Chapter 3 - Pharmacokinetics

Question 1

List the pharmacokinetic variables (ADME).

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

What are the four ways a drug gets across barriers

Answer 2

Aqueous diffusion
Lipid diffusion
Special carriers
Endocytosis and exocytosis

Question 3

Permeation refers to…

Answer 3

The ways to get drugs from outside of the body to where it’s going to work

Question 4

Describe Aqueous diffusion

Answer 4

Water soluble drugs crossing membranes into large aqueous compartments (ECF, blood, cytosol)

Cells may have water channels called aquaporins; Diffusion by concentration gradient

Highly charged molecules and molecules bound to large proteins carriers cannot cross via aqueous diffusion

Question 5

Describe Lipid diffusion

Answer 5

Lipid soluble drugs
diffusion by concentration gradient

Question 6

Describe Special carriers

Answer 6

Molecule binds to drug and moves across barrier

Active transport and facilitated transport

Question 7

Describe Endocytosis and Exocytosis

Give an example

Answer 7

Endocytosis: membrane engulfment- then membrane swallows the drug and spits it out on the other side

Exocytosis: merging of vesicle with membrane

Ex) Cathrin coated pit

Question 8

What does rational dosing refer to?

Answer 8

desired effects with minimal adverse effects

Once we give a certin dose, where will the drug be distributed to? How much will be eliminated? How much will actually make it to the site that is needed?

Question 9

What is Volume of distribution?

Answer 9

V(d)

The space available in the body to contain a drug.

It tells us how much of the drug stayed in the blood vs how much went to other areas

Question 10

What happens when V(d) is increased? Decreased?

Answer 10

When V(d) is high a lot leaves the blood

When V(d) is low alot stays in the blood

Question 11

What is the V(d) formula?

Answer 11

V(d) = (X(0) - Dose given) / (C(0) - drug concentration in the blood)

Question 12

What are the units for V(d)?

Answer 12

Liters

Question 13

When should you draw blood for drug concentration?

Answer 13

PO- after 30 mins
IV - 1-2 mins or immediately

Question 14

Standard drug dosing starts with ______ volunteers

Answer 14

Healthy

Question 15

What is Clearance?

Answer 15

The ability of the body to eliminate the drug

Refers to multiple body organs not just the kidneys

** Elimination changes based on clearance and they are NOT the same thing**

Question 16

What are the Whole blood values?

Answer 16

0.08L/Kg

5.6L in 70kg

Question 17

What are plasma values?

Answer 17

0.04L/kg

2.8L in 70kg

Question 18

What is concentration?

Answer 18

The amount of a drug in the blood

Question 19

What is the formula for dose?

Answer 19

V(d) x Target concentration

He will give us V(d)

Question 20

What are the units for dose?

Answer 20

mg or mcg / kg

Question 21

What is Target concentration?

Answer 21

The desired concentration of the drug in the body to achieve the desired effect

Pharmacokinetics play a role in this so different per person.

Question 22

What is Rate of Elimination?

Answer 22

How fast youre getting rid of the drug

Question 23

What is the Rate of elimination formula?

Answer 23

Rate of elimination = Concentraton x Clearance

Question 24

What is First-Order Elimination?

Answer 24

ROE = CL x C

ROE is dependent on concentration
Clearance is constant

Where Clearance will stay the same but the rate of elimination will vary because after time the amount of concentration decreases.

Question 25

What is Zero Order Elimination?

Answer 25

ROE = CL x C ROE is constant CL varies Elimination mechanisms are saturated and cant get rid of faster. The body's ability to eliminate a drug has reaches its maximum capacity. Dose/drug concentration increases = the amount of drug eliminated does NOT increase = fraction of drug removed declines.

Question 26

What are the 3 main drugs Zero order elimination applies to?

Answer 26

Phenytoin, Ethanol, and Aspirin **Any drug can reach Zero order elimination if given in a high enough dose/concentration (Michaelis-Menten therory)**

Question 27

What is a high extration drug?

Answer 27

A drug that is eliminated via an organ with unrestricted blood flow and highly sensitive to first pass metabolism

Question 28

What are the extration ratios?

Answer 28

>0.7 - high 0.3 - 0.7 - intermediate <0.3 - low

Question 29

How does the extration ratio (E) and blood flow (Q) effect Clearance?

Answer 29

High E ; High Q = High CL **All other combos are lowwww**

Question 30

What is Half-life (T1/2)? Example?

