hipertensi kuliah
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HipertensiHipertensi
Diagnosis, Pencegahan dan TerapiDiagnosis, Pencegahan dan Terapi
MUZAKKIR AMIR
110110atauatau180180 Stage 3Stage 3
100-109100-109atauatau160-179160-179 Stage 2Stage 2
90-9990-99atauatau140-159140-159 Stage 1Stage 1
Hypertension*Hypertension*
85-8985-89atauatau130-139130-139High-normalHigh-normal
<85<85dandan<130<130NormalNormal
<80<80dandan<120<120OptimalOptimal
DiastolicDiastolic(mm Hg)(mm Hg)
SystolicSystolic(mm Hg)(mm Hg)
CategoryCategory
Definisi Hipertensi (JNC VI)Definisi Hipertensi (JNC VI) Dikatakan Hipertensi apabila tekanan darah secara konsisten terbaca
140/90 mm Hg pada orang dewasa. Klasifikasi tekanan darah pada seseorang berumur 18 dan lebih
*Based on the average of two or more readings taken at each of two or more visits after an initial screening.
The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. November 1997. NIH publication 98-4080
WHO-ISH (1999) WHO-ISH (1999)
Klasifikasi Derajat Tekanan Darah menurut WHO-ISH 1999 yang diadaptasi dari JNC VI 1997
Kategori Sistolik Diastolik (mmHg) (mmHg)
1 Optimal 120 80
2 Normal 130 85
3 Normal Tinggi 130 - 139 85 - 89
4 Hipertensi derajat 1 (ringan) 140 - 159 90 - 99Subgrup : perbatasan 140 - 149 90 - 94
5 Hipertensi derajat 2 (sedang) 160 - 179 100 - 109
6 Hipertensi derajat 3 (berat) 180 110
7 Hipertensi Sistolik 140 90(Isolated Systolic Hypertension)
>>100100atauatau>> 160 160 Stage 2Stage 290-9990-99atauatau140-159140-159 Stage 1Stage 1
HipertensiHipertensi
80-8980-89atauatau120-139120-139Pre HipertensiPre Hipertensi
<80<80dandan<120<120NormalNormal
DiastolicDiastolic(mm Hg)(mm Hg)
SystolicSystolic(mm Hg)(mm Hg)CategoryCategory
Definisi Hipertensi (JNC VII)Definisi Hipertensi (JNC VII)
Klasifikasi tekanan darah pada seseorang berumur 18 dan lebih
Franklin, S.S., J Hypertens 1999; 17 (suppl 5): S29-S36
Hipertensi salah satu dari penyakit yang sering dijumpai di klinik
0
10
20
30
40
50
60
70
18-29 30-39 40-49 50-59 60-69 70-79 80+
SBP > 140 mm Hg DBP > 90 mm Hg
age (yrs)
pre
vale
nce
of
hyp
erte
nsi
on
(%
)
4 11
21
4454
64 65
Prevalensi dari HipertensiPrevalensi dari Hipertensi
Prevalensi :Prevalensi :
Berdasar kriteria Hipertensi WHO 1968 (tekanan darah > 160/95 mmHg), prevalensi hipertensi di dunia sekitar 5-18 %. Prevalensi hipertensi di Indonesia tidak jauh berbeda yaitu sekitar 6-15 %, walaupun dilaporkan adanya prevalensi yang rendah yaitu :
- Ungaran 1,8 %- Lembah Balim 0,6 %
serta adanya prevalensi yang tinggi :- Silungkang 19,4 %- Talang 17,8 %
Prevalensi Hipertensi di Jawa Timur hampir sama yaitu :- Sumberpucung (1976) 10 %- Lawang (1987) 11 %- Kampak (1987) 17 %
Presentasi pasien hipertensi yang terkontrol
Presentasi pasien hipertensi yang terkontrol
Adapted from G. Mancia / L. Ruilope
USA: JNC VI. Arch Intern Med 1997Canada: Joffres et al. Am J Hypertens 1997 England: Colhoun et al. J Hypertens 1998France: Chamontin et al. Am J Hypertens 1998
< 140/90 mmHg< 140/90 mmHg
Canada
16
USA
27
England6
France
24
Marques-Vidal P et al. J Hum Hypertens 1997
< 160/95 mmHg< 160/95 mmHg
Finland
20.5
