contra indications Agents that slow GI motility

DOSAGE 15microgm sc before each meal-upto60 in type 1-120 micro gm in type 2 DM .

INSULINMechanism of action Increased glucose utilization and other anabolic actions

EXAMPLE Regular,NPH,analogues

A1C Reduction No limit

Specific advantages Known safety profile


Injection,weight gain, hypoglycemia

Contra indications nil

DOSAGE According to requirement

PATIENT WITH TYPE 2 DIABETES

MNT,INCREASED PHYSICAL ACTIVITY,METFORMIN

REASSESS A1C

COMBINATION THERAPY,METFORMIN+OTHER AGENTS

REASSESS A1C

COMBINATION THERAPYMETFORMIN+2 OTHER AGENTS REASSESS A1C INSULIN+MET

SUMMARYInsulin is indicated in gestational

diabetes,Type 1 DM,Chronic kidney disease,medical or surgical emergencies.

Post prandial hyperglycemia is treated by acarbose,non sulphonylureas and amylin agonists,short acting insulins.

Serious complication of metformin is lactic acidosis.

Fasting hyperglycemia is treated by biguanides and sulphonylureas.

SUMMARYMetformin,amylin agonists, GLP1 agonsts

cause weight loss.Sulphonylureas,pioglitazone and insulin

causes weight gain.Pioglitazone causes fat redistribution and

thus reduces fatty liver,but causes weight gain,increased risk of fractures and aggravates cardiac failure.

Metformin and pioglitazone reduces insulin resistance.

1 MCQWhich antidiabetic causes weight loss1)metformin2)glibenclamide3)pioglitazone4)insulin

2 MCQAntidiabetic drug which induces ovulation in

polycystic ovarian disease1)sulphonyl ureas2)insulin3)metformin4)acarbose

3 MCQDrug of choice in gestational diabetes

mellitus is1)pioglitazone2)insulin3)amylin agonists4)glimepride

4 MCQ Which drug reduces postprandial

hyperglycemia1)glimepride2)metformin3)acarbose4)pioglitazone

5 MCQWhich antidiabetic drug is safe in chronic

kidney disease1)metformin2)gibenclamide3)pioglitazone4)insulin

PHARMACOKINETICSPREPARATION ONSET

hrsPEAK, hrs

DURATIONhrs

75/25-75%protamine lispro,25%lispro70/30-70%protamine aspart,30%aspart50/50-50%protamine lispro,50%lispro70/30-70%NPH,30%regular insulin50/50-50%NPH,50%reg

<0.25

<0.25

<0.25

0.5-10.5-1

1.5

1.5

1.5

Dual

dual

10-16

10-16

10-16

10-1610-16

Myristicacid

LysDetemir

ArgThrLysProGlyGlargine

ThrGluProLysAsnGlulisine

ThrProLysAsnLispro

ThrLysAsparticacid

AsnAspart

ThrLysProAsnAsnHuman

B31 AndB32

B30B29B28B3A21Source/Type

B- chain PositionA-chain

Position

Amino Acid Substitutons

Myristicacid

LysDetemir

ArgThrLysProGlyGlargine

ThrGluProLysAsnGlulisine

ThrProLysAsnLispro

ThrLysAsparticacid

AsnAspart

ThrLysProAsnAsnHuman

B31 AndB32

B30B29B28B3A21Source/Type

B- chain PositionA-chain

Position

Amino Acid Substitutons

GUIDELINES-CARE OF DMSelf monitoring of blood glucoseA1C testing-2-4 times/yearDiabetic education-annualMNT and education-annualEye examination-annualFoot examination-1-2 times/year by

physician,daily by patientDM nephropathy screening-annualBP measurement-quarterlyLipid profile,sr.creatinine-annualInfluenza,pneumococcal vaccinationsAntiplatelet therapy

PREPARATION ONSET,Hrs PEAK,Hrs Duration,hrSHORT ACTING,SCLISPRO,GLULISINEASPARTREGULAR

<0.25

0.5-1.0

0.5-1.5

2-3

3-4

4-6

SHORT ACTING,INHALED regular

<0.25 0.5-1.5 4-6

LONG ACTINGNPHDETEMERGLARGINE

1-41-41-4

6-10MIN 6-14HMIN PEAK

10-1612-2024

PHARMACOKINETICS

Drugs in diabetes

Health & Medicine

Transcript of Drugs in diabetes