Hypertension

Thorough understanding of disease with advanced treatment

2. Prepared By :-RuchitaBhavsar
1
st
year M.Pharm
Guided By :-Mr. SamareshPal Roy
Asst. Prof. of Pharmacology,
SDPC, Kim

3. Content
Introduction
Measurement of Blood Pressure
Factors influencing Blood Pressure
Etiology
Epidemiology
Types
Signs and symptoms
Pathophysiology
Diagnosis
Complication
Management

4. Introduction
Hypertensionisanabnormallyhighbloodpressure
especiallyarterialbloodpressure.Bloodpressureisthe
forceexertedbythebloodagainstthewallsofblood
vessels.
Hypertensionisusuallyindicatedbyanadultsystolicblood
pressuregreaterthan140mmHgoradiastolicblood
pressuregreaterthan90mmHgwithaconsensusacross
medicalguidelines.

5. Thismeansthesystolicreading(thepressureastheheart
pumpsbloodaroundthebody)isover140mmHg
(millimetersofmercury)and/orthediastolicreading(as
theheartrelaxesandrefillswithblood)isover90mmHg.
AccordingtoThe“SeventhReportoftheJointNational
CommitteeonDetection,EvaluationandTreatmentof
HighBloodPressure”(JNC-7),theHypertensioncanbe
categorizedintofollowing:

6. Measurement of Blood Pressure
RegulationofNormalBloodPressureiscarriedoutby:
SystemicVascularResistanceisanindexofarteriolar
complianceorconstrictionthroughoutthebody.Itisthe
resistancethatleftventriclemustovercometopumpblood
throughthesystemiccirculation.
CardiacOutputistheamountofbloodpumpedbythe
heartpermin.Thecardiacoutputisusuallyexpressedin
lit/min.Anormaladulthasacardiacoutputofaround5
litersofbloodperminute.
Blood Pressure=
Cardiac Output
(CO)
×
Systemic
Vascular Resistance

7. Cardiacoutputcanbecalculatedbyfollowing:
Heartrateisthespeedoftheheartbeatmeasuredbythe
numberofcontractionsoftheheartperminute(bpm).A
normalrestingheartrateforadultsrangesfrom60to90
beatsinaminute.Butideallyitis72beat/min.
Strokevolume(SV)isthevolumeofbloodpumpedfrom
theleftventricleperbeat.Thestrokevolumesforeach
ventriclearegenerallybeingapproximately70ml/beatina
healthyman.
Hence,cardiacoutput=72*70=5040ml/min
Anormaladulthasacardiacoutputofaround5litersof
bloodperminute.
Cardiac Output
(CO)
=
Heart Rate
(HR)
×
Stroke Volume
(SV)

8. Factors influencing Blood Pressure
Heart Rate
heart rate blood pressure
Vasoconstriction / Vasodilation
Vasoconstriction blood pressure
Vasodilation blood pressure
Fluid Volume
fluid volume blood pressure

9. Etiology
1.HypertensionmaytransferduetoHEREDITARY
TENDENCY.Ithavepasseddownthrough3generationsby
statisticallysignificantapplicationofMendel’slaw.
2.FAULTYDIETfrequentlyassociatedwithOVERWEIGHT.
Thepersonpredisposedtowardhypertensionona
hereditarybasismustfrequentlyacquirefaultydietary
habits.Theeffectofsaltyfoodoroveruseofsaltisalsowell
demonstratedinpatientsinwhomhypertensionhas
developed.

10. 3.Theconnectionbetweenbloodpressureandthe
emotions,especiallyANGERandFEARhaslongbeen
established.
4.Long-continuedincreasedTENSIONeventuallyproduces
degenerativechangesintheintimaandthickeningofthe
wallsofarterioles.

