Diabetic, pharmacology

1. PHARMACOLOGY
ANTI DIABETIC
The pancreas,locatedto the leftof and behindthe
stomach,isboth an exocrine andanendocrine gland.
The exocrine sectionof the pancreassecretesdigestive
enzymesintothe duodenum.The endocrine sectionhas
cell clusterscalled isletsofLangerhans.The alphaislet
cellsproduce glucagon,whichbreaksglycogendownto
glucose inthe liver,andthe betacellssecrete insulin,
whichregulatesglucose metabolism.
ANTIDIABETIC DRUGS
➜ Usedprimarilytocontrol diabetesmellitus,a
chronicdisease thataffectscarbohydrate
metabolism.
The two groupsof antidiabeticagents:
INSULIN
➜ An antidiabeticagentusedtocontrol diabetes
mellitus.
➜ A proteinsecretedfromthe betacellsof the
pancreas,necessaryforcarbohydrate metabolism
and playsan important role inproteinandfat
metabolism.
➜ The beta cellsmake up75% of the pancreas,and
the alphacellsthat secrete glucagons- a
hyperglycemicsubstance--occupyapproximately
20% of the pancreas.
ORAL HYPOGLYCEMIC(ANTIDIABETIC) DRUGS.
➜ Alsoknownasoral antidiabeticdrugs(toavoid
confusionwiththe termhypoglycemicreaction),
are,syntheticpreparationsthatstimulateinsulin
release orotherwise alterthe metabolicresponse
to hyperglycemia.
DIABETES MELLITUS
➜ A chronicdisease thatresultsfromdeficientglucose
metabolism, iscausedbyinsufficientinsulin
secretionfrombetacells.Thisresultsinhighblood
glucose (hyperglycemia).
➜ a disorderof the pancreas,whereasdiabetes
insipidusisadisorderof the posteriorpituitary
gland
THREE P’S:
1. polyuria(increasedurine output),
2. polydipsia(increasedthirst),and
3. Polyphagia(increasedhunger).
TYPE 1 DIABETES MELLITUS
Factors:
1. Viral infections,
2. Environmental conditions
3. Genetic
TYPE 2 DIABETES MELLITUS
➜ The most commontype of diabetes.
➜ Withtype diabetes,there issome beta cell function
withvaryingamountsof insulinsecretion.
Hyperglycemiamaybe controlledforsome type 2
diabetespatientswithoral antidiabetic
(hypoglycemic) drugsanddietprescribedbythe
AmericanDiabeticAssociation(ADA);however,
aboutone-thirdof patientswithtype 2diabetes
needinsulin.Patientswithtype 2diabeteswhouse
one or two oral antidiabeticdrugsmaybecome
insulindependentyearslater.
Major factors:
1. heredity
2. obesity
SECONDARY DIABETES MELLITUS
➜ Certaindrugsincrease bloodglucose andcancause
hyperglycemiainprediabeticpersons.Theseinclude
glucocorticoids(cortisone,prednisone),thiazide
diuretics(hydrochlorothfazide),andepinephrine.
➜ Usually the bloodglucose level returnstonormal
afterthe drug is discontinued.
GESTATIONAL DIABETES MELLITUS (GDM)
➜ Duringthe secondand thirdtrimestersof
pregnancy,the levelsof the hormones
progesterone,cortisol,andhumanplacental
lactogen(hPL) increase.
➜ These increasedhormone levelscaninhibitinsulin
usage.
➜ Glucose thenmobilizedfromthe tissue andfrom
lipidstorage sites.
➜ Afterpregnancy,the bloodglucose levelmay
decrease,however,some patientsmaydevelop
diabetesmellitus,whereasothersmaydeveloptype
2 diabetesinlateryears.

2. Typesof Diabetes
Mellitus
Percentage of
Occurrences
Type 1 10 % - 12%
Type 2 85 % - 90 %
Secondarydiabetes
(medications, hormonal
changes)
2 % - 3 %
Gestational diabetes
mellitus
1 % (2 % - 5 % of all
pregnancy)
INSULIN
➜ Released fromthe betacellsof the isletsof
Langerhansinresponse toan increase inblood
glucose,Oral glucose loadismore effective in
raisingthe seruminsulinlevelthananintravenous
(IV) glucose load.
➜ Insulinpromotesthe uptake of glucose,amino
acids,and fattyacidsand convertsthemto
substancesthatare storedinbodycells.Glucose is
convertedtoglycogeninthe liverandmuscle for
future glucose needs,therebyloweringthe blood
glucose level.
➜ The normal range for fastingbloodglucose is70to
99 mg/dl. For personwithoutdiabetes.Whenthe
bloodglucose level isgreaterthan180 mg/dL.
