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1.6.2 Pharmacologic Treatment

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  • GLB.IRB.06.12.01

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  • 1. JNC 7 - Algorithm for treatment of hypertension Hypertension with compelling indications Stage 1 hypertension (SBP 140-159 or DBP 90-99 mmHg) Thiazide-type diuretics for most May consider ACE inhibitor, ARB,  -blocker, CCB, or combination Stage 2 hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACE inhibitor or ARB or  -blocker or CCB) Drug(s) for compelling indications Other antihypertensive drugs (diuretics, ACE inhibitor, ARB,  -blocker, CCB) as needed Not at goal BP Lifestyle modifications JNC 7 VII, Hypertens. 2003;42:1206-1252. Not at goal BP (<140/90 mmHg or <130/80 mmHg for those with diabetes or chronic kidney disease) Initial drug choices Hypertension without compelling indications Optimize dosages or add additional drugs until goal BP is achieved Consider consultation with hypertension specialist For Internal Use Only
  • 2. ESH/ESC guidelines Pharmacological Treatment of Hypertension Consider : Blood pressure level before treatment Absence or presence of TOD and risk factors Two-drug combination at low dose Choose between : Single agent at low dose If goal BP not achieved : Previous agent at full dose Switch to different agent at low dose Previous combination at full dose Add a third drug at low dose If goal BP not achieved : Two-three drug combination Two-three drug combination ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 3.
    • “ The major classes of antihypertensive agents (diuretics, ß-blockers, calcium antagonists, ACE inhibitors, angiotensin-receptor antagonists) are suitable for the initiation and maintenance of therapy”
    ESH/ESC guidelines Position statement: Choice of antihypertensive drugs ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 4. ESH/ESC guidelines
    • The main benefits of antihypertensive therapy are due to lowering of blood pressure per se
    • There is also evidence that specific drug classes may differ in some effect, or in special groups of patients
    • Drugs are not equal in terms of adverse disturbances, particularly in individual patients
    • Emphasis on identifying the first class of drugs to be used is probably outdated by the need to use two or more drugs in combination in order to achieve goal BP
    Position statement: Choice of antihypertensive drugs ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 5. ESH/ESC guidelines
    • Recommendations for the role of ARBs:
      • Type 2 diabetic nephropathy
      • Diabetic microalbuminuria
      • Proteinuria
      • LV hypertrophy
      • ACE-inhibitor cough
    • Searching for microalbuminuria is recommended in all hypertensives
      • A continuous relation between urinary albumin excretion rate and cardiovascular, as well as non-cardiovascular mortality has been found
    ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 6. ESH/ESC guidelines
    • To reach diabetic hypertension goals, combination therapy is most often required
    • Evidence indicates that combinations including an ACE inhibitor in Type 1 diabetes and an ARB in Type 2 diabetes provide renoprotection benefits
    Diabetic hypertension ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 7. JNC 7: Goals and Recommendations
    • Goal: To reduce cardiovascular, renal morbidity and mortality
    • For patients older than 50 years, SBP  140 mm Hg is a more important CVD risk factor than DBP
    • Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or in combination with drugs from other classes
    • High-risk conditions are compelling indications for the initial use of specific antihypertensive drug classes
    • Most patients will require 2 or more antihypertensive agents to reach their goal blood pressure
    • If BP is  20/10 mm Hg above goal, consideration should be given to initiating therapy with two agents, one of which should usually be a thiazide-type diuretic
    JNC 7 VII, Hypertens. 2003;42:1206-1252 For Internal Use Only
  • 8. JNC-7 Guidelines Diabetic hypertension
    • Thiazide diuretics, ß-blockers, ACE inhibitors, ARBs and CCBs have been shown to reduce CVD and stroke incidence in diabetic hypertension
    • In diabetic hypertension, combinations of 2 or more medications are usually needed to achieve target BP of < 130/80 mmHg
    • ACE- and ARB-based treatments favourably affect the progression of diabetic nephropathy and reduce albuminuria
    • ARBs have been shown to reduce progression to macroalbuminuria
    Chobanian AV et al. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003;289:2560-72. For Internal Use Only
  • 9. ESH/ESC guidelines Elderly Patients
    • Cardiovascular events can be reduced by antihypertensive treatment also in older patients with isolated systolic hypertension
    • BP lowering should be gradual particularly in frail patients
    • Measure BP also in the erect posture to evaluate excessive postural effects
    • Tailor therapy on concomitant risk factors and disease (frequent in the elderly)
    • Use two or more drugs, if necessary
    • In subjects aged > 80 years, evidence of benefit from antihypertensive therapy is still weak
    ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 10. ESH/ESC guidelines Patients with Renal Impairment ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053
    • Renal protection in diabetes requires strict BP control (to less than 130/80 mmHg), but also in patients with non-diabetic nephropathy it appears
    • prudent to lower BP intensively
    • Proteinuria should be lowered to values as near to normal as possible
    • To reduce proteinuria either an angiotensin receptor antagonist or an ACE-inhibitor (or the combination of both) is required
    • To achieve the BP goal, combination therapy is usually required, with the addition of a diuretic, a calcium antagonist and other antihypertensive agents
    • Consider an integrated therapeutic intervention (antihypertensives, statins, antiplatelet therapy, etc.)