Spain
20
Australia
19
Germany
22.5
> 65 years
Scotland
17.5
India
9
Khattar, R.S. et al. Circulation 1999; 100:1071-4
Assessment of the 24-hour blood pressure load isa good clinical method to identify high-risk patients
even
ts/1
00 p
t/yr
s
200+
mm Hg
< 140 140-159 160-179 180-199
1
2
3
4
5
6
7
Systolic Blood PressureSystolic Blood Pressure
Total Mortality and Continuous Ambulatory Blood Pressure
Total Mortality and Continuous Ambulatory Blood Pressure
1
2
3
4
5
Diastolic Blood PressureDiastolic Blood Pressure
mm Hg
< 80 80-89 90-99 100-109 110+
Brown, M.J., Lancet 2000;355:653-4
Risiko Infark Miokard dan Stroke Risiko Infark Miokard dan Stroke
Systolic blood pressure (mm Hg)
5-ye
ar r
isk
(%)
0
5
10
15
0 100 200 300
StrokeStrokeMIMI
CHFCumulativeIncidence
(%)
Years From Baseline Exam
5 10 15
20
15
10
5
0
Lenfant C, Roccella EJ. J Hypertens Suppl. 1999;17:S3-S7.Data from Levy D et al. JAMA. 1996;275:1557-1562.
Stage 2+ hypertension
Stage 1+ hypertension
Normal BP
Cumulative Incidence of CHF : Normotensives and Stage 1 and 2 Hypertensives
Cumulative Incidence of CHF : Normotensives and Stage 1 and 2 Hypertensives
Benefits of Lowering BPBenefits of Lowering BP
Average Percent Average Percent
ReductionReduction
Stroke incidence Stroke incidence 35–40% 35–40%
Myocardial infarction Myocardial infarction 20–25% 20–25%
Heart failureHeart failure 50% 50%
HipertensiHipertensi
Berdasarkan penyebabnya dapat dibedakan :
• Primer (essential)– tidak ada penyebab yang spesifik yang dapat
diidentifikasi– 95% dari kasus hipertensi
• Sekunder– diketahui penyebabnya– 5% dari kasus hipertensi– penyakit ginjal merupakan penyebab dari 90%
kasus hipertensi sekunder
Hypertension :The Disease Continuum
Hypertension :The Disease Continuum
Early Paradigm
Elevated BP Target Organ Damage
Natural History of CVD ProgressionNatural History of CVD Progression
More Recent Paradigm
Vascular Dysfunction Elevated BP Target Organ Damage
A Proposed Future Paradigm
EndothelialDysfunction
LVHRenal
DamageMI Stroke
AnginaPectoris
VascularDysfunction
Elevated BP Target OrganDamage
?
Etiology HypertensionEtiology Hypertension• Secondary Hypertension :
– Renal disease :• Renal arterial disease• Renal parenchymal disease• Renal tumors• Arteritis (polyarteritis nodosa, neurofibromatosis)
– Endocrine Disorders• Cushing’s syndrome• Acromegaly• Primary aldosteronism• Pheochromocytoma
– Coarctation of the aorta– Neurologic disorders
• Increased intra cranial pressure (tumor)– Drug-induced hypertension
• Corticosteroids• Amphetamines• Oral contraceptives
– Psychogenic disorders
Komplikasi HipertensiKomplikasi Hipertensi
Kerusakan yang disebabkan oleh hipertensi tergantung :
• Besarnya peningkatan tekanan darah
• Lamanya kondisi tekanan darah yang tidak terdiagnosis dan tidak diobati
Kerusakan Target Organ!!Eyesretinopathy
Kidneysrenal failure
Brainstroke
Heartischaemic heart disease
left ventricular hypertrophyheart failure
Peripheral arterial disease
SymptomsSymptoms
• Headache
• Dizziness
• Fatigue
• Pounding of the heartSymptoms are not specific and no more frequent than in patients with normotension.
