Modifying factors of PK and PD Flashcards
_________ modifying factors include genetic, physiological, psychological and ________ modifying factors include substance and environmental.
Intrinsic; Extrinsic
Genetics = polymorphism for metabolic genes/genes responsible for pharmacodynamics
Physiological = body composition (muscle vs fat); changes distribution of lipophilic and hydrophilic compounds in the organism
(T/F) Modifying factors (vary across population) and can change bioavailability, dose response and time response.
True!
Briefly explain what is included in each category of intrinsic modifying factors:
1) Genetic
2) Physiological
3) Psychological
Genetic = gender, race, polymorphisms, genetic disease
Physiological = age, body weight, composition & size, heath-organ/tissue function, disease & co-morbidities, pregnancy, experience
Psychological = experience, belief, expectations
Briefly explain what is included in each category of extrinsic modifying factors:
1) Substance
2) Environmental
Substance: single/repeated exposure, formulation (mostly PK)
Environmental: climate, sunlight, culture, socio-economic (nutrition), stress, xenobiotic load (diet, alcohol, smoking, other exposures)
(T/F) Individual variability (intrinsic) and multiple substances (extrinsic) can influence pharmacokinetic/dynamics interactions.
True!
What is the definition of tolerance and sensitization in regards to pharmacokinetics?
Tolerance: DECREASED bioavailability of the xenobiotic of interest; reduced response
Sensitization: INCREASED bioavailability of the xenobiotic of interest; increased response(s)
What is the definition of tolerance and sensitization in regards to pharmacodynamics?
Tolerance: DECREASED effect of the xenobiotic/endogenous ligand of interest
Sensitization: INCREASED effect of the xenobiotic/endogenous ligand of interest
*can also lead to antagonism, additivity, synergism of different ligands on a same receptor.
What are some factors affecting bioavailability?
1) Chemical nature of drug
2) pH of GI/surrounding environment
3) Gastrointestinal motility (inflammatory diseases)
4) Hepatic/gastrointestinal metabolism (Liver disease can decrease metabolism)
5) Drug-drug or drug-food interactions
6) Drug formulation (immediate vs sustained, route of administration)
(T/F) Pharmacogenetic or toxicogenetic factors rarely act alone; they produce a phenotype in concert with other variant genes and environmental factors (often polygenic which can change expression and catalytic function).
True!
Polymorphisms is the variations in:
Drug-metabolizing enzymes, drug transporters, drug receptors, and ion channels.
What are the four phenotypes of metabolism?
1) poor/slow (lack functional alleles)
2) intermediate (heterozygous with a functional allele)
3) efficient, extensive or fast (homozygous with both normal alleles)
4) ultrarapid (multiple copies of alleles)
The human body has ____ microbes for every human cells and ____ microbial genes for every unique human gene.
10; 100
(T/F) Microflora affects immunity, inflammatory disease, obesity. Horizontal gene transfer facilitates microbial adaptation to drugs, toxins, and other populations.
True!
What are some biochemical interactions in the GI tract associated with oral absorption?
1) Food-food and food-drug interactions (full stomach increases residence time, fats increase availability of lipid soluble molecules)
2) Heme-iron is more readily absorbed than non-heme iron (presence of vitamin C enhances iron uptake)
3) Proteins are digested in the gut: animal more readily digested than plan protein
4) Hydration
Drug formulation is another modifying factor, a drug in tablet/capsule has a _________ dissolution, while a drug in small particles has the ________ dissolution.
Very limited; most
