Pharmacokinetics (Ch 3)

Question 1

ADME

Answer 1

absorption
permeation
distribution
metabolism
excretion

Question 2

describe the 4 ways a drug gets across barriers

Answer 2

1. aqueous diffusion
2. lipid diffusion
3. special carriers
4. endo/exo-cytosis

Question 3

Volume of Distribution (Vd)

Answer 3

space available in body to contain drug

how much of the drug gets distributed to other areas in addition to just the bloodstream

Question 4

Clearance (CL)

Answer 4

ability of body to eliminate the drug
this predicts the rate of elimination

CL = ROE/concentration

CL systemic is calculated by totaling the clearance of other organs (i.e. renal, liver, etc.)

Question 5

Concentration (C)

Answer 5

the total amount of drug in the bloodstream

Question 6

Rate of elimination (ROE)

Answer 6

ROE = CL x C

ex) drug = 75mg/L
clearance = 349 ml/min

ROE = CL x C
= 75 mg/L x 349 ml/min
= 75 mg/1000 ml x (349 ml/min)
= 26 mg/min

changes over time

Question 7

Target Concentration (TC)

Answer 7

the steady state concentration associated with the target drug effect

Question 8

aqueous diffusion

Answer 8

larger aqueous compartments (ECF – cytosol, interstitium)
aquaporins (water channels)
water soluble drugs cross by diffusion by [ ] gradient
molecules can be large (20,000 - 30,000 MW)

Question 9

lipid diffusion

Answer 9

limiting factor for drug permeation bc there are many lipid barriers to cross

ability to move between lipid and aqueous phases is important for good drugs

sometimes weak acids/bases can become uncharged while passing the membranes and then become charged again, depending on the areas

ex) cholesterol can cross via lipid diffusion

Question 10

special carriers

Answer 10

can keep exogenous things out of the blood stream (i.e. BBB) unless it’s the liver (the liver takes everything in)

molecules bind to drug and move across barriers

active transport and facilitated diffusion

ex) NET (norepi transporter)
ex) SERT
serotonin reuptake from synapse is normal, but SSRIs can inhibit reuptake of serotonin from synapse, which would keep serotonin in the synapse longer and would help with sx of depression

Question 10

differentiate endocytosis and exocytosis

Answer 10

endocytosis - membrane engulfs drugs (i.e. clatherin coated pits)

exocytosis - merging of vesicle with membrane

Question 11

Vd calculation

Answer 11

= dose/initial drug concentration in liters

Question 11

what is meant by a “high Vd”

Answer 11

a high Vd means that more of that drug is leaving the blood (to other areas of distribution)

Question 12

what is first order elimination?

Answer 12

CL is constant
ROE decreases over time (because the drug concentration decreases)

ex) 1000 mg of drug A bolused. after 1 hour, your body has removed 120 mg/60 min in the first hour, and your CL is 12%. you are left with 880 mg in your body.
in the second hour, your body removes 106 mg, leaving 774 mg left in your body, but your CL is STILL 12%.

Question 13

standard whole blood volume in liters for a 70kg person?

Answer 13

5.6 L

Question 14

standard plasma volume for a 70 kg person?

Answer 14

2.8 L

Question 15

what is zero order elimination?

Answer 15

ROE is constant
CL increases over time

ex) you ingested 1000 mg of a drug at 0 hours. after 1 hour, your body has eliminated 150 mg, leaving 850 mg left in the body, and your clearance is 15%.
in the second hour, you eliminated only 150 mg of that drug again, leaving 700 mg left and your CL is 18%.

ROE is constant bc the body’s ability to eliminate the drug has reached its maximum capacity – it cannot eliminate the drug any faster.

Question 16

what are 3 drugs that can reach zero order elimination?

Answer 16

APE:
ASA
Phenytoin
Ethanol

Question 17

calculate tylenol’s dose
Vd = 67L/70kg
TC = 15mg/L

Answer 17

dose = (Vd)(TC)
dose = (67L/70kg)(15mg/L)
dose = 14.35mg/kg OR 1005 mg/70kg

Question 17

in a 70kg patient, if aspirin has a Vd of 11 and carbamazepine has a Vd of 98, which drug stays in the blood more?