• Symptoms of complications : heart failure, chest pain, claudication, vision
Evaluasi Klinik Hipertensi : Evaluasi Klinik Hipertensi :
Evaluasi klinik dan laboratorium Hipertensi dilakukan untuk 4 tujuan :
1.Konfirmasi Hipertensi dan menentukan tingkatnya
2.Untuk menyingkirkan dan menemukan Hipertensi Sekunder
3.Untuk menentukan Kerusakan Organ Target
4.Untuk mencari Faktor Risiko Kardiovaskuler dan Kondisi Klinik lain yang mempengaruhi Prognosis dan Pengobatan Hipertensi.
Riwayat Klinik :Riwayat Klinik :• Riwayat keluarga HT, DM, dislipidemia, PJK, stroke atau penyakit ginjal
• Lama dan tingkat tekanan darah tinggi sebelumnya dan hasil pengobatan serta efek samping obat antihipertensi sebelumnya
• Riwayat atau gejala sekarang PJK dan gagal jantung, penyakit serebrovaskuler, penyakit vaskuler perifer, DM, pirai, dislipidemia, asma bronkhiale, penyakit ginjal, dan informasi obat yang diminum
• Penilaian faktor risiko termasuk diet lemak, natrium dan alkohol, jumlah rokok, tingkat aktifitas fisik, dan peningkatan berat badan sejak awal dewasa
• Riwayat obat-obatan atau bahan lain yang dapat meningkatkan tekanan darah termasuk kontrasepsi oral, obat anti-keradangan non-steroid, kokain dan amfetamin.
• Faktor pribadi, psikososial dan lingkungan yang dapat mempe-ngaruhi hasil pengobatan antihipertensi termasuk situasi keluarga, lingkungan kerja dan latar belakang pendidikan.
Pemeriksaan Fisik :Pemeriksaan Fisik :
• Pemeriksaan fisik lengkap termasuk pengukuran tekanan darah yang teliti
• Pengukuran tinggi dan berat serta kalkulasi BMI (Body mass Index) yaitu berat dalam kg dibagi tinggi dalam m2
• Pemeriksaan sistim kardiovaskuler terutama ukuran jan-tung, bukti adanya gagal jantung, penyakit arteri karotis, renal dan perifer lain serta koarktasio aorta
• Pemeriksaan paru adanya ronkhi dan bronkhospasme serta bising abdomen,
• Pemeriksaan fundus optikus dan sistim syaraf untuk mengetahui kemungkinan adanya kerusakan serebro-vaskuler.
Pengukuran Tekanan Darah :Pengukuran Tekanan Darah :• Karena adanya variasi yang besar TD, diagnosis hipertensi harus
berdasarkan beberapa kali pengukuran yang diambil pada beberapa kesempatan (waktu) yang terpisah.
• TD biasanya diukur secara tak langsung dengan sphygmo-manometer air raksa atau alat noninvasif lainnya pada posisi duduk atau telentang.
• sebelum pengukuran penderita istirahat 5 menit diruangan yang tenang
• ukuran manset lebar 12-13 cm serta panjang 35 cm, ukuran lebih kecil pada anak-anak dan lebih besar pada penderita gemuk (ukuran sekitar 2/3 lengan)
• diperiksa pada fosa kubiti dengan cuff setinggi jantung (ruang antar iga IV)
• TD dapat diukur pada keadaan duduk atau telentang, pada JNC VII dianjurkan pada posisi duduk
• TD dinaikkan sampai 30 mmHg (4.0 kPa) diatas tekanan sistolik (palpasi), kemudian diturunkan 2 mmHg/detik (0,3 kPa/detik) dan dimonitor dgn stetoskop diatas a brakhialis.
• tekanan sistolik ialah tekanan pada saat terdengar suara Korotkoff I sedangkan tekanan diastolik pada saat Korotkoff V menghilang. Bila suara tetap terdengar, dipakai patokan Korotkoff IV (muffling sound).
• pada pengukuran pertama dianjurkan pada kedua lengan terutama bila terdapat penyakit pembuluh darah perifer.
