A GENS-based approach to cardiovascular pharmacology: Impact on metabolism, pharmacokinetics and pharmacodynamics

Therapeutic Delivery

Volumn 2, Issue 11, 2011, Pages 1437-1453

  Franconi, Flavia ^a   Carru, Ciriaco ^a   Spoletini, Ilaria ^b   Malorni, Walter ^c   Vella, Stefano ^c   Mercuro, Giuseppe ^d   Deidda, Martino ^d   Rosano, Giuseppe ^b  

^a UNIVERSITY OF SASSARI   (Italy)

^b IRCCS SAN RAFFAELE PISANA   (Italy)

^c ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^d UNIVERSITY OF CAGLIARI   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPRENOLOL; AMLODIPINE; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTICOAGULANT AGENT; ANTIDEPRESSANT AGENT; ANTITHROMBOCYTIC AGENT; ATENOLOL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BISOPROLOL; CARVEDILOL; CYCLOSPORIN; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; FIBRINOLYTIC AGENT; FLECAINIDE; GLYCERYL TRINITRATE; LABETALOL; METHOTREXATE; METOPROLOL; NEBIVOLOL; NIFEDIPINE; ORAL CONTRACEPTIVE AGENT; PROPRANOLOL; RANITIDINE; SOTALOL; TORASEMIDE; UNINDEXED DRUG; VERAPAMIL; WARFARIN;

ADVERSE OUTCOME; AGE DISTRIBUTION; ANGINA PECTORIS; ANXIETY DISORDER; BODY COMPOSITION; BODY SIZE; BRUGADA SYNDROME; CORONARY ARTERY BLOOD FLOW; CRANBERRY; DEPRESSION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG METABOLISM; DRUG POTENTIATION; DRUG RESEARCH; DRUG SAFETY; ELECTROLYTE BALANCE; GLAUCOMA; HEADACHE; HEART ARRHYTHMIA; HEART DEATH; HEART FAILURE; HEART INFARCTION; HEART MUSCLE METABOLISM; HEART OUTPUT; HEART TRANSPLANTATION; HORMONAL REGULATION; HORMONE SUBSTITUTION; HUMAN; HYPERTENSION; HYPERTHYROIDISM; HYPOKALEMIA; HYPONATREMIA; KIDNEY FUNCTION; METABOLIC REGULATION; MIGRAINE; OBESITY; OSTEOPOROSIS; PHYSIOLOGICAL PROCESS; PREGNANCY OUTCOME; PRIORITY JOURNAL; QT PROLONGATION; REGENERATIVE MEDICINE; RESPIRATORY FUNCTION; REVIEW; SEX DIFFERENCE; SKIN ABSORPTION; STROKE; TREATMENT PLANNING; UNSPECIFIED SIDE EFFECT;

EID: 80054920376     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/tde.11.117     Document Type: Review

References (182)

1. Wizeman TM, Pardue MLE. Exploring the Biological Contributions to Human Health: Does Sex Matter? National Academies Press, Washington, DC, USA (2001).
2. Marino M, Masella R, Bulzomi P, Campesi I, Malorni W, Franconi F. Nutrition and human health from a sex-gender perspective. Mol. Aspects Med. 32, 1-70 (2011).
3. Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF. Sex differences in pharmacokinetics and pharmacodynamics. Annu. Rev. Pharmacol. Toxicol. 44, 499-523 (2004). Highlights sex-based differences in pharmacologic parameters.
4. Franconi F, Brunelleschi S, Steardo L, Cuomo V. Gender differences in drug responses. Pharmacol. Res. 55, 81-95 (2007). Summarizes gender differences in pharmacology, with a specific focus on drug response.
5. Donovan MD. Sex and racial differences in pharmacological response: effect of route of administration and drug delivery system on pharmacokinetics. J. Womens Health (Larchmt) 14, 30-37 (2005).
6. Kashuba AD, Nafziger AN. Physiological changes during the menstrual cycle and their effects on the pharmacokinetics and pharmacodynamics of drugs. Clin. Pharmacokinet. 34, 203-218 (1998).
7. Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet. 48, 143-157 (2009). Summarizes the sex-based differences in clinical pharmacology, with a specific focus on pharmacokinetics and pharmacodynamics.
8. Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin. Pharmacol. Ther. 82, 87-96 (2007).
9. Regitz-Zagrosek V. Therapeutic implications of the gender-specific aspects of cardiovascular disease. Nat Rev Drug Discov. 5, 425-438 (2006). Gender differences in cardiovascular pharmacology, their underlying pathophysiological mechanisms and implications for novel strategies of treatment are discussed.