11. Epidemiology
Overall,approximately20%oftheworld’sadultsare
estimatedtohavehypertension.
Worldwide,approx.1billionpeoplehavehypertension,
contributingtomorethan7.1milliondeathsperyear.
Theage-specificprevalencewas
3.3%ingroupaged18-29yr
13.2%ingroupaged30-39yr
22%ingroupaged40-49yr
37.5%ingroupaged50-59yr
51%ingroupaged60-74yr

12. Types
1.Essentialhypertension
Thistypeofhypertensionisdiagnosedafteradoctor
noticesthatyourbloodpressureishighonthreeormore
visitsandeliminatesallothercausesofhypertension.
Usuallypeoplewithessentialhypertensionhaveno
symptoms,butmayexperiencefrequentheadaches,
tiredness,dizzinessornosebleeds.
Althoughthecauseisunknown,researchersdoknow
thatobesity,smoking,alcohol,dietandheredityallplaya
roleinessentialhypertension.

13. 2.Secondaryhypertension.
Themostcommoncauseofsecondaryhypertensionisan
abnormalityinthearteriessupplyingbloodtothekidneys.
Othercausesincludeairwayobstructionduringsleep,
diseasesandtumorsoftheadrenalglands,hormone
abnormalities,thyroiddisease,andtoomuchsaltor
alcoholinthediet.
Drugscancausesecondaryhypertension,includingover-
the-countermedicationssuchasibuprofen(Motrin,Advil,
andothers)andpseudoephedrine(Afrin,Sudafed,and
others).
Thegoodnewsisthatifthecauseisfound,hypertension
canoftenbecontrolled.

14. Specialtype
Malignanthypertension.
Thishypertensiontypeoccursinonlyabout1percentof
peoplewithhypertension.
Withmalignanthypertension,highbloodpressureoccurs
suddenlyanddrastically.Apersonmightexperience
numbnessinthebodyaswellasvisionproblems,extreme
fatigue,confusion,anxiety,andseizures.
Malignanthypertensionisreversiblewhentheunderlying
conditioniscured.Malignanthypertensionisveryrareand
affectsbothchildrenandadults.

15. Isolatedsystolichypertension.
Bloodpressureisrecordedintwonumbers:Theupperor
firstnumberisthesystolicpressure,whichisthepressure
exertedduringtheheartbeat;thelowerorsecondnumber
isthediastolicpressure,whichisthepressureastheheart
isrestingbetweenbeats.
Thistypeofhypertensionisaresultofoldageandapoor
diet.Thearteriesbecomestiff,resultinginahighsystolic
numberwithanormaldiastolicnumber.Isolatedsystolic
hypertensiondoesnothaveanidentifiablecause.
Riskfactorsincludeoldage,obesity,usingtobacco
products,andhavingdiabetes.

16. Resistant hypertension.
If your doctor has prescribed three different types of
antihypertensive medications and your blood pressure is
still too high, you may have resistant hypertension.
Resistant hypertension may occur in 20 to 30 % of high
blood pressure cases.
At least four medications may be necessary to treat
resistant hypertension.
Resistant hypertension may have a genetic component and
is more common in people who are older, obese, female,
African American, or have an underlying illness, such
asdiabetesor kidney disease.

17. Signs & Symptoms
Severeheadache
Fatigue/confusion /dizziness
Visionproblems
Chest pain
Difficulty breathing
Irregular heartbeat
Blood in the urine
Pounding in neck or ears
ItisoftencalledSilentKiller
becauseitisfrequently
asymptomaticuntilithas
becomesevere.

18. Pathophysiology
Thepathophysiologybehindthisdiseasemainlyrelatedto
regulationofbloodpressure.
Bloodpressureisregulatedbyfollowingtheories:
1.SympatheticNervousSystem(Short-termRegulatory
Mechanism/NervousMechanism)
2.ReninAngiotensinAldosteroneSystem(Long-term
RegulatoryMechanism/RenalMechanism)
3.FluidVolumeRegulation

19. Sympathetic Nervous System
RegulationbySympatheticNervousSystemisalsocalled
Short-termRegulatoryMechanismwhichiscarriedoutby
2typesofreceptors:
1.Baro-receptors
2.Chemoreceptors
SympatheticNervousSystemactonregulationofblood
pressurebytheactiononRenin.
Reninisanenzymereleasedbythekidneytohelpcontrol
thebody'ssodium-potassiumbalance,fluidvolumeand
bloodpressure.
Reninreleaseisstimulatedbyβanddecreasedbyα
adrenoceptorstimulation.

