Basic Principles of Pharm/Pharmacokinetics/Pharmacodynamics Flashcards
adverse Drug Reactions
any harmful & unintended response to drug
occurs at normal prophylaxis treatment
side fx, allergies, drug interactions
Pharmacokinetics
Action of BODY on med (what body does to med) ADME process (absorption,distribution,metabolism,elimination)
Pharmacokinetics are used for:
design optimally beneficial drug therapy regimes
proper drug, route of administration, dosing schedule
Absorption
movement of drug from site of admin to central compartment
occurs via passive/active transport
Distribution phase 1
drug transported to site, reacts with tissue+receptors
distributes into interstitial fluid/intracellular fluid
rate of delivery depends on C.O, blood flow, capilalry permeability, tissue volume
well profused organ receive most drug initially (brain, liver, kidney)
Distribution Phase 2
delivery to muscle/viscera/skin/fat
slower (involves more body mass)
drug binding to plasma proteins & macromolecules of tissues limit concentration of free drug
Metabolism
convert active lipid soluble compounds to water-soluble substances that be excreted
Metabolism phase 1
hepatic enzyme (cpy 450)oxidize, demethylate, hydrolyze drugs cyp450 sensitive to induction/inhibition=DI
drugs w/short 1/2 life metabolize completly during 1st pass. less likely to have DI if metabolized completly
Metabolism Phase 2
large water soluble substances are attached to drug
compounds can circulate through 1-2 phases before water-soluble characteristics is present
Hepatic Microsomal Enzyme
phase 1 mixed function oxidase
More commonly induced/inhibited by drugs
(inhibiting=more active state=more outcome)
CYP450 System
responsible for oxidyzing many drugs
families CYP1, CYP2, CYP3, CYP4, primarily involved w/drug metabolism
Enzyme Inhibition
decrease rate of metabolism by obstructing metabolizing enzymes
leads to increase of drug concentration, increased 1/2life, accumulation, side effect/toxicity
Enzyme Induction
stimulates increase in CYP450 enzyme activity
increase clearance of drug, decrease drug concentration
Elimination/Excretion
removes drugs&metabolites
primarily through urine (also feces and lungs)
drugs are eliminated unchanged or converted to metabolites
lipid-soluble drugs not as readily converted to metabolites
Factors affecting pharmacokinetic principles
age/sex/wright/disease state/genetic factors
Pharmacdynamics
action of DRUG on body
biochemical+physiological effects of drugs and mechanisms of action
common mechanism for drug interactions
Types of Pharmacodynamics
synergism/antagonism/altered cellular transport/effects on receptor sites
Most Important Parameters Governing Drug Distribution
bioavailability/volume of distribution/clearance/elimination
Bioavailability (F)
fractional extent to which dose of drug reaches site of action
rout of drug administration should be based on understanding of what decreases F
Factors tha Decrease F
GI absorption/first pass effect/metabolism
Volume of Distribution
relates amount of drug in body to the concentration of drug in blood or plasma depending on fluid measured
volume that would be required to contain all drug in body at same concentration
Half Life
time it takes for plasma concentration to be reduced by 1/2
takes roughly 7 1/2 lives to get to point of steady concentraton
Steady State
rate in=rate out
takes approx. 5 1/2 lives to reach steadfy state
Amnt if drug administered in a period (maintenance dose)=amnt eliminated in same period
Drug Interaction
desired or undesired pharmacology results
effect of one drug (object drug) is changed by another drug (precipitate drug)
drug-drug, food-drug, drug-disease
Pharmacokinetic Drug Interaction
Occurs when ADME of 1 drug is affected by another drug/agent
Interactions with Absorption
GI-physiological problems w/GI can chane absorption
PH (taking something w/milk can cause oit to chelate/become innert)
increase&decrease motility can cause it to move through faster, change amounts of meds in system
changes in GI flora
Interactions with Distribution
plasma protein-if drug binds to protein youre not getting as much action
bond VS unbound: 1 med may be bound, then another drug kicks it off and it will bind mow other drug is free
Interactions with Metabolism
hepatic liver enzymes (cytochrome P-450, CYP 3A4)
inducers; induce hepatic liver enzymes (vigarette smoking, phenytoin)
inhibitors; inhibit hepatic liver enzymes (grapefruit, tagamet)
Interactions with Elemination
urinary ph-change in ph can effect weather or not drugs are exchanged or excreted
competition-some meds comete for elimination, so some meds will stay in body longer and get more of an effect from penecillin
Pharmacodynamic Drug Interactions
additive effects (synergistic) opposing effects (antagonistic)
Potentiation/Synergism
Interacton between 2 or more drugs resulting in pharmacological response greater than the sum of individual response to each
Antagonism
opposite in action/smaller than combines effect than with individual agents
get less than you expect from either one
During absorption, where is there high probability of DI to occur
the GI tract
