Pharmacokinetics

Question 1

name the two general types of transport

Answer 1

• transcellular transport

- intercellular transport

Question 2

name ways of transversing a cell membrane

Answer 2

• diffusion
• filtration
• facilitated diffusion
• active transport
• pinocytosis

Question 3

whats the most common and important mode of transversing biological mambranes

Answer 3

diffusion

Question 4

in which direction does diffusion go

Answer 4

down the cc gradient

Question 5

what significantly influences diffusion

Answer 5

• lipid-water partition of drug

- thiccness of the cell membrane

Question 6

how does the pk value influence drug transport

Answer 6

-different pk values will diffuse differently

Question 7

the cc gradient affects the rate of filtration t/f

Answer 7

t

Question 8

does facilitated diffusion requ. E ?

Answer 8

no

Question 9

is facilitated diffusion saturable

Answer 9

yes

Question 10

describe active transport

Answer 10

• requ. energy
• against cc gradient
• occurs only in one direction
• is saturable

Question 11

describe the phases of absorption

Answer 11

1 - administration
2 -has to be taken up into bloodstream
3 - uptake into target organ

Question 12

what could reduce compound absorption

Answer 12

• poor solubility
• chemical instability in stomach
• ianbility to penetrate int. wall

Question 13

define bioavailability

Answer 13

the fraction of drug that reaches the bloodstream unaltered
-measrement of the extent of a therapeutically active drug that reaches systemic circulation and is available @ site of action

Question 14

define absolute bioavailability

Answer 14

availability of active drug in circulation after non -IV admin.

Question 15

what is the absolute bioavailability of drug admin. IV

Answer 15

1

Question 16

name factors influencing bioav. (7)

Answer 16

• absorption rate
• degradation or metabolism of drug prior to hepatic absorption
• first pass effect
• food taken with p.o. admin
• other drugs
• intest. mot.
• liver state

Question 17

is distribution reversible

Answer 17

yes

Question 18

what does distribution depnd on

Answer 18

• permeability between tissues
• blood flow and perfusion rate
• ability of drug to bind to plasma proteins and tissues

Question 19

rank the flow of the organs liver, bone, fat, skin, muscle, kidney, brain

Answer 19

brain, liver, kidney>muscle, skin> fat, bone

Question 20

factors affecting drug distr.

Answer 20

• dose
• admin.
• membrane permeabilty
• blood perfusion
• lipid solubility
• ph-pka
• plasma protein binding
• intracellular binding

Question 21

how do drugs travel in plasma

Answer 21

free or bound to plasma proteins

Question 22

the drug plasma protein binding is always at least 10%

Answer 22

f

Question 23

name the main points of plasma protein binding

Answer 23

• generally reversible
• only the free drugs diffuse through capillary walls
• extensive binding may prolong duration of action
• some plasma proteins bind many different drugs some just one
• changes in PPB can lead to change in drug effect

Question 24

what is the volume of distr.

Answer 24

VD= volume of total body fluid in which the drug appears to be distributing

Question 25

how would you calculate the vd

Answer 25

amount of drug administered/initial plasma cc

Question 26

for the majority of the drugs the vd is an accurate representation of their actual distribution t/f

Answer 26

f

Question 27

the lower the VD of a drug the more it spreads through the body t/f

Answer 27

f

Question 28

What does a low VD indicate in regards to PPB

Answer 28

extensive plasma protein binding

Question 29

A very high VD may indicate extensive tissue binding t/F

Answer 29

t

Question 30

what ends the pharmacological acion of a parent drug

Answer 30

biotransformation

Question 31

what could biotransformation lead to

Answer 31

Metabolites that are: - inert and deactivate administered dose as well as reduce effect on body - similar or different in action to parent drug - toxic - even more active than parent drug ( pro-drug)

Question 32

define Xenobiotics

Answer 32

-compoundswith no metabolic function that can cause harm if accumulated

Question 33

Where is the majority of small molecule drug metabolism carried out

Answer 33

liver

Question 34

By what are the majority of small molecule drug metoblism reaction carried out

Answer 34

CYP450

Question 35

what factors may influence biotransformation

Answer 35

- prior administration? - diet - hormonal status - hydrolysis reaction - genetics - diseases - age - liver function

Question 36

Name the phases of biotransformation

Answer 36

1 nonsynthetic reaction | 2 synthetic reaction

Question 37

describe the nonsynthetic phase of biotransformation

Answer 37

- enzyme catalyzed biotrasn. without conjugation | - oxidations, reductions, hydrolysis

Question 38

describe the synthetic phase of biotransformation

Answer 38

- enzyme catalyzed combination of drug with an endogenous substance - a functional group acts as the active centre of conjugation

Question 39

which enzymes are inducible by drugs

Answer 39

those of the endoplasmatic reticulum

Question 40

How many Cytochrome families

Answer 40

18

Question 41

In which biotrans. stage is CYP most commonly involved in?

Answer 41

stage 1

Question 42

Which subfamily is responsible for a large amount of reactions in liver

Answer 42

CYP3A

Question 43

CYP3A is accountable for 10% of clinically imp. drugs metabolism t/F

Answer 43

f - 50%

Question 44

name tissues other than the liver where cyp is found abundantly

Answer 44

- adrenals - ovaries or testes - tissues inolved in stereogenesis - or steroid metabolism

Question 45

describe inhibtion

Answer 45

- competitive or non competitive - reduced metabolism of other drugs or endogenous substrates - major source of drug-drug interactions

Question 46

Which group of enzymes are commonly involved in phase 2 reactions

Answer 46

glucoronyl transferase

Question 47

name possible routes of excretion

Answer 47

- urine - faeces - saliva - sweat - tears - milk - lungs - bile

Question 48

Which organ is central in excretion of drugs

Answer 48

kidney

Question 49

What factors into the renal excretion of a drug

Answer 49

- drug filtered glomerulus - plus amount secreted by active transport mechanisms in the kidney - minus amount of drug passively reabsorbed throughout the tubule

Question 50

what's the glomerular filtration rate

Answer 50

30-40%

Question 51

name the 2 ways of reabsorption

Answer 51

- active reabsorption - endogenous compound such as glucose | - simple passive diffusion - un-ionized drugs

Question 52

does the urinary ph influence reabsorption

Answer 52

yes

Question 53

define renal clearance

Answer 53

-volume of plasma cleared of drug per unit time

Question 54

how would you calculate clearance

Answer 54

CL=U*V/P - U:cc of drug in urine - V: vol. urine - P: cc of drug in plasma

Question 55

if drug is excreted by filtration alone, what does that tell you regarding to clearance and glomerular filtration

Answer 55

Cl=GFR

Question 56

describe the first pass effect

Answer 56

orally taken drugs penetrate int. membrane and enter the portal vein and liver before entering circulation