    For Internal Use Only
  • 11. First line therapy Compelling indication for others Compelling indication for others Compelling indication for others - 2 drug combo 2 drug combo Low dose Diuretics Any of 5 (A,A,B,C,D) Thiazide-type Diuretics WHO-ISH ESH-ESC JNC 7 For Internal Use Only JNC 7 Report . JAMA 2003; 289: 2560-2572 ESH/ESC Guidelines. J Hypertens 2003 ; 21: 1011-1053 Guidelines Sub-Committee. 1999 WHO/ISH. J Hypertens 1999; 17:151–183
  • 12. Recommended combinations Di ACE I CCB ARB  B  B WHO-ISH ESH-ESC JNC VII Di + any Di + ACE I/ ARB/ CCB/  B For Internal Use Only JNC 7 Report . JAMA 2003; 289: 2560-2572 ESH/ESC Guidelines. J Hypertens 2003 ; 21: 1011-1053 Guidelines Sub-Committee. 1999 WHO/ISH. J Hypertens 1999; 17:151–183
  • 13. Resistant hypertension
    • Look for reasons (drugs, alcohol, compliance, secondary HTN)
    • ‘ more diuretic’ vs ‘a fresh start’
    • (JNC 7) (ESH)
    For Internal Use Only
  • 14. SBP Control in Trials * 10604 M FACET Micro HOPE CAPPP INSIGHT HOT VALUE STOP-2 UKPDS LIFE RENAAL IDNT IRMA ABCD 130 140 150 160 170 180 190 200 mmHg 120 Diabetics B T ALLHAT 1 HOPE PROGRESS CAPPP INSIGHT NORDIL HOT STONE STOP-2 LIFE ALLHAT 2 ANBP2 INVEST SCOPE ASCOT VALUE All patients 130 140 150 160 170 180 190 200 mmHg B T * Most patients under ≥ 2 drugs Mancia G and Grassi G, J Hypert 2002;20:1461-1464 For Internal Use Only
  • 15. Combination Therapy in Large Trials 0 10 20 30 40 100 90 80 70 60 50 Average VA SYST-EUR STOP-2 STOP-1 SHEP NORDIL MRC II MRC I MAPHY INSIGHT HOT  90 LIFE EWPHE COOPE ANBP 62% 100% 41% 55% 66% 45% 52% 51% 34% 48% 54% 60% 90% 35% 93% 33% % ALLHAT 41% INVEST 82% Updated from Coca A. J Cardiovasc Pharmacol 1999; 34 (Suppl 3): 29-35 For Internal Use Only
  • 16. Multiple Antihypertensive Agents Are Often Needed to Achieve Target BP 1 No. of Antihypertensive Agents 2 3 4 SBP  140/DBP  90 ALLHAT 7 SBP  135/DBP  85 IDNT 6 MAP  92 AASK 5 DBP  80 HOT 4 MAP  92 MDRD 3 DBP  75 ABCD 2 DBP  85 UKPDS 1 Target BP (mm Hg) Trial DBP- diastolic blood pressure MAP - mean arterial pressure ; SBP- systolic blood pressure 1. UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713. 2. Estacio RO et al. Am J Cardiol. 1998;82:9R-14R. 3. Lazarus JM et al. Hypertension. 1997;29:641-650. 4. Hansson L et al. Lancet. 1998;351:1755-1762. 5. Kusek JW et al. Control Clin Trials. 1996;16:40S-46S. 6. Lewis EJ et al. N Engl J Med. 2001;345:851-860. 7. ALLHAT. JAMA . 2002;288:2998-3007. For Internal Use Only
  • 17. Compliance to Treatment Related to Daily Number of Pills Prescribed Average number of daily pills 0 10 20 30 40 50 60 70 1 2 3 8 Compliance to treatment (%) Mancia G et al. Am J Hypertens 1997 ; 10: 153S-158S For Internal Use Only
  • 18. Fixed-dose Combination Therapy Increases Compliance to Treatment Persistence rates of one pill of lisinopril/HCTZ in fixed-combination vs two separate pills of lisinopril and HCTZ 100 95 90 85 80 75 70 65 60 55 50 0 1 2 3 4 5 6 7 8 9 10 11 12 Months Persistence (%) 68.7 57.8 18.8% Lisinopril/HCTZ (1 pill) Lisinopril and HCTZ (2 pills) Dezii CM . Manag Care 2000; 9 (Suppl): s2-s6 For Internal Use Only
  • 19. JNC 7 2003 Guidelines Pharmacological Treatment
    • Most patients with hypertension will require 2 or more antihypertensive medications to achieve their BP goals...
