Chapter 3: Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

ADME

-Reaching site of action
a. Most drugs have to travel through several membranes (uncharge more likely to cross membranes)

-Absorption
a. Permeation

-Distribution

Question 2

Aqueous Diffusion

Answer 2

-Larger aqueous compartments (cytosol, interstitial space)

-Aqueous channel/Aquaporins
a. Allow H2O to pass through, so molecule going with H2O
Flux: amount of flow through aqueous channel (directly proportional to concentration gradient)

• Diffusion by concentration gradient
  a. Greater concentration to lower

-Molecules can be quiet large

Question 3

Lipid Diffusion

Answer 3

-No transporter or pore to travel through
–Lipid soluble drugs

pH vs. pKa
- Uncharged more likely to cross through barrier

Question 4

Special Carriers

Answer 4

Molecules bind to drug & move across barrier

Types:

A. Active Transport
-Require ATP to move against concentration gradient

B. Facilitated Diffusion
-Moves through with gradient without the use of ATP

NET –> Norepi reuptake
SERT –> Serotonin reuptake
MDR1 –> xenobiotics
VMAT –> dopamine and norepinephrine

Question 5

Endocytosis vs. Exocytosis

Answer 5

Endocytosis:
- Membrane engulfment
a. Receptor mediated endocytosis (ex. clathrin coated pits)
b. Outside cell to inside cell

Exocytosis:
- merging of vesicle with membrane
-inside cell to outside cell

Question 6

Volume of Distribution (Vd)

Answer 6

• Amount of drug in body to concentration in blood per 70 kg
  a. Conc. L/ 70 kg
• Whole blood: 0.08 L/kg
• Plasma: 0.04 L/kg
• High Vd means it preferentially leaves the blood stream/distributed outside of the blood stream

Multiply by % to get Vd

Question 7

Clearance (CL)

Answer 7

Predicts rate of elimination in relation to Concentration (C)

CL= ROE/C

-Clearance is additive if eliminated in different parts of the body

Question 8

Rate of Elimination (ROE)

Answer 8

Rate at which drug leaves body

Types:

1. First Order
2. Zero Order (Capacity Limited)
3. Flow Dependent

Question 9

Half-life (T 1/2)

Answer 9

Amount of time it takes to reduce concentration by half the amount

After 4 half-lives, effectively eliminate drug

-Accumulation: will build up until dosing stops, especially if dosing interval is less than 4 half-lives

Question 10

Bioavailability (F)

Answer 10

Fraction of unchanged drug reaching systemic circulation

-Only IV administration will have 100%

Question 11

Capacity Limited Clearance/ Zero order Elimination

Answer 11

Rate of elimination is constant

• Clearance varies
• Amount of drug being cleared is constant (ROE) because all transporters are being used
• If given enough drug (toxic level, maybe) first order elimination drugs can turn into zero order

Question 12

First Order Clearance

Answer 12

Drug eliminated at a constant clearance, so amount of drug being eliminated is less and less

• ROE decreases

Question 13

Flow Dependent Elimination

Answer 13

Depends on blood flow through an organ (I.e liver)
-First pass effect

“High Extraction Drugs”
- Every time they go through that organ, large proportion will be removed

CL(org)= Q x E

Q: blood flow through organ
E: Extraction Ratio

High Q and High E results in High CL (L/hr)

Question 14

Routes of Drug Administration

Answer 14

1. IV –> 100 % Bioavailable
2. IM 75 to < or = 100% Bioavailable
3. SQ 75 to < or = 100% Bioavailable
4. Oral 5 to < 100% bioavailable
5. Rectal 30 to <100%
6. Inhalation 5 to <100%
7. Transdermal 80 to < or = 100%

Question 15

Loading Dose/ Bolus Dose

Answer 15

Used to achieve TC more rapidly than 4 half-lives

Considers Vd

LD= Vd x TC

Question 16

Maintenance Dose

Answer 16

Maintain steady state of drug by giving just enough to replace amount being eliminated

-Clearance most important factor
-Dosing Rate= CL x TC
- F <100%; DR= DR calc/ F (bioavailable)

Intermittent
-Dose Rate x Dosing interval

Question 17

Ideal Body Weight Calculation

Answer 17

Male: 52 + (1.9 kg x inches over 5 ft)
Female: 49 + (1.7 kg x inches over 5 ft)

Question 18

Therapeutic Drug Monitoring

Answer 18

-Peak: Usually taken after drug reaches blood stream
a. make sure enough target concentration is bioavailable to have appropriate effect

-Trough: Drawn prior to next dose
b. make sure drug is leaving system appropriately so not to build up toxic levels
ex) gentamicin, vancomycin, phenytoin

Question 19

Kidney Function test

Answer 19

Creatinine clearance

Question 20

Target Concentration (TC)

Answer 20

Concentration needed to produce desired effect

Takes 4 half-lives to reach target concentration

Determined for every drug, every individual, determined experimentally

TC is therapeutically determine
ex) Digoxin 2 ng/mL for Afib but 1 ng/mL for Heart Failure