pharmokinetics - drug distribution

Question 1

drug distribution is the process when a drug — leaves blood stream and enters —-

Answer 1

• reversibly
• extrceullular fluid or cells of tissue ( intracellular )

Question 2

the extent of distribution of a drug from plasma into the cell determines 1.the relationship between — and the total amount of — in the body
2. the amount of – that has to be administered in order to produce a particular —- which is why we use a — dose for a certain drugs as dogpxin
3. its a —- which is the apparent —–

Answer 2

• plasma concentration
• amount of drug
• drug
• plasma concentration
• loading dose ( high dose )
• descriptive parameter
• apparent volume of distrubution ( Vd) so its basically hypothetical

Question 3

—- is a theoretical volume of fluid a drug would occupy if the total amount of drug in the body was in solution at the same concentration as in the
plasma

Answer 3

volume of distribution ( Vd)

Question 4

Vd is not — as its a — volume but reflects the ratio of — in — space relative to — space
Vd also gives us a measure of – of a drug move out of the —- to some other sites

Answer 4

• real
• physical
• drug
• extravascular
• plasm
• tendency
• plasma

Question 5

—– is fluid volume that would be required to contain the total amount of drug present in the body at the same concentration as in the plasma.

Answer 5

Vd and its caulcated as:
Vd= total amount of drug in body / plasma concentration
aka
= dose/plasma concentration at time zero
example:
A patient is administered an intravenous analgesic at a dose of 30mg. A few minutes after, a blood
sample is taken and the concentration of analgesic in the blood is 0.5mg/ml.
What is the volume of distribution (in litres) of the analgesic?
Vd = D/C
= 30mg / 0.5mg/ml = 30,000mg / 0.5mg/ml
= 60,000ml = 60 litres

Question 6

clinical uses of volume distribution :

Answer 6

Reflects size of distribution space
* Large Vd- need higher dose to fill (load)
* Small Vd- need lower dose to load
* Vd used to calculate loading dose(LD)
* Loading dose given so therapeutic concentrations
are achieved quickly
LD= Vd x desired plasma conc

Question 7

ranges of distribution : true or false
1. digotoxins: are mainly located in tissue very little in plasma
2. thepphyline has similar contractions in both plasma and tissue
3. salsilyic acid is localised mainly in plasma less in tissue
4. less than 10 is considered to be low as slasilyic acid

Answer 7

all true

Question 8

drug elimination is the — loss of drug from the body occurs by 2 process which are:

Answer 8

• irreversible
  1. metabolism: usually converts lipid soluble chemical to water soluble species
  – Phase 1 (oxidation, reduction, hydrolysis)
  – Phase 2 (conjugation)
  2. excretion:
  – Fluids (urine, bile, sweat, tears, milk)
  – Solids (faeces, hair)
  – Gases (expired air)

Question 9

routes of drug excretion:
- major routes of elimination includes:
- significant for other reason include :

Answer 9

1. major;
   – Renal
   – Biliary/Gastrointestinal
   – Pulmonary
2. others :
   – Mammary
   – Salivary, Skin & Hair

Question 10

the 3 renal processes accounting for renal drug excretion :

Answer 10

– Glomerular filtration
– Active tubular secretion
– Reabsorption

Question 11

true or false:
- urinary excretion is important for low molecular weight polar/water soluble substances

Answer 11

true

Question 12

1. glomerular filteration:
   - molecules less than —kda filtered and enters filtrate
   - protein bound drugs are — ( plasma albumin is 68kda)
2. tubular secretion:
   - —- mediated elimination
   - secretory mechanism for both —- and — compounds
   - can transport —- electrochemical gradient and when drug protein bound
3. reabsorption:
   - — diffussion back across tubular epithelium
   - — soluble drugs with high — are exerted —-
   - polar water soluble remains in —
   - the – partitioning relevant

Answer 12

• 20
• not filtered
• active carrier mediated
• acidic and basic
• against
• passive
  -lipid
• permeability
• slow
  -urine
• pH

Question 13

the biliary excretion:
1. hepatocytes uptake of — soluble drugs and metabolite and excreted into —
- they get reabsorbed along w the bulk of — in —-
- are not excreted —–
2. only works effectively if the molecular weight is —-
3. conjunction to — often increases — for biliary excretion
4. bile is significant route of excretion for:

Answer 13

• lipid
• bile
• water
• small intestine
• efficiently
• high enough so more than 500Da (Most drugs’ Mol. Wt. too low for efficient biliary excretion)
• glucornide ( +200Da)
• mol. weight
• – Glucuronide conjugates (e.g. morphine) and Limited number of ionised drugs with very high Mol. Wt.

