1. HYPERTENSION EMERGENCIES DR. BASDEN ONWUBERE

2. What Is Blood Pressure? Directly related to cardiac output (CO) and peripheral vascular resistance (PVR) Hypertension worsens the prognosis of cardiovascular disease when combined with other risk factors (hyperlipidemia, diabetes, cigarette, obesity, family history)

3. Hypertensive Urgency “…desirable to reduce blood pressure within a few hours.” Examples: optic disc oedema, progressive target organ complications perioperative states

4. Hypertensive Emergency “…those rare situations that require immediate blood pressure reduction (not necessarily to normal ranges)…”

5. Hypertensive Emergency rare - occurs in <1% of people with hypertension no “absolute number” (e.g. pre-eclampsia)

6. Hypertensive Emergency Examples: acute left ventricular failure with pulmonary edema hypertensive encephalopathy intracranial hemorrhage unstable angina dissecting aortic aneurysm eclampsia

7. Hypertensive Emergency Initial goal - reduce MAP by no more than 25% within minutes to 2 hours Work toward 160/100 mm Hg within 2 to 6 hours Avoid excessive falls in pressure, leading to renal, cerebral, or coronary ischemia

8. Hypertensive Emergency - Symptoms any persistent headache any blurred vision subconjunctival hemorrhage nosebleed funny feelings good opportunity for teaching

9. Approach - History prior history hypertension medication history, especially MAO-I, clonidine and compliance CNS symptoms - headache, vision changes CV symptoms - chest pain, SOB GU - renal disease, pregnancy

10. Approach - Physical Exam determine BP with proper size cuff if patient >95 kg or arm circumference >35 cm, standard cuffs give falsely elevated readings large cuffs do not, however, give spuriously low readings in “normal” sized individuals

11. Approach - Physical Exam check BP in both arms eye-grounds - ?fuzzy discs neck - ?bruits ?JVP lungs - ?rales heart - ?gallop abdomen - ?bruits neurologic - ?mentation ?focality

12. Diagnostic Studies - Lab CBC - ?histiocytes ?target cells potassium - ?low (may be in high-renin states) BUN & creatinine - ?high (may suggest severity of episode) Urinalysis - ?protein ?red cells ?red cell casts (suggests nephritis)

13. Other Studies - ECG, CXR ECG - ?ischemia ?LVH ?tachycardia CXR - ?CHF ?wide mediastinum (dissection or coarctation of aorta) CT head - if signs of encephalopathy

14. Hypertensive Emergencies Involving the Central Nervous System

15. Hypertensive Encephalopathy cerebral hyperperfusion loss of autoregulation loss of blood-brain barrier persistent pressure elevation  vascular necrosis  release of oxygen-free radicals

16. Hypertensive Encephalopathy Signs & Symptoms - headache, nausea & vomiting, lethargy, confusion, coma Physical Exam - cranial nerve palsies, blindness, aphasia, hemiparesis

17. Hypertensive Encephalopathy Fundoscopy - hemorrhage, exudates, “cotton wool” spots, Papilloedema

18. Differential Diagnosis all types of strokes and intracranial bleeds meningoencephalitis brain tumor metabolic coma

19. Hypertensive Encephalopathy Treatment goal - lower mean arterial pressure to normalize cerebral blood flow in controlled fashion over 30 to 60 minutes Goal in chronic hypertensive - get mean arterial pressure to ~ 120 mm Hg

20. Hypertension with CNS Dysfunction Cause-and-effect between HTN and CNS dysfunction difficult to determine with any certainty Cushing’s effect - increased ICP causes BP increase.

21. Hypertension with CNS Dysfunction In majority of ED patients, high BP is RESULT not CAUSE of stroke If longstanding HTN, rapid reduction to “normal” can cause reduced cerebral blood flow and worsen the ischemia

22. Hypertension with Intracranial Bleed AV malformation congenital berry aneurysm acquired mycotic aneurysm bleeding from brain tumors bleeding diatheses trauma

23. Hypertension with Intracranial Bleed In most patients, hypertension is transitory and is secondary to increased ICP (Cushing’s effect) and to irritation of autonomic nervous system Hypertension disappears rapidly and has little effect on long-term clinical outcome

