MISCELLANEOUS ANTIHYPERTENSIVES


See also Nitroprusside

I. Angiotensin II receptor antagonists ("ARB's")

  1. Block binding of angiotensin II to the ATII type 1 receptor
  2. Potential adverse effects
    1. Angioedema (very rare)
    2. Hyperkalemia
    3. Potential association with cancer?
      1. "Candessartan in Heart failure Assessment of Reduction in Mortality and Morbidity" ("CHARM") trial showed a small but sig. higher incidence of Ca-related mortality in pts randomized to candesartan vs. placebo
      2. In a meta-analysis of five randomized trials (mostly with telmisartan), ARB recipients had sig. higher incidence of Ca than control pts (7.2% vs. 6.0%, RR 1.08) (Lancet ePublication June 2010-JW; http://dx.doi.org/10.1016/S1470-2045(10)70106-6),
  3. Contraindicated (category D) in 2nd or 3rd trimester of pregnancy
  4. Protective effect against diabetes mellitus
    1. The LIFE Study showed lower incidence of diabetics randomized to Losartan vs. Atenolol, though it was not a primary outcome of the study (see link for details)
    2. In a study in 9,306 pts with impaired glucose tolerance AND (known cardiovascular disease OR one cardiovascular risk factor) and not on ACEs or ARBs randomized to valsartan 80-160mg/d vs. placebo, valsartan pts had sig. lower incidence of diabetes (33.1% vs. 36.8%), thre was no sig. diff. in incidence of (HF, MI, CVA, unstable angina, arterial revascularization, or cardiovascular death).  The summary did not state the mean follow-up interval.  ("Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research" ("NAVIGATOR") Trial; NEJM 362:1477, 2010-AFP).
  5. Also of benefit in patients with Congestive Heart Failure--click on link for details
  6. Ditto for Diabetic Nephropathy
  7. Specific agents:
    1. Losartan* (Cozaar) 25-100mg divided QD-BID
    2. Valsartan* (Diovan) 80-320mg QD
    3. Irbesartan (Avapro) 150-300mg QD
    4. Candesartan (Atacand) 8-32mg QD
    5. Telmisartan (Micardis) 40-80mg QD
    6. Eprosartan (Teveten) 400-800mg divided QD-BID
    7. Olmesartan (Benicar) 20-40mg QD
    8. Azilsartan (Edarbi) 80mg QD (start at 40mg if volume-depleted e.g. on high-dose diuretics); Specific to AT1 receptor subtype

II. Direct vasodilators

  1. Can cause HA, fluid retention, tachycardia
  2. Specific agents:
    1. Hydralazine* 40-200mg divided BID-QID (can cause headache, vomiting, and drug-induced lupus); 10-20mg IV or 10-50mg IM
    2. Minoxidil 2.5-40mg divided QD-BID (can cause hirsutism)

III. Alpha-1 adrenergic antagonists ("alpha blockers")

  1. Can cause postural hypotension, esp with first dose; also can cause anticholinergic effects and priapism
  2. Concern over assocation w/CAD & CVA--see results of the ALLHAT study (click link for details)
  3. Specific agents
    1. Doxazosin (Cardura) 1-16mg QD
    2. Terazosin (Hytrin) 1-20mg QD
    3. Prazosin (Minipress) 1-20mg divided BID-TID--ass'd with more first-dose hypotension than the others
    4. Alpha-blockers designed specifically to treat Benign Prostatic Hyperplasia
      1. Tamsulosin (Flomax) 0.4-0.8mg QD-associated with "intraoperative floppy iris syndrome," a complication of ataract surgery, when tamsulosin is started soon before surgery
      2. Alfuzosin (Uroxatral) 10mg QD-Contraindicated in pts with mod-severe hepatic impairment (Med. Lett. 46:2, 2004)
      3. Siludosin (Rapaflo) 8mg QD with food (in renal impairment-CrCl 30-50mL/min-reduce to 4mg/d)

IV. Centrally acting agents (alpha-adrenergic agonists)

  1. Can cause sedation, depression, dry mouth, bradycardia, withdrawal HTN, lupus-like syndromes, and hemolytic anemia
  2. Can cause paradoxical HTN when used in conjunction w/beta-blockers
  3. Specific agents
    1. Clonidine* (PO 0.1-0.6 mg/d divided BID-TID; transdermal 0.1-0.3mg/d, one patch weekly)--may potentiate anesthetic agents
    2. Guanabenz 4-64 mg/d divided BID
    3. Guanfacine 1-3mg QD
    4. Methyldopa* 250-2000mg divided BID (can cause hepatic dysfunction and "autoimmune" reactions; may increase serum lithium levels)

V. Peripheral adrenergic agents

  1. Can cause postural hypotension and diarrhea
  2. Specific agents
    1. Guanadrel 10-75mg divided BID
    2. Guanethidine 10-50mg QD
    3. Reserpine 0.05-0.1 mg QD (can worsen depression and PUD, causes sedation and nasal congestion too)

VI. Direct renin inhibitors

  1. Aliskiren (Rasilez) 150-300mg PO QD
    1. Reduces plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I
    2. Can cause hyperkalemia when used in conjunction with ACE inhibitors.
    3. Available as a combination with amlodipine and HCTZ as "Amturnide" with aliskiren-amlodipine-HCTZ doses as follows:
      1. 150/5/12.5
      2. 300/5/12.5
      3. 300/5/25
      4. 300/10/12.5
      5. 300/10/25

VII. Fenoldopam (Med. Lett. 40:57, 1998--AFP)

  1. A peripheral dopamine-1 agonist for parenteral tx of severe HTN
  2. Induces arteriolar vasodilation; increases renal blood flow
  3. Also has direct diuretic and natriuretic effect on renal tubular cells
  4. Not much tolerance or rebound HTN after d/c
  5. Has been used to tx CHF; reduces afterload and increases cardiac output but didn't decrease PCWP
  6. Can cause side f/x due to vasodilation: hypotension, flushing, dizziness, HA, tachycardia; also nausea & hypokalemia
  7. Can increase intraocular pressure
  8. Don't use in combination w/beta-blockers b/c the latter could inhibit reflex tachycardia and result in severe hypotension
  9. Dosing: 0.1-1.6 ug/kg/min (start low, titrate up 0.05-0.1ug/kg/min Q15min)

VIII. Endothelin antagonists

  1. Investigational as of 2009
  2. Darusentan
  3. Can be associated with increases in serum Cr levels and decreased GFR; also edema

*--Available in combination with diuretics