10. Yang Y, Carlin AS, Faustino PJ et al. Participation of women in clinical trials for new drugs approved by the food and drug administration in 2000-2002. J. Womens Health (Larchmt) 18, 303-310 (2009).
11. Wenger NK. Coronary heart disease in women: highlights of the past 2 years - stepping stones, milestones and obstructing boulders. Nat. Clin. Pract. Cardiovasc. Med. 3, 194-202 (2006).
12. Rogers W. Evidence-based medicine and women: do the principles and practice of EBM further women's health? Bioethics 18, 50-71 (2004).
13. Pirmohamed M, James S, Meakin S et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 329, 15-19 (2004). Large prospective observational study demonstrating that, among the adverse drug reactions causing admission to hospital, low-dose aspirin, diuretics, warfarin and nonsteroidal anti-inflammatory drugs other than aspirin were most commonly implicated.
14. Patel H, Bell D, Molokhia M et al. Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998-2005. BMC Clin. Pharmacol. 7, 9 (2007).
15. Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V. Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. Eur. Heart J. 26, 1585-1595 (2005).
16. Pilote L, Dasgupta K, Guru V et al. A comprehensive view of sex-specific issues related to cardiovascular disease. CMAJ 176, S1-S44 (2007). Both sex and gender differences may account for the worst outcomes in cardiovascular medicine observed in women than in men. However, the interaction between sex-and gender-related factors and cardiovascular outcomes in women still remains unknown.
17. Franconi F, Carru C, Malorni W, Vella S, Mercuro G. The effect of sex/gender on cardiovascular pharmacology. Curr. Pharm. Des. 17, 1095-1107 (2011).
18. Case AM, Reid RL. Effects of the menstrual cycle on medical disorders. Arch. Intern. Med. 158, 1405-1412 (1998).
19. Khalil RA. Sex hormones, vascular function and the outcome of hormone replacement therapy in cardiovascular disease. Future Cardiol. 3, 283-300 (2007).
20. Olson BR, Forman MR, Lanza E et al. Relation between sodium balance and menstrual cycle symptoms in normal women. Ann. Intern. Med. 125, 564-567 (1996).
21. Van de Werf F, Barron HV, Armstrong PW et al. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA. Eur. Heart J. 22, 2253-2261 (2001).
22. Mead J. Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity. Am. Rev. Respir. Dis. 121, 339-342 (1980).
23. Rohatagi S, Calic F, Harding N et al. Pharmacokinetics, pharmacodynamics, and safety of inhaled cyclosporin A (ADI628) after single and repeated administration in healthy male and female subjects and asthmatic patients. J. Clin. Pharmacol. 40, 1211-1226 (2000).
24. Berg UB. Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors. Nephrol. Dial. Transplant 21, 2577-2582 (2006).
25. Kielstein JT, Bode-Boger SM, Frolich JC, Ritz E, Haller H, Fliser D. Asymmetric dimethylarginine, blood pressure, and renal perfusion in elderly subjects. Circulation 107, 1891-1895 (2003).
26. Dias VC, Tendler B, Oparil S, Reilly PA, Snarr P, White WB. Clinical experience with transdermal clonidine in African-American and Hispanic-American patients with hypertension: evaluation from a 12-week prospective, open-label clinical trial in community-based clinics. Am. J. Ther. 6, 19-24 (1999).
27. Roy SD, Flynn GL. Transdermal delivery of narcotic analgesics: pH, anatomical, and subject influences on cutaneous permeability of fentanyl and sufentanil. Pharm. Res. 7, 842-847 (1990).
28. Freire AC, Basit AW, Choudhary R, Piong CW, Merchant HA. Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. Int. J. Pharm. 415, 15-28 (2011).
29. Soldin OP, Chung SH, Mattison DR. Sex differences in drug disposition. J. Biomed. Biotechnol. 2011, 187103 (2011).
30. Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab. Rev. 41, 67-76 (2009).
31. Hunt CM, Westerkam WR, Stave GM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem. Pharmacol. 44, 275-283 (1992).
32. Zhu B, Liu ZQ, Chen GL et al. The distribution and gender difference of CYP3A activity in Chinese subjects. Br. J. Clin. Pharmacol. 55, 264-269 (2003).
33. Anakk S, Ku CY, Vore M, Strobel HW. Insights into gender bias: rat cytochrome P450 3A9. J. Pharmacol. Exp. Ther. 305, 703-709 (2003).
34. Flockhart DA, Rae JM. Cytochrome P450 3A pharmacogenetics: the road that needs traveled. Pharmacogenomics J. 3, 3-5 (2003).