• kadang perlu pengukuran pada posisi duduk/telentang dan berdiri untuk mengetahui ada tidaknya hipotensi postural terutama pada orang tua, diabetes mellitus dan keadaan lain yang menimbulkan hal tersebut (pemberian penyekat alfa).
Pengukuran Tekanan Darah :Pengukuran Tekanan Darah :
Pengukuran tekanan darah ambulatoryPengukuran tekanan darah ambulatory
Sekarang terdapat alat otomatis untuk mengukur tekanan darah selama 24 jam atau lebih.
Indikasi pemeriksaan tersebut (ABPM = Ambulatory Blood Pressure Monitoring) ialah sebagai berikut :
1. Adanya variasi tekanan darah yang besar
2. Office hypertension
3. Dicurigai adanya episode hipotensi
4. Hipertensi yang resisten terhadap pengobatan
Pemeriksaan lain-lainPemeriksaan lain-lain• Pemeriksaan Laboratorium :
• Urinalisis untuk darah, protein dan gula serta pemeriksaan mikroskopik urin• Serum kalium, kreatinin, gula darah puasa & 2 jam dan profil lemak, asam urat• Pemeriksaan tambahan :
– Pemeriksaan hormonal seperti pengukuran aktifitas renin plasma, aldosteron plasma dan katekolamin urine atas indikasi khusus (hipertensi sekunder)
• Pemeriksaan EKG• Pemeriksaan foto polos dada• Ekhokardiografi diperiksa bila mencurigakan adanya keru-sakan organ
target (LVH atau kelainan jantung yang lain)• Ultrasonografi vaskuler bila mencurigakan adanya penyakit arteri karotis,
aorta atau perifer yang lain• Ultrasonografi renal bila dicurigai adanya penyakit ginjal• Angiografi
Goals of Therapy(JNC-VII)
Goals of Therapy(JNC-VII)
Reduce CVD and renal morbidity and mortality.
Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.
Achieve SBP goal especially in persons >50 years of age.
Minimal BP Goal of TherapyMinimal BP Goal of Therapy
Recommendations (SBP/DBP mmHg)
Patient Type
Uncomplicated HTN
Hypertension with diabetes mellitus
Heart failure
Hypertension with renal impairment†
JNC VI
< 140/90
< 130/85 < 130/80*
< 130/85
< 125/75
(Bakris GL, et al for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000) (JNC VI. Arch Intern Med. 1997)
*National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.†Proteinuria > 1 g/24h.
CVD Risk FactorsCVD Risk Factors
Hypertension* Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia* Diabetes mellitus* Microalbuminuria or estimated GFR <60 ml/min Age (older than 55 for men, 65 for women) Family history of premature CVD
(men under age 55 or women under age 65)
* Components of the metabolic syndrome.
Target Organ Damage Target Organ Damage
Heart• Left ventricular hypertrophy• Angina or prior myocardial infarction• Prior coronary revascularization• Heart failure
Brain• Stroke or transient ischemic attack
Chronic kidney disease
Peripheral arterial disease Retinopathy
Terapi HipertensiTerapi Hipertensi
• Terapi Non-farmakologis
– Menurunkan berat badan (5-20 mmHg/10 kg)
– Latihan dan olah raga (4-9 mmHg)
– Menghindari alkohol yang berlebihan
– Mengurangi asupan garam (2-8 mmHg)
– Stop merokok
– Menurunkan asupan lemak jenuh
Terapi HipertensiTerapi Hipertensi
• Terapi Farmakologis– tujuan terapi antihipertensi
• Memperbaiki fx. Endothel (?)• untuk menurunkan resistensi vaskular sistemik• mempertahankan curah jantung• mempertahankan suplai darah ke organ dan
jaringan– Pengobatan diberikan seumur hidup– Kepatuhan yang buruk merupakan penyebab
