pharmocokinetics II Flashcards
biotransformation
- chemically altering the original compound so that it is no longer active
- fast process within min or hours
excretion
- active form is excreted (via kidney)
- slow process, not very effective
What components are essential in eliminating drugs?
- biotransformation
- excretion
What is the responsible organ for biotransformation?
liver (the primary) and others
Oxidation
- oxygen is added or hydrogen is removed from original compound
- oxidation comprise predominant method of drug biotransformation in body and primarly enzymes that catalyze these reactions: cytochrome P450 monooxygenase cells aka DMMS (drug microsomal metabolizing system)
- smooth ER
Reduction
- remove oxygen or add hydrogen to original compound
- enzymes located in cell cytoplasm are responsible
Hydrolysis
- original compound broken in separate parts
- enzymes located several sites in cell
conjugation
- intact drug or the metabolite of one of the reactions is coupled to an endogenous substance (aceytl coenzyme A), glucuronic acid, amino acid
- enzymes catalyzing drug conjugations are found in cytoplasm and ER
What happens after reactions occur?
- biotransformation create polar compound
- after reaction remaining drug metabolite tends to be ionized in body fluids
- ionized metabolite is more water soluble and transprorted more easily to blood stream and kidneys
- at kidneys the polar metabolite excreted through urine
enzyme induction
- prolonged use of certain drugs induces body to adjust and enzymatically destroy the drug more rapidly than expected
- usually because either more metabolizing enzymes are being manufactured or fewer of them are being degraded
tolerance
- induction decrease drug effects and leads to tolerance
- the need for increased drug dosages to produce same effect
Drug excretion
- kidneys primarily
- nephron is functional unit
- traps water soluble (ionzied) compounds for elimination via urine
- other routes: lungs, GI, liver to bile, breast milk, sweat, saliva
pathway of drug excretion
- metabolized or conjugated version of drug reaches nephron
- filtered at glomerulus
- filtration
- compound tranverses the proximal convoluted tubule
- loop of henle
- distal convoluted tubule
- collecting ducts in renal meduall
* if compound not reabsorbed while in nephron then excreted in urine
What compounds get trapped in nephron and not absorbed back into body?
- metabolite
- polar drugs
- ionized
What gets reabsorbed?
- nonpolar compounds filtered by kidney are lipophilic reabsorbed by diffusing passively through wall of nephron
What role does lungs play?
- serve as route of both drug administration and excretion
- excreting volatile drugs
drug elimination rates
- helps to determine amt and frequency of its dosage
- drug administrated faster than elimniated (excessive accumulation and maybe reach toxic levels)
- elimination faster than administraton (doesnt reach therapeutic levels)
- two primary measures to indicate rate at which drug is eliminated
1. clearance
2. half life
clearance
- single organ or tissue ability
- CL depends on organ or tissues ability to extract the drug from the plasma and the perfusion of the organ
- systemic clearance: the sum of all organs and tissues abilities to eliminate the drug
What determines how much drug will be delivered to the organ for eliminiation?
blood flow
half life
- amt of time required for 50% of the drug remaining in the body to be eliminated
- a function of both clearance and volume of distribution Vd
- disease states that affect either clearance or Vd will affect the drugs half life
dosing schedules and plasma concentration
desireable to bring plasma concentrations of the drug up to certain level and maintain there
if dosing interval is relatively long what does that mean for the dose?
the dose must be considerably large to provide the same relative plasma concentration that would exisit in shorter dosing interval.
larger doses given farther apart results in?
greater plasma fluctuations that is greater maximum and minimum plasma levels over the dosing period
giving smaller doses more frequently
provides and equivalent average concentration w/o extreme peaks or valleys associated with longer intervals
Variations in drug response and metabolism
- genetics: difference might influence drug response
- disease: damage to tissue or organ responsible for drug metabolism and excretion
- drug interactions: cumulative, adverse, or additive effects
- age
- diet
- gender
- smoking, alcohol, obesity, chronic and acute exercise, extensive burn injuries
