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  1. Antihypertensives Dr. M. Ahsan, MBBS, MD
  2. Learning Outcomes… • What are antihypertensive agents • Classify different types of antihypertensives • Describe the utilization of antihypertensives • Describe the mode of action and side effects of antihypertensives • Discuss the rationale for combined antihypertensive therapy
  3. Overview • Elevated blood pressure is a common disorder, affecting approx. 30% of adults • Hypertension is an important risk factor for: Heart disease Stroke Chronic kidney disease • The risk of organ damage is directly related to the extent of elevation of BP BP of the patient should be measured in more than two occasions and he/she should have been resting for at least 5 mins and should not have consumed coffee or smoked during the last 30 mins
  4. Overview • Hypertension is classified into four categories Systolic (mm Hg) Diastolic (mm Hg) Normal < 120 And < 80 Elevated 120 – 129 Or < 80 Stage 1 hypertension 130 – 139 Or 80 – 89 Stage 2 hypertension ≥ 140 Or ≥ 90
  5. Etiology of hypertension • Essential hypertension (90% cases) • Secondary hypertension (10 – 15%) A healthy lifestyle decreases blood pressure, enhances antihypertensive drug efficacy and decreases the overall cardiovascular risk:  Weight reduction  Increase in physical activity  Dietary sodium reduction  Limited fat intake  Increased fibre intake  Restriction on alcohol consumption  Stopping tobacco products
  6. Mechanism for controlling blood pressure • Arterial blood pressure is directly proportional to cardiac output and peripheral vascular resistance • Most antihypertensives lower BP by reducing cardiac output and/or decreasing peripheral resistance
  7. Cardiac output and peripheral resistance are controlled by: Baroreflexes Renin-angiotensin-aldosterone system
  8. Classification of antihypertensives Diuretics • Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide • High ceiling: Furosemide • K+ Sparing: Spironolactone, Amiloride ACE inhibitors • Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Fosinopril Angiotensin (AT1 receptor) blockers • Losartan, Candesartan, Irbesartan, Valsartan, Telmisartan Direct renin inhibitor • Aliskiren Calcium channel blockers • Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine, Nitrendipine, Lacidipine β Adrenergic blockers • Propranolol, Metoprolol, Atenolol β+ α Adrenergic blockers • Labetalol, Carvedilol α Adrenergic blockers • Prazosin, Terazosin, Doxazosin Phentolamine, Phenoxybenzamine Central sympatholytics • Clonidine, α-Methyldopa Vasodilators • Arteriolar: Hydralazine, Minoxidil, Diazoxide • Arteriolar+venous: Sodium nitroprusside
  9. Diuretics • Diuretics can be used as first-line drug therapy. • Diuretics decrease blood volume which ultimately leads to decrease in blood pressure • Routine serum electrolyte monitoring should be done in all patients receiving diuretics
  10. Diuretics Thiazides are most commonly used as antihypertensives Actions: • Lower blood pressure by increasing Na and water excretion • Decrease in extracellular volume, Decrease in cardiac output and renal blood flow • With long-term treatment, plasma volume approaches a normal value, but peripheral resistance decreases. • Potassium-sparing diuretics are often used combined with thiazides.
  11. Diuretics Therapeutic uses: • Thiazide diuretics are particularly useful in the treatment of black or elderly patients. • Counteract the sodium and water retention observed with other agents (eg, hydralazine). Thiazides are not effective in patients with inadequate kidney function (creatinine clearance, <50 mL/min) ……..Loop diuretics may be required in these patients
  12. Diuretics Adverse effects: Thiazides induce: • Hypokalemia and • Hyperuricemia • Hyperglycemia • Hypomagnesemia Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias
  13. Diuretics Loop diuretics • Loop diuretics act even in patients with poor renal function or who have not responded to thiazides or other diuretics. • Loop diuretics cause decreased renal vascular resistance and increased renal blood flow. Loop diuretics increase the Ca2+ content of urine, whereas thiazide diuretics decrease it.
  14. Diuretics Potassium-sparing diuretics. • Inhibitors of epithelial sodium transport at the late distal and collecting ducts : Amiloride and triamterene • Aldosterone-receptor antagonists: Spironolactone and eplerenone • Spironolactone has the additional benefit of diminishing the cardiac remodeling that occurs in heart failure.
