therapeutic drug monitoring

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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 ?
Identification of new genetic factors associated with AD will lead to a better understanding of the molecular mechanisms underlying the disease and provide a basis for new approaches to diagnosis, treatment, and prevention.
But they lead him to suspect that certain genetic factors may outweigh the value of dental hygiene measures for some groups and may account for the sometimes conflicting results of fluoridation efforts.
We believe that understanding the perilipin genetic factors, which are found commonly in the population, could assist some women in achieving and maintaining a healthy weight.
In addition to studying neurodegenerative and neuropsychological disorders, USC researchers and clinicians will use the BeadLab to explore the interconnection and interplay between environmental and genetic factors in the development, treatment and prevention of other complex diseases including cancer.
The gene-environment analyses revealed that early genetic factors were pervasive in accounting for developmental trends, explaining most of the stability and change in physical aggression," Lacourse said.
ISLAMABAD, February 08, 2012 (Balochistan Times): Coffee buffs, you can now blame your genes for downing another cup of the hot beverage, for a new study has claimed that genetic factors could explain why some people consume large amounts of caffeine.
Aitken, a clinical psychologist in the UK and the author of other books on autism, discusses the range of genetic conditions associated with autism spectrum disorders, explains the biology and genetics of these disorders, and summarizes the genetic factors involved for clinicians and researchers.
Researchers have suspected for years that genetic factors account for part of the racial difference in risk.
The authors further suggest that genetic factors such as skin color may modify the effect of arsenic on melanoma risk.
Genetic factors control many of the patterns of comorbidity of internalizing and externalizing disorders, reported Dr.
If we look at this issue world-wide, it appears that there are genetic factors which affect fracture rate in some areas where we would expect protein intake to be low.
On the other hand, unknown genetic factors may be to blame, Isaacs said.