kegagalan terapi antihipertensi yang paling besar
Pilihan terapi antihipertensiPilihan terapi antihipertensi
Diuretik
Beta-blocker
Antagonis kalsium
ACE-inhibitor
Angiotensin II receptor antagonis (AIIRA)/ARB
Alpha1-blocker (sentral & perifer)
Risk Stratification and Treatment(JNC-VI)
Risk Stratification and Treatment(JNC-VI)
Risk Group BRisk Group B Risk Group CRisk Group C(At Least 1 Risk(At Least 1 Risk (TOD/CCD and/or(TOD/CCD and/or
Risk Group ARisk Group A Factor, Not IncludingFactor, Not Including Diabetes, With orDiabetes, With orBlood Pressure StagesBlood Pressure Stages (No Risk Factors(No Risk Factors Diabetes; NoDiabetes; No Without Other RiskWithout Other Risk(mmHg)(mmHg) No TOD/CCD)No TOD/CCD)†† TOD/CCD)TOD/CCD) Factors)Factors)
High-normalHigh-normal LifestyleLifestyle LifestyleLifestyle Drug therapyDrug therapy§§
(130-139/89-89)(130-139/89-89) modificationmodification modificationmodification
Stage 1Stage 1 LifestyleLifestyle LifestyleLifestyle Drug therapyDrug therapy(140-159/90-99)(140-159/90-99) modificationmodification modificationmodification‡‡
(up to 12 months)(up to 12 months) (up to 6 months)(up to 6 months)
Stages 2 and 3 Stages 2 and 3 Drug therapyDrug therapy Drug therapyDrug therapy Drug therapyDrug therapy((>> 160/ 160/>> 100) 100)
For example, a patient with diabetes and a blood pressure of 142/94 mmHg plus left ventricular hypertrophy should be classified as having stage 1 hypertension with target organ disease (left ventricular hypertrophy) and with another major risk factor (diabetes). This patient would be categorized as Stage 1, Risk Group C, and recommended for immediate initiation of pharmacologic treatment.
Algorithm for Treatment of HypertensionAlgorithm for Treatment of Hypertension
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling Indications
Lifestyle Modifications
Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension(SBP 140–159 or DBP 90–99
mmHg) Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
Without Compelling Indications
Not at Goal Blood Pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
Classification and Management of BP for adults
Classification and Management of BP for adults
* Treatment determined by highest BP category.† Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡ Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.
Two-drug combination for mostTwo-drug combination for most†† (usually thiazide-type diuretic (usually thiazide-type diuretic and ACEI or ARB or BB or and ACEI or ARB or BB or CCB). CCB).
Yes Yes or or >>100 100 >>160 160 Stage 2 Stage 2 Hypertension Hypertension
Drug(s) for the Drug(s) for the compelling indications.compelling indications.‡‡
Other antihypertensive Other antihypertensive drugs (diuretics, ACEI, drugs (diuretics, ACEI, ARB, BB, CCB) as ARB, BB, CCB) as needed. needed.
Thiazide-type diuretics for most. Thiazide-type diuretics for most. May consider ACEI, ARB, BB, May consider ACEI, ARB, BB, CCB, or combination. CCB, or combination.
Yes Yes or 90–99 or 90–99 140–159 140–159 Stage 1 Stage 1 Hypertension Hypertension
Drug(s) for compelling Drug(s) for compelling indications. indications. ‡‡
No antihypertensive drug No antihypertensive drug indicated. indicated.