  15. ACE inhibitors • These drugs block the ACE that cleaves angiotensin I to form the potent vasoconstrictor angiotensin II • ACE inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output, rate, or contractility. • By reducing circulating angiotensin II levels, ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention
  16. Physiological regulation of electrolytes, plasma volume and blood pressure by the renin-angiotensin system
  17. ACE inhibitors
  18. ACE inhibitors: Therapeutic uses Hypertension: • The ACE inhibitors are first line drugs in all grades of hypertension • ACE inhibitors are highly effective and first choice drugs in renovascular and resistant hypertension • Particularly suitable for diabetic hypertensives
  19. ACE inhibitors: Therapeutic uses They offer the following advantages: No postural hypotension Safe in asthmatics, diabetics and peripheral vascular disease patients Secondary hyperaldosteronism and K+ loss due to diuretics is prevented No rebound hypertension on withdrawal Left ventricular hypertrophy is reversed No hyperuricaemia, no deleterious effect on plasma lipid profile Minimum worsening of quality of life parameters like general wellbeing, work performance, sleep, sexual performance, etc.
  20. ACE inhibitors: Therapeutic uses • CHF • Myocardial infarction (MI) • Diabetic nephropathy • Scleroderma crisis
  21. ACE inhibitors: Adverse effects • Hypotension • Hyperkalaemia • Cough • Rashes, urticaria • Angioedema • Dysgeusia • Foetopathic • Acute renal failure: in patients of bilateral renal artery stenosis Dry cough: It is not dose related and appears to be caused by inhibition of bradykinin/substance P breakdown in the lungs of susceptible individuals
  22. Angiotensin II receptor blockers • These drugs block the AT1 receptors. • Pharmacologic effects are similar to those of ACE inhibitors • ARBs do not increase bradykinin levels. Their adverse effects are similar to those of ACE inhibitors Risks of cough and angioedema are significantly decreased. ARBs are also fetotoxic.
  23. Renin inhibitors • Aliskiren is a selective renin inhibitor, used for the treatment of hypertension Aliskiren can cause diarrhea, especially at the higher doses. Aliskiren can also cause cough and angioedema Contraindicated during pregnancy.
  24. Calcium channel blockers • Calcium-channel antagonists block the inward movement of calcium by binding to L-type calcium channels (in the heart and in smooth muscle of the coronary and peripheral vasculature.) • Causes vascular smooth muscle to relax, dilating mainly arterioles. • They are recommended first-line agents (especially in black patients)
  25. Classes of calcium channel blockers Diphenylalkylamines: Verapamil Benzothiazepines: Diltiazem Dihydropyridines: • First-generation: Nifedipine • Second-generation: Isradipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine, Lacidipine, Lercanidipine
  26. Calcium channel blockers: Therapeutic uses Hypertension: • Safe in cases of COPD and peripheral vascular disease (β blockers are contraindicated) • Black hypertensives respond well to calcium-channel blockers • Intrinsic natriuretic effect and, therefore, do not require addition of a diuretic.
  27. Calcium channel blockers: Therapeutic uses Angina pectoris Cardiac arrhythmias • Verapamil and diltiazem for PSVT and supraventricular arrhythmias Hypertrophic cardiomyopathy Other uses • Premature labour (nifedipine) • Nocturnal leg cramps (verapamil) • Raynaud’s episodes (DHPs)
  28. Calcium channel blockers Adverse effects: • Palpitation, flushing, ankle edema • Hypotension, headache, drowsiness and nausea • First-degree AV block • Constipation • Urine voiding difficulty in elderly males (nifedipine) • Gastroesophageal reflux may be worsened (all DHPs) • Gingival hyperplasia (nifedipine) Verapamil and diltiazem should be avoided in heart failure and AV block due to negative inotropic effect
  29. Beta blockers • First-line drug therapy for hypertension when concomitant disease is present, eg. with heart failure Actions: • Decrease cardiac output • Decrease sympathetic outflow from the central nervous system (CNS) • Inhibit the release of renin from the kidneys • Propranolol……acts at both β-1 and β-2 receptors. • Metoprolol and atenolol…..…Selective blockers of β-1 receptors • More effective in white than in black patients Selective β-blockers are preferred in asthmatics
  30. Beta blockers • Conditions that discourage the use of β-blockers: severe COPD 1st and 2nd degree heart block Severe peripheral vascular disease • β-blockers are useful in treating conditions that may coexist with hypertension, such as: supraventricular tachyarrhythmia previous MI angina pectoris migraine headache Chronic heart failure
  31. Beta blockers Adverse effects: • Bradycardia • Hypotension • Fatigue, lethargy, insomnia, and hallucinations • Decrease libido and cause impotence • Alterations in serum lipid patterns: decrease in HDL and increase in TGs Drug withdrawal: Abrupt withdrawal may induce angina, myocardial infarction, or even sudden death in patients with ischemic heart disease
  32. Alpha blocking agents • Competitive blockers of α1-adrenoceptors • Dilatation of both arteries and veins  tpr  BP • Reflex tachycardia and Postural hypotension often occur at the onset of treatment and with increase in dose….slow titration of dose is required Prazosin Doxazosin Terazosin
  33. Alpha + beta blocking agents • Labetalol and carvedilol block both α1- and β1- and β2- receptors. • Carvedilol: Nonselective β + weak selective α1 blocker Additional antioxidant/free radical scavenging properties. Used for long-term treatment of CHF, and is approved as an antihypertensive as well. Labetalol: Used for rapid BP reduction in hyperadrenergic states, cheese reaction, clonidine withdrawal, eclampsia, etc.