35. Waxman DJ, Holloway MG. Sex differences in the expression of hepatic drug metabolizing enzymes. Mol. Pharmacol. 76, 215-228 (2009).
36. Bebawy M, Chetty M. Gender differences in p-glycoprotein expression and function: effects on drug disposition and outcome. Curr. Drug Metab. 10, 322-328 (2009).
37. Sakuma T, Kawasaki K, Jarukamjorn K, Nemoto N. Sex differences of drug metabolizing enzymes: female predominant expression of human and mouse cytochrome P450 3A isoforms. J. Health Sci. 55, 325-337 (2009).
38. Tracy TS, Korzekwa KR, Gonzalez FJ, Wainer IW. Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil. Br. J. Clin. Pharmacol. 47, 545-552 (1999).
39. Krecic-Shepard ME, Barnas CR, Slimko J, Jones MP, Schwartz JB. Gender-specific effects on verapamil pharmacokinetics and pharmacodynamics in humans. J. Clin. Pharmacol. 40, 219-230 (2000).
40. Schwartz JB, Capili H, Wainer IW. Verapamil stereoisomers during racemic verapamil administration: effects of aging and comparisons to administration of individual stereoisomers. Clin. Pharmacol. Ther. 56, 368-376 (1994).
41. Krecic-Shepard ME, Barnas CR, Slimko J, Schwartz JB. Faster clearance of sustained release verapamil in men versus women: continuing observations on sex-specific differences after oral administration of verapamil. Clin. Pharmacol. Ther. 68, 286-292 (2000).
42. Gupta SK, Atkinson L, Tu T, Longstreth JA. Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. Br. J. Clin. Pharmacol. 40, 325-331 (1995).
43. Doki K, Homma M, Kuga K et al. Gender-associated differences in pharmacokinetics and anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia. Eur. J. Clin. Pharmacol. 63, 951-957 (2007).
44. Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics? Clin. Pharmacokinet. 41, 329-342 (2002).
45. Luzier AB, Killian A, Wilton JH, Wilson MF, Forrest A, Kazierad DJ. Gender-related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Clin. Pharmacol. Ther. 66, 594-601 (1999).
46. Johnson JA, Akers WS, Herring VL, Wolfe MS, Sullivan JM. Gender differences in labetalol kinetics: importance of determining stereoisomer kinetics for racemic drugs. Pharmacotherapy 20, 622-628 (2000).
47. Salazar DE, Much DR, Nichola PS, Seibold JR, Shindler D, Slugg PH. A pharmacokinetic-pharmacodynamic model of d-sotalol Q-Tc prolongation during intravenous administration to healthy subjects. J. Clin. Pharmacol. 37, 799-809 (1997).
48. Melander A, Stenberg P, Liedholm H, Schersten B, Wahlin-Boll E. Food-induced reduction in bioavailability of atenolol. Eur. J. Clin. Pharmacol. 16, 327-330 (1979).
49. Leopold G, Pabst J, Ungethum W, Buhring KU. Basic pharmacokinetics of bisoprolol, a new highly β 1-selective adrenoceptor antagonist. J. Clin. Pharmacol. 26, 616-621 (1986).
50. Thurmann PA, Haack S, Werner U et al. Tolerability of β-blockers metabolized via cytochrome P450 2D6 is sex-dependent. Clin. Pharmacol. Ther. 80, 551-553 (2006).
51. Holbrook AM, Pereira JA, Labiris R et al. Systematic overview of warfarin and its drug and food interactions. Arch. Intern. Med. 165, 1095-1106 (2005).
52. Baris N, Kalkan S, Guneri S, Bozdemir V, Guven H. Influence of carvedilol on serum digoxin levels in heart failure: is there any gender difference? Eur. J. Clin. Pharmacol. 62, 535-538 (2006).
53. Shammas FV, Dickstein K. Clinical pharmacokinetics in heart failure. An updated review. Clin. Pharmacokinet. 15, 94-113 (1988).
54. Zordoky BN, El-Kadi AO. Modulation of cardiac and hepatic cytochrome P450 enzymes during heart failure. Curr. Drug Metab. 9, 122-128 (2008).
55. Catananti C, Liperoti R, Settanni S et al. Heart failure and adverse drug reactions among hospitalized older adults. Clin. Pharmacol. Ther. 86, 307-310 (2009).
56. Havranek EP, Ware MG, Lowes BD. Prevalence of depression in congestive heart failure. Am. J. Cardiol. 84, 348-350, A349 (1999).
57. Gottlieb SS, Khatta M, Friedmann E et al. The influence of age, gender, and race on the prevalence of depression in heart failure patients. J. Am. Coll. Cardiol. 43, 1542-1549 (2004).