Yes Yes or 80–89 or 80–89 120–139 120–139 Prehypertension Prehypertension
Encourage Encourage and <80 and <80 <120 <120 Normal Normal
With compelling With compelling indicationsindications
Without compelling Without compelling indication indication
Initial drug therapyInitial drug therapy Lifestyle Lifestyle
modificationmodification DBP* DBP*
mmHg mmHg SBP* SBP*
mmHgmmHg BP classificationBP classification
Compelling Indications for Individual Drug Classes
Compelling Indications for Individual Drug Classes
Clinical Trial BasisClinical Trial BasisInitial Therapy Options Initial Therapy Options Compelling Indication Compelling Indication
ALLHAT, HOPE, ALLHAT, HOPE, ANBP2, LIFE, ANBP2, LIFE, CONVINCE CONVINCE
ACC/AHA Post-MI ACC/AHA Post-MI Guideline, BHAT, Guideline, BHAT, SAVE, Capricorn, SAVE, Capricorn, EPHESUSEPHESUS
ACC/AHA Heart Failure ACC/AHA Heart Failure Guideline,Guideline, MERIT-HF, MERIT-HF, COPERNICUS, CIBIS, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, SOLVD, AIRE, TRACE, ValHEFT, RALES ValHEFT, RALES
THIAZ, BB, ACE, CCB THIAZ, BB, ACE, CCB
BB, ACEI, ALDO ANT BB, ACEI, ALDO ANT
THIAZ, BB, ACEI, ARB, THIAZ, BB, ACEI, ARB, ALDO ANT ALDO ANT
High CAD risk High CAD risk
PostmyocardialPostmyocardialinfarction infarction
Heart failure Heart failure
Compelling Indications for Individual Drug Classes
Compelling Indications for Individual Drug Classes
Recurrent stroke Recurrent stroke prevention prevention
Chronic kidney disease Chronic kidney disease
Diabetes Diabetes
Clinical Trial BasisClinical Trial BasisInitial Therapy Options Initial Therapy Options Compelling Indication Compelling Indication
PROGRESS PROGRESS
NKF Guideline, NKF Guideline, Captopril Trial, Captopril Trial, RENAAL, IDNT, RENAAL, IDNT, REIN, AASK REIN, AASK
NKF-ADA Guideline,NKF-ADA Guideline, UKPDS, ALLHAT UKPDS, ALLHAT
THIAZ, ACEI THIAZ, ACEI
ACEI, ARB ACEI, ARB
THIAZ, BB, ACE, ARB, THIAZ, BB, ACE, ARB, CCB CCB
Reasons of inadequate BP ControlReasons of inadequate BP Control
• Acceptance of inadequate control by physician
• Difficulty achieving BP control with one agent/suboptimal
regimens
• BP goals are more aggressive than in previous years
• Lack of compliance due to :
– perceived side effects of antihypertensive
medication(s)
– frequency of dosing/multiple agents to attain control
(Adapted from JNC VI. Arch Intern Med. 1997)
HipertensiHipertensi• Secondary Hypertension :
Renal diseaseRenal disease Interference with renal control systems over cardiovascularInterference with renal control systems over cardiovascularsystem - activation of renin-angiotensin-aldosterone (RAA)system - activation of renin-angiotensin-aldosterone (RAA)system, leading to increased blood volume & hence hypertensionsystem, leading to increased blood volume & hence hypertension
Renal arteryRenal artery Atherosclerotic narrowing of decreased vasodilatory mechanismsAtherosclerotic narrowing of decreased vasodilatory mechanismsstenosisstenosis leading to reduced renal blood flow and activation of RAA systemleading to reduced renal blood flow and activation of RAA system
Endocrine disordersEndocrine disordersHyperaldosteronismHyperaldosteronism Excessive aldosterone production leading to salt and waterExcessive aldosterone production leading to salt and water(Conn(Conn’’s syndrome)s syndrome) retention and increased blood volumeretention and increased blood volumeCushingCushing’’s syndromes syndrome Excessive ACTH secretion leading to salt and water retention andExcessive ACTH secretion leading to salt and water retention and
increased blood volumeincreased blood volume
PhaeochromocytomaPhaeochromocytoma Tumour of the adrenal medulla producing excessive adrenaline,Tumour of the adrenal medulla producing excessive adrenaline,causing vasoconstrictioncausing vasoconstriction
PregnancyPregnancy Complex, involving fluid volume and hormonal fluctuationsComplex, involving fluid volume and hormonal fluctuations
Coarctation of theCoarctation of the Congenital localised narrowing of the aortic lumen, causingCongenital localised narrowing of the aortic lumen, causingaortaaorta increased afterload and peripheral resistance in the upper bodyincreased afterload and peripheral resistance in the upper body
Certain drugs,Certain drugs, Complex and variousComplex and variouse.g. corticosteroids,e.g. corticosteroids,oral contraceptivesoral contraceptivesand vasoconstrictorsand vasoconstrictors
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