20. Baro-receptors(PressureReceptors)incarotidartery&
aorticarchrespondtochangesinbloodpressureand
influencearteriolardilationandarteriolarconstriction.
Whenstimulatedtoconstriction,thecontractileforce
strengthens,increasingtheheartrateandaugmenting
peripheralresistance,thusincreasingcardiacoutputand
hencebloodpressure.

23. Renin–AngiotensinSystem
Whenthekidneysreleasetheenzymerenininresponseto
certainconditions(highbloodpotassium,lowblood
sodium,decreasedbloodvolume),itisthefirststepinwhat
iscalledtherenin-angiotensin-aldosteronecycle.
Thiscycleincludestheconversionofangiotensinogento
inactivepeptideangiotensinI,whichinturnisconvertedto
activeoctapeptideangiotensinIIinthelungbypresenceof
AngiotensinConvertingEnzyme.
AngiotensinIIisapowerfulbloodvesselconstrictorandits
actionstimulatesthereleaseofaldosteronefromanareaof
theadrenalglandscalledtheadrenalcortex.
Themainsourceofreninisthejuxtaglomerularapparatus
ofthekidney.

24. Thisjuxtaglomerularapparatussensestherenalperfusion
pressureandthesodiumconcentrationinthedistal
tubularfluid.
Together,angiotensinandaldosteroneincreasetheblood
pressureandthebloodsodiumtore-establishthebody's
sodium-potassiumandfluidvolumebalance.

27. Fluid Volume Regulation
Sodiumandwaterretentionareassociatedwithanincrease
inbloodpressure.Itispostulatedthatsodium,viathe
sodium–calciumexchangemechanism,causesanincrease
inintracellularcalciuminvascularsmoothmuscle
resultinginincreasedvasculartone.
Theprimarycauseofsodiumandwaterretentionmaybe
anabnormalrelationshipbetweenpressureandsodium
excretionresultingfromreducedrenalbloodflow,reduced
nephronmass,andincreasedangiotensinor
mineralocorticoids.

29. Diagnosis
Manometer:Mercury,anaeroidorelectronicdevicesis
usedinmeasurementofbloodpressure.Itshouldbe
calibratedfrequentlyandroutinelyagainststandards
(typicallyevery6months)toassureaccuracy.
Electrocardiogram:Atestthatmeasurestheelectrical
activity,rate,andrhythmofyourheartbeatviaelectrodes
attachedtoyourarms,legs,andchest.Theresultsare
recordedongraphpaper.
Echocardiogram:Thisisatestthatusesultrasoundwaves
toprovidepicturesoftheheart'svalvesandchambersso
thepumpingactionoftheheartcanbestudiedand
measurementofthechambersandwallthicknessofthe
heartcanbemade.

31. Complication
Heartattackorstroke:Highbloodpressurecancause
hardeningandthickeningofthearteries(atherosclerosis),
whichcanleadtoaheartattack,strokeorother
complications.
Heartfailure:Topumpbloodagainstthehigherpressurein
yourvessels,yourheartmusclethickens.Eventually,the
thickenedmusclemayhaveahardtimepumpingenough
bloodtomeetyourbody'sneeds,whichcanleadtoheart
failure.
Aneurysm:Increasedbloodpressurecancauseyourblood
vesselstoweakenandbulge,formingananeurysm.Ifan
aneurysmruptures,itcanbelife-threatening.
RenalFailure:Weakenedandnarrowedbloodvesselsinthe
kidneyscanpreventtheseorgansfromfunctioningnormally.