58. Sherwood A, Blumenthal JA, Trivedi R et al. Relationship of depression to death or hospitalization in patients with heart failure. Arch. Intern. Med. 167, 367-373 (2007).
59. O'Connor CM, Jiang W, Kuchibhatla M et al. Antidepressant use, depression, and survival in patients with heart failure. Arch. Intern. Med. 168, 2232-2237 (2008).
60. Glassman AH, O'Connor CM, Califf RM et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 288, 701-709 (2002).
61. Tata LJ, West J, Smith C et al. General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction. Heart 91, 465-471 (2005).
62. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N. Engl. J. Med. 321, 406-412 (1989).
63. Whang W, Kubzansky LD, Kawachi I et al. Depression and risk of sudden cardiac death and coronary heart disease in women: results from the Nurses' Health Study. J. Am. Coll. Cardiol. 53, 950-958 (2009).
64. Smoller JW, Allison M, Cochrane BB et al. Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Women's Health Initiative study. Arch. Intern. Med. 169, 2128-2139 (2009).
65. Onder G, Penninx BW, Landi F et al. Depression and adverse drug reactions among hospitalized older adults. Arch. Intern. Med. 163, 301-305 (2003).
66. Regitz-Zagrosek V, Petrov G, Lehmkuhl E et al. Heart transplantation in women with dilated cardiomyopathy. Transplantation 89, 236-244 (2011).
67. Pina IL, Kokkinos P, Kao A et al. Baseline differences in the HF-ACTION trial by sex. Am. Heart J. 158, S16-23 (2009).
68. Rathore SS, Foody JM, Wang Y et al. Sex, quality of care, and outcomes of elderly patients hospitalized with heart failure: findings from the National Heart Failure Project. Am. Heart J. 149, 121-128 (2005).
69. Taylor DO, Edwards LB, Boucek MM et al. Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult heart transplantation report - 2006. J. Heart Lung Transplant 25, 869-879 (2006).
70. Tsai FC, Marelli D, Bresson J et al. Recent trends in early outcome of adult patients after heart transplantation: a single-institution review of 251 transplants using standard donor organs. Am. J. Transplant. 2, 539-545 (2002).
71. Kirsch M, Baufreton C, Naftel DC, Benvenuti C, Loisance DY. Pretransplantation risk factors for death after heart transplantation: the Henri Mondor experience. J. Heart Lung Transplant 17, 268-277 (1998).
72. Prendergast TW, Furukawa S, Beyer AJ 3rd, Browne BJ, Eisen HJ, Jeevanandam V. The role of gender in heart transplantation. Ann. Thorac. Surg. 65, 88-94 (1998).
73. Schlechta B, Kocher AA, Ofner P et al. Impact of gender mismatch on the outcome of heart transplantation. Transplant. Proc. 31, 3340-3342 (1999).
74. Welp H, Spieker T, Erren M, Scheld HH, Baba HA, Stypmann J. Sex mismatch in heart transplantation is associated with increased number of severe rejection episodes and shorter long-term survival. Transplant. Proc. 41, 2579-2584 (2009).
75. Zeier M, Dohler B, Opelz G, Ritz E. The effect of donor gender on graft survival. J. Am. Soc. Nephrol. 13, 2570-2576 (2002).
76. Herity NA, Lo S, Lee DP et al. Effect of a change in gender on coronary arterial size: a longitudinal intravascular ultrasound study in transplanted hearts. J. Am. Coll. Cardiol. 41, 1539-1546 (2003).
77. Kuypers DR. Immunotherapy in elderly transplant recipients: a guide to clinically significant drug interactions. Drugs Aging 26, 715-737 (2009).
78. Morgan ET, Li-Masters T, Cheng PY. Mechanisms of cytochrome P450 regulation by inflammatory mediators. Toxicology 181-182, 207-210 (2002).
79. Kahan BD, Kramer WG, Wideman C, Flechner SM, Lorber MI, Van Buren CT. Demographic factors affecting the pharmacokinetics of cyclosporine estimated by radioimmunoassay. Transplantation 41, 459-464 (1986).
80. Pea F, Pavan F, Furlanut M. Clinical relevance of pharmacokinetics and pharmacodynamics in cardiac critical care patients. Clin. Pharmacokinet. 47, 449-462 (2008).
81. Aroldi A, Tarantino A, Montagnino G, Cesana B, Cocucci C, Ponticelli C. Effects of three immunosuppressive regimens on vertebral bone density in renal transplant recipients: a prospective study. Transplantation 63, 380-386 (1997).
