2. A Flashcards by Jordan Cyr

What are frequency distribution curves?

a graphical representation of the number of patients responding to a drug at different doses during clinical trials
-follows normal distribution

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What is the ED50?

median effective dose
the dose required to produce a specific therapeutic response in 50% of a group of patients
-standard or average dose

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True or false: the ED50 applies to everyone

false

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What is the TD50?

median toxicity dose
the dose required to produce a given toxicity in 50% of a group of patients

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At what stage of studies are lethal doses observed? Is it tested in humans?

pre-clinical stage (in cells and animals)
we dont test lethal dose in humans, we determine toxicity from adverse effects

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Describe the dose-response relationship.

looking at an individuals response to a drug, three phases
phase 1: very few targeted cells are affected by the drug
phase 2: shows the linear relationship between amount of drug administered and degree of response obtained
phase 3: plateau, no further responses

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Why do we plateau in phase 3 of the dose-response relationship?

all receptors are occupied, obtained 100% relief

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True or false: not all drugs demonstrate a linear relationship

true

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What is the goal of a dosage regimen?

attain and maintain therapeutic concentrations to treat a condition effectively

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Why should another dose be given before the minimum effective concentration is reached?

our goal is a plateau (steady state, Css) drug plasma level

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How many half lives does it take to reach plateau?

5-7 half lives of the drug

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What is the therapeutic window?

the range of drug plasma concentration which produces desired clinical response in a patient
the goal is to be between toxic and sub-therapeutic

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What is the therapeutic range?

the dose needed to achieve the therapeutic window of a population

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Why do we use the dose ranges of a sample population instead of the individuals therapeutic window?

we dont know the individuals therapeutic window

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What is the therapeutic index?

the ratio of toxic plasma concentration to effective plasma concentration values, comparing the amount of drug that causes the effect to the amount of drug that causes toxicity
wide index: safe drug, monitoring unnecessary
narrow index: monitoring necessary

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What is a loading dose?

how we attain the desired therapeutic concentration
sometimes we cant wait 5-7 half lives to reach Css
only once

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What is a maintenance dose?

how we maintain the desired therapeutic concentration, the regular dose that we want to maintain

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How do we calculate maintenance dose?

MD=Css x Cls/S x F

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What is pharmacokinetics?

drug movement in the body
study of time course of drug in the body (ADME)

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Explain what happens to Cp with linear and non-linear PK.

linear PK: proportional increase in Cp with increased dose (predictable)
non-linear PK: disproportional increase in Cp with increases dose (unpredictable)

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Explain each component of ADME.

Absorption: drug moving from site of administration to circulation
Distribution: where the drug is going in the body
Metabolism: changes drug to inactive/drug and/or make it more likely to be excreted
Excretion: drug leaving body

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Why do we need pharmacokinetics?

allows us to predict drug plasma concentrations

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What are the primary PK parameters? How are they determined?

absorption rate constant (Ka)
oral bioavailability (F)
hepatic clearance (Clh)
renal clearance (Clr)
volume of distribution (Vd)
determined by the physiology of the individual

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What are the secondary PK parameters? How are they determined?

elimination half life (t1/2)
elimination rate constant (K)
fraction excreted unchanged (fe)
determined by primary PK parameters

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What is pharmacodynamics?

what the drug is doing to the body what is happening at the drug receptor

What does the rate of absorption tell us?

onset of action

What are the parameters that describe absorption?

absorption rate constant (Ka): primary PK parameter, rate of absorption bioavailability (F): primary PK parameter, extent of absorption Cmax: descriptive PK parameter, extent of absorption, max concentration reached Tmax: descriptive PK parameter, rate of absorption, time at which Cmax occurs

What are the parameters that describe distribution?

volume of distribution: extent of distribution fraction unbound: extent of distribution

Explain the volume of distribution.

volume of distribution represents the apparent volume into which the drug is distributed to provide the same concentration as it currently is in the blood plasma amount of fluid necessary for drug concentrations that result in a clinical response

Explain fraction unbound.

the amount of drug that is free to bind to receptors drugs can bind to proteins, forming a complex=unable to bind to receptors

When does elimination start?

as soon as the drug is absorbed

Which processes make up elimination?

metabolism and excretion

What is systemic clearance?

the efficiency of elimination mechanisms involved in drug removal from the body the sum of all individual and simultaneously occurring elimination pathways liver and kidney are principal clearance mechanisms

What determines hepatic clearance?

hepatic blood flow (most important factor) fraction of drug unbound intrinsic clearance

What is intrinsic clearance?

maximum ability of the drug to be removed by the liver in the absence of anything impeding blood flow and no protein binding occurred

What determines renal clearance?

glomerular filtration rate tubular secretion tubular reabsorption

What is half-life? What does it determine?

amount of time it takes for a drugs serum concentration to decrease by half determines: time it takes to reach Css and dosing intervals

What is the elimination rate constant?

the fraction of drug eliminated per unit of time describes elimination but also takes distribution into account

What determines the transport of a drug?

size ionization solubility

What are the characteristics of drugs that can use passive diffusion to pass through polarized epithelia?

small non-ionized lipid soluble

What is the bile salt export pump? What happens if a drug inhibits the BSEP?

transports bile salts out of hepatocytes for excretion if inhibited then toxic levels of bile salts are possible

What are the elements of the dosage regimen?

attain (loading dose) and maintain (maintenance dose)

What are the determinants of the dosage regimen?

Activity-toxicity Pharmacokinetics Clinical factors Other factors

What are the components of the plasma concentration vs time curve?

onset: patient is starting to receive a response intensity: the effects of the drug have peaked, phase 2 duration: how long the effects of the drug lasted

What are the units for therapeutic index?

none its a ratio

How do we calculate loading dose?

LD=Cther x Vd/S x F

How do we calculate Css?

Css=dosage regimen/systemic clearance =MD/Cls

What are the determinants of the dosage regimen?

activity-toxicity pharmacokinetics clinical factors (state of patient and management of therapy) other factors

Explain how PK and PD are related.

PK assumes that there is a relationship between drug plasma concentration and the drug concentration at the receptor site this is how PK connects to the clinical response

Explain why distribution is reversible.

there is a constant transfer between systemic circulation and the tissue, it exists it in a state of constant equilibrium this is not the same as absorbing

What is the biophase?

the effect site of the drug

During pharmacokinetics, when does the response occur?

distribution

What is the formula for Vd?

Vd=dose/Co (plasma concentration)

If a drug has a large Vd, what can we infer?

the drug is distributed widely throughout the tissues

If we say that warfarin is 99% plasma-protein bound, what does this mean?

only 1% of the warfarin gets to the receptors 99% of the warfarin cannot bind to a receptor as it has formed a complex with a protein

Why do we have to take elimination into consideration when we look at dosage regimens?

drug concentrations are always changing, the drug is constantly distributing and eliminating

Why is systemic clearance so important in the dosage regimen?

systemic clearance determines the steady state concentration we must know variables that affect Cls in order to determine dosage regimens

What are the methods of transport across polarized epithelia?

passive diffusion endo/exocytosis carried mediated -facilitated diffusion -active

What are the primary PK parameters and what do they measure?

absorption: -absorption rate constant (Ka) -bioavailability (F) distribution -volume of distribution (Vd) metabolism and excretion (elimination) -hepatic clearance (Clh) -renal clearance (Clr)

What is the measurement for elimination?

volume of blood cleared of the drug per unit of time ex: mg/min