Genetic factors can account for 20 to 95 percent of patient variability. Genetic polymorphisms for many drug-metabolizing enzymes and drug targets (e.g., receptors) have been identified.
What factors affect drug metabolism?
Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be sub-divided into internal (physiological and pathological) and external (exogenous) factors as indicated below: Internal: species, genetic (strain), sex, age, hormones, pregnancy, disease. External: diet, environment.
How is genetic variation related to the use of drugs?
Population differences in drug response, including susceptibility to adverse drug reactions, are affected by genetic polymorphisms. Genetic variation frequencies differ among different ethnicities, which may be associated with variation of susceptibility to adverse drug reactions among the different populations.
What is genetic polymorphism Why is it important in drug dosing?
Genetic polymorphisms in drug transporters such as P-gp may predict the partitioning characteristics of a drug between cells and plasma. This may aid either in determining the therapeutic range or avoiding specific drugs with a particularly high risk of efficacy failure or toxicity.
What factors can affect drug metabolism in an elderly?
Aging results in a number of significant changes in the human liver including reductions in liver blood flow, size, drug-metabolizing enzyme content, and pseudocapillarization. Drug metabolism is also influenced by comorbid disease, frailty, concomitant medicines, and (epi)genetics.
What are the phases of drug metabolism?
Drug metabolism reactions comprise of two phases: Phase I (functionalization) reactions such as oxidation, hydrolysis; and Phase II (conjugation) reactions such as glucuronidation, sulphate conjugation. Oxidation reactions are the most common and vital.
What is drug response?
drug response refers to the pharmacodynamics (PD) response to the drug, which is all the effects of the drug on any physiologic and pathologic process, in relation to effectiveness and adverse reactions.
How do you identify genetic variation?
Genetic variation can also be identified by examining variation at the level of enzymes using the process of protein electrophoresis. Polymorphic genes have more than one allele at each locus.
Should genetics be considered before giving a person a drug?
There are several situations where genetic testing before starting a medication is standard of care today. When there is a well-understood drug-gene interaction, knowing the genotype before starting treatment can avoid dangerous side effects.
What is an example of polymorphism in humans?
Other examples of allelic polymorphism include human blood groups, two-spotted ladybugs, and grove snails. In the case of human blood groups, someone could have blood type A, B, AB, or O. Each version represents a polymorphic form of the trait for blood type.
What is genetic polymorphism in humans?
Genetic polymorphism is defined as the inheritance of a trait controlled by a single genetic locus with two alleles, in which the least common allele has a frequency of about 1% or greater. Genetic polymorphism is a difference in DNA sequence among individuals, groups, or populations.
What is first pass metabolism of drug?
The first-pass metabolism or the first-pass effect or presystemic metabolism is the phenomenon which occurs whenever the drug is administered orally, enters the liver, and suffers extensive biotransformation to such an extent that the bioavailability is drastically reduced, thus showing subtherapeutic action (Chordiya …
What is the most common medication problem in the elderly?
Warfarin is one of the most common causes of medication-related hospitalizations in older adults. To reduce the risk of serious problems, one may need to apply extra care in monitoring warfarin effect (via the prothrombin blood test) and extra care in checking for interactions when a new drug is prescribed.
Why are elderly more sensitive to drugs?
4. Increased Sensitivity to Many Drugs: The problems of decreased body size, altered body composition (more fat, less water), and decreased liver and kidney function cause many drugs to accumulate in older people’s bodies at dangerously higher levels and for longer times than in younger people.
What is the most common adverse drug effect seen in the elderly?
Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations.