Obez Hastalarda İlaç Kullanımı
Özet
Obezite ile birlikte ortaya çıkan fizyolojik ve morfolojik değişiklikler, ilaçların farmakokinetik ve farmakodinamik parametrelerini değiştirerek dağılım hacmi ile klirensini önemli ölçüde etkilemektedir. Birçok ilacın standart dozu normal ağırlıktaki bireylere göre belirlendiğinden, obez hastalarda bu standart dozların kullanımı subterapötik etkiye veya supraterapötik dozlarla toksisite riskine yol açabilmektedir. Bu nedenle, özellikle yoğun bakım ünitesinde yatan kritik durumlardaki obez hastalarda ilaç dozlarının bireyselleştirilmesi ve optimize edilmesi gerekmektedir. Doz hesaplamalarında doğru ağırlık ölçütünün (toplam vücut ağırlığı, ideal vücut ağırlığı, yağsız vücut ağırlığı veya düzeltilmiş vücut ağırlığı) seçilmesi tedavinin etkinliği ve güvenliği açısından kritik bir öneme sahiptir. Antikoagülanlar, antimikrobiyaller, anestezikler, analjezikler, kortikosteroidler ve vazopressörler gibi klinik uygulamada yaygın kullanılan pek çok ilaç grubunda, ilacın hidrofilik veya lipofilik kimyasal yapısına göre uygun vücut ağırlığı parametresi seçilmelidir. Klinik araştırmalarda obez popülasyonun yeterince temsil edilmemesi nedeniyle bu alandaki kanıt düzeyinin yetersiz olduğu görülmektedir. Güvenli ve etkili bir tedavi süreci için dar terapötik aralıklı ilaçlarda terapötik ilaç izleminin yapılması ve multidisipliner bir sağlık ekibinin koordinasyon içerisinde çalışması en doğru yaklaşım olarak kabul edilmektedir.
Physiological and morphological changes associated with obesity significantly alter the pharmacokinetic and pharmacodynamic parameters of drugs, substantially affecting their volume of distribution and clearance. Since standard doses of most medications are determined based on individuals with normal body weight, utilizing these standard doses in obese patients can lead to subtherapeutic efficacy or a risk of toxicity due to supratherapeutic levels. Therefore, individualizing and optimizing drug doses is crucial, particularly for critically ill obese patients in the intensive care unit. Selecting the appropriate body weight metric (total body weight, ideal body weight, lean body weight, or adjusted body weight) in dosage calculations is of paramount importance for therapeutic efficacy and safety. For various commonly used drug classes—such as anticoagulants, antimicrobials, anesthetics, analgesics, corticosteroids, and vasopressors—the suitable weight parameter must be selected according to the hydrophilic or lipophilic chemical properties of the drug. The level of clinical evidence remains limited due to the underrepresentation of the obese population in clinical trials. For a safe and effective therapeutic process, conducting therapeutic drug monitoring for narrow therapeutic index drugs and collaborating within a multidisciplinary healthcare team is established as the most appropriate approach.
Referanslar
https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
https://sggm.saglik.gov.tr/Eklenti/39936/0/obezitemedyaklavuzupdf.pdf.
https://data.tuik.gov.tr/Bulten/Index?p=Turkiye-Saglik-Arastirmasi-2019-33661
Zuckerman M, Greller HA, Babu KM. A review of the toxicologic implications of obesity. J Med Toxicol. 2015; 11(3): 342-54.
Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis. Crit Care. 2021; 25(1): 77.
Polso AK, Lassiter JL, Nagel JL. Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review. J Clin Pharm Ther. 2014; 39(6): 584-608.
Al-Dorzi HM, Al Harbi SA, Arabi YM. Antibiotic therapy of pneumonia in the obese patient: dosing and delivery. Curr Opin Infect Dis. 2014; 27(2): 165-73.
McCaughan GJB, Favaloro EJ, Pasalic L, Curnow J. Anticoagulation at the extremes of body weight: choices and dosing. Expert Rev Hematol. 2018; 11(10): 817-28.