  34. Centrally acting adrenergic drugs • Two important antihypertensive agents act primarily in the brain: Clonidine and methyldopa • Both drugs are α2-adrenergic receptor agonists • Decrease sympathetic outflow from the brain to the cardiovascular system • Both drugs are well absorbed orally [clonidine is also available as a transdermal patch] Clonidine Methyldopa
  35. Alpha methyldopa • α-methyldopa is converted to α-methylnorepinephrine in the brain • α-methylnorepinephrine activates CNS α2-receptors  decrease sympathetic outflow  reduced total peripheral resistance  decreased BP • Used in hypertensive pregnant patients Adverse effects: • Sedation and drowsiness.
  36. Clonidine • Clonidine decreases central sympathetic outflow • The only difference is that clonidine acts directly on α2-receptors, whereas methyldopa must first be converted to α-methylnorepinephrine
  37. Clonidine • Used for hypertension that has not responded adequately to treatment with two or more drugs. • Does not decrease renal blood flow  useful in the treatment of hypertension complicated by renal disease • Can cause sodium and water retention (add diuretic) Adverse effects: Sedation and drying of the nasal mucosa. Rebound hypertension on abrupt withdrawal Rebound hypertension is due to supersensitivity of adrenergic receptors caused by chronic clonidine-induced reduction in sympathetic outflow
  38. Vasodilators • Vasodilators decreases tpr  decreases blood pressure • Produce reflex stimulation of the heart ……..This can cause angina pectoris, myocardial infarction, or cardiac failure in predisposed individuals. • Vasodilators also increase plasma renin concentration, resulting in sodium and water retention. • Undesirable side effects can be blocked by concomitant use of a diuretic and a β-blocker Hydralazine Minoxidil Diazoxide Sodium nitroprusside The three drugs together decrease cardiac output, plasma volume and peripheral vascular resistance
  39. Vasodilators Hydralazine: • Acts primarily on arteries and arterioles • Used in pregnancy-induced hypertension. Adverse effects: • Headache, tachycardia, nausea, sweating, arrhythmia, and precipitation of angina. • A lupus-like syndrome can occur with high dosage, but it is reversible on discontinuation of the drug
  40. Vasodilators Minoxidil: • Causes dilation of resistance vessels (arterioles) but not of capacitance vessels (venules). • Used for severe to malignant hypertension that is refractory to other drugs. Adverse effects: • Sodium and water retention, leading to volume overload, edema, and congestive heart failure. • Hypertrichosis (the growth of body hair)….used for treating male pattern baldness
  41. Neuroendocrine pathways activated when vasodilators are given These pathways lead ultimately to an increase in blood pressure and compromise the effectiveness of vasodilators. The effectiveness can be preserved by coadministration of propranolol and diuretics
  42. Vasodilators: Sodium nitroprusside • Acts rapidly (within seconds) and briefly (2 – 5 mins)….vascular tone can be titrated with the rate of i.v. infusion. • Relaxes both resistance and capacitance vessels • Endothelial cells, RBCs (and may be other cells) split nitroprusside to generate NO which relaxes vascular smooth muscle • Side effects mainly due to vasodilatation are — palpitation, nervousness, vomiting, perspiration, pain in abdomen, weakness, disorientation, and lactic acidosis (caused by the released cyanide). Nitroprusside is light sensitive, and when in solution, it should be protected from light.
