Suhardi

Scomec samarinda, 7 November 2015

 Update in hypertension
Global mortality 2000: impact of hypertension
and other health risk factors

High blood pressure (BP)

Tobacco
High cholesterol
Underweight
Unsafe sex
High BMI
Physical inactivity
High-mortality, developing region
Alcohol Low-mortality, developing region
Indoor smoke from fuels Developed region
Iron deficiency
0 1000 2000 3000 4000 5000 6000 7000 8000
Attributable mortality
(In thousands; total 55,861,000)

Adapted from Ezzati et al, Lancet, 2002.

 Prevalence of Hypertension
Hypertension is one of the most frequent clinical discorders.
prevalence of hypertension (%)

70
SBP > 140 mm Hg 65
60 64
DBP > 90 mm Hg
50 54

40 44

30
20 21
10 4 11
0
age (yrs) 18-29 30-39 40-49 50-59 60-69 70-79 80+

Franklin, S.S., J Hypertens 1999; 17 (suppl 5): S29-S36

 COMPLICATIONS OF HYPERTENSION

Acute Complication Chronic complication

- Abruptly - Gradually
- Related with accelerated - Related with duration
elevation of BP of hypertension
- BP must be decreased - BP managed smartly
aggressively

Hypertensive Crisis
 Prevalence of Hypertensive crisis

• Hypertensive crisis represented 27 % of all medical

emergencies encountered over a year interval
(zampaglione et al, Turin, Italy, 1996)
• Hypertensive emergencies occur most frequently in
patients previously diagnosed with primary hypertension
but who are non compliant.
• At present + 1 % of patient with primary hypertension will
progress to an accelerated-malignant form

5
Definitions

Hypertensive Crisis
Acute increasing of BP
>180/120 mmHg
Need immediate treatment

Hypertensive Urgency Hypertensive Emergency

Markedly elevated BP Markedly elevated BP

Without severe symptoms or With acute or progressing
progressive target organ damage target organ damage
BP should be reduced within hours BP should be reduced immediate
ORAL AGENTS PARENTERAL AGENTS

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9 th Ed, Lippincott Williams & Wilkins 2006:609-630
 Definition...
Hipertensive Emergencies
Diastolic blood pressure> 120 mmHg accompanied by 1 /> acute
conditions :
1. Acute ischaemia or haemorrhagic stroke
2. Hypertensive encephalopathy
3. Acute aortic dissection
4. Eclampsia
5. Funduscopic KW III or IV
6. Acute renal insufficiency
7. Acute miocardial infarction
8. Acute pulmonary edema
9. Conditions of excess catecholamine
10. Bleeding
 Definition...
Hipertensive Urgency

1. Severe hypertension with diastolic

blood pressure more ≥120 mmhg without
target organ damage
2. Post operative hypertension
3. Uncontroled (severe) hypertension
4. Funduscopic KW I or II
 Etiology
Causes of hypertension emergencies :
Essenstial hypertension
Renal disease
chronic pyelonephritis
Primary glomerulonephritis
Vascular/ glomerular disease : SLE,systemic sclerosis, renal vasculitides
(microscopic polyarteritis nodosa, Wegener’s granulomatosis)
Tubulointerstitial nephritis
Renovascular disease
Renal artery stenosis : fibromuscular dysplasia
Atherosclerotic renovascular disease
Drugs
Abrupt withdrawal of centrally acting α1 adrenergic agonist (clonidin, methyldopa)
Phencyclidine, cocain or other sympathomimetic drug intoxication
Interaction with monoamine oxidase inhibitors (tranylpromine, phenelzine, and selegiline)
Pregnancy : eclampsia/ severe pre-eclampsia
Endocrine : Pheochromocytoma,primary aldosteronism,glucocorticoid excess, renin secreting tumors
Central nervous system disorders : CVA infarction/ hemorrhage, head injury

Kaplan et al. 2010

Patophysiology
 Severe hypertension
Endocrine disorder Essential
hypertension
pregnancy
Renal disorder
Critical degree of HT
Drug
or rapid rate of rise &
↑ vascular resistance

Local effects (PG, free radical) Spontaneous

natriuresis
Endothelial damage Intravascular vol depletion

↑ Endothelial permeability ↑ vasoconstrictors

Platelet & fibrin deposition Vasodilators ↓

Further increase in BP

Mitogenic & migration fc Severe BP ↑

Myointimal proliferation & End organ
Tissue ischaemia
fibrinoid necrosis dysfunction
 DIAGNOSIS
OF HYPERTENSION

