@article{3061525,
    title = "Stress can affect drug pharmacokinetics via serum/tissues protein binding and blood flow rate alterations",
    author = "Antonia, K. and Anastasia, A. and Tesseromatis, C.",
    journal = "European Journal of Drug Metabolism and Pharmacokinetics",
    year = "2012",
    volume = "37",
    number = "1",
    pages = "1-7",
    issn = "0378-7966, 2107-0180",
    doi = "10.1007/s13318-011-0077-2",
    keywords = "albumin;  ampicillin;  anticoagulant agent;  beta lactam antibiotic;  cefapirin;  cinoxacin;  ciprofloxacin;  diazepam;  fatty acid;  flurbiprofen;  human serum albumin;  hydrocortisone;  ibuprofen;  ketoprofen;  lidocaine;  local anesthetic agent;  metoprolol;  morphine;  niflumic acid;  nonsteroid antiinflammatory agent;  norfloxacin;  ofloxacin;  oxyphenbutazone;  pefloxacin;  plasma protein;  propranolol;  quinoline derived antiinfective agent;  salicylic acid;  unindexed drug;  warfarin, adaptive immunity;  area under the curve;  binding site;  blood flow velocity;  blood vessel function;  drug activity;  drug blood level;  drug clearance;  drug distribution;  drug elimination;  drug half life;  drug metabolism;  drug potentiation;  drug protein binding;  drug tissue level;  host resistance;  human;  immunoregulation;  lipid transport;  liver blood flow;  mental stress;  nonhuman;  review;  seizure;  tissue blood flow;  treatment outcome;  unspecified side effect, Animals;  Blood Flow Velocity;  Blood Proteins;  Fatty Acids, Nonesterified;  Humans;  Pharmacokinetics;  Protein Binding;  Stress, Psychological",
    abstract = "Binding of drugs to plasma and tissue proteins is critically involved in their pharmacokinetics and pharmacodynamics. Stress affects drugs' protein binding via alterations in plasma proteins' levels and excessive increase of free fatty acids due to cortisol-induced fat mobilisation. Free fatty acids play a crucial antagonistic role to drugs for the binding sites on albumin, the major binding plasma protein, resulting in subtherapeutic or toxic levels of many medications' pharmacological classes (oral anticoagulants, beta-lactames, fluoroquinolones, local anaesthetics). Upon stress, changes in blood flow rate and vascular function are also important parameters that can alter drug distribution and pharmacokinetics. Many cases are reported where stress-induced pharmacokinetic alterations led to serious clinical consequences. However, the stress affected drug activity do not always deteriorate the clinical outcome, due to the adaptive and defensive mechanisms of healthy organism. Sensitive population as patients with serious underlying diseases or after trauma or surgery should be given special attention. Clinicians should be alert and monitor cases where stress-induced drugs' pharmacokinetic modifications can have negative impact on the clinical outcome. © 2011 Springer-Verlag France."
}