Insulin and oral hypoglycemic drugs short.ppt

Insulin and oral hypoglycemic drugs short.ppt

2. Diabetes Mellitus (DM)
Diabetesmellitusmeanssweeturine
Def:Ametabolicdisordercharacterizedby
hyperglyceamiaandglucosuriaresultedfrom
partialorcompleteinsulininsufficiency
Classification of diabetes:
1-TypeIdiabetes:InsulinDependentDM(IDDM)
thebodyproducesnoinsulin.
2-TypeIIdiabetes:NonInsulinDependentDM
(NIDDM;Insulinisnotsufficienttometbodyneeds)
3-GestationalDiabetesMellitus(GDM)
4-Otherrelativelycommon formsofinsulin
resistancesuchasinwomenwithpolycystic
ovariansyndrome,wilsondisorder.

4. Treatment:
Type 1 diabetics:
Treatedbyexogenous(injected)insulintocontrolhyperglycemia
andavoidketoacidosis.
Someoralhypoglycemicscouldbeusedasadjuncttherapy
Pramlintideasyntheticanalogofamylin,maybeusedasan
adjuncttoinsulintherapy

5. TreatmentforTypeIIDiabetesmellitus:
1.Initsearlieststages,TypeIIdiabetescanoftenbecontrolled
effectivelybybecomingmoreactive,modestweightloss,
andbymanagingfood(controllingcarbohydrateintake
throughtheday).
2.Whenthediseasehasprogressed:severaltypesoforal
medications(seelater)and/orinsulinmaybeusedsingly
orincombination

6. INSULIN and its analogues
Absorption, metabolism, and excretion
Taken by injections
Plasma half life is less than 10 minutes.
Hepaticinsulinasesdestroyapproximately50%ofcirculating
insulin,withtheremainderdegradedbycirculatingproteases.
InsulinPreparationsaccordingtosource
Three Sources:
1.Beef 2. Pork 3. Human
Differprimarilyintheironsetanddurationofactionand
incidenceofallergicreaction.
HumaninsulinisproducedbyrecombinantDNAtechnology

7. Insulin Preparations according to
onset and duration of action
1-Rapid-acting insulin analogues(insulin lispro, insulin aspartand
insulin glulisine)
Generallytheonsetis5to15minutesafteradministration.
Theyareadministeredtomimictheprandial(mealtime)releaseofinsulin
Controltheupwardglycemicexcursionsthatoccurimmediatelyaftermealsin
diabetics.
Suitableforintravenousadministration,althoughregularinsulinismostcommonly
used
2-Short-actinginsulinanalogues
Regularinsulin(HumulinR,NovolinR)asoluble,crystallinezincinsulin.
Givensubcutaneously(orI.Vinemergenciese.g.,diabetesketoacidosis)
Take30minutestobegintoexerttheireffectandhavealongerdurationofactionthan
rapid-actinginsulin.
Itcontrolpostprandialhyperglycemia.
Preparationofchoiceforglucosemanagementduringsurgery,trauma,shock,ordiabetic
ketoacidosis.

8. 3-Intermediate-acting preparations
A-Isophaneinsulinsuspension(NeutralprotamineHagedorn,NPH)
Shouldonlybegivensubcutaneously(neverI.V.)
givenalongwithrapid-orshort-actinginsulinformealtimecontrol.
B-Neutralprotaminelispro(NPL)insulin.
C-Lentinsulin(Insulinzincsuspension)usuallygivenonceortwiceaday.
4. Long-acting insulin preparations
A-Insulin glargine: (Lantus)
itmustbegivensubcutaneously.
B-Insulindetemir:(Levemr)

9. Adverse reactions to insulin therapy
1.Hypoglycemia,tremors,lethargy,hunger,confusion,motorandsensory
deficits,seizures,andunconsciousness.
2.Adrenergicmanifestationsincludeanxiety,palpitations,tachycardia,and
diaphoresis
3.Weightgain
4.Allergicreactionsduetotheuseofanimal-derivedinsulins
5.Locallipodystrophy(lipohypertrophyorlipoatrophy
6.Hypokalemiafromacuteinsulinadministration

10. .
Oral Agents
A-Insulin Secretagogues
B -Insulin Sensitizers
C -ɑ-Glucosidase Inhibitors
D-Drugs affecting incretin: Dipeptidyl Peptidase-IV Inhibitors
A-Insulin Secretagogues
1-Sulfonylureas; 2-Meglitinide
TheyaretreatmentforpatientswhohaveType2diabetesbutwhocannot
bemanagedbydietalone.
Theyaretreatmentforpatientwhohashaddiabeteslessthan5years
Patientswithlong-standingdiseasemayrequireacombinationof
hypoglycemicdrugswithorwithoutinsulin.
ShouldnotbegiventopatientswithType1diabetes.