  43. Hypertensive emergencies • Systolic BP > 180 or diastolic BP > 120 mm Hg with evidence of impending or progressing end organ damage is labelled ‘hypertensive emergency’, • Controlled reduction of BP over minutes (in emergencies) or hours (in urgencies) is required to counter threat to organ function • Mean BP should be lowered by no more than 25% over a period of minutes or a few hours and then gradually to not lower than 160/100 mm Hg.
  44. Hypertensive emergencies • Drugs employed are: Sodium nitroprusside Glyceryl trinitrate Hydralazine Esmolol Phentolamine Labetalol Fenoldopam Furosemide Nicardipine
  45. Individualized care • Hypertension may coexist with other conditions…it is important to match the antihypertensive to the patient Concomitant disease Drug classes indicated in treating hypertension Stable ischemic heart disease β-blocker ACE inhibitor ARBs CCBs Diabetes Diuretics ACE inhibitor ARBs CCBs Recurrent stroke Diuretics ACE inhibitor ARBs Heart failure Diuretics β-blocker ACE inhibitor ARBs Aldosterone receptor antagonist Previous myocardial infarction β-blocker ACE inhibitor Aldosterone receptor antagonist Chronic kidney disease ACE inhibitor ARBs
  46. Resistant hypertension • Resistant hypertension is defined as blood pressure that remains elevated despite administration of an optimal three-drug regimen that includes a diuretic Causes: Poor compliance Excess ethanol intake Concomitant conditions (diabetes, obesity, sleep apnea, hyperalsosteronism, high salt intake, metabolic syndrome) Concomitant medications (sympathomimetics, NSAIDs, corticosteroids), insufficient dose, use of drugs with similar mechanism of action
  47. Hypertension in pregnancy • α-methyldopa, β-blockers and vasodilators are preferred during pregnancy • ACE inhibitors and ARBs are contraindicated in pregnancy
  48. Treatment strategies • The goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality • Antihypertensive therapy is indicated in case of : • SBP ≥150 mm Hg or DBP ≥90 mm Hg [at age 60 years or more] • SBP ≥140 mm Hg or DBP≥ 90 mm Hg [age < 60 years] Current recommendation is to initiate therapy with a thiazide diuretic, ACE inhibitor, ARB or CCB  If BP is inadequately controlled after 1 month of therapy, either increase dose or add another drug  Add a third drug if two drugs don’t control the BP  If SBP is greater than 20 mm Hg or DBP is 10 mm Hg above goal…..start with 2 drugs
  49. Rational drug combinations • The main objective of drug combinations is to achieve additional blood pressure reduction by using drugs that act by different mechanisms: Minimization of adverse effects Block opposing effects on the homeostatic mechanism Permits the use of lower dose (less adverse effects)
  50. Drug combinations in hypertension Fully additive drug combinations (Preferred combination) • Diuretics + β-blocker • Diuretics + ACE inhibitors • CCB +β-blocker • CCB + ACE inhibitor Questionable drug combinations • Nonadditive: • β-blocker + ACE inhibitor • ARB + ACE inhibitor • Side effect additive • β-blocker + Verapamil • α blocker + CCB Preferred combinations with patients with associated conditions • Angina: β-blocker + CCB • Heart failure: Diuretic + ACE inhibitor • Diabetes: ACE inhibitor + CCB • COPD: Diuretic + CCB
  51. Key points: Rational Drug combinations • Drugs which increase plasma renin activity— diuretics, vasodilators, CCBs, ACE inhibitors may be combined with drugs which lower plasma renin activity—β blockers, clonidine, methyldopa. • All sympathetic inhibitors (except β blockers) and vasodilators, except CCBs, cause fluid retention leading to tolerance. Addition of a diuretic checks fluid retention and development of tolerance. • Use of combined formulation improves compliance and usually lowers cost.
  52. Key points: Rational Drug combinations • Hydralazine and DHPs cause tachycardia which is counteracted by β blockers, while the initial increase in t.p.r. caused by nonselective β blockers is counteracted by the vasodilator. • ACE inhibitors/ARBs are particularly synergistic with diuretics; this combination is very good for patients with associated CHF or left ventricular hypertrophy.