82. Csete M. Gender issues in transplantation. Anesth. Analg. 107, 232-238 (2008).
83. Pond GR, Lipton JH, Messner HA. Long-term survival after blood and marrow transplantation: comparison with an age- and gender-matched normative population. Biol. Blood Marrow Transplant. 12, 422-429 (2006).
84. Fuge R, Bird JM, Fraser A et al. The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation. Br. J. Haematol. 113, 58-64 (2001).
85. Bai Y, Sun T, Ye P. Age, gender and diabetic status are associated with effects of bone marrow cell therapy on recovery of left ventricular function after acute myocardial infarction: a systematic review and meta-analysis. Ageing Res. Rev. 9, 418-423 (2011).
86. Edelman AB, Cherala G, Stanczyk FZ. Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review. Contraception 82, 314-323 (2011).
87. Rakusan K. Drugs in pregnancy: implications for a cardiologist. Exp. Clin. Cardiol. 15, e100-e103 (2011).
88. Hameed AB, Sklansky MS. Pregnancy: maternal and fetal heart disease. Curr. Probl. Cardiol. 32, 419-494 (2007).
89. Anderson GD, Carr DB. Effect of pregnancy on the pharmacokinetics of antihypertensive drugs. Clin. Pharmacokinet. 48, 159-168 (2009).
90. Yoder SR, Thornburg LL, Bisognano JD. Hypertension in pregnancy and women of childbearing age. Am. J. Med. 122, 890-895 (2009).
91. Podymow T, August P. Antihypertensive drugs in pregnancy. Semin. Nephrol. 31, 70-85 (2011).
92. Kher A, Bauersachs R, Nielsen JD. The management of thrombosis in pregnancy: role of low-molecular-weight heparin. Thromb. Haemost. 97, 505-513 (2007).
93. Anderson GD. Pregnancy-induced changes in pharmacokinetics: a mechanistic-based approach. Clin. Pharmacokinet. 44, 989-1008 (2005).
94. Pavek P, Ceckova M, Staud F. Variation of drug kinetics in pregnancy. Curr. Drug Metab. 10, 520-529 (2009).
95. Ho RH, Kim RB. Transporters and drug therapy: implications for drug disposition and disease. Clin. Pharmacol. Ther. 78, 260-277 (2005).
96. Maeno Y, Hirose A, Kanbe T, Hori D. Fetal arrhythmia: prenatal diagnosis and perinatal management. J. Obstet. Gynaecol. Res. 35, 623-629 (2009).
97. Mattison DR. Transdermal drug absorption during pregnancy. Clin. Obstet. Gynecol. 33, 718-727 (1990).
98. Hebert MF, Easterling TR, Kirby B et al. Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: a University of Washington specialized center of research study. Clin. Pharmacol. Ther. 84, 248-253 (2008).
99. Davis RL, Eastman D, McPhillips H et al. Risks of congenital malformations and perinatal events among infants exposed to calcium channel and β-blockers during pregnancy. Pharmacoepidemiol. Drug Saf. 20, 138-145 (2011).
100. Brancazio LR, Roperti KA, Stierer R, Laifer SA. Pharmacokinetics and pharmacodynamics of subcutaneous heparin during the early third trimester of pregnancy. Am. J. Obstet. Gynecol. 173, 1240-1245 (1995).
101. Blomback M, Bremme K, Hellgren M, Lindberg H. A pharmacokinetic study of dalteparin (Fragmin) during late pregnancy. Blood Coagul. Fibrinolysis 9, 343-350 (1998).
102. Norris LA, Bonnar J, Smith MP, Steer PJ, Savidge G. Low molecular weight heparin (tinzaparin) therapy for moderate risk thromboprophylaxis during pregnancy. A pharmacokinetic study. Thromb. Haemost. 92, 791-796 (2004).
103. Buchanan ML, Easterling TR, Carr DB et al. Clonidine pharmacokinetics in pregnancy. Drug Metab. Dispos. 37, 702-705 (2009).
104. Weinera CP, Buhimschib C, Swaanc P. Drug-prescribing challenges during pregnancy. Curr. Obstet. Gynaecol. 15, 157-165 (2005).
105. Hardie C, Bain C, Walters M. Hormone replacement therapy: the risks and benefits of treatment. J. R. Coll. Physicians Edinb. 39, 324-326 (2009).
106. Shufelt CL, Bairey Merz CN. Contraceptive hormone use and cardiovascular disease. J. Am. Coll. Cardiol. 53, 221-231 (2009).
107. Mwinyi J, Cavaco I, Pedersen RS et al. Regulation of CYP2C19 expression by estrogen receptor α: implications for estrogen-dependent inhibition of drug metabolism. Mol. Pharmacol. 78, 886-894 (2011).
