Pharmocokinetics

Question 1

Liquid tablet

Answer 1

Slower transport so okay for headaches but not for MI

Question 2

Focal administration

Answer 2

Targeted concentration to the required site

High conc to the site of action
Less systemic absorption
Fewer side effects

Question 3

Focal areas

Answer 3

Eyes
Skin
Inhalation

Question 4

Enteral

Answer 4

Deliver to mouth and intestines. Administration via:

Oral
Sublingual
Rectal

Question 5

Parenteral

Answer 5

Delivery through other routes. Administration via:

IV
Inhalation 
Subcutaneous
Intramuscular
Transdermal

Question 6

Valproate

Answer 6

Weak acid
Mainly unprotonated and charged
Cannot pass bilayer

10% protonated can pass bilayer

Question 7

Physiochemical factors

Answer 7

GI surface area and length
Drug lipophilicity
OAT/OCT number

Question 8

GI physiology

Answer 8

Blood flow
GI motility
Food / pH

Question 9

First pass

Answer 9

The concentration of drug not metabolized travels via the portal vein to the liver where some may be metabolised by hepatic enzymes and deactivated or activated.

Cytochrome P 450s - phase 1 enzymes
Conjugating enzymes- Phase 2 enzymes

Question 10

Bioavailability

Answer 10

Concentration of drug that has not been metabolized and reaches the circulatory system unchanged

Question 11

Drug distribution factors

Answer 11

capillary permeability
Lipophilicity
concentration of protein or lipoprotein drug

Question 12

Therapeutic ratio/ window

Answer 12

Maximum tolerated dose / minimum effective dose

LD50 / ED50

Question 13

Small therapeutic window

Answer 13

May overdose

Question 14

Fast release

Answer 14

At same dose can exceed LD50

Question 15

Slow release

Answer 15

Fall below ED50 quicker therefore more doses required - longer time to reach therapeutic window

Question 16

Plasma concentration

Answer 16

Lower the plasma concentration. The more the drug has distributed

Decrease in plasma concentration = increase in volume of distribution

Question 17

Apparent volume of distribution

Answer 17

Theoretical if all conc was given at site of action

Obtained by extrapolating elimination phase to time 0

Question 18

Volume of distribution

Answer 18

Total amount of drug in body (dose) / plasma drug conc at t0

Question 19

Smaller Vd

Answer 19

Higher plasma conc so less drug distributed to tissues

Question 20

Highly charged hydrophilic Vd
Protein bound Vd
Distributed in TBW
Highly lipophilic (hydrophobic)

Answer 20

Low Vd - more in plasma
Low Vd - more in plasma as not free
High Vd - less in plasma
High Vd

Question 21

Protein binding interactions important when:

Answer 21

High proportion of protein bound drug
Small therapeutic window
Small Vd

Question 22

Class 1 drug

Answer 22

Lower dose than number of protein binding sites

Equilibrium between free drug conc and free binding site conc

Low affinity

Warfarin

Question 23

Class 2

Answer 23

Dose is higher than the protein binding sites as all bind them left over = free drug

High affinity

Displaces Class 1

Aspirin and phenytoin

Question 24

Transient binding interaction

Answer 24

When drug conc increase rate of elimination increases

Steady state is restored

Question 25

Excretion

Answer 25

Predominantly renal - glomerulus

Question 26

Metabolisation

Answer 26

Predominantly liver Make small, uncharged, lipophilic, hydrophobic molecules more soluble Add a group so it can be filtered and not taken back up

Question 27

Phase 1 metabolisation

Answer 27

Mainly redox - add charge Deacylation Hydrolysis By cytochrome P450s

Question 28

Phase 2 metabolisation

Answer 28

Conjugation enzymes Add hydrophilic group Add charge Therefore can be eliminated by kidney More rapid than phase 1

Question 29

Cytochrome P450s

Answer 29

Affinity for lipophilic drugs | Inducible and inhabitable so can be controlled

Question 30

First order kinetics

Answer 30

Rate of elimination proportional to drug concentration Half life is constant Safer Predictable and can estimate therapeutic effect from dose increases

Question 31

Zero order kinetics

Answer 31

Rate so elimination constant More dangerous Less predictable At high doses of drug, rate of elimination is already maxed so cannot increases anymore. Therefore bioavailability increase exponentially which means it can exceed the LD50 (max tolerated dose) - side effects

Question 32

Drug elimination kinetics important for:

Answer 32

Zero order kinetic drugs Small therapeutic window If drug is used at minimum effective dose

Question 33

Clearance rate

Answer 33

Elimination rate/ plasma drug concentration

Question 34

Half life

Answer 34

Period of time taken to reduce concentration to half

Question 35

Half life factors

Answer 35

Drug elimination kinetics Vd - more distributed - longer half life CL - faster cleared - shorter half life

Question 36

Steady state

Answer 36

5 half lives = steady state

Question 37

Long half life

Answer 37

Steady state will take to long to reach - give higher bolus loading dose

Question 38

Weak acids

Answer 38

HA If more acidic urine : pH less than Pka More H+ Protonate Uncharged pass through membrane - increased absorption

Question 39

Weak base

Answer 39

BH+ If alkali urine: pH more than PKa Less H+ available Deprotonates (B) Uncharged - pass through membrane Increase reabsorption