THE ROLE OF NICARDIPINE IN THE MANAGEMENT OF

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THE ROLE OF NICARDIPINE IN THE MANAGEMENT OF HYPERTENSIVE CRISIS Haerani Rasyid 2016

What is Hypertension? JNC-7 (American) Classification of Blood Pressure Category

Systolic

Diastolic

Optimal

<120

and / or

<80

Normal

<130

and / or

<85

High-Normal

130-139

and / or

85-89

Stage 1 (mild hypertension )

140-159

and / or

90-99

Stage 2 (moderate to severe hypertension)

160

and / or

100-109

Isolated Systolic Hypertension (ISH)

140

and

<90

The category pertains to the highest risk blood pressure *ISH=Isolated Systolic Hypertension.

JAMA 2003;289:2560-72

Hypertensive patients

Asymptomatic Severe Hypertension

Hypertensive Urgencies

Hypertensive Emergencies

(70-75%)

(25-30%)

Hypertensive Crisis

Asymptomatic Severe Hypertension - Blood pressure 180/110 mmHg

Hypertensive Urgencies

Hypertensive Emergencies

≥ - No absolute blood pressure - Usually very high blood level. Usually blood pressure ≥180/110 mmHg

pressure (often > 220/140 mmHg)

- Incidental findings in - Rapidity of BP elevation of - Rapidity of BP elevation of asymptomatic patient. greater import than magnitude of the elevation

greater import than magnitude of the elevation

- Abscence of symptoms beyond mild or - Presence of symptoms beyond - Accompanied by evidence moderate headache mild or moderate headache of life-threatening organ dysfunction

- Without evidence of - Without evidence of target organ damage acute target organ damage

acute

Prim Care Clin Office Pract 2008; 35: 475–487

Epidemiology of Hypertensive crisis •

Recently, came down to < 1 % of hypertensive patients, due to better management.



Common in the black & elderly patients.



Majority of patients have previous history of HTN and

treatment •

Formed 1/4 of the medical urgencies and emergencies



Hypertensive urgencies constituted 76 % of the hypertensive crises while emergencies were 24%. Zampaglione et al, Hypertension 1996; 27(1)144-147

Causes of Hypertensive Crisis  Essential 

hypertension

Medication noncompliance

 Secondary         

hypertension

Aortic coarctation Cushing’s syndrome Elevated ICP Renal dysfunction Pregnancy Hyperparathyroidism Hyperthyroidism Pheochromocytoma Primary aldosteronism JNC 7, JAMA 2003; 289:2560-2572.

Some Examples of Hypertensive Emergencies and Urgencies Hypertennsive Emergencies

Accelerated/malignant hypertension Hypertensive encephalopathy Acute left ventricular failure Acute aortic dissection Intracranial hemorrhage Pheochromacytoma crisis Monoamine oxidase inhibitor and tyramine interaction Eclampsia Substances/drug-induced acute hypertension

Hypertensive Urgencies

Accelerated/malignant hypertension* Severe hypertension associated with coronary artery disease Severe HT in the organ transplant patient Preoperative hypertension Hypertension associated with burns Severe, uncontrolled HT *Also can be considered an emergency on the basis of acute target organ dysfunction

Fenves et al. Semin. Nephrol. 2005;25:272-280

Pathophysiology  Not

well understood

 Failure

of normal autoregulation and an abrupt rise in systemic vascular resistance

PATHOPHYSIOLOGY

Endothelial damage

Severe Hypertension

Critical level or rapid rate of rise and increased vascular resistance

↑ Endothelial permeability

Spontaneous natriuresis

Intravascular volume depletion

Platelet and fibrin deposition Activates coagulation & inflammation

Fibrinoid necrosis and intimal proliferation Severe BP elevation

Increase in vasoconstrictors (renin-angiotensin, catecholamines)

Further increase in BP

Tissue ischemia End-organ dysfunction

Vaidya et al. Hospi.Physician.2007:43-50

Principle of Treatment The initial goal of antihypertensive therapy is not to rapidly normalize BP but rather to prevent damage to target organ by gradually decreasing mean arterial pressure (MAP), while minimizing the risk of hypoperfusion

Asymptomatic severe hypertension Admission

may be necessary in those on newly diagnozed or severe non-compliance is suspected. Patients already on treatment need to be reviewed and appropriate measures taken which include optimising treatment by using effective combination therapy

Hypertensive crisis Hypertensive urgencies  



These patients need to be admitted Blood pressure measurement should be repeated after 30 minutes of bed rest. Initial treatment should aim for about 25% reduction in blood pressure over 24 hours.

Hypertensive emergencies   



All these patients most be admitted The blood pressure need to be reduced relatively quickly It is suggested that the blood pressure be reduced by 25% over 3 to 12 hours This is best achieved with parenteral drugs.

Management of Hypertensive Emergency (general) 

 1. 2. 3.

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 : Patients with ischemic stroke Aortic dissection SBP should < 100 mmHg 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 nitroprusside

0.25-10 ugr/kg/min

Immediate

1-2 minutes after infusion stopped

Nitroglycerin

5-500 ug/min

1-3 minutes

5-10 minutes

Labetalol HCl

20-80 mg every 10-15 min or 0.5-2 mg/min

5-10 minutes

3-6 minutes

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 bolus, then 50-100 ug/kg/min by infusion; may repeat bolus after 5 minutes or increase infusion to 300 ug/min

1-2 minutes

10-30 minutes

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 Nicardipine Esmolol Enalapril Hydralazine Nipride NTG

5 – 20 mg every 15’ NA 250 ug/kg IVP loading dose 1,25-5 mg IVP every 6 h 5 – 20 mg IVP every 30’ NA NA

