What properties affect the distribution of drugs - drug size, charge, chemical structure, pH, molecular size, lipid or water solubility
first pass metab... [Show More] olism - metabolism by the liver following oral administration
Phase 1 reactions - Oxidation, reduction, hydrolysis or non-synthetic reactions that prepare the drug for further metabolism - to make the drug more water soluble
Phase II reactions - synthetic or conjugation reactions, something is added to drug to make it more water soluble and more easily excreted by the kidneys
CYP P450 - Liver *enzyme* that detoxifies substances,
Makes them easier to be excreted.
single nucleotide polymorphism (SNP) - minor mutations that can result in metabolic activity changes, including increased and decreased drug responses
primary organ of excretion for drugs - kidney
blood flow differences in infants - increased blood flow to muscles 1-6 mo EXCEPT during illness, can cause slower or rapid perfusion
Pediatric GI function - pH increases gradually- reaches adult levels @ 20-30 months preemies are even slower
Diarrhea and kids - kids with diarrhea have poor absorption of oral drugs
Pediatric skin absorption - Kids have thinner stratum corneum so topical medications are absorbed more readily: increased risk of toxicity
Infants and Lipid Soluble drugs - decreased volume distribution, less plasma proteins for binding, require higher doses of hydrophilic drugs
CYP1A2 (phase 1 enzyme) pediatric - reaches adult level by 4 mo and then higher than adult levels through childhood then declines
CYP2D2 (Phase 1 enzyme) pediatric - absent or 5% active at birth reaches adult levels by 3-5 yrs but has significant genetic variability
CYP2D6 ultrametabolizers - up to 20 percent of Ethiopians are 2D6 ultra-metabolizers but 3.4-6.5 percent of non-Ethiopian African Americans are ultra-metabolizers, same for caucasians
small intestine and drug metabolism - small intestine is a major site of drug metabolism d.t. CYP450 enzymes and may be a large variation in capacity of SB to metabolize drugs
Common drugs metabolized in phase II - acetaminophen, morphine, Propofol, and caffeine
Body Fat and drugs - women have more body fat means a larger volume of distribution for lipophilic agents, women experience more adverse reactions after drugs saturate all sites in adipose tissues and more drugs stay in the blood stream
CYP3A4 and Women - activity higher in women : group of isoenzymes responsible for drug metabolism ex: azole antifungal, calcium channel blocker, antihistamines, anticonvulsants, antimicrobials, and corticosteroids
CYP1A2 and Women - activity lower in women enzyme responsible for metabolizing many drugs :theophylline, cruciferous foods like broccoli and cabbage may induce drug metabolism apiaceous vegetables like carrots, parsnip, celery, or parley may inhibit CYP1A2 activity [Show Less]