32. Retinopathy:Thickened,narrowedortornbloodvesselsin
theeyescanresultinvisionloss.
Metabolicsyndrome.Thissyndromeisaclusterofdisorders
ofthebody'smetabolism,includingincreasedwaist
circumference;hightriglycerides;lowhigh-density
lipoprotein(HDL)cholesterol,the"good"cholesterol;high
bloodpressure;andhighinsulinlevels.Theseconditions
makethepersonmorelikelytodevelopdiabetes,heart
diseaseandstroke.
Troublewithmemoryorunderstanding.Uncontrolled
highbloodpressuremayalsoaffecttheabilitytothink,
rememberandlearn.Troublewithmemoryorunderstanding
conceptsismorecommoninpeoplewithhighblood
pressure.

33. Management
Non-ClinicalManagement
Non-pharmacologicalmanagementplaysanimportantrole
inthemanagementofhypertensionandinimproving
overallcardiovascularhealth.
1.LifestyleModification
Weightreduction:Weight-reducingdietsinoverweight
hypertensivepersonscanresultinmodestweightlossin
therangeof3-9%ofbodyweightandareassociatedwith
bloodpressurereductionofabout3-6mmHg.Itis
advisableforoverweighthypertensivepatientstoloseat
least5%oftheirweight.
Quitsmoking:Tobaccoabuseinanyformisfoundto
increasebloodpressureacutely.

34. Avoidanceofalcoholintake:Moderationofalcohol
consumptionisadvised.AlcoholconsumptionelevatesBP
acutely.Metaanalyseshaveshownthat,interventionsto
reducealcoholconsumptioncausedasmallbutsignificant
reduction(3.3/2mmHg)inbothsystolicanddiastolic
bloodrespectively.
Physicalexercise:Aerobicphysicalexercisefor20–30
minutesperdayforatleast5daysperweekimprovesblood
pressureandreducescardiovascularmorbidity.

35. 2. DietaryModification
Adietrichinfruits,vegetablesandlowfatdairyproducts
withreducedsaturatedandtotalfatcansubstantiallylower
BPduetohighpotassiumcontent.Morerecently,diethigh
inL-ArgininehasbeenshowntobeabletoreduceBPby
5.4/2.3mmHg.

36. Lowsodiumdiet:Highsaltintakeisassociatedwith
significantlyincreasedriskofstrokeandtotal
cardiovasculardisease.TypicalIndianfoodprovides4–5
gmofsodiumperday.Pickles,saltedvegetablesand
cannedfisharerichinsodiumandshouldbeavoided.
Intakeof2-3gmofsodiumorlessisrecommendedasper
dietaryapproachestostophypertension.Evidencefrom
publishedsystematicreviewandmetaanalysesshowed
thatrestrictingsodiumintakeinpeoplewithelevated
bloodpressureintheshorttermleadstoreductionsin
bloodpressureofupto10.5mmHgsystolicand2mmHg
diastolic.

38. Clinical Treatment
There are following class of drugs useful for the
treatment of Hypertension :
1.AngiotensinConverting Enzyme (ACE) Inhibitors
2.AngiotensinReceptor Blockers
3.Diuretics
4.Calcium Channel Blockers
5.β blockers
6.α blockers
7.Centrally acting agents
8.Direct Vasodilators

39. Overall Mechanism of Drug

40. AngiotensinConverting Enzyme (ACE) Inhibitors
Theseagentsreduceblood
pressurebyblockingthe
renin-angiotensinsystem.
Theydothisbypreventing
conversionofangiotensin
Itothebloodpressure
raising hormone
angiotensinII.Theyalso
increaseavailabilityofthe
vasodilatorbradykininby
blockingitsbreakdown.