    • When BP is more than 20/10 mmHg above the goal, consideration should be given to initiating therapy with two drugs, either as separate prescriptions or in fixed-dose combinations
    • Use of fixed-dose combination drugs should be considered to reduce prescription costs...
    JNC 7 Report. JAMA 2003; 289: 2560-2572 For Internal Use Only
  • 20. ESH/ESC 2003 Guidelines Pharmacological Treatment
    • To reach target BP, it is likely that a large proportion of patients will require combination therapy...
    • According to the baseline BP and the presence or absence of complications, it appears reasonable to initiate therapy with a low-dose combination of two agents
    • Fixed low-dose combinations are available in Europe, allowing the administration of two agents within a single tablet, thus optimizing compliance
    ESH/ESC Guidelines. J Hypertens 2003; 21: 1011-1053 For Internal Use Only
  • 21. The 3 Classes of Diuretics and Their Primary Sites of Action in the Nephron For Internal Use Only Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 22. Thiazide Diuretics
    • Duration of action of 12–24 hours
    • Blood pressure lowering effect with low doses
    • Additive blood pressure lowering effect when used in combination with other antihypertensive drugs
    • Main side effects:
    • - hypokalemia
    • - hyponatremia
    • - hyperglycemia
    • - altered plasma lipid concentration
    • - hyperuricemia or gout
    • - impotence (reversible on withdrawal of treatment)
    Bendroflumethiazide 1.25-2.5 mg once daily Chlorthalidone 12.5-25 mg once daily Hydrochlorothiazide 12.5-25 mg once daily Indapamide 2.5 mg once daily or 1.5 mg of sustained release (SR) preparation For Internal Use Only Lip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 23. Loop Diuretics
    • Bumetanide 0.5 – 2 mg/d
    • Furosemide 20 – 80 mg/d
    • Torsemide 2.5 – 10 mg/d
    • Most commonly used for powerful diuresis (renal failure, severe heart failure with oedema)
    • Rapid onset of action:
    • - 1 hour after oral administration
    • - peak at 30 min after intravenous administration
    • Useful when blood pressure require extremely rapid lowering (brisk diuresis)
    • Main side effects:
    • Hypokalemia
    • hyponatremia
    Lip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 24. Diuretics that Cause Potassium Retension
    • Triamterene 50 - 100 mg/d
    • Amiloride 5 – 10 mg/d
    • Spironolactone 25 – 100 mg/d
    • Weak diuretics
    • Little effect on blood pressure
    • Cause retention potassium
    • Combined to thiazide or loop diuretics to prevent or remedy hypokalemia
    • Main side effects:
    • - hyperkalemia
    • - hyponatremia
    • - rashes
    Lip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 25. The Mechanism of Calcium-Channel Blockade For Internal Use Only Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 26. Calcium-Channel Blockers
    • Class I (phenylalkylamine): (e.g. verapamil) act as antihypertensive agents by causing vasodilation of peripheral blood vessels. They also depress sinoatrial and atrioventricular nodal conduction, slowing the heart rate.
    • Class II (dihydropyridine): (e.g. amlodipine and nifedipine) primarily cause vasodilation of both coronary and peripheral arteries. They have little or no effect on the strength of cardiac contractions or electrical conduction through the heart.
    • Class III (benzothiazepine): (e.g. diltiazem) have peripheral and coronary vasodilator properties, and also inhibit cardiac conduction.
