Flashcards in Uptake/Distribution Deck (35):
What is pharmacokinetics? What does it consist of? What are the measured parameters?
What the body does to a drug
Consists of: MADE- Metabolism, Absorption, Distribution, Excretion
Measured parameters: elimination half-time, bioavailability, clearance, volume of distribution
What is pharmacodynamics and what does it consist of?
What a drug does to the body
Mechanism of effect, sensitivity, responsiveness
Note: The most common mechanism is interaction with receptors
What's the difference between the central and peripheral theoretical space?
Central: highly perfused tissues, "vessel rich" (kidney, liver, lungs, heart, brain) and rapid uptake of drug. Receives 75% of CO but only makes up 10% of body mass
Peripheral: large volume, extensive uptake of drug
Does rate of transfer between central and peripheral compartments increase or decrease with aging?
Decreases leading to greater plasma concentration in some drugs (thiopental)
What type of drugs do the lungs hold on to (instead of quickly releasing)? Acidic/Basic? Hydrophilic/lipophilic?
The lungs act as a reservoir by uptaking basic lipophilic drugs
The blood brain barrier prevents which drugs from crossing to the brain circulation? Ionized/nonionized? Water soluble/ lipid soluble?
BBB prevents ionized water soluble from crossing
What is the mathematical equation for volume of distribution?
Vd = dose of IV drug / plasma concentration before elimination
What is the relationship between volume of distribution and lipid solubility?
Directly related, the more lipophilic, the larger Vd
What is the relationship between volume of distribution and binding to plasma proteins?
They are inversely related, the more a drug binds to plasma proteins, the less Vd
What is the relationship between volume of distribution and molecular size?
Inverse, the bigger the size, the smaller the Vd
What percent of a drug is gone after 1 half life? 2? 3? 4?
3: 87.5% (1/8 left)
4: 93.8% (1/16 left)
What is the first pass effect?
Drugs absorbed from GI enter portal venous blood and pass through the liver before entering systemic circulation, this is why you give a higher dose of PO than IV
Do sublingual, buccal, or transmucosal have the first pass effect?
No, they are absorbed directly to systemic circulation
Distribution half-time vs. elimination half-time vs. elimination half-life?
Distribution half-time: half the drug transfers from central to peripheral
Elimination half-time: half the drug leave the PLASMA (directly proportional to Vd and inverse to clearance)
Elimination half-life: half the drug is eliminated from the BODY
What makes rectal administration of drugs unpredictable?
In the proximal rectum, first pass effect happens, in the distal rectum, the portal system is bypassed or the drug can be too distal and ineffective
Ionized vs. Nonionized?
Ionized: charged, water soluble
Nonionized: uncharged, lipid soluble, can diffuse across membranes easier
Caution should be used when giving a patient with renal failure ionized or nonionized drugs?
Caution giving a drug with high ionized fraction because the kidneys are responsible for getting rid of the ionized agents that are not metabolized
What should you consider when giving an acidic drug to someone with acidosis or alkalosis?
Acidosis: dosage may need to be decreased because of increased availability, more of a nonionized agent
Alkalosis: the drug will become more ionized, use in caution with patients that have renal issues
What is ion trapping? What is an example?
Ion trapping is when a nonionized drug moves across a membrane into a more acidic environment and becomes ionized and trapped
ex: stomach, placenta, CNS toxicity
What is the relationship between potency and protein binding?
The higher the protein binding, the lower the potency (and lower volume of distribution)
What is clearance and what does the rate depend on?
Clearance is getting rid of the drug through metabolism and excretion. Almost all drugs given at a therapeutic dose are cleared at a rate proportional to the amount of drug present in the plasma (first order kinetics)
First order kinetics vs. Zero order kinetics?
First: Clearing a drug at a rate proportional to the concentration of the drug in the plasma (constant fraction of drug is metabolized, ex: 10% per min)
Zero: constant amount of drug cleared per unit of time because it exceeds the metabolic capacity of the body to clear drugs by first order kinetics (alcohol, aspirin, dilantin), ex: 10mg/min
What is perfusion-dependent elimination vs. capacity-dependent elimination?
Perfusion-dependent: hepatic extraction greater than 0.7, clearance of drug depends on hepatic blood flow
Capacity-dependent: hepatic extraction less than 0.3, changes in blood flow have minimal changes in clearance
What is the goal of metabolism?
Turn active, lipid soluble drugs into water soluble (ionized) usually inactive drugs
Note: some drugs have active metabolites such as versed
What do phase 1 and 2 of metabolism consist of?
Phase 1: oxidation, reduction, hydrolysis
Phase 2: water-soluble conjugates are formed when a metabolite reacts with a substrate
List the sites of metabolism
Liver (hepatic microsomal enzymes in the smooth ER), plasma, kidneys, lungs, GI tract
Microsomal vs. Nonmicrosomal Enzymes
Microsomal has cytochrome P-450, protein enzymes that are involved in oxidation, reduction, and conjugation of a large number of drugs, enzyme induction
Nonmicrosomal mostly metabolize by conjugation and hydrolysis, also in the liver, does not undergo enzyme induction, genetic
What is the receptor occupancy theory?
The more receptors occupied, the more effect a drug will have
Agonist vs. Antagonist drugs?
Agonist drugs mimic cell signaling molecules by activating the same receptors to cause similar effects
Antagonist drugs competitively bind to receptors preventing an effect from the cell signaling molecules
Stereoisomers, chiral molecules that mirror each other
Same bonds and compound in a different configuration
Efficacy vs. potency
Efficacy: ability of a drug to produce a desired effect, how quickly does the drug work
Potency: dose needed to get the desired effect
Therapeutic index, ED 50, LD 50
Therapeutic index: how selective the drug is in producing desired effects, ratio of LD 50 to ED 50
ED 50: median effective dose
LD 50: median lethal dose
Hyper-reactive vs. hypersensitive
Hyper-reactive: people who only need a low dose to get the desired effect of a drug
Hypersensitive: people who are allergic the drug