41. Use:Thesedrugshaveestablishedclinicaloutcomebenefits
inpatientswithheartfailure,post–myocardialinfarction,left
ventricularsystolicdysfunction,anddiabeticandnon-
diabeticchronickidneydisease.
SideEffects:Theyarewelltolerated.Theirmainsideeffectis
cough.Angioedemaisanuncommonbutpotentiallyserious
complicationthatcanthreatenairwayfunction.
Thesedrugscanincreaseserumcreatinineby30%dueto
reducepressurewithintherenalglomeruluswhichisnot
harmful.
Thesedrugsmustnotbeusedinpregnancy.
Egs.,Ramipril
Captopril
Enalapril
Perindopril

42. AngiotensinReceptor Blockers
Angiotensinreceptor
blockersantagonizethe
reninangiotensinsystem.
Theyreduceblood
pressurebyblockingthe
actionofangiotensinII
onitsAT1receptorand
thus prevent the
vasoconstrictoreffectsof
thisreceptor.
Egs.,Losartan
Valsartan
Telmisartan
Candesartan

43. Use:Thesedrugshavethesamebenefitsoncardiovascular
andrenaloutcomesasangiotensin-convertingenzyme
inhibitorslikeheartfailure,post–myocardialinfarction,left
ventricularsystolicdysfunction,anddiabeticandnon-
diabeticchronickidneydisease.
SideEffect:Theyarewelltoleratedbecausetheydonot
causecoughandonlyrarelycauseangioedemaandhave
effectssimilartoACEinhibitors,theyaregenerallypreferred
overACEinhibitorsiftheyareavailableandaffordable.They
alsocanincreaseserumcreatininewhichisnotharmful.
Thesedrugsmustnotbeusedinpregnancy.

44. Diuretics
Theseagentsworkby
increasingexcretionof
sodiumbythekidneys
andadditionallymay
havesomevasodilator
effects.
2typesofdiureticsare
usedinthetreatment
ofHypertension:
Thiazidediuretic
Loopdiuretic

45. Clinicaloutcomebenefitshavebeenbestestablishedwith
chlorthalidone,indapamide,andhydrochlorothiazide.
Chlorthalidonehasmorepowerfuleffectsonbloodpressure
thanhydrochlorothiazideandhasalongerdurationofaction.
SideEffect:Themainsideeffectsofthesedrugsaremetabolic
(hypokalemia,hyperglycemia,hyperuricemia).Thelikelihood
oftheseproblemscanbereducedbyusinglowdosesorby
combiningwithACEinhibitorsorangiotensinreceptor
blockers,whichhavebeenshowntoreducethesemetabolic
changes.Diureticsaremosteffectivewiththesetwo
combinations.Combiningdiureticswithpotassium-sparing
agentsalsohelpstopreventhypokalemiaandwithcalcium
channelblockersarealsoeffective.

46. Calcium Channel Blockers
Theseagentsreduce
bloodpressureby
blockingtheinward
flowofcalciumions
throughtheLchannels
ofarterialsmooth
musclecells.
Egs.,
Nondihydropyridines:
Diltiazem
Verapamil
Dihydropyridines:
Nifedipine
Amlodipine

47. Thereare2maintypesofcalciumchannelblockers:
dihydropyridines,suchasamlodipineandnifedipine,which
workbydilatingarteries;andnondihydropyridines,suchas
diltiazemandverapamil,whichdilatearteriessomewhatless
butalsoreduceheartrateandcontractility.Hence
Nondihydropyridinearenotrecommendedinpatientswith
heartfailure.
SideEffect:Themainsideeffectofcalciumchannelblockers
isperipheraledema,whichismostprominentathighdoses.
Theyhavepowerfulbloodpressurereducingeffects,when
combinedwithACEinhibitorsorangiotensinreceptor
blockers.