24. Hypertension + pregnancy Blood pressures > 125/75 before 32 weeks of pregnancy have been associated with increased fetal risk Toxaemia (eclampsia) is hypertension + seizure + oedema + proteinuria after the 20th week of pregnancy Pre-eclampsia is toxaemia without the seizure

25. Hypertension + pregnancy SBP usually < 160 mm Hg Optic fundi have arteriolar narrowing, glistening fundus - may see hemorrhages and exudates, retinal detachment Brisk DTR’s and clonus

26. Hypertension + pregnancy If BP >140/90, give magnesium sulfate IM to prevent seizures Treat blood pressure with hydralazine 25 mg every 6 hrs Diuretics should be avoided, as these patients are usually volume contracted despite their oedema

27. Hypertension + pulmonary edema Treat the pulmonary oedema aggressively with morphine, furosemide, oxygen, nitroglycerine, etc., and the BP will improve There may be a significant percentage of people in whom hypertension is the precipitating factor - would need to treat hypertension primarily with iv anti- hypertensive.

28. Hypertension + myocardial ischemia If severe hypertension and unstable angina are present, immediate lowering of blood pressure will be necessary to prevent infarct Drug of choice: nitroglycerin

29. Hypertension + aortic dissection Associated with history of hypertension If carotids involved  cerebral ischemia If proximal section of aorta involved  coronary arteries  ischemia If spinal arteries involved  hemi- or paraplegia Cardiac tamponade also possible

30. Hypertension + aortic dissection Drugs of choice - trimethaphan (Arfonad®), nitroprusside (Nipride®), and/or propranolol (Inderal®) If tear is proximal, surgery is indicated when blood pressure is controlled

32. Hypertension + renal failure Actual or relative increase in extracellular volume secondary to sodium retention by diseased kidneys Elevated BUN and creatinine Proteinuria with casts in urine Diazoxide is contraindicated Nitroprusside is the drug of choice

33. Catecholamine-induced hypertension Pheochromocytoma - catecholamine- secreting tumor of the adrenal medulla MAO-inhibitor + sympathomimetic = hyperstimulate adrenergic receptors Clonidine withdrawal + beta-blockers withdrawal =severe rebound HTN Treatment - alpha/beta blocker, like labetalol

34. Primary Agents for Use in Hypertensive Emergencies

35. Vasodilators Directly relax vascular smooth muscle Lower BP regardless of aetiology No inhibition of sympathetic nerve activity Relax arteriolar > venous smooth muscles

36. Vasodilator - sodium nitroprusside (Nipride®) given IV for hypertensive emergencies relaxes both arterial and venous smooth muscle decreases venous return to heart limits compensatory increase in CO onset within 30 seconds duration of action <3 minutes

37. Vasodilator - sodium nitroprusside (Nipride®) hypotension due to excess dose if pressure falls too quickly, sweating, restlessness, chest pain, confusion, palpitations cyanide toxicity - prolonged use confusion, disorientation, muscle twitching, delirium, overt psychosis treat with thiosulfate or hydroxycobalamin

38. Combined Alpha / Beta- blocker - labetolol carvedilol (Coreg®) - oral only labetolol (Normodyne®, Trandate®) lowers BP with less effect on CO and HR than other beta-blockers excellent drug for true hypertensive emergency

39. Intravenous Nitroglycerin Nitroglycerin causes arteriolar dilation venodilation coronary artery dilation Onset: immediate Half-life: 4 minutes Drug of choice for hypertension accompanying ischemic coronary events

40. Agents for Use in Hypertensive Urgencies

41. Calcium Channel Blockers mechanism of action inhibit calcium influx through slow voltage- gated channels decreases contractility of heart and vascular smooth muscle vasodilation  decreased peripheral vascular resistance

42. Calcium Channel Blockers - chemical classes diphenylalkylamine verapamil - Calan®, Isoptin®, Verelan® benzothiazepine diltiazem - Cardizem®, Dilacor® dihydropyridines amlodipine - Norvasc® felodipine - Plendil® isradipine - DynaCirc® nicardipine - Cardene® nifedipine - Adalat®, Procardia®

43. Calcium Channel Blockers - adverse effects AV block (verapamil & diltiazem) tachycardia, headache, peripheral edema (nifedipine) constipation (verapamil - most common side effect)