Glycosuria-glucose inthe urine-canoccur.
➜ Increasedbloodglucose actsasan osmoticdiuretic,
causingpolyuria.Whenbloodglucose remains
elevated(>200mg/dL), diabetesmellitus occurs.
HEMOGLOBIN ALC (HBA1C)
➜ A derivativeof the interactionof glucose with
hemoglobininredbloodcells(RBCs),isusedforthe
diagnosisof diabetesasrecommendedbythe ADA.
Because RBCshave a lifespan of approximately120
days,the HbA1c level reflectsthe average glucose
level forupto months.
BETA-CELL SECRETION OF INSULIN
➜ The beta cellsinthe pancreassecrete
approximately0.2to 0.5 units/kg/dayof insulin.
➜ A patientwhoweighs70kg (154 pounds) secretes
14 to 35 unitsof insulinperday,althoughmore
insulinsecretionmayoccurif the personconsumes
more calories.
➜ A patientwithdiabetesmellitus mayrequire 0.2to
1 units/kg/day.The higherrange maybe because of
obesity,stress,ortissue insulinresistance.
CommerciallyPreparedInsulin
Early insulinpreparationsutilizedpancreastissue
extractedfromanimals-eitherpigsorcattle.Porkinsulin
isstructurallyclosertohuman insulinthanbeef insulin.
Today,insulinsare currentlymanufactured
biosyntheticallyusingrecombinantDNA technology.
Human insulin
➜ Duplicatesinsulin producedbythe pancreasof the
humanbody
o examplesof humaninsulininclude Humulin
R and Novolin N.
➜ The use of humaninsulinhasa low incidence of
bothallergiceffectsandinsulinresistance.
➜ Human insulinanaloguesare modificationsof
humaninsulinwithalterationsinonsetand
durationof action.
o Insulin lispro and insulin aspartare
examplesof humaninsulinanalogues.
Insulinsare usuallyadministeredsubcutaneously,
abdominal injectionsof insulinare absorbedfasterthan
those at otherbodysitesandhave beenfoundtobe
more consistent.
➜ The concentrationof insulinis100 units/mLor 500
units/mL
➜ (U100/mL or U500/mL., respectively),andthe
insulinispackagedina10-mL vial.
➜ Insulinin500 units/mLisonlyavailableinshort-
actingregularinsulin.
➜ Insulinin500 units/mL.isseldomusedexceptin
emergenciesandforpatientswithseriousinsulin
resistance (>200 U/day).
➜ Insulinin40 units/mLisno longerusedinthe
UnitedStates,althoughitisstill usedinother
countries.Insulinsyringesare typicallymarkedin
unitsof 100 U/mL or 50 U/0.5 mL forinsulinU100.
Insulinsyringesmustbe usedforaccurate dosing.To
preventdosage errors,the nurse mustbe certainthat
there isa match of the insulinconcentrationwiththe
calibrationof unitsonthe insulinsyringe.Beforeuse,
the patientor nurse mustroll--notshake-cloudyinsulin
bottlestoensure thatthe InsulinandItsingredientsare
well mixed.Shakingabottle of insulincancause
bubbles,whichcanleadtoan inaccurate dose.Insulin
requirementsvary;usuallylessinsulinisneededwith

3. increasedexercise,andmore insulinneededwith
infectionsandhighfever.
TYPES OF INSULIN
Several standardtypesof insulinare availablethat
include rapid-,short-,intermediate,orlong-actingtypes
and combinationsof these.
Rapid- andshort-actinginsulinsare ina clearsolution
withoutanyaddedsubstance toprolonginsulinaction.
Intermediate-actinginsulinsare cloudyandmaycontain
protamine,aproteinthatprolongsthe actionof insulin,
or zinc,whichalsoslowsthe onsetof actionand
prolongsthe durationof activity.
Rapid- acting insulinsinclude insulinlispro(human
analogue),humaninsulinaspart(recombinantDNA
[rDNA] linglulisine,andhumanoral inhalationinsulin.
Insulinlisproisformedbyreversingtwoaminoacidsin
human.Insulinaspart(rDNA origin) isanotherhuman
insulinanalogueinwhichasingle aminoacid(proline)
has beensubstitutedwithasparticacidtohelpprevent
the moleculesfromclumpingtogethertoallowquicker
entryintobloodcirculation.Insulinlispro,insulin aspart,
insulinglulisine,andhumanoral inhalationinsulinact
fasterthan regularinsulin, theymustbe administered
within
10 to 15 minutesbefore mealtime(foodshouldbe
presentbefore administeringthese insulins). Patients
whoare insulindependent
and take rapid-actinginsulinusuallyrequire
Intermediate-actinginsulinaswell.
