therapeutic drug monitoring

(redirected from Concomitant disease)

therapeutic drug monitoring

Clinical pharmacology The regular measurement of serum levels of drugs requiring close 'titration' of doses in order to ensure that there are sufficient levels in the blood to be therapeutically effective, while avoiding potentially toxic excess; drug concentration in vivo is a function of multiple factors Common TDM drugs Carbamazepine, digoxin, gentamycin, procainamide, phenobarbital, phenytoin, theophylline, tobramycin, valproic acid, vancomycin
Therapeutic drug levels in vivo–factors involved
Patient compliance  Ingestion of drug in the doses prescribed
Bioavailability Access to circulation, interaction with cognate receptor(s); ionized and 'free', or bound to a carrier molecule, often albumin
Pharmacokinetics Drug equilibrium requires 4-6 half-lives of drug clearance (a period of time for1/2 of the drug to 'clear', either through metabolism or excretion, multiplied by 4-6); the drug is affected by
Interaction with foods or other drugs at the site of absorption, eg tetracycline binding to cations or chelation with binding resins, eg bile acid-binding cholestyramine that also sequesters warfarin, thyroxine and digitoxin or interactions of various drugs with each other, eg digitalis with quinidine resulting in a 3-fold ↓ in digitalis clearance
Absorption may be changed by GI hypermotility or large molecule size
Lipid solubility, which affects the volume of distribution; highly lipid-soluble substances have high affinity for adipose tissue and a low tendency to remain in the vascular compartment, see Volume of distribution.
Biotransformation, with 'first pass' elimination by hepatic metabolism, in which polar groups are introduced into relatively insoluble molecules by oxidation, reduction or hydrolysis; for elimination, lipid-soluble drugs require the 'solubility' steps of glucuronidation or sulfatation in the liver; water-soluble molecules are eliminated directly via the kidneys, weak acidic drugs are eliminated by active tubular secretion that may be altered by therapy with methotrexate, penicillin, probenecid, salicylates, phenylbutazone and thiazide diuretics
First order kinetics Drug elimination is proportional to its concentration
Zero order kinetics Drug elimination is independent of the drug's concentration
Physiological factors
Age Lower doses are required in both infants and the elderly, in the former because the metabolic machinery is not fully operational, in the latter because the machinery is decaying, with ↓ cardiac and renal function, enzyme activity, density of receptors on the cell surfaces and ↓ albumin, the major drug transporting molecule
Enzyme induction, which is involved in a drug's metabolism may reduce the drug's activity; enzyme-inducing drugs include barbiturates, carbamazepine, glutethimide, phenytoin, primidone, rifampicin
Enzyme inhibition, which is involved in drug metabolism, resulting in ↑ drug activity, prolonging the action of various drugs, including chloramphenicol, cimetidine, disulfiram (Antabuse), isoniazid, methyldopa, metronidazole, phenylbutazone and sulfonamides
Genetic factors play an as yet poorly defined role in therapeutic drug monitoring, as is the case of the poor ability of some racial groups to acetylate drugs
Concomitant disease, ie whether there are underlying conditions that may affect drug distribution or metabolism, eg renal disease with ↓ clearance and ↑ drug levels, or hepatic disease, in which there is ↓ albumin production and ↓ enzyme activity resulting in a functional ↑ in drug levels, due to ↓ availability of drug-carrying proteins

ther·a·peu·tic drug mon·i·tor·ing

(TDM) (thār'ă-pyū'tik drŭg mon'i-tŏr-ing)
Clinical measurement of the effects of a drug in a specific patient rather than reliance on normative ranges (e.g., some old people need a lower dosage than their weight might suggest). Such procedures verify that therapy is as accurate as possible.
References in periodicals archive ?
The TDR agreement complements Skila's current roster of healthcare information partners and offers its clients detailed disease code descriptions, diagnostic criteria and other information that accompanies TDR's Incidence and Prevalence Database, a comprehensive database with information on epidemiology, incidence, prevalence, morbidity, mortality, census data, cost analysis, and concomitant disease.
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The results, presented during the American College of Rheumatology's (ACR) 2011 Annual Scientific Meeting in Chicago, November 5-9, are from an open-label extension of the REALISTIC (RA EvALuation In Subjects receiving TNF Inhibitor Certolizumab pegol) study, and demonstrated consistent efficacy and improved physical function irrespective of prior anti-TNF therapy, concomitant disease modifying antirheumatic drugs (DMARDs), or duration of disease.
Of the 61 patients included in the analysis, 39 also had at least one concomitant disease or were on at least one drug that was also associated with hyponatremia and/or seizures.
For women at average risk of ovarian cancer who are undergoing a hysterectomy for benign conditions, the decision should be individualized after appropriate informed consent, including a careful analysis of personal risk factors, concomitant disease, presence of gynecologic disease (endometriosis, chronic pain, infection), and age," wrote members of the SGO's clinical practice committee.
Thus, the presence of this entity should prompt a search for concomitant disease.
Of the 61 patients, 39 also had at least one concomitant disease or were on at least one drug that was also associated with hyponatremia and/or seizures.
One patient suffered from an unexpected serious AE (acute intermittent porphyria), which was a concomitant disease already known to the patient prior to inclusion into this observational study.
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