48. β AdrenoreceptorBlockers
βblockersreduce
cardiacoutputand
alsodecreasethe
releaseofreninfrom
thekidney.
Egs.,Propranolol
Atenolol
Metoprolol
Carvediol
Acebtalol

49. Use:Theyhavestrongclinicaloutcomebenefitsinpatients
withhistoriesofmyocardialinfarctionandheartfailureand
areeffectiveinthemanagementofanginapectoris.
SideEffect:Themainsideeffectsassociatedwithb-blockers
arereducedsexualfunction,fatigue,andreducedexercise
tolerance.
Manyoftheseagentshaveadverseeffectsonglucose
metabolismandthereforearenotrecommendedinpatients
atriskofdiabetes,especiallyincombinationwithdiuretics.
Theymaysometimesalsobeassociatedwithheartblock.
Thecombinedαandβblocker,LABETALOL,iswidelyused
intravenouslyforhypertensiveemergenciesandisalsoused
orallyfortreatinghypertensioninpregnantandbreastfeeding
women.

50. α Adrenergic Blockers
αBlockersreduce
bloodpressureby
blockingarterialα
adrenergicreceptors
andthuspreventing
thevasoconstrictor
actionsofthese
receptors.
Egs.,Prazosin
Terazosin
Doxazosin

51. Use:Thesedrugsarelesswidelyusedasfirst-stepagentsthan
otherclassesbecauseclinicaloutcomebenefitshavenotbeen
wellestablished.However,theycanbeusefulintreating
resistanthypertensionwhenusedincombinationwithagents
diuretics,βblockers,andACEinhibitors.
Tobemaximallyeffective,theyshouldusuallybecombined
withadiuretic.Sinceαblockerscanhavesomewhatbeneficial
effectsonbloodglucoseandlipidlevels,theycanpotentially
neutralizesomeoftheadversemetaboliceffectsofdiuretics.
Theαblockersareeffectiveintreatingbenignprostatic
hypertrophyandsocanbeavaluablepartofhypertension
treatmentregimensinoldermenwhohavethiscondition.

52. Centrally Acting Agents
Thesedrugs,themostwell-
knownofwhichare
clonidineandmethyldopa
workprimarilybyreducing
sympatheticoutflowfrom
thecentralnervoussystem.
Egs.,Methyldopa
Clonidine
Clonidinepatch

53. SideEffect:Bothersomesideeffectssuchasdrowsinessand
drymouthhavereducedtheirpopularity.
Treatmentwithaclonidineskinpatchcausesfewerside
effectsthantheoralagent,butthepatchisnotalways
availableandcanbemorecostlythanthetablets.
Incertaincountries,includingtheUnitedStates,α
methyldopaiswidelyemployedfortreatinghypertensionin
pregnancy.

54. Direct Vasodilators
Becausetheseagentsoften
causefluidretentionand
tachycardia,theyaremost
effectiveinreducingblood
pressurewhencombined
withdiureticsandβ
blockersorsympatholytic
agents.Forthisreason,they
arenowusuallyusedonlyas
fourth-lineorlateradditions
totreatmentregimens.
Egs.,Hydralazine
Minoxidil

55. Hydralazineisthemorewidelyusedoftheseagents.The
powerfuldrugminoxidilissometimesusedbyspecialistsin
patientswhosebloodpressuresaredifficulttocontrol.Fluid
retentionandtachycardiaarefrequentproblemswith
minoxidil,aswellasunwantedhairgrowth(particularlyin
women).Furosemideisoftenrequiredtocopewiththefluid
retention.

56. Overall Mechanism of Action

58. Maintenance Therapy & Reassessment
Fixeddrugcombinationsshouldbeavoidedintheinitial
stagestilloptimalcontrolisachievedasfineadjustmentin
dosageofindividualcomponentsmayberequired.
Oncethepatientisonastablemaintenancedoseofdrugs,
combinationtherapymaybeusedtoimprovecompliance.
Somedrugcombinationsshouldbeavoided:–
Twodrugsofsameclass
Diureticswithβ-blockers:Reportedtoincreaseincidence
ofnewonsetdiabetesmellitus
β-blockerswithverapamil:Precipitatesconductionblocks