2 mg/min (max 300mg/d) 5-15 mg/h 25-300 ug/kg/m NA 1,5-5 ug/kg/m 0,1-10 ug/kg/m 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 / Systolic dysfunction

Nicardipine, fenoldopam, or nitropruside combined with nitrogliceryn and loop diuretic

Acute Pulmonary edema/ Diastolic dysfunction

Esmolol, metoprolol, labetalol, verapamil, combined with 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 / microangiopathic anemia

Nicardipine or fenoldopam

Sympathetic crises/ cocaine oveerdose

Verapamil, diltiazem, or nicardipine combined with benzodiazepin

Acute postoperative hypertension

Esmolol, Nicardipine, Labetalol

Acute ischemic stroke/ intracerebral bleeding

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

USE OF NICARDIPINE • Nicardipine : . Dihydropiridine class of CCB • Reduce peripheral resistance --- blood pressure • water soluble, light insensitive, -- can be parenteraly used (difference with nifedipine / sodium nitroprusid)

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 organs : Renal, coronary artery, cerebral

Actions to increase organ blood flow Pharmacodynamic action

Perdipine: 3 g/kg/min  20 min ⊿%) Blood flow change rate

60 40

Mean blood pressure

Vertebral artery blood flow

Renal blood flow

Coronary blood flow

(Hypertensive patients, n = 9)

Baseline value Mean blood pressure

Mean blood pressure change rate

20 0

-10

103  11 mmHg

Vertebral artery blood flow

183  65 mL/min

Renal artery blood flow

563  29mL/min

Coronary artery blood flow

121  42 mL/min

-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 Drug

Coronary Vasodilation

Suppression of Cardiac Contractility

Suppression of SA Node

Suppression of AV Node

Verapamil (phenylalkylamine)

++++

++++

+++++

+++++

Diltiazem (benzothiazepin)

+++

++

+++++

++++

Nicardipine (dihydropyridine )

+++++

0

+

0

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

DOSIS

PERDIPINE DIV (g/kg/min)

Bolus (g/kg)

Acute hypertensive crises during surgery

2 - 10

10 – 30

Hypertensive emergencies

0.5 – 6

Acute hypertensive crises during surgery

Hypertensive emergencies

0.5

1

2

6

(g/kg/min)

10

Dosage and Administration Start with the lowest dose. Eg 0.5 mcg/BW/min  15 drops  monitoring, if in 5-15 minutes there’s no significant blood pressure reducing  Increasing drip until 20 drop , and then can be increased until desirable blood pressure achieved ( about 3-5 drops each after monitoring) Monitoring blood pressure and heart rate frequently

Before choose to switch to oral, 1 hour before Perdipine is stopped, give oral drugs and Perdipine is tappered of

Nicardipine for the Treatment of Severe Hypertension in Pregnancy: A Review of the Literature Aim of study: To evaluate the efficacy and safety of intravenous nicardipine for the treatment of severe hypertension in pregnancy Sources: Medline and Cochrane Patients: Had chronic or gestational hypertension with or without marked proteinuria Primary outcomes: •Reduction of systolic/diastolic and/or mean arterial pressure •Reduction of time to target blood pressure, and •Reduction of severe maternal (hypotension, tachycardia) or severe fetal side effects (CTG abnormalities needing direct intervention) Results: •All patients had a significant reduction of both diastolic and systolic blood pressure. •Treatment resulted in a 91% success rate in studies that defined success and 20% reduction of mean arterial blood pressure or systolic/diastolic blood pressure in 87%. •Target blood pressure was reached within 23 minutes in 70% of the patients, 91% reached target blood pressure within 130 minutes Conclusion: Nicardipine is a very effective therapy for treatment of severe hypertension in pregnancy and may be a better alternative to other available treatment options Bijvank SWAN, Duvekot JJ. Obgyn Survey 2010; 65(5):342-7

Bijvank SWAN, Duvekot JJ. Obgyn Survey 2010, 65(5):342-7

Nicardipine Treatment of Hypertension During Pregnancy Objective: To assess the effects of nicardipine, a dihydropyridine CCB, on the fetus and mother in hypertensive pregnant women Methods: -40 pregnant patients with mild or moderate hypertension received oral nicardipine 20 mg 3x/day (mean duration of treatment 9 + 2.1 weeks) -20 patients with severe preeclampsia (diastolic blood pressure ≥110 mmHG and 24-h proteinuria ≥500 mg) received nicardipine IV at 2, 4, or 6 mg/Kg/h (mean duration of treatment 5.3+3.6 days)

Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14

Results:

Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14

Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14

Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14

Nicardipine Treatment of Hypertension During Pregnancy Conclusion: Oral or IV nicardipine seems to be safe in hypertensive pregnant patients with the dose used in our study

Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14

Objective: To evaluate the safety of long-term nicardipine treatment in severely pre-eclamptic women and their fetuses newborns. Methods: We divided 50 pregnant women into three groups according to the length of their treatment: short-term treatment of severely pre-eclamptic women (7 days or less n20); medium-term treatment also of severely pre-eclamptic women (8-28 days, n20); and long-term treatment of women with severe superimposed pre-eclampsia (29 days or more, n10.)

Conclusion Suggest that long-term treatment with nicardipine for severe pre-eclampsia is as effective and safe as a short- and medium-term treatment.

Objectives: To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy. Design: Randomized prospective study. Setting: The obstetric ward of the teaching hospital of Monastir Tunisia. Patients: Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension.

Conclusion Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy.

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

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THE ROLE OF NICARDIPINE IN THE MANAGEMENT OF

THE ROLE OF NICARDIPINE IN THE MANAGEMENT OF HYPERTENSIVE CRISIS Haerani Rasyid 2016 What is Hypertension? JNC-7 (American) Classification of Blood ...

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