Pharmacokinetics in medicine Flashcards
What is variability in pharmacogenetics?
Variability is a serious problem that can result in:
* Lack of efficacy
* Unexpected harmful effects
Variability can be classified as pharmacokinetic or pharmacodynamic.
What are the main causes of variability in drug response?
- Age
- Genetic factors
- Immunological factors
- Disease
- Drug interactions
- Ethnicity
The concept of ethnicity is questioned by anthropologists due to diversity within racial groups.
How does age influence drug action?
Age influences drug action primarily due to less efficient drug elimination in newborns and older individuals.
Drugs commonly have greater and prolonged effects at the extremes of life due to inefficient elimination.
What is the Glomerular Filtration Rate (GFR) in newborns?
GFR in newborns, normalized to body surface area, is only about 20% of adult values.
Renally eliminated drugs have longer plasma elimination half-lives in neonates due to immature renal function.
What happens to GFR with aging?
GFR declines gradually from around 20 years old, decreasing by about 25% at 50 years and 50% at 75 years.
This decline impacts drug elimination and can lead to toxicity.
What are pharmacodynamic interactions?
Pharmacodynamic interactions modify the pharmacological effect of another drug without altering its concentration in tissue fluid.
An example is β-adrenoreceptor antagonists reducing the effectiveness of β-adrenoreceptor agonists.
What are pharmacokinetic interactions?
Pharmacokinetic interactions alter the concentration of another drug at its site of action.
The major processes involved are absorption, distribution, metabolism, and excretion (ADME).
What is the role of genetic variation in drug responsiveness?
Genetic variation can influence drug response through rare genetic traits or complex multifactorial traits involving genetic and environmental factors.
Polymorphisms, such as SNPs, are common genetic variants that can influence drug response.
What is a single nucleotide polymorphism (SNP)?
SNPs are the most common genetic variations, occurring once every 300 bases in the human genome.
They can influence physiological function if located within or near a gene.
What is the classical Mendelian model in pharmacogenetics?
The classical Mendelian model applies to single-gene disorders where a mutation in a single gene is the primary cause of the disorder.
These disorders typically have predictable inheritance patterns.
What is acute intermittent porphyria?
Acute intermittent porphyria is an inherited disorder affecting porphyrin biosynthesis, characterized by mutations in the PBGD gene.
It can be triggered by environmental factors, including certain drugs.
What are some therapeutic drugs for acute intermittent porphyria?
Givosiran is a small interfering RNA that reduces ALA synthase mRNA, alleviating neurotoxin build-up implicated in polyphyria attacks.
This is an expensive but effective treatment option.
What challenges exist in pharmacogenetic testing adoption?
Challenges include:
* Barriers to implementation
* Reimbursement contingent on cost-effectiveness
* Need for randomized control trials
These factors hinder the widespread use of pharmacogenomics in clinical practice.
True or False: Ethnic categories based on outward appearance are sufficient for personalizing medicine.
False
Comprehensive genetic testing offers a more accurate approach than outdated ethnic classifications.
Fill in the blank: The _______ in drug metabolism can lead to serious conditions like kernicterus and ‘grey-baby’ syndrome.
[lack of conjugating activity in newborns]
How do drug interactions account for adverse drug reactions?
Drug interactions account for 5%–20% of adverse drug reactions (ADRs), with approximately 30% of fatal ADRs due to drug interactions.
This highlights the importance of monitoring drug combinations, especially in elderly patients.
What are informed prescribing strategies?
Strategies that consider complex multifactorial traits influencing drug response.
What influences drug response?
Multiple genes, genetic variants, and environmental factors.
