what is the thoeretical volume necessary to account for the total amount of drug in the body if it were present throughout the body in the same concentration as in the plasma

volume of distribution (Vd)

can you measure Vd?

no its theoretical

what is the shortened definition for Vd

theoretical volume measuring the amount of drug concentration you gave in the plasma

what is the theoreical volume of plasma that is completly cleared (100% cleared) of drug in a given period of time, the units are in mL/min. Also can be defined as the bodies ability to eliminate a drug

Clearance (Cl)

what is the time it take for the plasma concentration of a drug to fall by one-half

Elimination half time (T 1/2 Beta)

what is the time it takes for the TOTAL AMOUNT OF THE DRUG in the body to decrease by one-half?

elinination half-life

volume of Distribution: (Vd)

how do you calculate Vd?

by dividing the amount of drug injected by the plasma concentration

Vd = Q/C

volume of Distribution: (Vd)

what is the Vd? do the math

Q=12

C= 2

Vd = Q/C

Vd = 12 / 2

Vd = 6 mL

volume of Distribution: (Vd)

what is the voume of distribution

Q = 12

C = 1

Vd = Q / C

Vd = 12/1

Vd = 12 mL

volume of Distribution: (Vd)

what is the Volume of distribution

Vd = Q /C

Vd = 12 / 3

Vd = 4mL

volume of Distribution: (Vd)

which one has a LOW VD?

what type of drugs are these?

C

water loving drugs

Muscle relaxants (polar)

volume of Distribution: (Vd)

which one has a large VD?

What drugs are these?

B

Induction agents (non-polar)

what is Pharmacokinetics?

what the BODY does to the DRUG

Body compartments:

The human body is schematically represented in the following figure. shown are the plasma volume (PV), interstitial Volume (ISV), intracellular volume (ICV), and fat adipose tissue.

Body compartments:

what makes up the extra-cellular volume (ECV)

ISV and PV

ECV = ISV + PV

Body compartments:

outline the ECV

Body compartments: Distribution of drugs:

drugs with different properies have different volumes of distribution. MR, which are ionized are restricted to where?

extracellular space

Body compartments: Distribution of drugs:

describe drugs that are confined to the ECV

ECV = ISV + PV

Muscle relaxants

Small Vd

Water Soluble

Ionized (polar-charged)

(bc they are water loving they are charged, charged molecules do not cross the lipid bylayers thus stay in the ECV and does not get into adipose tissue and have Small Vd)

\Body compartments: Distribution of drugs:

what is the numerical value for SMALL Vd

0.3-0.5 L/kg

Body compartments: Distribution of drugs:

what type of Vd does this picture depict

Large Vd

b/c the drug has moved into the ICV and adipose tissue

Body compartments: Distribution of drugs:

describe drugs that have cause this

Induction agents

large Vd

Lipid Soluble

fat loving non-polar -uncharged

Body compartments: Distribution of drugs:

what is the numerical value for a large Vd

2.0-2.5 L/kg

Body compartments: Distribution of drugs:

comparison b/t ped and adult

on a weight basis the noenate/infant have an expanded ECV. see picture

why do noenated need more SCh on a mg/kg basis? give 2 reasons

- greater Vd
- immature NMJ
- the NMJ is immature b/c they have inadequate number of nicotinic receptors, or the receptors may not be responsive to ACh.
- THE ECV of a neonate/infant is twice that of an adult.

if neonate/infants need more SCh why do they need the same amount of NDMR as the adult on a weight base mg/kg basis?

- more NDMR is needed bc the ECV of the neonate is larger.
- Less drug is needed however b/c the NMJ is immature
- so less drug is needed to block the channels
- thus the cancel themselfs out and equal the same dose as an adult

Kinetics:

what type is when a constant amount of the drug is eliminated per unit of time? ex 2 mp/min

Zero order kinetics

Kinetics:

what does the graoh look like with zero order kinetics?

the concentration of the drug in the plasma falls linerally with time

Kinetics:

what are the ONLY 3 drugs that are eliminated by zero order kinetics

ETOH

Phenytoin

ASA

Kinetics:

is zero order an amount per unit of time or a fraction per unit time

an amount per unit time

Kinetics:

Most drugs are eliminated how?

1st order kinetics

Kinetics:

define 1st order kinetics

a constant fraction of a drug is eliminated per unit of time

Kinetics:

drugs that are eliminated by 1st order behave in one of which 2 ways?

1 compartment

or

2 compartments

Kinetics:

how can you always tell 1st order graph

it will have a log (ln) on the Y axis

Kinetics:

what does the graph with 1st order 1 compartment model look like

like zero order but with a Log on the Y axis

Kinetics:

what is the only drug that is eliminaed by 1st order kinetics 1 compartment model?

Albumin

Kinetics:

what does the graph look like for 1st order 2 compartment elimination

a fast curvilinear line

Kinetics:

name the drugs that are eliminated by 1st order 2 compartment model

all other drugs besides the zero order (ASA, ETOH, and Phenytoin) and the 1st order 1 compartment drug (albumin)

Kinetics: 1st order 2 compartment

when in the graph is the Alpha phase and what does it represent?

distibution phase

Kinetics: 1st order 2 compartment

where is the beta phase and what dose it represent?

elimination phase

Kinetics: 1st order 2 compartment

where is the point of equilibrium?

Kinetics: problem

what kind of plot is this? and how do you know?

1st order, 2 compartment

- it’s curved
- its a log (Y axis goes from 10 - 1,000)

side note

when doing Vd i said the formula was

Vd= Q/C

flip to see real formula

Vd = Q / Cp (t=0)

you never have to worry obout the t=0 b/c we always assume it is just that 0 so i shortened it

Kinetics: problem

label the distribution part and the elimiantaion part

as well as the alpha and beta

Kinetics: problem

find the concentration of the drug at t = 0 if the drug is distributed instantaneously into its volume of distribution (and describe how you found it)

find the equilibrium point and follow angle of the beta slope

100 mg/L

Kinetics: problem

2500 mg of a drug was administered and plotted on the graph. what is the Vd if this drug

Vd = Q / Cp (t=0)

Q= 2500 mg

Cp (t=o) = 100 mg/L

Vd = 2500 / 100

Vd = 25 L

Kinetics: problem

what is the T 1/2(beta) of this drug?

or the half-time elimination

find the concentration at equilibrium time 0. (100)

then find 1/2 that (50)

see where it meets the graph on the beta axis

answer 4 hrs

Kinetics: problem

2 mg of a drug is given what is the Vd?

watch the trick plasma concentration is in mcg and the drug is in mg- convert one to the other

Cp(t=o) = 100mcg/L

Q = 2mg or 2000mcg

2000/100 = 20 L

Vd = 20 L

half life problems:

a drug is eliminated by 1st order kinetics and has a 1/2 life of 6 hours how much drug remains after 18 hours if 10 mg is administered

1.25 mg

half life problems:

160 mg of a drug is administed and 20 mg remain 30 hours later. how much of the is lost in the next 20 hours, if the drug is eliminated by first ordr kinetics

15 mg more will be lost

half life:

how may 1/2 lives (1/2 times) are required to eliminate 98% of a drug

6

Pharmacokinetics: Hepatic metabolism

how many phases of reactions are there?>

3

Pharmacokinetics: Hepatic metabolism

what phase is when the reactions involving chemical biotransformation of a molecule, usually to more water soluble and often inactive metabolites

Phase I

Pharmacokinetics: Hepatic metabolism

what are the 4 types of phase I reactions

oxidation

reduction

methylation

hydrolysis

Pharmacokinetics: Hepatic metabolism

what enzyme is responsible for many of the phase I reactions (oxidation, reduction, methylation, hydrolysis).

cytochrome P-450 system

Pharmacokinetics: Hepatic metabolism

what phase reaction invlove conjugation of a drug or its metabolite w/ endogenous molecules; conjugation reactions make drugs water soluble for excretion by the kidneys or billary system.

Phase II

Pharmacokinetics: Hepatic metabolism

what are types of Phase II reactions

glucuronidation, gluthathione conjugation, sulfation and ACETYLATION

Pharmacokinetics: Hepatic metabolism

what phase reaction are eliminatin reactions that involve ATP-binding cassette (ABC) transport proteins?

Phase III

Pharmacokinetics: Hepatic metabolism

Quickly describe each Phase reaction

- Phase I- oxidation, reduction, methylation, hydrolysis
- Phase II- Acetylation
- Phase III- ATP-binding cassette (ABC)

Pharmacokinetics: protein binding

most drugs bind to what?

plasma proteins

Pharmacokinetics: protein binding

what is the most abundant plasma protein

Albumin

Pharmacokinetics: protein binding

do protein bound drugs leave circulation

no- only free unbound drugs do

Pharmacokinetics: protein binding

patients who have ______ are more sensitive to injected drugs b/c protein binding is reduced. thus more of the drug is free or unbound

Hypoproteinuria (hypoalbuminemia)

Pharmacokinetics: protein binding

when protein binding is decreased what happens to Vd?

it is increased