Jan 18, 2001

Clinical Assessment of Hypertension

History

Physical examination

Additional examination
HISTORY

 The duration and severity of hypertension

 Anti hipertensive drug used and the level of
compliance
 Age
 Neurological disorder
 Renal system disorder
 Cardiovascular system disorder
 History of previous illness
 History of pregnancy

Maria AR. et al. Cardiology in review. 2010

Clinical sign & symptom

SOB

Neurological disorder

Maria AR. et al. Cardiology in review. 2010

Vidt D. Emergency room management of hypertensive urgency & emergency. 2001
 Physical Examination

 Blood pressure measurement

 Pulse palpation in all extremities
 Auscultation of the carotid arteries ,renal
arteries and abdominal aorta
 Cadio pulmonary :
rales , gallop, murmur

Maria AR. et al. Cardiology in review. 2010

Abdul M. Krisis hipertensi, aspek klinis dan pengobatan. 2004
Joseph V. et al. Journal of geriatric cardiology. 2007
Vidt D. Emergency room management of hypertensive urgency & emergency. 2001
 Additional Examination

 Blood test
 Urinalysis
 ECG
 Echocardiography
 Chest x-ray
 Funduscopic : retinopathy st III, and/ papiledema
(rethinopathy st IV)
 Renal function test
 Intracerebral examination (CT scan, MRI)
 Management
A doctor must perform appropriate triage
action to achieve therapeutic goals both
short and long term in patients with
increased blood pressure

Christopher J. Hebert. et al. 2008

Management

Christopher J. Hebert. et al. 2008

 Management ...

Drugs used in hypertensive urgency

Elisenda G. et al. 2010

 Management of
Hypertensive Emergency (general)

 Patients should be admitted to an Intensive Care Unit for

continuous monitoring of BP and parenteral
administration of an appropriate agent
 The initial goal therapy is to reduce mean arterial BP by
no more than 25% (within minutes to 1 hour).
 Then if stable, to 160/100 to 110 mmHg within the next 2
to 6 hours.
 Excessive falls in pressure that may precipitate renal,
cerebral, or coronary ischemia should be avoided.

Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

Management of
Hypertensive Emergency (general)
 If this level of BP is well tolerated and the
patients is clinically stable , further gradual
reductions toward a normal BP can be
implemented in the next 24 to 48 hours.
 Exceptions :
1. Patients with ischemic stroke
2. Aortic dissection SBP should < 100 mmHg
3. Patients whom BP is lowered to enable the use
of thrombolytic agents

Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

Parenteral Drugs for Treatment of
Hypertensive Emergencies based on JNC 7
Drugs Dose Onset Duration of
Action
Sodium 0.25-10 ugr/kg/min Immediate 1-2 minutes after
nitroprusside infusion stopped
Nitroglycerin 5-500 ug/min 1-3 minutes 5-10 minutes

Labetolol HCl 20-80 mg every 10-15 5-10 minutes 3-6 minutes

min or 0.5-2 mg/min
Fenoldopan HCl 0.1-0.3 ug/kg/min <5 minutes 30-60 minutes

Nicardipine HCl 5-15 mg/h 5-10 minutes 15-90 minutes

Esmolol HCl 250-500 ug/kg/min IV 1-2 minutes 10-30 minutes

bolus, then 50-100
ug/kg/min by infusion;
may repeat bolus after 5
minutes or increase
infusion to 300 ug/min
Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70
Parenteral Drugs for Treatment of
Hypertensive Emergencies based on
ASA Guideline

Drug I.V. Bolus Dose Continous Infus

Rate
Labetalol 5 – 20 mg every 15’ 2 mg/min (max 300mg/d)
Nicardipine NA 5-15 mg/h
Esmolol 250 ug/kg IVP loading dose 25-300 ug/kg/m
Enalapril 1,25-5 mg IVP every 6 h NA
Hydralazine 5 – 20 mg IVP every 30’ 1,5-5 ug/kg/m
Nipride NA 0,1-10 ug/kg/m
NTG NA 20-400 ug/m

This parenteral drugs are approved for hypertensive emergency

in acute ischemic stroke and intracerebral hemmorhage
AHA/ASA Guideline, 2007 update. Stroke. 2007;38: 2001-2023.
Parenteral Drugs for Treatment of
Hypertensive Emergencies based on CHEST 2007
Acute Pulmonary edema / Nicardipine, fenoldopam, or nitropruside combined with
Systolic dysfunction nitrogliceryn and loop diuretic
Acute Pulmonary edema/ Esmolol, metoprolol, labetalol, verapamil, combined with
Diastolic dysfunction low dose of nitrogliceryn and loop diuretics
Acute Ischemia Coroner Labetalol or esmolol combined with diuretics
Hypertensive encephalopaty Nicardipine, labetalol, fenoldopam
Acute Aorta Dissection Labetalol or combined Nicardipine and esmolol or
combine nitropruside with esmolol or IV metoprolol
Preeclampsia, eclampsia Labetalol or nicardipine
Acute Renal failure / Nicardipine or fenoldopam
microangiopathic anemia
Sympathetic crises/ cocaine Verapamil, diltiazem, or nicardipine combined with
oveerdose benzodiazepin
Acute postoperative Esmolol, Nicardipine, Labetalol
hypertension
Acute ischemic stroke/ Nicardipine, labetalol, fenoldopam
intracerebral bleeding

Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62

Nitroglycerin

Nitroglycerin is a potent venodilator and only at high doses affect

arterial tone. It reduces BP by reducing cardiac
ouput and preload which are undesirable effects in patient with
compromised cerebral and renal perfusion

Nifedipine
Nifedipine has been widely used via oral or sublingual
administration in the management of hypertensive
emergencies. This mode of administration has not been
approved by FDA and since JNC VI because it may cause
sudden uncontrolled and severe reductions in blood pressure
may precipitate cerebral, renal, and myocardial ischemia that
have been associated with fatal outcomes
 USE OF NICARDIPINE

• Nicardipine :
. Dihydropiridine class of CCB

• Reduce peripheral resistance --- blood pressure

• water soluble, light insensitive, -- can be

parenteraly used (deference with nifedipine /
sodium nitroprusid)
 Calcium Channel Blocker Mechanism

Ca++ Ca++
Blocking
effect of CCB
 

Ca++ plus Calmodulin Ca++ plus Calmodulin

 
Myosin Kinase Myosin Kinase

   
Actin-Myosin Interaction
 Contraction

 
Ca++ Ca++
PRIMARY HEMODYNAMIC OF
NICARDIPINE EFFECT

• peripheral vasodilatation
• preserve or enhanced cardiac pump activity
------ improve tissue perfusion
• fall in systemic blood pressure, maintain at desired
level
• in comparison with sodium nitropruside – equally
effective, but no cyanide toxic effect in long term use
• not associated adverse effect on cardiovascular and
renal function
 NICARDIPINE
CHARACTERISTIC
1.VASOSELECTIVITY
Nicardipine selectivity 30.000 x in smooth muscle cells
blood vessels compared with myocardium
2. Myocardial depression (-)
3. Negative inotropic (-)
4. Rapid and stable antihypertensive effects, reduce blood
pressure gradually < 25% in 2 hours, minimal effects to
heart rate
5. Increase blood flow in major organ : Renal, coroner,
cerebral
 Actions to increase organ blood
flow Pharmacodynamic action

Perdipine: 3 g/kg/min  20 min

⊿%)
Mean blood Vertebral Renal Coronary (Hypertensive patients, n = 9)
pressure artery blood flow blood flow
60
Blood flow change rate

blood flow

Baseline value
40
Mean blood pressure 103  11 mmHg

20 Vertebral artery
183  65 mL/min
blood flow
Renal artery
563  29mL/min
0 blood flow
Mean blood pressure

Coronary artery
121  42 mL/min
change rate

blood flow
-10

-20
(⊿%)
(Shoji Suzuki, et al., The 20th Annual Scientific Meeting of the Japanese Society of Hypertension: 1997)
Tissue selectivity between
Calcium Antagonist

Bristow et al. Br J Pharmacol1984; 309:82

Comparison between Calcium Antagonist

Suppression
Coronary Suppression Suppression
Drug of Cardiac
Vasodilation of SA Node of AV Node
Contractility

Verapamil
++++ ++++ +++++ +++++
(phenylalkylamine)

Diltiazem
+++ ++ +++++ ++++
(benzothiazepin)

Nicardipine
+++++ 0 + 0
(dihydropyridine)

Kerins DM. Goodman Gilman’s.10th ed.2001:843-70

 Prognosis

In a study of 315 patients with malignant hypertension,

40% will be alive after 33 months. Most deaths due to renal
failure (39.7%), myocardial infarction (11.1%), stroke
(23.8%), and heart failure (10.3%)

Paul E. Marik.2007
Vidt D. 2001
 SUMMARY
 Hypertensive Crises is an urgent situation that need rapid
management to prevent organ damage

 Antihypertensive agent that preffered in this condition should be fast

action, parenteral, and titratable

 Nicardipine is the only Calcium Antagonist recommended by JNC 7,

AHA, 2007, CHEST 2007 to manage hypertensive emergency

 Nicardipine has favorable antiischemic profile because of an increase

myocardial , brain, and kidney oxygen supply
 THANK YOU FOR YOUR ATTENTION

TAKE CARE OF YOUR HEART, BRAIN, AND KIDNEY