Answer 30

Time required to change drug in body to 1/2 of concentration Drug concentration is 10. Half life is 4. -After 4 hours the concetration is 5 -after 8 hours the concentration is 2.5 -after 12 hours the concentration is 1.25

Question 31

What is the Half-life formula?

Answer 31

T(1/2) = (0.7 x V(d)) / CL

Question 32

Why is half life important?

Answer 32

Tells us how often and when we should dose the patient Tells us how soon theyll reach target concentration or how soon they'll get to 0 concentration

Question 33

What does a high Clearance indicate?

Answer 33

The drug will be eliminated at a higher rate

Question 34

How long does it take to reach target concentration without a bolus?

Answer 34

4 half lifes Ex) half life 4 hours 16 hours to reach target concentration

Question 35

How long does it take for a drug concentration to effectively reach 0?

Answer 35

4 half lifes

Question 36

What is the purpose of steady state dosing?

Answer 36

to keep the patient at the desired effect; to replace what we're getting rid of.

Question 37

What effects half life?

Answer 37

Disease states. THINK what affects clearance? Kidney failure... liver failure... etc depends on what is metabolizing/eliminating the drug

Question 38

What does accumulation mean?

Answer 38

Drug accumulates until dosing stops Needs to wait 4 half lifes before taking next dose!!!!!! Can reach toxic levels

Question 39

What is bioavailability?

Answer 39

How much of the drug reaches systemic circulation (CVS).

Question 40

What is the bioavailability of IV?

Answer 40

100%

Question 41

What is the bioavailability of PO?

Answer 41

5 - 100%

Question 42

What is 1st-Pass Elimination

Answer 42

In PO meds... Portal circulation: Biotransformaton may occur prior to reaching circulation PO drugs absorbed in the small intestines via tiny blood vessles and taken to the liver 1st where the bioavilability changes (Drug could be eliminated/metabolized, could be stronger, could become weaker) Therefore high gut absorption does not equate to high bioavailability

Question 43

How do you bypass the 1st-Pass elimination?

Answer 43

Non-PO route. **Inhalation has some 1st pass effects**

Question 44

Describe rectal suppositories and the 1st pass elimination

Answer 44

The rectum vessels bypass portal circulation. Suppositories usually migrate upward therefore about 50% bypass portal circulation

Question 45

List the 7 routes of drug administration

Answer 45

1. PO 2. Parenteral (IV,IM,SQ) 3. Topical 4. Transdermal 5. Inhalation 6. Sublingual 7. Rectal

Question 46

Dose ________ equal concentration

Answer 46

Does not

Question 47

Target concentration is _____________

Answer 47

Therapeutically determined

Question 48

What is the formula for dosing rate for steady state at 100% bioavailability?

Answer 48

Dosing rate (ss) = (CL x TC) x (Pt WT)

Question 49

What is the formula for dosing rate for bioavailability less than 100%?

Answer 49

Dosing rate (oral) = Dosing rate (calc) / F(oral) F = bioavailbility

Question 50

What is the formula for intermittent doses?

Answer 50

Called maintenance dose Maintenance dose = dosing rate x dosing interval

Question 51

Describe Therapeutic Drug Monitoring (Peak and trough).

Answer 51

Therapeutic drug monitoring involves measuring peak and trough drug concentrations to ensure the drug is within the therapeutic range. The peak is measured 5-10 mins after iv administration Trough is measured 30 mins prior to next dose

Question 52

List the test used to determine kidney function.

Answer 52

Glomerular Filtratration Rate (GFR) Can be estimated using the creatinine clearane

Question 53

What is a Loading Dose?

Answer 53

A bolus when we need to reach steady state quickly

Question 54

What must we consider when giving a loading dose?

Answer 54

The Volume of distribution THINK; whats going to happen if we give this drug in 1 push? Loading dose doesnt mean push... Normally over a faster period of time like 5 minutes

Question 55

What is the loading dose formula?

Answer 55

LD = V(d) x TC

Question 56

When do we use the Ideal body weight formula instead of the actual body weight?

Answer 56

When the drug does not penetrate fat **professor will tell us if the drug does***

Question 57

What is the formula for Ideal body weight?

Answer 57

IBW(men) = 52 + (1.9kg x (# of inches over 5 ft)) IBW(women) = 49 + (1.7kg x (# of inches over 5 ft))