HYPERTENSION Emergencies & Urgencies

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HYPERTENSIONEmergencies Urgencies

• Stephen S. Levin, D.O.

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Definitions

• Emergencies
• Symptomatic
• Acute End-Organ Damage
• Diastolic B.P. usually gt130 mmHg
• Urgencies
• Asymptomatic
• NO Acute End-Organ Damage
• Diastolic B.P. usually gt110 mmHg Systolic B.P.
  usually gt180 mmHg

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Begin Treatment! This is a Hypertensive
Emergency Begin to look for other causes of
symptoms
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(No Transcript)
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Principles of Therapy

• Lower B.P. over hours
• Initial goal B.P. ? 160s/90s
• Too rapid lowering may cause dire consequences
  (CVA, MI)
• May take several days to get to reasonable levels
• Avoid medications that cannot be controlled
  (sublingual nifedipine)

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Hypertensive Emergencies Treatment

• For most patients the greatest risk of
  treating a hypertensive emergency is the risk
  of accompanying hypotension.
• Treat with short acting, easily titratable, I.V.
  drug.

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Parenteral Drugs for Treatment of Hypertensive
Emergencies
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Parenteral Drugs for Treatment of Hypertensive
Emergencies
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Parenteral Drugs for Treatment of Hypertensive
Emergencies
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Parenteral Drugs for Treatment of Hypertensive
Emergencies
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Parenteral Drugs for Treatment of Hypertensive
Emergencies
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Parenteral Drugs for Treatment of Hypertensive
Emergencies
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Fenoldopam Indications

• In-hospital, short-term (up to 48 hours)
  management of severe hypertension when rapid, but
  quickly reversible, emergency reduction of blood
  pressure is clinically indicated, including
  malignant hypertension with deteriorating end
  organ function.
• Transition to oral therapy with another agent can
  begin at any time after blood pressure is stable
  during fenoldopam infusion.

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Physiologic Effects Fenoldopam
Does not cross BBB
Systemic Vasodilation

• Coronary Vasodilation
• without steal
• (in animals)
• Reflex tachycardia

• Metabolized by conjugation
• No P450 interaction

• ? RBF
• ? Na excretion
• ? H2O excretion
• Maintains GFR during BP lowering

• Mesenteric vasodilation
• ? Mucosal PO2
• (in animals)

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Fenoldopam Receptor Activity

• Selective peripheral dopamine-1 (DA1) receptor
  agonism
• Systemic vasodilation
• Regional vasodilation (especially renal)
• Renal proximal and distal tubular effects
• No binding to DA2 or beta-adrenergic receptors
• No alpha-adrenergic agonism, but is an alpha1
  antagonist
• Does not cross blood brain barrier

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Mechanism of Action of Fenoldopam
Fenoldopam infusion
Selective stimulation of D1-dopamine receptors
Direct increase in sodium excretion
Adenylyl cyclase activation
Increase in intracellular concentration of cAMP
Vascular smooth muscle relaxation
Vasodilation of coronary arteries
Vasodilation of mesenteric arteries
Vasodilation of systemic arteries
Vasodilation of renal arteries
Decrease in systemic vascular resistance
Maintenance of blood flow to vital organs
Decrease in blood pressure
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Fenoldopam Metabolism

• Metabolism via conjugation
• Metabolites pharmacologically inactive
• No cytochrome P450 interactions
• No known metabolic drug interactions
• 88 albumin bound
• Elimination 90 urine, 10 feces
• No dose adjustment for renal or hepatic impairment

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Fenoldopam Pharmacokinetics

• ? t½ ( 5 min)
• ? Small volume of distribution
• ? Rapid attainment of steady state ( 30 min)
• ? Plasma concentrations proportional to dose
• No alteration in pharmacokinetics over
• 48 hr infusion
• ? Rapid elimination upon discontinuation

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Fenoldopam Pharmacodynamics

• Predictable hemodynamic effect
• ? Rapid onset of effect
• ? Predictable dose response for lowering BP
• ? No rebound hypertension

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Fenoldopam Potential Benefits
? Rapid, predictable, dose-dependent blood
pressure decrease (without overshoot) ? Short t½,
rapid attainment of steady state titration ?
Linear pharmacokinetics ? No cytochrome P450
interactions ? Dose-response curves well
defined ? No dosing adjustment for pre-existing
renal or hepatic impairment ? Increases
renal blood flow and maintains GFR ? Ease of use
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FenoldopamAdverse Events

• Headache
• Flushing
• Nausea
• Hypotension
• Hypokalemia

• EKG Abnormalities
• Tachycardia
• Vomiting
• Dizziness
• Extrasystoles
• Dyspnea

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Nicardipine Characteristics

• Dihydropyridine
• Reflex tachycardia
• Useful when
• ß-Blockers contraindicated
• Water soluble and light stable
• (allows for IV infusion)

• Slow onset and offset
• Arterial catheter not mandatory
• May accumulate
• Variable duration of hypertensive effect
• Good in patients with renal disease

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Nitroprusside

• Onset 1-4 min., half-life 1-2 min.
• Metabolized by RBC to cyanide then by liver to
  thiocyanate, cleared by kidneys
• Caution with hepatic /or renal disease

• Toxicity related to total dose
• SS met. acidosis, confusion, air hunger,
  hyper-reflexia, confusion, and seizures.
• Reversible by hydroxycobalamine, sodium nitrate,
• (?) methylene blue

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Therapy Hypertensive Urgencies

• Oral meds. Preferred
• Close monitoring
• Fast follow-up
• Start with short acting forms
• (not Ca2 channel blockers)

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Drugs for Urgencies

• Clonidine
• ?-Blockers, ??-? Blockers
• Captopril, Enalapril
• Minoxidil (if already on ?-blocker diuretic)
• Hydralazine

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Drug Related Malignant Hypertension

• MAO Inhibitors
• Cold Preparations
• Withdrawal Antihypertensive Meds
• Clonidine, ?-Blockers
• Street Drugs
• Cocaine, PCP