Question 14

the entro hepatic circulation:
1. drug conjugates hydrolysed mainly by — in —-
2. active drugs released — and free drug is — and cycle repeats
3. creates a – of recirculating drugs , prolong drug action

Answer 14

• bacteria
• small intestine
• one more
• reabsorbed
• reservoir

Question 15

pulmonary excretion refers to the excretion via —-
this signigcant route of excretion for some molecules are:

Answer 15

• lungs and breath
  -anaesthetics, ethanol

Question 16

mammary:
- concentration in milk generally reflects — in maternal blood
- clinical significance for effect of a drug on a breast feeding baby:

Answer 16

• free concentration
  1. Tetracyclines: Incorporated into teeth which become weakened
  and ‘mottled’
  2.Chloramphenicol: Bone marrow toxicity and ‘grey baby’ syndrome,
  (baby’s liver cannot metabolise the drug effectively)

Question 17

most drugs are eliminated by

Answer 17

first order process

Question 18

the first order process refers to the amount of drug is —- to the serum drug concentration ( which in turn is proportional to drug )
- the fraction of drug eliminated is —- but not the amount of drug eliminated

Answer 18

• directly proportional
• constant ( so only the fraction is constant not the amount )
  example of constant fraction:
  constant fraction = 50% eliminated per unit time
  Drug plasma conc. 80mg/ml – 40 – 20 – 10 – 5

Question 19

rate of reaction:
in zero order kinetics the elimination occurs at a — max rate and is — of drug concentration
example:
- the graph of kinetic is —

Answer 19

• fixed
  -independent
• protein mediated reactions as metabolism of ethanol (*rate of oxidation by the enzyme alcohol dehydrogenase reaches a maximum at low ethanol
  concentrations because of limited availability of the cofactor NAD+ , bc its zero order the only thing that eliminated this is time )
• saturated
  .

Question 20

rate of reaction:
first order kinetics is when the rate of elimination is —- to the amount od drugs as:

Answer 20

• proportional
• globular filteration
• its a non saturating kinetics (check graph slide 22)

Question 21

Elimination of a constant quantity per time unit of the drug quantity
present in the organism is;

Answer 21

zero order elimination kinetics

Question 22

Elimination of a constant fraction per time unit of the drug quantity
present in the organism. The elimination is proportional
to the drug concentration is:

Answer 22

1st order elimination kinetics
(check slide 24 plssss sooo important)

Question 23

plasma half life t1/2 determined by activity of — or — mehcnaims aka —
also its determined by the — of drug between blood into tissue so high Vd ( drug mainly located in tissue) results in —- t1/2

Answer 23

• metabolising enzyme
• excretion mechanism aka clearance
• distribution
• prolonged
  ( check slide 25 sooo important ,, General rule:
  4 half-lives after stopping
  drug plasma conc. will have
  fallen by ~94%)

Question 24

With infusion & first order elimination, at a certain point in therapy, the amount of drug administered during a dosing interval exactly —- the amount of drug excreted.
* When this equilibrium occurs (rate in = rate out), —– is reached.
this aims to maintain steady state concentration of drug within the — range

Answer 24

• replaces
• steady state ( aka equilibrium point)
• therapeutic range
  ( CHECK SLIDE 27 SO IMPORTNT )

Question 25

—- is the time necessary for the concentration of drug in the plasma to decrease by half.

Answer 25

• half life ( t 1/2 ) and the general rules are;
  – 4 half-lives after stopping drug plasma conc will have fallen by ~94%
  – 4 half-lives after starting drug plasma conc at steady-state

Question 26

—–most important routes for drug elimination.
* Enterohepatic circulation increases the elimination half-life of many
drugs (thus prolonging their action)

Answer 26

renal and fecal