108. Zingone MM, Guirguis AB, Airee A, Cobb D. Probable drug interaction between warfarin and hormonal contraceptives. Ann. Pharmacother. 43, 2096-2102 (2009).
109. Frohlich M, Albermann N, Sauer A, Walter-Sack I, Haefeli WE, Weiss J. In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins. Biochem. Pharmacol. 68, 2409-2416 (2004).
110. Sims ST, Rehrer NJ, Bell ML, Cotter JD. Endogenous and exogenous female sex hormones and renal electrolyte handling: effects of an acute sodium load on plasma volume at rest. J. Appl. Physiol. 105, 121-127 (2008).
111. Bloemenkamp KW. Epidemiology of oral contraceptive related thrombosis. Thromb. Res. 115(Suppl. 1), 1-6 (2005).
112. Olah L, Valikovics A, Bereczki D, Fulesdi B, Munkacsy C, Csiba L. Gender-related differences in acetazolamide-induced cerebral vasodilatory response: a transcranial Doppler study. J. Neuroimaging 10, 151-156 (2000).
113. Bierman AS, Pugh MJ, Dhalla I et al. Sex differences in inappropriate prescribing among elderly veterans. Am. J. Geriatr. Pharmacother. 5, 147-161 (2007).
114. Johnell K, Weitoft GR, Fastbom J. Sex differences in inappropriate drug use: a register-based study of over 600,000 older people. Ann. Pharmacother. 43, 1233-1238 (2009).
115. Sikdar KC, Alaghehbandan R, MacDonald D et al. Adverse drug events in adult patients leading to emergency department visits. Ann. Pharmacother. 44, 641-649 (2011).
116. Rivero A, Curtis AB. Sex differences in arrhythmias. Curr. Opin. Cardiol. 25, 8-15 (2011).
117. Jones SG, Momin SR, Good MW, Shea TK, Patric K. Distal upper and lower limb fractures associated with thiazolidinedione use. Am. J. Manag. Care 15, 491-496 (2009).
118. Borchers AT, Keen CL, Gershwin ME. Drug-induced lupus. Ann. NY Acad. Sci. 1108, 166-182 (2007).
119. Onder G, Liperoti R, Soldato M, Cipriani MC, Bernabei R, Landi F. Depression and risk of nursing home admission among older adults in home care in Europe: results from the Aged in Home Care (AdHOC) study. J. Clin. Psychiatry 68, 1392-1398 (2007).
120. Zender R, Olshansky E. Women's mental health: depression and anxiety. Nurs. Clin. North Am. 44, 355-364 (2009).
121. Barsky AJ, Peekna HM, Borus JF. Somatic symptom reporting in women and men. J. Gen. Intern. Med. 16, 266-275 (2001).
122. Beijer HJ, de Blaey CJ. Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of observational studies. Pharm. World Sci. 24, 46-54 (2002).
123. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279, 1200-1205 (1998).
124. Rodenburg EM, Stricker BH, Visser LE.Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands. Br. J. Clin. Pharmacol. 71, 95-104 (2011).
125. Lansky AJ, Pietras C, Costa RA et al. Gender differences in outcomes after primary angioplasty versus primary stenting with and without abciximab for acute myocardial infarction: results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation 111, 1611-1618 (2005).
126. Hreiche R, Morissette P, Turgeon J. Drug-induced long QT syndrome in women: review of current evidence and remaining gaps. Gend. Med. 5, 124-135 (2008).
127. Eckardt L. Gender differences in Brugada syndrome. J. Cardiovasc. Electrophysiol. 18, 422-424 (2007).
128. Gaborit N, Varro A, Le Bouter S et al. Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts. J. Mol. Cell. Cardiol. 49, 639-646 (2011).
129. James AF, Choisy SC, Hancox JC. Recent advances in understanding sex differences in cardiac repolarization. Prog. Biophys. Mol. Biol. 94, 265-319 (2007).
130. Kurokawa J, Suzuki T, Furukawa T. New aspects for the treatment of cardiac diseases based on the diversity of functional controls on cardiac muscles: acute effects of female hormones on cardiac ion channels and cardiac repolarization. J. Pharmacol. Sci. 109, 334-340 (2009).
131. Coker SJ. Drugs for men and women - how important is gender as a risk factor for TdP? Pharmacol. Ther. 119, 186-194 (2008).
132. Di Diego JM, Cordeiro JM, Goodrow RJ et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation 106, 2004-2011 (2002).
133. Shimizu W, Antzelevitch C, Suyama K et al. Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J. Cardiovasc. Electrophysiol. 11, 1320-1329 (2000).
