Pharmacokinetics Flashcards
Actions of body on drug
. Absorption
. Distribution
. Metabolism
. Excretion
Pharmacokinetics
. Quantitiative description of time course for absorption, distribution, metabolism., and excretion. Of drugs
Pharmacodynamics
Quantitative description of biochemical and physiological effects of drugs and mechanisms underlying effects
For most drugs, the duration of action is related to the time the blood level is above ________
the minimal effective concentration
Factors that determine blood levels of drug
. Dose . Route of administration . Rate and extent of absorption . Distribution of tissues (sites of actions/loss) . Rate and extent of metabolism . Rate and extent of excretion
Oral administration
,. Most common
. Not appropriate for all drugs
. Slow onset
. Not good if patient unconscious
Parenteral drug administration
. IV, IA , subQ
. Rapid onset
. Drug must be water soluble and non irritating
. Invasive procedure
Most common transport of drugs across biological membranes
. Passive diffusion
Chemical properties of drug
Water solubility
. Lipid solubility
. Stability in stomach
Bioavailability
Percentage of an orally ministered drug that reaches the systemic circulation
How blood flow affects drug
Highly perfused organs like lungs, heart, liver, and kidneys receive the most drug
Drug binding to plasma proteins characteristics
. Albumin most important
. Bound drug can’t distribute to tissues
. Drug interactions mean one drug can displace another from the protein binding sites
Distribution of drugs to liver
. Large blood flow
. Site of drug metabolism
. Portal-hepatic circulation where drug undergoes first pass metabolism
. Major site for metabolism
Distribution of drugs to kidney
. High blood flow
. Site of excretion for many drugs and metabolites
Distribution of drugs to fat
. Low blood flow
. Slow accumulation of lipid soluble drugs
. Site of loss
. Redistribution of drugs from other sites
Distribution of drugs to brain
. BBB
. Small lipid soluble drugs can cross
Distribution of drugs to fetus
Placental barrier is not strong barrier and many drugs can cross
Volume of distribution
. Measure of how drug is distributed in the body
. Volume in which a drug would have to be dissolved in order to account for all of the drug at the concentration present in the plasma
. Vd=amount of drug in body/Cpss
. Amount of drug in body is equal to the dose if drug is given via IV
. High number means more drug in tissues
. Lower number means drug is mostly in plasma
Typical volumes of body water compartments
. Total water = 40-45L
. Extracellular = 12-16L
. Blood 5-6L
. Plasma = 2.5-3.0L
Ways of terminating drug action
. Excrete drug from body
. Metabolize drug to inactive form
. Most effective and most common = metabolism and excretion
Types of metabolism reactions
. Microsomal oxidation . Non-microsomal oxidation . Reductions . Hydrolysis . Conjugations
Microsomal oxidation
. Main route for many drugs
. Micro some pinched off pieces of smooth ER formed during homogenization
. Contain a family of enzymes and cytochromes that can oxidize drugs (mixed function oxidase or cytochrome isozymes)
. Highest conc. In liver
. Induction and inhibition by drugs
, potential for drug rxns
. Effects caused by altered hepatic function
. Occasionally can form toxic metabolites
Examples of rxns catalyzed by mixed function oxidase
. Side chain oxidation . Hydroxylation . N-oxidation . Sulfoxidation . N-dealkylation
Conjugation rxns
. Phase II reactions
. Involve the coupling of drug or metabolites to small polar molecules
. Glucuronide conjugation
. Sulfate conjugation
Kinetics of drug metabolism
. Most drugs first order where rate of metabolism spends on concentration of the drug in blood
. Zero order means rate of metabolism doesn’t depend on conc. Of blood
Factors affecting drug metabolism
. Age . Disease . Nutrition . Genetic factors . Other drugs . Duration of treatment
Filtration of drugs
. Low molecular weight drugs are readily filtered
. Drug bound to plasma protein is not excreted
. Alterations in GFR Cana defect the rate of drug excretion
Tubular secretion of drugs
. Active process
. System for organic acids
. System for organic bases
. Competition of drugs for transport systems
Reabsorption of drugs
. Passive diffusion
. Lipophilic drugs reabsorbed
. Hydrophilic or ionized drugs remain in tubule and be excreted
. Acidic urine favors excretion of basic drugs whereas basic urine favors the excretion of acidic drugs
Clearance
. Clearance = rate of elimination/Cp
. Cp is conc, of drug in plasma
. Describes volume of plasma that is cleared of drug in a unit time
First order elimination
. Rate of elimination depends on conc. Of drug that is present
. Exponential relationship
. Fixed half life
Characteristics of zero order kinetics
. rate of metabolism is constant and does not depend on conc. Of drug
. Linear relationship
. No fixed half life
Time for onset of action in drug
. Time between administration and first measurable response
Tome to peak effect for drug
. Time needed to reach max effect
Duration of action
. Time from first measurable effect to time when effect is no longer measurable
Alpha and beta phase of drug decline in blood
. Alpha : rapid decline in conc. From drug moving into tissues
. Beta: metabolism and excretion of drug phase, slower decline than alpha phase
Plateau principle
All drugs at any dosage will reach a steady state blood level after 4-5 half lives
Peak/trough values will decrease if _________
. Drug is administered at dosage intervals that are much shorter than the T 1/2 for elimination of the drug
Estimation of half lives
T1/2= (0.963)(Vd)/CLp
. Vd is volume of distribution
. CLp is clearance from plasma
Loading dose calculation
Loading dose = target Cp x Vd/F
. Cp is desired plasma conc.
. Vd is volume of distribution
. F fractional bioavailability
Calculation of maintenance dose
. Dosing rate= target Cpss x CLp/F
. Cpss is steady state conc. In plasma
. CL is rare if clearance
. F is fractional bioavailability ( 1 if dose if through IV)
Estimation of drug clearance
. CLp= F x dose per unit time/Css . CLp = (0.693)(Vd)/ T1/2 patient . F is bioavailability . CSS is steady state conc. In patient . T 1/2 patient is the elimination of half life for drug in patient