  53. Key points: Drug combinations Combinations to be avoided: • An α or β adrenergic blocker with clonidine: apparent antagonism of clonidine action has been observed • Hydralazine with a DHP or prazosin; because of similar pattern of haemodynamic action • Verapamil or diltiazem with β blocker, because marked bradycardia, A-V block can occur • Methyldopa with clonidine or any two drugs of the same class
  54. Lifestyle modifications as per JNC 7 and AHSA-ASA Greater results are achieved when 2 or more lifestyle modifications are combined: • Weight loss helps to prevent hypertension (range of approximate systolic BP reduction [SBP], 5-20 mm Hg per 10 kg); recommendations include the DASH (Dietary Approaches to Stop Hypertension) diet (range of approximate SBP reduction, 8-14 mm Hg), which is rich in fruits and vegetables and encourages the use of fat-free or low-fat milk and milk products • Limit alcohol intake to no more than 1 oz (30 mL) of ethanol per day for men (ie, 24 oz [720 mL] of beer, 10 oz [300 mL] of wine, 2 oz [60 mL] of 100-proof whiskey) or 0.5 oz (15 mL) of ethanol per day for women and people of lighter weight (range of approximate SBP reduction, 2-4 mm Hg)
  55. Lifestyle modifications as per JNC 7 and AHSA-ASA • Reduce sodium intake to no more than 100 mmol/d (2.4 g sodium or 6 g sodium chloride; range of approximate SBP reduction, 2-8 mm Hg) • Maintain adequate intake of dietary potassium (approximately 90 mmol/d) • Maintain adequate intake of dietary calcium and magnesium for general health • Stop smoking and reduce intake of dietary saturated fat and cholesterol for overall cardiovascular health • Engage in aerobic exercise at least 30 minutes daily for most days (range of approximate SBP reduction, 4-9 mm Hg)
  56. Key messages of JNC 8 • In the general population, pharmacologic treatment should be initiated when blood pressure is 150/90 mm Hg or higher in adults 60 years and older, or 140/90 mm Hg or higher in adults younger than 60 years • In patients with hypertension and diabetes, pharmacologic treatment should be initiated when blood pressure is 140/90 mm Hg or higher, regardless of age • Initial antihypertensive treatment should include a thiazide diuretic, calcium channel blocker, ACE inhibitor, or ARB in the general nonblack population or a thiazide diuretic or calcium channel blocker in the general black population. • If the target blood pressure is not reached within one month after initiating therapy, the dosage of the initial medication should be increased, or a second medication should be added.
  57. Case 1 • A 19 year old male comes to your clinic to get a physical examination for college sports. He has no h/o illnesses and is on no medication. During clinic you notice a BP of 150/96 mm Hg. • How would you manage this patients high BP?
  58. Case 2 • A 42 year old male comes for follow up of his DM. His BP has been a little high for the last two clinic visits (144/90 mm Hg, 142/96 mm Hg). He is currently on glipizide and metformin. He has no history of allergies. • What is his BP goal? • What medication do you want to start him on? • What do you want to monitor
  59. Case 3 • A 56 year old male with h/o HTN, CHF and fibromyalgias. Today his BP is 152/102 mm Hg and HR is 84/ min. He is currently on hydrochlorthiazide 25 mg po qd. All his lab reports are normal and patient reports compliance with medication. • What drug can you add for better control of his BP? What things do you want to monitor?
  60. References • Lippincott Illustrated Reviews: Pharmacology(6th ed.). Philadelphia, PA: Wolters Kluwer. • Clinical Medicine: A Textbook for Medical Students &amp; Kumar PJ and Clark ML (8th ed.); Elsevier Saunders • Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) • Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)

Notas del editor

  1. Secondary hypertension (10 – 15%): may occur secondary to other diseases eg. Pheochromocytoma, Cushing’s disease, primary aldosteronism, renal artery stenosis, coarctation of aorta
  2. About 50% patients respond to monotherapy with ACE inhibitors and rest to their combination with diuretics or β-blockers
  3. In unstable angina/non-ST segment elevation MI (NSTEMI), long-term ACE inhibitor therapy reduces recurrent MI and need for coronary angioplasty Diabetic nephropathy Prolonged ACE inhibitor therapy has been found to prevent or delay end-stage renal disease in type I as well as type II diabetics Scleroderma crisis The marked rise in BP and deterioration of renal function in scleroderma crisis is mediated by Ang II
  4. Hypotension: an initial sharp fall in BP occurs especially in diuretic treated and CHF patients; persistent hypotension may be troublesome in MI patients. Hyperkalaemia: more likely in patients with impaired renal function and in those taking K+ sparing diuretics, NSAIDs or β blockers Cough: a persistent brassy cough occurs in 4–16% patients within 1–8 weeks, often requires discontinuation of the drug—subsides 4–6 days thereafter Dysgeusia: reversible loss or alteration of taste sensation Foetopathic: foetal growth retardation, hypoplasia of organs and foetal death may occur if ACE inhibitors are given during. ACE inhibitors must be stopped when the woman conceives Acute renal failure: is precipitated by ACE inhibitors in patients with bilateral renal artery stenosis due to dilatation of efferent arterioles and fall in glomerular filtration pressure. ACE inhibitors are contraindicated in such patients
  5. They produce arteriolar and venous dilation and block aldosterone secretion, thus lowering blood pressure and decreasing salt and water retention.