Short-acting insulinhasan onsetof action of 30
minutes.The peak actionoccursin 1.5 to 3.5 hours,and
the duration of action is4 to 12 hours.Regular
(unmodified,crystalline) insulinisshort-actinginsulin
that can be administeredintravenouslyor
subcutaneously.Regularinsulinisgenerallygiven30to
60 minutesbefore meals.
Intermediate-actinginsulinsinclude neutral protamine
Hagedorn(NPH).Isophane insulinslike NPHcontain
protamine,aproteinthat prolongsthe actionof insulin.
The onsetof intermediate-actinginsulin is1to 2 hours,
peakactionoccurs in 4 to 12 hours,andthe duration
ofactionis14 to 24 hours.
Insulinglargine islong-actinginsulinwithanonsetof 1
to 1.5 hours.It isevenlydistributedovera24-hour
durationof action therefore itisadministeredonce a
day,usuallyat bedtime.The incidence of nocturnal
hypoglycemiaisnotas commonas withotherinsulins
because of itscontinuoussustainedrelease.Insulin
detemirisanotherlong-actinginsulinthatpeaksin6 to
8 hoursand lastsfor of hour,peaksat 12 hours,and24
hours,and insulindegludec,along-actingInsulin,has
lastsfor 42 hours;these insulinsanonset DNA-origin
humaninsulinforpatientswithtypes are analoguesof
humaninsulin.Glargine wasthe firstlong-actingand2
diabetes. Glargine,detemir,anddegludecare available
ina prefilledcartridge painatthe injectionsitewiththe
administrationof glarginethan forthe OptiPeninsulin
pendevice. Some patientscomplainof more withpain
at the injectionsitewiththe administrationof glargine
than withNPHinsulin.
Combinationinsulins are commercially premixed.These
include NPH70/regular30 and NPH50/ regular50.
These combinationare widelyused.The NPH70/regular
30 is available invialsorasprefilled disposable pens.
The exteriorof an insulinpen resemblesafountain pen.
It can be storedat roomtemperature forupto 10 days.
Withthese combinationsof insulin,the patientdoesnot
have to mix regularandNPH Insulinsaslong one of
these combinationsiseffective. However,some
patientsneedlessthan25% or 30% regularinsulinand
more intermediate-actinginsulin.Thesepatientsneed
to mix the twoinsulinsinthe prescribedproportions.
Regularinsulincanbe mixedwithotherinsulininthe
same syringe. However,mixinginsulincanalterthe
absorptionrate.
InsulinResistance
Antibodies developovertime inpersonstakinganimal
insulin. Thisslow the onsetof insulinactionand extend
itsdurationof action. Antibodydevelopmentcancause
insulin resistance andinsulinallergy, andobesitycan
alsobe a causative factorfor insulinresistance.Skin
testswithdifferentinsulinpreparationsmaybe
performedtodetermine whetheranallergiceffectis
present.Humanandregularinsulins produce fewer
allergens.
Storage of Insulin

4. Unopenedinsulinvialsare refrigerateduntil needed.
Once an insulin vial hasbeenopened,itmaybe kept at
room temperature for1month or inthe refrigeratorfor
3 months;insulin islessirritatingtothe tissueswhen
injectedatroomtemperature.Insulinvialsshouldnot
be put inthe freezer,norshouldthey be placedindirect
sunlightorina high-temperaturearea.Prefilledsyringes
shouldbe storedinthe refrigeratorandshouldbe used
within1 to 2 weeks.Openedinsulinvials lose their
strengthafterapproximately3months.
Sliding-Scale InsulinCoverage
Insulinmaybe administeredinadjusteddosesthat
dependonindividual bloodglucose restresults.When
the diabeticpatienthasextreme variancesininsulin
requirements-suchaswithstressfromhospitalization,
surgery,illness,orinfection- adjusteddosingorsliding-
scale insulincoverage providesmore constantblood
glucose level.Bloodglucosetestingisperformedseveral
timesa dayat specifiedintervals, usuallybefore meals
and at bedtime. A presetscale usuallyinvolves
directionsforthe administrationof rapid- orshort-
actinginsulin.
InsulinPenInjectors
An insulinpenresemblesafountainpen butcontainsa
disposable needle andadisposable insulin-filled
cartridge.
Insulinpenscome intwo types,
1. prefilled
2. reusable
and consideredtodeliveramore accurate dose than
the traditional 100-unitsyringe andvial.
➜ To operate the insulinpen,the insulindose is
obtainedbyturningthe dial tothe numberof
insulinunitsneeded.The capacityof these prefilled
and reusable insulinpens is150 to 300 units,or 1.5
to 3 mL; the 1.5-mL replaceable cartridgesfor
insulinpensare beingphasedout.
