Lecture 5 - Oct 1 (ONLY HALF - FINAL EXAM)

Question 1

absorption

Answer 1

-absorption = application to bloodstream

Question 2

distribution

Answer 2

distribution = bloodstream - tissue

Question 3

-placental barrier:

Answer 3

-extremely permeable to lipid soluble molecules (everything is soluble to lipid soluble)
-parturient capillaries are fenestrated
-the basal lamina is NOT thick and cells have tight junctions (this is more like blood brain barrier)
-pinocytosis occurs at placental barrier

Question 4

most important factor in determining concentration of a drug in human milk

Answer 4

-lactating person’s plasma level (plasma level determines amount that can be distributed)

Question 5

-volume of distribution is the amount of drug in body as a measure of plasma volume

Question 6

-drug strongly bound to plasma proteins will have a low volume distribution (will stay in plasma and not distributed)

Question 7

drug is an opiod
-what does this tell you

Answer 7

-when drug is an opioid it is classified by precursor (narcotic is the effect)

Question 8

-drug label consists of..

Answer 8

lot number
generic name
and strength of medication,
NOT dose of mediation (dose is how many you take and how often which is on instructions, not bottle label)

Question 9

-under 188/24 midwives can prescribe hormonal contraceptives

Question 10

Drug Dosing and Administration:

Answer 10

-need to know how much to give in order to have therapeutic effect
-how much we need to give depends on the drugs pharmacokinetic profile (absorption, distribution, metabolism, elimination)

Question 11

Volume of Distribution Definition:

Answer 11

-scavenger hunt
–how much plasma we need to sample to find ALL of the drug given

Question 12

Calculating Vd:

Answer 12

-to calculate Vd we need to know:
-amount of drug added (dose) = D (in mg)
-concentration in plasma before the drug beings to get broken down which is called C0

Question 13

Vd

Answer 13

Vd = volume distribution
hypothetical amount of plasma we need to search to find all of drug

Question 14

Vd = D/ C0

Answer 14

Vd volume of distribution (L) = D (dose in mg) / C0 (mg/L)

Question 15

slide 8 practice calculation

Question 16

Loading Dose:

Answer 16

-single large dose designed to bring concentration of drug to therapeutic levels right away and then taper down

-examples:
-loperamide/immoidum take 2 capsules then 1 capsule after each unformed stool
-azithromycin/zithromax - take 500mg as single dose on day 1 then 250mg each subsequent day

Question 17

calculating loading dose using Vd

Answer 17

-loading dose can be calculated if you know the volume of distribution

Vd = D/C0 is rearranged to
D = Vd x C0

Question 18

practice problem on slide 10

Question 19

practice problem worksheet on teams

Question 20

Drug Dosing:

Answer 20

-drug dosing (how much you give and how often) is intended to maintain therapeutic effect
-want to avoid overdose and underdose
-number of parameters to consider (size/body weight, plasma clearance rate and factors that affect it, volume of distribution specific to each drug)

-most drugs have standard doses to prevent miscalculation

-kidney/liver disfunction can lead to inappropriate drug levels
-demerol/meperidine is given at a dose of 50-1000mg IM or SC but someone who is 50kg gets double the amount of someone who is 100kg

Question 21

Drug Clearance

Answer 21

-clearance (Clp): measure of body’s efficiecy at removing a drug from circulation expressed as L/h
-clearance of drug depends on plasma cleared per hour which is constant for each drug
-amount of drug cleared depends on concentration which changes (more drug there is the faster the body works to clear it )

Question 22

elimination

Answer 22

measure of time taken for clearance; expressed as half life (t1/2) in hours
-half life is constant
-only drugs eliminated by first order kinetics have a half life
-determined by drug metabolism

Question 23

first order kinetics

Answer 23

-the more drug in circulation, the more drug is cleared from circulation
-distibution phase is fast
-clearance phase has fast intial descent and then decreases slowly (slide 13)

Question 24

drug clearance definition

Answer 24

removing drug from systemic circulation (expressed as volume of plasma leared of drug in litres/hour)

Question 25

drug elimination definition

Answer 25

time taken for drug clearance (expresses as drugs half life which is amount of time for drug concentration to decrease by 1/2)

Question 26

half life

Answer 26

half life t1/2 is rate of change of a drug -knowing drugs half life is essential to planning dose regimens

Question 27

slide 16-17-18, 20

Question 28

zero order kinetics

Answer 28

-drug broke down at exactly same rate every minute -these drugs don't have a half life -rate of clearance is not related to dose -graph is linear -is how alcohol is cleared - why the say have 1 drink an hour (eliminated in a linear way, whereas if alcohol was 1st order kinetics then drinking more would mean it's eliminated faster) -rate of clearance is consistent and NOT related to amount of drug in circulation -much less common clearance problem

Question 29

first vs zero order kinetics

Answer 29

-1st order = concentration dependent -0 order = time dependent

Question 30

clinical pharmacokinetics

Answer 30

-movement of drugs in the body 3 drugs dollow zero order kinetics: ethanol, aspirin and phenytoin

Question 31

Css Steady state concentration

Answer 31

-if a drug is given by IV then an equilibrium will form between administration and clearance -steady state concentration happens after 4-5 half lives

Question 32

slide 24

Question 33

Css and Iv

Answer 33

-drug clearance increases with increased infusion rate until equilaibrium (input=output) -the higher the rate of infusion then the higher th Css

Question 34

Calculating Css eqation

Answer 34

Css (mg/L) = Ro (mg/h) / Clp (L/h) infusion rate = Ro plasma clearance rate = Clp

Question 35

slide 26 calculation

Question 36

Maintenance dose

Answer 36

=dose regime that keeps blood levels of a drug in therautic range Ro (mg/h) = Css x Clp ro = maintantece dose Css = steady state cincentration (constant level of drug desired) Clp - clearance rate -high infusion rate required if drug has high plasma clearance

Question 37

slide 27 bottom practice problem

Question 38

plasma clearance rate

Answer 38

-volume of plasma that is cleared of a substance per unit of time -can calcualte Clp from half life and Vd clp = k(h-1) x Vd -drugs with short half lives have fast elimination -drugs with short half-lives and large volumes of distribution have high plasma clearance rates

Question 39

slide 29

Question 40

what happens if you infused a zero order kinetics drug

Answer 40

slide 30 picture -because this drug will never reach a steady state, sooner or later the rate of infusion will lead to overdose

Question 41

slide 31-34

Question 42

multiple dosing and the average Css

Answer 42

-drugs given by tablets or discrete injections cannot reach a true Css slide 35

Question 43

Other dose calculation methods

Answer 43

most doses are based on size (weight) -sa can be used as it is well correlated with cardiac output, glomerular filtration and rates of biotransformation -seen in nomograms