Answer 17

aspirin.
98 > 11, therefore, carbamazepine has a greater amount of drug that LEAVES the blood

Question 18

calculate a lasix dose
Vd = 7.7L/70kg
TC = 5mg/L

Answer 18

dose = (Vd)(TC)
= 7.7L/70kg x 5mg/L
= 0.55mg/kg OR 38.5mg/70kg

Question 19

half-life (T 1/2)

Answer 19

the time it takes the body to get rid of HALF the drug [ ]

T 1/2 = (0.7 x Vd)/CL

ex) 10 mg bolus given; T 1/2 = 4 hours. After 4 hours, there would be 5mg in the body. After another 4 hours, there would be 2.5 mg, etc.

Question 20

steady state dosing

Answer 20

the amount in blood during constant rate admin after X amt half-lives; and the amount left in blood after stopping admin after X amt of half-lives

you’re giving JUST ENOUGH drug to balance what the body is eliminating; usually bolus is given FIRST and then steady state dosing

assumed to require 4x half-lives to achieve FULL effects of drug (or to see drug eliminated after stopping)

ex) if your T_1/2 is 4 hours, it will take **16 hours **to get to TC (4hrs x 4 half lives, if NO bolus was given)

Question 21

accumulation

Answer 21

very important for PO drugs

drug accumulates until dosing stops; you can reach toxicity very quickly! take as directed!

ex) if T 1/2 is 2 hours; you wait 8 hours (4 full half-lives) until the NEXT dose; we want to make sure the body is able to effectively eliminate the drug before next drug to prevent accumulation and toxicity

Question 22

bioavailability (F)

Answer 22

Fraction of unchanged drug reaching systemic circ

Question 23

7 routes of drug admin

Answer 23

1. IV
2. IM
3. SQ
4. PO
5. PR
6. inhalation
7. transdermal

Question 24

what factors affect bioavailability

Answer 24

physical properties of drug (hydrophylicity, pKa, solubility, etc)
forumulation/route
GI - diet, gastric emptying, transporters
polypharmacy
overall health/disease state (liver disease)
circadian

Question 25

first-pass elimination

Answer 25

the liver will biotransform some drugs prior to reaching the systemic circulation (if given PO)

Question 26

routes bypassing first pass-effect

Answer 26

IV
IM
SQ
Inhalation: has its own metablism (lungs have same enzymes as liver); has SOME first-pass effect
SL (blood vessels under the tongue)
transdermal (lipid soluble)
PR (some suppositories migrate upward, and therefore only 50% bypass hepatic circ)

Question 27

target concentration

Answer 27

the [ ] that will produce the desired effect

factors are individualized to determine dose – what is the GOAL for the patient?

ex) digoxin
+2 ng/ml - controls afib
+1 ng/ml - manages HF

Question 28

maintenance dosing: steady state dosing

Answer 28

dosing rate_ss = ROE_ss

OR

dosing rate: CL (l/h) x TC
dosing rate is usually mg/hr

Question 29

maintenance dosing: bioavailability <100%

Answer 29

dosing rate_oral = CL x TC/F_oral

dosing rate_oral = CL x TC/BIOAVAILABILITY_oral

F = 0.X (usually a percent; 0.2 = 20%)

Question 30

maintenance dosing: intermittent doses

Answer 30

maintenance dose = dosing rate x dosing interval

maintenance dose = CL x TC x (time interval in hours)

you have to give more if the bioavailability is less!

Question 31

loading dose

Answer 31

LD = Vd x TC

slow admin is key – fast enough to reach steady state quickly, but not so fast that it doesn’t have time to distribute

assumed if given over 5 mins

Question 32

peak and trough

Answer 32

3 draw types:
1. peak (5-10 min after IV drug admin)
2. trough (30 mins PRIOR to next dose of drug)
3. random (any time)

pts own enzymes can transform drugs, so individual response should be monitored

Question 33

ideal body weight

Answer 33

Vd calculated using body weight
drugs that do not penetrate fat
“preferentially in serum”

IBW
men = 52 + 1.9kg x inches over 5 ft
women: 49 + 1.7kg x inches over 5 ft

ex) 5 ft 5 male pt weighing 120 kg would have an IBW of 62 kg (52 + (1.9 kg x 5))

Question 34

creatinine clearance

Answer 34

muscles produce a steady amount of creatinine – a breakdown product of creatine in the muscles

everybody produces around the same amount at the same time (except for body builders/crush injury patients, etc)

the creatinine clearance gives us a picture of the overall health of the kidneys