Pharmacokinetics 1 & 2 Flashcards
Intention of a regimen (dosage wise)
To provide a dosage that can keep concentrations of the drug in a certain therapeutic window to keep it effective
Volume Distrivution (Vd)
Apparent volume in which a drug is dissolved in the body
Indicates how much is absorbed by cells vs how much is still lingering in blood
(Conc at T=0 is plasma conc)
Clearance (CL) (and units)
The volume of plasma cleared of a drug in unit time
ml/min or L/h
What is clearance of a drug composed of
Clearance = Renal Clearance + Hepatic Clearance (some combination of the two, different per drug)
**note that renal clearance is where the relevance of eGFR comes from
Exponential Decay and First Order Elimination
Drugs are cleared from the body in an exponential correlation with time;
Thus when drug concentration is logged and plotted against time, there is a negative linear relationship (first order)
First Order Kinetics and Formula
Rate of elimination is proportional to concentration of drug
Formula allows you to predict plasma concentrations of drug at some point in future
Rate constant (k) of first order kinetic formula
k is fraction eliminated per unit time
e.g. k=0.1/day, 10% eliminated per day
Thus, k= CL/Vd or CL = k x Vd
How to keep drugs in steady state
Administration dose = Elimination dose
Keeps drugs at equilibrium desired level
Why do some drugs (like digoxin) have very low plasma concentrations
Those drugs become concentrated in fat and other tissue, reducing the concentration in plasma - High Volume of Distribution
Discuss IV Infusion
Most reliable and straight forward type of drug infusion
What would be used in an emergency
IV infusion is a zero-order process. Plasma concentration just goes up alone with dosage
What two simultaneous things are occurring to blood plasma during IV administration
Zero-order infusion of a drug; (mostly) first-order elimination
How to calculate the infusion rate of a maintenance dose
Infusion Rate = Clearance x Css
Css = concentration steady state
Units for infusion rate (vague)
Unit / Time
Use Aminophylline to calculate maintenance infusion rate
Only 80% of the drug is the active ingredient (theophylline)
Clearance = 0.039 L/h/kg
and thus 70kg man ->2.73 L/h
Css = 10-20 mg/L (15)
(Used sometimes in severe asthmatic attacks as a bronchodilator; Given by IV infusion)
Infusion = CL x Css = 2.73*15
= 40.95 mg/h
But the drug is infused as active; so
40.95/0.8 = 51 mg/h (FINAL ANSWER)
What factors affect overall plasma concentration in oral dosing
Rate of Dissolution
Rate of Absorption
For graph, think liquid vs fine pills vs big pills (of the same drug)
When are sustained release oral drugs generally used
Used in longer term control; half life is reduced due to the bottle neck as rate of absorption is slower than administration
Compare the rise to peak and after peak portions of a rapid release vs sustained release oral dosing
Rapid Release:
Rise to peak - Absorption + elimination
After peak - Elimination only
Sustained Release
Prolonged absorption super-imposed on half life
(half-life is a contextual one, not a true one in this case as absorption occurs simultaneously)
Bioavailability
Fraction of drug absorbed (F)
F = AUC oral /AUC iv
(AUC is area under curve)
**Because IV would be 100% absorption
Why are pschoactive drugs given at night
If taken at night, the adverse effects (like sleepiness) are avoided
Calculate dose given based on bioavailability
Dose given = Amount needed/F
Approximately how many half lives does it take for repeated oral drugs to reach steady state (and why)
Approximately 5 half lives
50% –> 25% + 50% –> 12.5% + 75% –> 6.25% + 87.5% –> 3.125% + 93.75 = approx 97%
Why some penicillins are taken before food
If taken with food, they would get taken up in the stomach and be dissolved by the stomach acid
Formula for dosage of repeated oral regiment
Css is concentration at steady state
(CL x Css is infusion rate)
Tau is dosage interval (twice a day would be 12 [hrs])
F is bioavailability
Calculate Loading Dose and maintenance dose for ugent medication
Loading Dose = (Target Css x Vd)/F
Maintenance dose = (Target Css x CL x tau)/F
Purpose of Loading Dose
To achieve a rapid rise of plasma conentration to reach Css (used for emergencies)
How to avoid toxicity with a loading dose
Giving the drugs in divided doses
Compare the doses given for drugs of large vs smalls Therapeutic windows
Large TW (e.g. Penicillins) have a maximal dose strategy, so less doses are given, but each dose is towards the upper end of the TW
Small TW have a target level strategy, often given intravenously
Managing drugs with a short half life
Short half life (approx 1h) with wide therapeutic window: 3-4 times daily
Short half life with narrow TW: IV
Managing drug dosages with a medium half life
Its kind of just about being logical at this point. Look at the half life and calculate tau around that
Managing drug dosages with a long half life
> 24 hours
e.g. digoxin
Maintenance dose = amount eliminated in 24 hours (to improve adherence)
tau = 1 (day)
Dose = (Css x Clearance x tau) / F
Gentamicin
Antibacterial used IV
An exception to standard drug dosages
Its trough must be sub therapuetic to avoid toxicity in the ears and kidney
Half life is significantly impaired with patients with abnormal kidneys
Creatinine clearance
This rate is related to the kidney; abnormal levels indicate kidney damage
The value is needed when determining suitability and dosage of gentamicin
Single Daily Dose Gentamicin
Single dose of gentamicin is given over 30-60 mins
6-14 hours afterwards, plasma sample is taken and it is plotted onto a hartford nomogram to figure out the ideal dosage
Short vs Long Acting Drugs
Short (e.g. salbutamol) are more of a current treatment while long (e.g. salmeterol) are more preventative
Short has quick onset and offset; long has the opposite