134. Cohen M, Alexander KP, Rao SV. Bleeding after anti-thrombotic therapy in patients with acute ischemic heart disease: is it the drugs or how we use them? J. Thromb. Thrombolysis 26, 175-182 (2008).
135. Hallas J, Gram LF, Grodum E et al. Drug related admissions to medical wards: a population based survey. Br. J. Clin. Pharmacol. 33, 61-68 (1992).
136. Zuern CS, Lindemann S, Gawaz M. Platelet function and response to aspirin: gender-specific features and implications for female thrombotic risk and management. Semin. Thromb. Hemost. 35, 295-306 (2009).
137. Toth B, Nikolajek K, Rank A et al. Gender-specific and menstrual cycle dependent differences in circulating microparticles. Platelets 18, 515-521 (2007).
138. Gorton HJ, Warren ER, Simpson NA, Lyons GR, Columb MO. Thromboelastography identifies sex-related differences in coagulation. Anesth. Analg. 91, 1279-1281 (2000).
139. Lowe GD, Rumley A, Woodward M et al. Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use. Br. J. Haematol. 97, 775-784 (1997).
140. Faraday N, Goldschmidt-Clermont PJ, Bray PF. Gender differences in platelet GPIIb-IIIa activation. Thromb. Haemost. 77, 748-754 (1997).
141. Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 295, 306-313 (2006).
142. Boersma E, Harrington RA, Moliterno DJ et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 359, 189-198 (2002).
143. Antiplatelet Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324, 71-86 (2002).
144. Ridker PM, Cook NR, Lee IM et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N. Engl. J. Med. 352, 1293-1304 (2005).
145. Berger JS, Bhatt DL, Cannon CP et al. The relative efficacy and safety of clopidogrel in women and men a sex-specific collaborative meta-analysis. J. Am. Coll. Cardiol. 54, 1935-1945 (2009).
146. Cho L, Topol EJ, Balog C et al. Clinical benefit of glycoprotein IIb/IIIa blockade with Abciximab is independent of gender: pooled analysis from EPIC, EPILOG and EPISTENT trials. Evaluation of 7E3 for the prevention of ischemic complications. Evaluation in percutaneous transluminal coronary angioplasty to improve long-term outcome with abciximab GP IIb/IIIa BLOCKADE. Evaluation of platelet IIb/IIIa inhibitor for stent. J. Am. Coll. Cardiol. 36, 381-386 (2000).
147. Fernandes LS, Tcheng JE, O'Shea JC et al. Is glycoprotein IIb/IIIa antagonism as effective in women as in men following percutaneous coronary intervention?. Lessons from the ESPRIT study. J. Am. Coll. Cardiol. 40, 1085-1091 (2002).
148. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy. N. Engl. J. Med. 339, 436-443 (1998).
149. Lincoff AM, Harrington RA, Califf RM et al. Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial. Circulation 102, 1093-1100 (2000).
150. Huynh T, Theroux P, Snapinn S, Wan Y. Effect of platelet glycoprotein IIb/IIIa receptor blockade with tirofiban on adverse cardiac events in women with unstable angina/non-ST-elevation myocardial infarction (PRISM-PLUS Study). Am. Heart J. 146, 668-673 (2003).
151. Poli D, Antonucci E, Grifoni E, Abbate R, Gensini GF, Prisco D. Gender differences in stroke risk of atrial fibrillation patients on oral anticoagulant treatment. Thromb. Haemost. 101, 938-942 (2009).
152. Alexander KP, Chen AY, Newby LK et al. Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) initiative. Circulation 114, 1380-1387 (2006).
153. McRae S, Tran H, Schulman S, Ginsberg J, Kearon C. Effect of patient's sex on risk of recurrent venous thrombo-embolism: a meta-analysis. Lancet 368, 371-378 (2006).
154. Mazziotti G, Canalis E, Giustina A. Drug-induced osteoporosis: mechanisms and clinical implications. Am. J. Med. 123, 877-884 (2011).
155. Rejnmark L, Vestergaard P, Mosekilde L. Fracture risk in users of oral anticoagulants: a nationwide case-control study. Int. J. Cardiol. 118, 338-344 (2007).
156. Duhl AJ, Paidas MJ, Ural SH et al. Anti-thrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thrombo-embolism and adverse pregnancy outcomes. Am. J. Obstet. Gynecol. 197, 457 e451-e421 (2007).
157. Levin A, Ben-Artzi M, Beckerman P et al. Factors associated with bleeding in elderly hospitalized patients treated with enoxaparin sodium : a prospective, open-label, observational study. Drugs Aging 26, 77-85 (2009).