    Amlodipine 5-10 mg once daily Felodipine 5-10 mg once daily Nifedipine LA 20-60 mg once daily Diltiazem LA 120-540 mg once daily Verapamil modified release (MR) 240 mg once to twice daily Lip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 27. Calcium-Channel Blockers
    • Main side effects:
    • - Flushing, headaches and dizziness (short-acting Class II)
    • - Reflex tachycardia (short-acting Class II)
      • - Peripheral edema (short-acting Class II)
    • - Bradycardia
    • * Class I (verapamil)
    • * Class II (diltiazem)
    • - Constipation (commonly occurs with verapamil)
    Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 28. The Mechanism of Beta-Blockade Reduced cardiac output Reduced blood pressure Impulse Smooth muscle presynaptic sympathetic neurons Cardiac tissue (contains beta 1 receptors) Increased bronchial resistance and vasoconstriction Impulse Smooth muscle presynaptic sympathetic neurons Tissue of the peripheral blood vessels, smooth muscle cells or lungs (contains beta 2 receptors) Beta-blocker Nonadrenaline or adrenaline Beta 1 receptors Beta 2 receptors Reduced heart rate and force of constriction Beta 1 receptor blocked by beta-blocker Beta 2 receptor blocked by beta-blocker Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 29. Beta-Blockers
    • * They are effective antihypertensive drugs:
    • - reduce cardiac output
    • - alter baroreceptor reflex sensitivity
    • - block peripheral beta-adrenergic receptors
    • * Cardioselective beta-blockers
    • - Act on beta1 receptors (found mainly in the heart) and results in:
    • * reduction of heart rate
    • * reduction of myocardial contractility
    • * reduction in the rate of conduction of impulses through the heart
    • * reduction of blood pressure
    • * suppression of adrenergic-induced renin release and breakdown of fat
    • * Non-selective beta-blockers
    • - Act on beta1 and beta2 receptors (found in bronchial tissue and peripheral blood vessels) and results in:
    • * increased bronchial resistance
    • * inhibition of catecholamine-induced glucose metabolism
    • * increased vasoconstriction.
    Atenolol 50-100 mg once daily (selective) Bisoprolol 5-10 mg once daily (selective) Metoprolol 50-100 mg twice daily (selective) Propranolol 40-160 mg twice daily (non selective) Carvedilol 25-50 mg twice daily (non selective) Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 30. Beta-Blockers
    • Beta-blockers are effective antihypertensives
    • Beta-blockers can be combined with other antihypertensive drugs with different modes of action for an additive effect
    • Main side effects:
    • - Peripheral vasospasm (Raynaud’s phenomenon)
    • - Bronchoconstriction
    • - Bradycardia
    • - Neuropsychological effects (fatigue, apathy, nightmares)
    • - minor adverse effects on plasma lipid profile and glycemia
    Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 31. The Mechanism of Alpha-Blockade Total peripheral resistance increased Blood Pressure rises Constriction of blood vessel Impulse Smooth muscle presynaptic sympathetic neurons Vascular smooth muscle cell Total peripheral resistance decreased Blood pressure falls Blood vessel remains dilated Impulse Smooth muscle presynaptic sympathetic neurons Alpha 1 receptor blocked so muscle cells do not contract Alpha 1 receptor blocker Nonadrenaline or adrenaline Alpha 1 receptors Alpha 2 receptors For Internal Use Only Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 32. Alpha-Blockers
    • Two classes of alpha-blockers:
    • * selective: act only on alpha1 receptors
    • - produce vasodilation by blocking the action of noradrenaline at postsynaptic alpha1 receptors in both arterioles and veins. This causes a drop in peripheral resistance and thus blood pressure
    • - can be used in combination with other antihypertensive drugs
    • - lead to modest improvement in plasma lipid profile and glucose tolerance
    • * non-selective: act on both alpha1 and alpha2 receptors.
    • - mainly used to treat pheochromocytoma
    • Main side effects:
    • - Postural hypotension
    • - Dizziness, vertigo, fatigue
    • - Urinary frequency and incontinence
    • - Gastrointestinal disturbances (nausea, diarrhea)
    Doxazosin 1-16 mg once daily Terazosin 1-10 mg once daily Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only
  • 33. The Mechanism of Action of ACE-inhibitors Angiotensin I Bradykinin ACE Inhibitor ACE (from lungs) Angiotensinogen (from liver) Renin (from kidney) Angiotensin II Inactive kinins Vasodilation Blood pressure decreases Retention of salt and water Increased aldosterone Increased blood volume Increased total Peripheral resistance Vasoconstriction Blood pressure increase Bradykinin pathway RAA System For Internal Use Only Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 34.
    • * ACE inhibitors are particularly indicated for hypertension in patients with type 1 diabetes and nephropathy.