44. Vasodilator - hydralazine (Apresoline®) predominantly affects arterial smooth muscle little effect on venous vessels postural hypotension not a problem not used alone metabolized in liver & bowel

45. Vasodilator - hydralazine (Apresoline®) reflex sympathetic nervous system response - headache, flushing, nasal congestion, tachycardia, palpitations, possibly myocardial ischemia and CHF dose-related rheumatoid-like disease which resembles disseminated lupus

46. Vasodilator - minoxidil (Loniten®) greater decrease in PVR and BP than with hydralazine little effect on venous capacitance postural hypotension not a problem does not depend on kidney for termination, so can be used in chronic renal insufficiency

47. Vasodilator - minoxidil (Loniten®) side effects similar to hydralazine usually not seen when given with beta-blocker

48. Vasodilators Effectiveness limited by autonomic reflexes Usefulness increased by combining with beta-blockers and diuretics hydralazine (Apresoline®) minoxidil (Loniten®)

49. Central Alpha-Adrenergic Agonists clonidine (Catapres®) guanabenz (Wytensin®) guanfacine (Tenex®) methyldopa (Aldomet®)

50. Central Alpha-Adrenergic Agonists mechanism - activation of central presynaptic alpha 2 receptors peak level 2-4 hrs after oral dose adverse effects - drowsiness, dry mouth, parasympathetic activity if stopped suddenly, can develop severe rebound hypertension

51. ACE inhibitors Angiotensin-converting enzyme inhibitor inhibits renin release orally effective very few side effects at low doses may be “drug” or “prodrug”

52. ACE inhibitors benazepril - Lotensin® captopril - Capoten® enalapril - Vasotec® fosinopril - Monopril® lisinopril - Prinivil®, Zestril® quinapril - Accupril® ramipril - Altace® trandolapril - Mavik®

53. Angiotensin Receptor Antagonists (ACE-I II) candesartan - Atacand® irbesartan - Avapro® losartan - Cozaar® telmisartan - Micardis® valsartan - Diovan®

54. Adjuvant Agents in the Treatment of Hypertension

55. Diuretics Have little use in treatment of true hypertensive emergencies May be useful in combination therapy (e.g., diazoxide plus furosemide) Helpful when combined with other anti-hypertensives which may cause sodium and water retention

56. Diuretics Loop diuretics bumetanide - Bumex® ethacrynic acid - Edecrin® furosemide - Lasix® torsemide - Demadex® Potassium-Sparing amiloride - Midamor® spironolactone - Aldactone® triamterene - Dyrenium®

57. Diuretics Thiazide diuretics chlorothiazide - Diuril® hydrochlorothiazide - Esidrix® chlorthalidone - Hygroton® indapamide - Lozol® metolazone - Zaroxolyn®

58. Beta-adrenergic blockers atenolol (Tenormin®) betaxolol (Kerlone®) bisoprolol (Zebeta®) metoprolol (Lopressor®, Toprol ®) nadolol (Corgard®) propranolol (Inderal®) timolol (Blocadren®)

59. Beta-adrenergic blockers with sympathomimetic activity acebutolol (Sectral®) carteolol (Cartrol®) penbutolol (Levatol®) pindolol (Visken®)

60. Beta-blockers initially decrease HR and CO with no change in BP with chronic treatment, decreased BP correlates with decrease in PVR decreased blood volume mechanism as antihypertensive is unknown

61. Beta-blockers - Relative Contraindications congestive heart failure - may obtund compensatory mechanisms asthma or COPD - may promote bronchoconstriction

62. Alpha-blocker - phentolamine (Regitine®) non-selective alpha receptor antagonist reflex increase in heart rate postural hypotension is a problem drug of choice for managing pheochromocytoma prior to and during surgery

63. Alpha-blockers (selective) prazosin (Minipress®) terazosin (Hytrin®) doxazosin (Cardura®) selective alpha 1 blockers short half-life (2 - 4 hr), but prolonged effect (10 hr) side effects - postural hypotension, syncope

64. Rapid withdrawal from antihypertensive - What can happen? normalized blood pressure requiring no therapy (<5%) gradual return to pretreatment BP over few weeks asymptomatic return to pretreatment BP sudden return to pretreatment BP “overshoot” of pretreatment BP

65. FEW QUESTIONS ONLY