Patanwala AE, Seaman SM, Kopp BJ, Erstad BL. Heparin dosing for venous thromboembolism prophylaxis in obese hospitalized patients: An observational study. Thromb Res. 2018; 169: 152-6.
Sanderink GJ, Le Liboux A, Jariwala N, Harding N, Ozoux ML, Shukla U et al. The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther. 2002; 72(3): 308-18.
Tellor KB, Nguyen SN, Bultas AC, Armbruster AL, Greenwald NA, Yancey AM. Evaluation of the impact of body mass index on warfarin requirements in hospitalized patients. Ther Adv Cardiovasc Dis. 2018; 12(8): 207-16.
Sebaaly J, Kelley D. Direct oral anticoagulants in obesity: An updated literature review. Ann Pharmacother. 2020; 54(11): 1144-58.
Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing in obese patients. Clin Infect Dis. 1997; 25(1): 112-8.
Janson B, Thursky K. Dosing of antibiotics in obesity. Curr Opin Infect Dis. 2012; 25(6): 634-49.
Meng L, Mui E, Holubar MK, Deresinski SC. Comprehensive guidance for antibiotic dosing in obese adults. Pharmacotherapy. 2017; 37(11): 1415-31.
David n. Gilbert. RCM J, George M. Eliopoulos., Henry F. Chambers., Michael S. Saag. The Sanford Guide To Antimicrobial Therapy 2013; 43.
Bahap M, Bakır-Ekinci P, Semiz E, Bayraktar-Ekincioğlu A, Demirkan K. Obez hastalarda antimikrobiyal ilaç dozları. Sted. 2020; 29(2): 137-52.
Erstad BL, Barletta JF. Drug dosing in the critically ill obese patient-a focus on sedation, analgesia, and delirium. Crit Care. 2020; 24(1): 315.
Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth. 2010; 105(1): 16-23.
Rolle A, Paredes S, Cortinez LI, Anderson BJ, Quezada N, Solari S et al. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients. Br J Anaesth. 2018; 120(5): 969-77.
Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med. 2004; 30(1): 18-32.
Renew JR, Naguib M. Management of neuromuscular blockade in the elderly and morbidly obese patient: What does the data show? Current Anesthesiology Reports. 2020; 10(2): 107-16.
Patanwala AE, Holmes KL, Erstad BL. Analgesic response to morphine in obese and morbidly obese patients in the emergency department. Emerg Med J. 2014; 31(2): 139-42.
Abernethy DR, Greenblatt DJ. Ibuprofen disposition in obese individuals. Arthritis Rheum. 1985; 28(10): 1117-21.
Davis RL, Quenzer RW, Bozigian HP, Warner CW. Pharmacokinetics of ranitidine in morbidly obese women. DICP. 1990; 24(11): 1040-3.
Bruley des Varannes S, Coudsy B, Waechter S, Delemos B, Xiang J, Lococo J et al. On-demand proton pump inhibitory treatment in overweight/obese patients with gastroesophageal reflux disease: are there pharmacodynamic arguments for using higher doses? Digestion. 2013; 88(1): 56-63.
Milsap RL, Plaisance KI, Jusko WJ. Prednisolone disposition in obese men. Clin Pharmacol Ther. 1984; 36(6): 824-31.
Dunn TE, Ludwig EA, Slaughter RL, Camara DS, Jusko WJ. Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity. Clin Pharmacol Ther. 1991; 49(5): 536-49.
Johnston AJ, Steiner LA, O'Connell M, Chatfield DA, Gupta AK, Menon DK. Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients. Intensive Care Med. 2004; 30(1): 45-50.
Barletta JF. CCSAP Book 2, Issues in Critical Care Practice. Bradley A. Boucher & Curtis E. Haas (Eds), Drug dosing in special populations: Obesity and geriatrics. Lenexa, KS: American College of Clinical Pharmacy Publishing. 2020: 7-30.
