Lecture 5 - Oct 1 (ONLY HALF - FINAL EXAM) Flashcards
absorption
-absorption = application to bloodstream
distribution
distribution = bloodstream - tissue
-placental barrier:
-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
most important factor in determining concentration of a drug in human milk
-lactating person’s plasma level (plasma level determines amount that can be distributed)
-volume of distribution is the amount of drug in body as a measure of plasma volume
-drug strongly bound to plasma proteins will have a low volume distribution (will stay in plasma and not distributed)
drug is an opiod
-what does this tell you
-when drug is an opioid it is classified by precursor (narcotic is the effect)
-drug label consists of..
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)
-under 188/24 midwives can prescribe hormonal contraceptives
Drug Dosing and Administration:
-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)
Volume of Distribution Definition:
-scavenger hunt
–how much plasma we need to sample to find ALL of the drug given
Calculating Vd:
-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
Vd
Vd = volume distribution
hypothetical amount of plasma we need to search to find all of drug
Vd = D/ C0
Vd volume of distribution (L) = D (dose in mg) / C0 (mg/L)
slide 8 practice calculation
Loading Dose:
-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
calculating loading dose using Vd
-loading dose can be calculated if you know the volume of distribution
Vd = D/C0 is rearranged to
D = Vd x C0
practice problem on slide 10
practice problem worksheet on teams
Drug Dosing:
-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
Drug Clearance
-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 )
elimination
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
first order kinetics
-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)
drug clearance definition
removing drug from systemic circulation (expressed as volume of plasma leared of drug in litres/hour)
drug elimination definition
time taken for drug clearance (expresses as drugs half life which is amount of time for drug concentration to decrease by 1/2)
half life
half life t1/2 is rate of change of a drug
-knowing drugs half life is essential to planning dose regimens
slide 16-17-18, 20
zero order kinetics
-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
first vs zero order kinetics
-1st order = concentration dependent
-0 order = time dependent
clinical pharmacokinetics
-movement of drugs in the body
3 drugs dollow zero order kinetics: ethanol, aspirin and phenytoin
Css Steady state concentration
-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
slide 24
Css and Iv
-drug clearance increases with increased infusion rate until equilaibrium (input=output)
-the higher the rate of infusion then the higher th Css
Calculating Css eqation
Css (mg/L) = Ro (mg/h) / Clp (L/h)
infusion rate = Ro
plasma clearance rate = Clp
slide 26 calculation
Maintenance dose
=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
slide 27 bottom practice problem
plasma clearance rate
-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
slide 29
what happens if you infused a zero order kinetics drug
slide 30 picture
-because this drug will never reach a steady state, sooner or later the rate of infusion will lead to overdose
slide 31-34
multiple dosing and the average Css
-drugs given by tablets or discrete injections cannot reach a true Css
slide 35
Other dose calculation methods
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
