Vorlesung 3

Question 1

Zero Order kinetics

Answer 1

rate of elimination of a
compound is a constant and is independent of the
concentration of the chemical in the blood.

Question 2

First order kinetics

Answer 2

rate of elimination of a
compound is dependent on the concentration of the
chemical in the blood. The higher the concentration, the
more rapidly the chemical is eliminated, unless the
elimination mechanisms have been saturate eliminated,
unless the elimination mechanisms have been saturated.
At that point, the kinetics become zero-order. This is
known as saturation saturation kinetics

Question 3

Half life time formula

Answer 3

t1/2 = ln2 / k

Question 4

Which three modification of dosage forms are known?

Answer 4

Normal effect, rapid effect, delayed effect

Question 5

Impact in Cmax and tmax with rapid effect and what leads to rapid effect?

Answer 5

Cmax increases, tmax decreases

Micronization
Amorphous drugs
Optimal disintegration
Lingual tablets
Solutions
Effervescent tablets
Addition of surfactant

Question 6

Impact on Cmax and tmax with delayed effect and what leads to delayed effect?

Answer 6

Cmax decreases, tmax increases

Drug embedding
Matrix tablets
Nanocapsules
Pellets
Microcapsules
Resinates

Question 7

What is absolute Bioavailability? Formula as well

Answer 7

Absolute bioavailability is a ratio of areas under the curves. IV, intravenous;
PO, oral route. C is plasma concentration (arbitrary units).
F(abs)=100((AUC_poD_iv)/(AUC_iv*D_po))

Question 8

Formula F(rel)

Answer 8

F(rel)=100((AUC_AD_B)/(AUC_B*D_A))

Question 9

5 phases pharmacokinetic processes

Answer 9

Drug leads to liberation, absorption and distribution (auch untereinander von liberation zu Distribution), then metabolism and excretion

LADME

Question 10

What is important with liberation?

Answer 10

dosage form
particle size
crystalline structure
sustained-release
preparation
food intake

Question 11

What is important with absorption?

Answer 11

EXTERNAL
MEMBRANE
BARRIERS
skin
G.I. tract
lungs
BBB

Question 12

What is important with distribution?

Answer 12

Blood Plasma <-> Tissues, pools, depots, sinks

Question 13

Phases metabolism

Answer 13

PHASE-1: Oxidation
PHASE-2: conjugation

Question 14

Ways for excretion?

Answer 14

KIDNEYS
LIVER
lungs
saliva
sweat
breast milk

Question 15

Which structural model is used for the cell membrane and what explains it?

Answer 15

The ‘lipid sieve’ model
explain how lipophilic
small cpds can permeate
through the membrane by
passive diffusion

Question 16

Can hydrophilic cpds permeate?

Answer 16

hydrophilic cpds cannot
permeate unless there is a
specific membrane
transport channel or pump

Question 17

Which three passages across membranes are known?

Answer 17

Passive, facilitated, active

Question 18

Passive transport is determined by…?

Answer 18

• Permeability of surface
• Concentration gradient
• Surface area

Question 19

Permeability depends on…?

Answer 19

• size
• shape
• lipid solubility
• charge of chemical
• pH of medium
• pK of chemical

Question 20

Lipid/water distribution coefficient three states and impact on solubility and penetration

Answer 20

Lipophilic: high; low solubility and high penetration
Hydrophilic: low; high solubility and low penetration
Ambiphily

Question 21

Example drugs for all states lipid/water distribution coefficient

Answer 21

Lipophilic: digitoxine
Ambiphily: digoxine
Hydrophilic: strophanthine

Question 22

Factors affecting absorption?

Answer 22

• Dissolution in the aqueous medium surrounding the absorbing surface.
• Determinants of Passive Transfer (lipid solubility, pH, pK, area,
concentration gradient).
• Blood flow

Question 23

Factors Affecting GI Absorption

Answer 23

• Blood flow
• Motility and mixing in GI tract
• Disintegration of dosage form and dissolution of particles
• Chemical stability of chemical in gastric and intestinal juices and enzymes
• Presence and type of food
• Rate of gastric emptying
• Total adsorption area

Question 24

What leads to rapid lung absorption?

Answer 24

Large surface area
thin barrier
high blood flow

Question 25

What can be measured in the blood for lung absorption?

Answer 25

air partition coefficient tissue partition coefficient

Question 26

What defines distribution and is it a rapid or slow process?

Answer 26

where in the body a drug will go after absorption; rapid process relative to absorption and elimination

Question 27

What determines the distribution?

Answer 27

Initial is determined by blood flow and later phases determined by tissue affinity

Question 28

By what is the magnitude of the chemical’s distribution give?

Answer 28

By the apparent volume of distribution (Vd)

Question 29

Formula Vd

Answer 29

Vd=(amount of drug in the body)/(concentration in plasma)

Question 30

What does a primary toxic substance with a non-toxic metabolite?

Answer 30

Detoxification

Question 31

Primary non-toxic substance with toxic metabolite

Answer 31

Toxification (metabolic activation)

Question 32

4 examples phase 1 metabolism

Answer 32

• Cytochrome P450 enzymes (CYP) • Flavin dependent Monooxygenases (FMO) • Monoaminoxidases (MAO) • Cyclooxygenases (COX)

Question 33

Nomenclature Cytochrom P450 Genfamily

Answer 33

Family, subfamily, Isoenzyme, allel

Question 34

To and via what is codeine metabolized?

Answer 34

to Morphine via CYP2D6

Question 35

Polymorphism: effects on pharmocokinetics

Answer 35

PM: lost or very slow metabolism, leads to toxicity and side effects IM: decreased, slowed down metabolism, leads to side effects EM: normal metabolism, effective UM: increased metabolism, ineffective