  6. The intracellular concentration of calcium plays an important role in maintaining the tone of smooth muscle and in the contraction of the myocardium. Calcium enters muscle cells through special voltage-sensitive calcium channels. This triggers release of calcium from the sarcoplasmic reticulum and mitochondria, which further increases the cytosolic level of calcium. High doses of short-acting calcium channel blockers should be avoided because of increased risk of myocardial infarction due to excessive vasodilation and marked reflex cardiac stimulation.
  7. Some of the newer agents, such as amlodipine and nicardipine, have the advantage that they show little interaction with other cardiovascular drugs, such as digoxin or warfarin, which are often used concomitantly with calcium-channel blockers.
  8. β-blockers should be employed cautiously in acute heart failure or peripheral vascular disease.
  9. β-blockers are orally active. Propranolol undergoes extensive and highly variable first-pass metabolism. The β-blockers may take several weeks to develop their full effects.
  10. Breakdown of nitroprusside to NO: This occurs both enzymatically and nonenzymatically. The enzymes involved are different from those that produce NO from glyceryl trinitrate. Nonenzymatically it is converted to NO (and CN) by glutathione. This may be responsible for the different pattern of vasodilator action compared to nitrates, as well as for the fact that no nitrate like tolerance develops to nitroprusside action
  11. Nitroprusside is administered intravenously and causes prompt vasodilation with reflex tachycardia. It is capable of reducing blood pressure in all patients regardless of the cause of hypertension. Nitroprusside metabolism results in cyanide ion production. It can be effectively treated with an infusion of sodium thiosulfate to produce thiocyanate, which is less toxic and is eliminated by the kidneys. [Note: Nitroprusside is poisonous if given orally because of its hydrolysis to cyanide.] Labetalol is given as an intravenous bolus or infusion in hypertensive emergencies. It does not cause reflex tachycardia. The major limitation is a longer half-life, which precludes rapid titration Nicardipine, a calcium-channel blocker, can be given as an intravenous infusion. The major limitation of nicardipine in treating hypertensive emergency is its long half-time (approximately 8 hours), which precludes rapid titration Fenoldopam is a peripheral dopamine-1 receptor agonist that is given as an intravenous infusion. Fenoldopam maintains or increases renal perfusion while it lowers blood pressure. The drug is contraindicated in patients with glaucoma
  12. Key messages in JNC 7: Prehypertension (systolic 120-139 mm Hg, diastolic 80-89 mm Hg) requires health-promoting lifestyle modifications to prevent the progressive rise in BP and cardiovascular disease In uncomplicated hypertension, a thiazide diuretic, either alone or combined with drugs from other classes, should be used for the pharmacologic treatment of most cases In specific high-risk conditions, there are compelling indications for the use of other antihypertensive drug classes (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], beta blockers, calcium channel blockers) Two or more antihypertensive medications will be required to achieve goal BP (< 140/90 mm Hg or < 130/80 mm Hg) for patients with diabetes and chronic kidney disease For patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using 2 agents, one of which usually will be a thiazide diuretic, should be considered Regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan
  13. Key messages in JNC 7: Prehypertension (systolic 120-139 mm Hg, diastolic 80-89 mm Hg) requires health-promoting lifestyle modifications to prevent the progressive rise in BP and cardiovascular disease In uncomplicated hypertension, a thiazide diuretic, either alone or combined with drugs from other classes, should be used for the pharmacologic treatment of most cases In specific high-risk conditions, there are compelling indications for the use of other antihypertensive drug classes (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], beta blockers, calcium channel blockers) Two or more antihypertensive medications will be required to achieve goal BP (< 140/90 mm Hg or < 130/80 mm Hg) for patients with diabetes and chronic kidney disease For patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using 2 agents, one of which usually will be a thiazide diuretic, should be considered Regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan