PD, PK, ADME

Question 1

PD

Answer 1

Pharmaco dynamics:
What a drugs doet to body
Example: Which receptor does it activate

Question 2

PK

Answer 2

Pharmacokinetics: What the body does to the drug.
- How does the drug get in the body?
- How does the body get rid of the drug?
ADME

Question 3

ADME

Answer 3

Absorption, distribution, Metabolism, Excreation

Question 4

T1/2

Answer 4

Time to remove halve of [] cmax out of body

Question 5

C max

Answer 5

Max [] of drugs in plasma > Predict therapeutic affect and side effects

Question 6

T max

Answer 6

Time it takes for Cmax

Question 7

AUC

Answer 7

Total exposure time of drug

Is a function of high the [drug] gets and how fast it is excreted

Question 8

5 ways of administration&raquo_space; Cause [drug] in blood plasma

Answer 8

• Topic: Locally administrated
• Systemic: Transport via blood/lymph
• Transcutan: Via skin
• Enteral: Via Gi
• Parental: Not via GI but via injection

Question 9

Route in body

Answer 9

Gut > Liver > Vein > Heart > Lungs > Heart > Artery > Rest of body

Question 10

[drug] plasma

Answer 10

Cmax: highest via inhalation and smaller Tmax than intraveneus and orally.
But all AUC identicall qua surface&raquo_space; So dose is the same

Question 11

Excretion:

Answer 11

First order kinetics:

- Higher [] > Quicker rate of extrection.

Question 12

Four major compartments for distribution

Answer 12

Blood
Fat
Extra cellular compartment
Intracellular compartment

Small compartements: CSF/ Peritoneum/ Fetus

Question 13

Blood: Drug binding

Answer 13

Drug bounds to protein (albumin)

• Unbound is active and can move through compartments.
• Everywhere equilibrium of bound and unbound > At the end [] is equal.
• Low amount of unbound drugs

Due to drug binding&raquo_space; Increases drug storage in body

Question 14

Blood: Equilibrium

Answer 14

Balance determined by:
Vd = Volume of distribution &laquo_space;How much needed of a drug to get a [drug] in blood.

Kc = Balance: Number of forward and backward direction between compartments. 
Dependent on:
- Permeability of barriers
- pH of compartment
Binding capacity of proteins

Question 15

Vd berekening

Answer 15

VD = Total amount of drug in body / [drug] plasma

Question 16

Metabolism

Answer 16

Chemical breakdown of compound in body in metabolites

Question 17

Cyp actions

Answer 17

Cytochrome P450 (in liver) >> Cyp-enzymes. 
Metabolise compounds by: Hydro-oxidation, hydralase and oxidation

Cyps are important for prodrugs.

> > Infects PK

• Cyp enzymes zorgen voor phase I
• Phase II by GDP-GT > Act on OH group > Drugs more soluble / hydrophobic > Easily excreted

Question 18

Excretion

Answer 18

Irreversible removal of drug:

• Lungs (exhalation)
• Skin
• Via breakdown > Biotransformation.

Most:
- Kidney
- Liver : Hepatobilary system
Liver excretes drugs in bile and then via faeces

Question 19

Excretion via kidney: How fast?

Answer 19

Clearence = (Cu x Vu) / Cp

Vu = Rate urine produced
Cp = [drug] plasma
Cu= [drugs] urine

Clearance is Amount of drugs that is cleared.

Question 20

Factors important for clearence:

Answer 20

• Dose
• Glomerular filtration rate = Volume urine produced
• Cu : Decreased by reabsorbtion. Penicillin active excreted and increases Cu and clearence.
• Older people > Kidney’s dont work well.

Question 21

Kinetics of clearance

Answer 21

First order:
More [drug] plasma&raquo_space; More [drug] in urine.
T1/2 is constant

Zero order:
T1/2 isn’t constant
- More drug > No more secretion due to enzyme activity.
- Limited amount of prodrug can be given. > Otherwise overdosis easily.
- When [enzyme] becomes back higher than [drug]&raquo_space; Back to first order

Question 22

Lipinski rule of five:

Answer 22

Molecular properties important for ADME and so drug likeness.

• Important in developing medication
• Does not say if a lead will be good as drug
• When lead breaks to rules > Development is stopped.

I: Not >5 H bond donors (OH/NH)
II: Not >10H bond acceptors (N/O)
III: Weight <500
IV: LogP <5