    • * ACE inhibitors may be used in patients with heart failure, evidence of left ventricular dysfunction or postmyocardial infarction.
    • ACE inhibitors can be used with other antihypertensive drugs for an additive blood pressure lowering effect.
    • Main side effects:
    • - Persistent irritating dry cough (20% of patients)
    • - Angiodema
    • - First-dose hypotension
    • - Hyperkalemia
    • - Gastrointestinal effects (dyspepsia, nausea, diarrhea)
    ACE-inhibitors Captopril 12.5 mg twice daily - 50 mg three times daily Enalapril 5-40 mg once daily Lisinopril 2.5-40 mg once daily Ramipril 1.25-10 mg once daily Perindopril 2-8 mg once daily Trandolapril 1-8 mg once daily For Internal Use Only Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 35. Mechanism of Action of Angiotensin II Receptor Blockers (ARBs) Adapted from Unger T. Am J Cardiol 2002; 89 (suppl):3A-10A. AT 1 Receptor Na reabsorption Aldosterone release Sympathetic outflow Vasopressin secretion Vasoconstriction Vascular and cardiac hypertrophy Angiotensinogen Angiotensin I Angiotensin II Non-ACE enzymes (cathepsin, chymase) Renin Bradykinin ACE Inactive Fragments AT 2 Receptor Vasodilation Growth inhibition Apoptosis Blood Pressure ARBs For Internal Use Only
  • 36. Pharmacologic Characteristics of ARBs HTN HTN, post MI, CHF HTN HTN, Nephropathy T2DM + HTN, Morbi-Mortality reduction and stroke prevention in HTN with LVH HTN HTN, CHF HTN, Nephropathy T2DM + HTN Indications Digoxin no no Rifampin, Fluconazole no no no Drug interract 24h 6h 12-18h 2h 5-9h 9h 11-15h T 1/2 Minimal yes none minimal yes none none Food effect 0.5-1h 2-4h 1-2h 3-4h 3h 3-4h 1.5-2h Tmax 42-58% 25% 26% 33% 13% 15% 60-80% Bioavail Boeh Ingelh Novartis/ Beaufour Menar/Sank MSD Solvay AstZen/Tak SA/BMS Company Telmisartan (Micardis) Valsartan (Diovan) Olmesartan (Benicar) Losartan (Cozaar) Eprosartan (Teveten) Candesartan (Atacand) Irbesartan (Avapro/ Aprovel) For Internal Use Only Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 37. ARBs Summary
    • Actions of ARBs
    • - ARBs block the RAA system further downstream than ACE inhibitors
    • - They block the actions of angiotensin II by binding to the AT1 receptor
    • - They lower blood pressure by inhibiting the effects of angiotensin II
    • Uses of ARBs
    • - All ARBs are indicated for the treatment of hypertension (HTN).
    • - Aprovel and losartan are indicated for the treatment of renal disease in patients with
    • HTN and type 2 diabetes
    • - Losartan is indicated for stroke prevention in patients with HTN and LVH.
    • - Valsartan is indicated postmyocardial infarction in patients with left ventricular failure or left ventricular systolic dysfunction.
    • - ARBs are usually prescribed in a once-daily regimen.
    • - Candesartan is the only ARB licensed for the treatment of essential hypertension and
    • for patients with heart failure and impaired left ventricular systolic function as add-on
    • therapy to ACE inhibitors or when ACE inhibitors are not tolerated.
    • Tolerability of ARBs
    • - ARBs have a good tolerability (comparable to placebo)
    • - They don’t provoke persistent dry cough (no inhibition of bradykinin breakdown)
    • - Occasionally: hypotension, hyperkalemia
    For Internal Use Only Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006
  • 38. Other antihypertensive agents
    • Centrally-acting drugs (methyldopa, moxonidine)
    • Direct vasodilator (hydralazine, minoxidil)
    • Poorly tolerated
    • - headache, palpitation, edema
    • - drug-induced lupus syndrome (hydralazine)
    • - hirsutism in women (minoxidil)
    • Used when other treatments have failed
    • Used in special conditions (pregnancy)
    Moxonidine 200 mg once daily – 300 mg twice daily Hydralazine 25-5- mg twice daily Minoxidil 2.5-50 mg in 1-2 doses Adapted from: Oparil S and Weber MA. Hypertension.Elsevier/Sanders 2nd ed. 2005; L ip G and Bakris G. Handbook Hypertension Management. CMG 2006 For Internal Use Only