158. Campbell NR, Hull RD, Brant R, Hogan DB, Pineo GF, Raskob GE. Different effects of heparin in males and females. Clin. Invest. Med. 21, 71-78 (1998).
159. Oldgren J, Johnston N, Siegbahn A. Xa inhibition and coagulation activity - the influence of prolonged dalteparin treatment and gender in patients with acute coronary syndrome and healthy individuals. Am. Heart J. 155, 493 e491-e498 (2008).
160. Warkentin TE, Sheppard JA, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 108, 2937-2941 (2006).
161. Schindewolf M, Schwaner S, Wolter M et al. Incidence and causes of heparin-induced skin lesions. CMAJ 181, 477-481 (2009).
162. Reed MD, Bell D. Clinical pharmacology of bivalirudin. Pharmacotherapy 22, 105S-111S (2002).
163. Lansky AJ, Mehran R, Cristea E et al. Impact of gender and antithrombin strategy on early and late clinical outcomes in patients with non-ST-elevation acute coronary syndromes (from the ACUITY trial). Am. J. Cardiol. 103, 1196-1203 (2009).
164. Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy 20, 318-329 (2000).
165. Stangier J, Stahle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin. Pharmacokinet. 47, 47-59 (2008).
166. Peterson ED, Lansky AJ, Kramer J, Anstrom K, Lanzilotta MJ. Effect of gender on the outcomes of contemporary percutaneous coronary intervention. Am. J. Cardiol. 88, 359-364 (2001).
167. Malenka DJ, Wennberg DE, Quinton HA et al. Gender-related changes in the practice and outcomes of percutaneous coronary interventions in northern New England from 1994 to 1999. J. Am. Coll. Cardiol. 40, 2092-2101 (2002).
168. Soumerai SB, McLaughlin TJ, Ross-Degnan D, Christiansen CL, Gurwitz JH. Effectiveness of thrombolytic therapy for acute myocardial infarction in the elderly: cause for concern in the old-old. Arch. Intern. Med. 162, 561-568 (2002).
169. Angeja BG, Rundle AC, Gurwitz JH, Gore JM, Barron HV. Death or nonfatal stroke in patients with acute myocardial infarction treated with tissue plasminogen activator. Participants in the National Registry of Myocardial Infarction 2. Am. J. Cardiol. 87, 627-630, A629 (2001).
170. MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335, 765-774 (1990).
171. Sutton-Tyrrell K, Wildman R, Newman A, Kuller LH. Extent of cardiovascular risk reduction associated with treatment of isolated systolic hypertension. Arch. Intern. Med. 163, 2728-2731 (2003).
172. Thoenes M, Neuberger HR, Volpe M, Khan BV, Kirch W, Bohm M. Antihypertensive drug therapy and blood pressure control in men and women: an international perspective. J. Hum. Hypertens. 24, 336-344 (2011).
173. Hwang KS, Kim GH. Thiazide-induced hyponatremia. Electrolyte Blood Press. 8, 51-57 (2011). Discusses thiazide-induced hyponatremia and its possible pathophysiological mechanisms.
174. Chow KM, Szeto CC, Wong TY, Leung CB, Li PK. Risk factors for thiazide-induced hyponatremia. QJM 96, 911-917 (2003).
175. Sharabi Y, Illan R, Kamari Y et al. Diuretic induced hyponatremia in elderly hypertensive women. J. Hum. Hypertens. 16, 631-635 (2002).
176. Grikiniene J, Volbekas V, Stakisaitis D. Gender differences of sodium metabolism and hyponatremia as an adverse drug effect. Medicina (Kaunas) 40, 935-942 (2004).
177. Kjeldsen K. Hypokalemia and sudden cardiac death. Exp. Clin. Cardiol. 15, e96-e99 (2011).
178. Rahman AR, McDevitt DG, Struthers AD, Lipworth BJ. Sex differences in hypokalaemic and electrocardiographic effects of inhaled terbutaline. Thorax 47, 1056-1059 (1992).
179. Indiana University School of Medicine. Drug interactions: cytochrome P450 drug interaction table. http://medicine.iupui.edu/flockhart/table.htm
180. American Heart Association. Heart transplants: statistics 2009. http://americanHeartorg/presenter.jhtml?identifier=4588
181. WHO. Medical eligibility criteria for contraceptive use. www.who.int/reproductivehealth/publications/family-planning/9789241563888/en/ index.html
182. Faculty of Sexual and Reproductive Health Care. UK medical eligibility criteria for contraceptive use. www.fsrh.org/admin/uploads/UKMEC2009.pdf