Lecture 1.5: Uptake and Distribution Flashcards
What form of drug will have an effect on the brain?
non ionized, lipophilic
What form of drug will be excreted by kidneys?
ionized
What is happening in the liver?
non ionized to ionized, lipophilic to hydrophilic
Degree of ionization depends on:
dissociation constant and pt’s pH
Give acidic drug to acidic pt:
give lower dose
Give basic drug to acidic pt:
give higher dose
Ion trapping example
give basic drug to alkalemic mother - nonionized drug passes to fetus
fetus pH is acidic - ionizes drug, can’t pass back to mother
Difference in pH of mother/fetus
fetus more acidic than mother
Protein binding trends
acids bind to albumin (main one)
bases bind to alpha 1 glycoproteins
Drugs that are highly protein bound:
warfarin, propranolol, phenytoin, diazepam
What is clearance
the volume of plasma cleared by metabolism and excretion
What is first order kinetics
drug cleared at rate proportional to amount in plasma
What is zero order kinetics
drug cleared at constant rate per unit of TIME
Eg: ASA, Dilantin, ETOH
Hepatic clearance
if hepatic extraction is > 0.7, depends on hepatic blood flow
(perfusion dependent elimination)
If hepatic extraction ration < 0.3
hepatic clearance depends on enzyme activity
capacity dependent elimination
Renal clearance
most important organ for eliminating ionized drugs
Renal clearance of lipophilic drugs
little to no excretion
Metabolism definition
converting lipid soluble to water soluble
usually become inactive (midazolam is example of exception)
Phase I metabolism
oxidation-reduction or hydrolysis
Phase II metabolism
parent or metabolite reacts to something in liver to form water soluble conjugate
Sites of metabolism
liver, plasma, kidney, lungs, GI tract
What is CP-450
enzymes in hepatic smooth endoplasmic reticulum
Enzyme induction
drugs can stimulate and increase enzymes
Eg chronic alcohol use
Enzyme induction drug example
phenobarbital (other anti seizure meds) will induce liver enzymes, will need to shorten dose intervals for anesthetics
Non enzyme metabolism forms and drug examples
conjugation, hydrolysis
in liver mostly, do not undergo enzyme induction
determined genetically
Eg: succhs, esmolol
How does pharmacodynamics mainly work?
through Mu receptors, also kappa and delta receptors
Concentration of receptors
up-regulation and down-regulation in response to stimuli
Concentration of receptor example
stopping beta blocker abruptly - hypertensive crisis due to up-regulated receptors
State of receptor activation theory
non-activated receptors that are converted to active by the drug
Receptor occupancy theory
More receptors occupied by drug, more effective the drug
Non-receptor drug action example
antacids
Most antagonist drugs are what kind?
competitive antagonists (Narcan)
What kind of mixture do our drugs tend to come in?
racemic mixture
What is Efficacy?
Ability of drug to produce desired effect
What is Potency?
Relationship between therapeutic effect and dose necessary to achieve effect
Lower dose, higher effect, higher potency
Therapeutic index equation
LD50 / ED50
Hyper-reactive effect
unusually low dose produces effect
Hyper-sensitivity effect
Allergy
Additive effect and example
1+1=2
Eg: Fentanyl and Propofol
Synergetic effect and example
1+1=3
Eg: Fentanyl and Midazolam