➜ The use of insulinpensincreasesthe patient's
compliance withthe insulinregimen.The
convenienceof the penismostappealing,and
patientsmaychoose touse the insulinpenforits
portability;itcanbe usedat work or while traveling,
whereasthe traditional methodforadministering
insulinmaybe usedatothertimes.
➜ The cost of insulininvialsissomewhatlessthanthe
prefilledpens,butmostpatient’sstate thanwith
the lessinjectionpainisassociatedwithinsulinpens
traditional insulinsyringe.
InsulinPumps
➜ Insulinpumpsare analternative todailyinsulin
injectionsusedinassociationwithbloodglucose
monitoringand carbohydrate counting.
➜ These computerizeddeviceshave aninsulin
reservoirandprogrammingcapacitytodeliver
continuousrapid-actinginsulininvaryingamounts
at differenttimesthroughouta24-hourperiod.
➜ These pumpsare smallerthanmostmobile phones,
and the typesof insulinpumpsinclude Implantable
and portable.
IMPLANTABLE INSULIN PUMP
➜ surgicallyimplantedinthe abdomenanddelivers
bothbasal infusion (continuousreleaseof a,small
amountof insulin)andbolas(additional) doseswith
meals.Itis administeredintraperitoneally.Withthe
use of implantableinsulinpumps,fewer
hypoglycemicreactionsoccur,andbloodglucose
levelsare controlled.Long-termeffectivenessof the
pumpis currentlyunderstudy.
EXTERNAL OR PORTABLE INSULINPUMPS
➜ Alsocalledcontinuoussubcutaneousinsulin
infusion(CSI1),mayhave atube or infusionset
placedunderthe skin.The needle isinsertedinto
the abdomen,upperthigh, orupperarm.
➜ Thistype of pumpisworn outside the bodyandis
placedina pocketor bra. The external tubeless
pumpliesdirectlyonthe skinandinjectsinsulin
throughthe skinwithouttubes.
➜ The external insulinpumpkeepsbloodglucose
levelsasclose tonormal as possible.
➜ A battery- operateddevice thatusesrapid-acting
insulin,whichisstoredinareservoirsyringe placed
inside the device.
➜ It deliversbothbasal insulininfusionandbolus
doseswithmeals.Infusionsare programmedbythe
patient.Aboutthree basal ratesare programmed
perday; however,the patientcanadjustthe rate
accordingto changesin activity, the patientpushes
a buttonto deliverabolusdose atmeals.Only
rapid-actinginsulinisused;modified(NPH)insulins
are notusedbecause of unpredictable control of

5. bloodglucose.The pumpdeliversexactlyasmuch
insulinasthe patientprograms.
INSULINJET INJECTORS
➜ InsulinJetinjectorsshootinsulin,withoutaneedle,
directlythroughthe skinintothe fattytissue.
➜ The insulinisdeliveredunderhighpressure,
stinging,pain,burning,andbraisingmayoccur.
➜ This method of insulininsertion isnotindicatesfor
childrenorolderadults.
➜ Thistype of device isalsoexpensive,costing
approximately2o 10 timesas muchas the
subcutaneousdose.
ORAL ANTIDIABETIC (HYPOGLYCEMIC) DRUGS
First- and Second-GenerationSulfonylureas
Oral antidiabeticdrugs,alsocalledoral hypoglycemics,
shouldbe usedbythose withtype 2 diabetes;persons
withtype 1 diabetesshouldnotuse them.
Sulfonylureas
➜ a group of antidiabetics chemicallyrelatedto
sulfonamidesbutlackingantibacterial activity,
stimulate pancreaticbetacellstosecrete more
insulin.
➜ Thisincreases the insulincellreceptors,which
increasesthe abilityof the cellstobind insulinfor
glucose metabolism.
➜ The sulfonylureasare classified asfirst- andsecond-
generation drugs.First-generationsulfonylureasare
dividedintoshort-,intermediate-,andlong-acting
antidiabetics.
SECOND- GENERATIONSULFONYLUREAS
➜ Increase the tissue responsetoinsulinanddecrease
glucose productionbythe liver.Theyhave greater
hypoglycemicpotencythanthe first-generation
sulfonylureas.
➜ the second -generationdrugsalsohave alonger
durationof actionand cause fewerside effects.
➜ The second-generation drugsalsohave less
displacementpotential fromprotein-bindingsites
by otherhighlyprotein-bounddrugs,suchas
salicylatesandwarfarin, thandofirst-generation
drugs.
➜ Second-generationsulfonylureas shouldnotbe
usedwhenliverorkidneydysfunctionis present.A
hypoglycemicreactionismore likelytooccurin
olderadults.