11. 1-Sulfonylureas
Theseagentsareclassifiedasinsulinsecretagogues,becausetheypromote
insulinreleasefromtheß-cellsofthepancreas.
Mechanismsofactionofthesulfonylureas:
Theseinclude
1)stimulationofinsulinreleasefromtheß-cellsofthepancreasbyblocking
theATP-sensitiveK+effluxchannels
2)reductioninhepaticglucoseproduction
3)increaseinperipheralinsulinsensitivity.
Examples
Glibenclamide
Acetohexamidewithuricosuricactivity,maybeofbenefitindiabetic
patientswithgout.
Chlorpropamide(usedinpituitaryADHdeficiency)

12. Adverse effects:
weight gain, hyperinsulinemia, and hypoglycemia.
Hepatic or renal insufficiency delayed excretion of the drug resulting in its
accumulation may cause hypoglycemia.
Glyburide/glibenclamidehas minimal transfer across the placenta and
may be a reasonably safe alternative to insulin therapy for diabetes in
pregnancy.

13. 2-Meglitinide analogs
This class of agents includes repaglinideand nateglinide
AugmentingthereleaseofinsulininpresenceofglucoseONLY
Meglitinidesseemlesslikelytocausefastinghypoglycemia.
Meglitinidesmaybehelpfulinpatientswithaknownallergytosulfa
drugs.
Mechanism of action:
They bind to a distinct site on the sulfonylurea receptor of ATP-sensitive
potassiumchannels leading to the release of insulin.

14. Oral Agents
B -Insulin Sensitizers
Twoclassesoforalagentsthebiguanidesandthiazolidinediones
Theseagentslowerbloodsugarbyimprovingtarget-cellresponseto
insulinwithoutincreasingpancreaticinsulinsecretion.
1-Biguanides
Metformin(Glucophage):theonlycurrentlyavailablebiguanide
Doesnotaffectinsulinsecretionbutrequiresthepresenceofinsulinto
beeffective
Hyperinsulinemiaisnotaproblem.thus,theriskof
hypoglycemiaisfarlessthanthatwithsulfonylureaagents
TheADA(AmericanDiabetesAssociation)treatment
recommendsmetforminasthedrugofchoicefor
newlydiagnosedType2diabetics.

15. Mechanism of action:
1-Reductionofhepaticglucoseoutput
2-Slowsintestinalabsorptionofsugars
3-Improvesperipheralglucoseuptakeandutilization.
Thepatientoftenlosesweightbecauseoflossofappetite.
USES
First-linetherapyinthetreatmentofmildtomoderatetypeIIoverweightdiabeticswho
demonstrateinsulinresistance.
Treatpolycysticovariansyndrome.Itsabilitytolowerinsulinresistanceinthesewomencanresult
inovulationand,possibly,pregnancy.
Adverseeffects:gastrointestinalsymptoms(nausea,vomiting,anorexia,metallictaste,abdominal
discomfort,anddiarrhea).
Metforminisalsocontraindicatedinpersonswithhepaticdysfunctionand/orrenaldisease,acute
myocardialinfarction,ordiabeticketoacidosis.

16. Thiazolidinediones (TZDs) or Glitazones (Pioglitazoneand
Rosiglitazone )
Althoughinsulinisrequiredfortheiraction,thesedrugsdo
notpromoteitsreleasefromthepancreaticß-cells;thus,
hyperinsulinemiadoesnotresult.
Usedasmonotherapyorincombinationwithotherhypoglycemics
orwithinsulin.
Theglitazonesarerecommendedasasecond-linealternativefor
patientswhofailorhavecontraindicationstometformin
WeightincreasethroughtheabilityofTZDstoincrease
subcutaneousfatorduetofluidretention.
Rosiglitazoneincreasedriskofmyocardialinfarction.

17. Oral Agents
C -ɑ-Glucosidase Inhibitors
AcarboseandMiglitolareorallyactivedrugsusedforthetreatmentof
patientswithType2diabetes.
Mechanismofaction
Thesedrugsaretakenatthebeginningofmeals.Theyactbydelayingthe
digestionofcarbohydrates,resultinginlowerpostprandialglucoselevels.
Acarbosereversiblyinhibitingpancreaticɑ-amylaseandintestinalɑ-
glucosidaseresponsibleforthehydrolysisofstarchtooligo-saccharides
thentoglucoseandothersugars.
Thesedrugsdonotstimulateinsulinrelease,nordotheyincreaseinsulin
actionintargettissues.

19. Drugs affecting Incretin
1-Dipeptidyl Peptidase-IV Inhibitors
Sitagliptinandsaxagliptinareanorallyactivedipeptidyl
peptidase-IV(DPP-IV)inhibitor.
Mechanismofaction
TheyinhibittheenzymeDPP-IV,whichisresponsibleforthe
inactivationofincretinhormones,suchasglucagon-likepeptide-
1(GLP-1).
Prolongingtheactivityofincretinhormonesresultsinincreased
insulinreleaseinresponsetomealsandareductioninsecretion
ofglucagon.
Maybeusedasmonotherapyorincombinationwitha
sulfonylurea,metforminoraglitazone
Adverseeffects
nasopharyngitisandheadache.