Drug Administration and pharmacokinetics 1 Flashcards
What are the common abbreviations for drug frequency
Once daily = o.d.
Twice daily = b.d.
Thrice daily = t.d.s.
Four times daily = q.d.s
As required = p.r.n
What are the common abbreviation for routes of drug administration
Orally = po Intramuscularly = im Intravenously = iv Subcutaneously = sc Nebuliser = neb
What are the advantages and disadvantages of administering drugs via the intravenous route?
Advantages : rapid effect, no need to swallow , permits titration of dose (adjustment based on response of patient) , suitable for large volume and irritating substances
Disadvantages : increased risk of adverse effects including embolisms, not suitable for oily solutions/insoluble substances, requires IV access
Compare the bioavailability of a drug that is administered orally vs i.v.
Log of [plasma] plotted against time
For oral, increase of [plasma] at first as its absorbed via G.I , then decrease due to metabolism
For i.v , high [plasma] straight away as its directly acting
Area under oral administration is smaller than that under i.v administration due to lower bioavailability
Describe the advantages and disadvantages of intramuscular drug administration
Advantages : prompt from aq solution, slow and sustained from repository preparation (gel), suitable for moderate volumes, oily substance and some irritating substances
Disadvantages : painful and danger of injecting at incorrect site
Desribe the advantages and disadvantages of subcutaneous drug administration
Advantages: prompt effect if aqueous sol used, makes drug effect slow and sustained when repository preparations are used, suitable for some insoluble suspension and implantation of large pellets
Disadvantages : painful and risk of necrosis , not suitable for large volumes
What is the main disadvantage of oral administration
Variable bioavailability - different patients absorb different amounts of the drug
What can affect absorption of a drug
Way of administration - oral or parenterally (i.v. , i.m. , s.c.)
Presence of food
What does ‘first pass’ metabolism mean?
Drugs that are broken down by the liver as soon as they reach it, so only a fraction of the drug reaches circulation
What are zero-order and first-order processes?
Zero-order means rate of reaction is independent of conc ; occurs when system is saturated ; iv administration is zero-order; a constant amount (eg. a specific number of milligrams) of drug is eliminated per unit time
First-order means rate of reaction is dependant on conc ; elimination is first order; a constant proportion of drug is eliminated per unit time
How to calculate bioavailability
Denoted by F
It is the fraction of the drug absorbed
F= Area under oral log curve/ area under iv curve
What affects bioavailability
Surface area of drug
method of administration
Formulation of drug
How do we calculate the dose given using bioavailability
Dose given = amount needed / F
What is salt factor?
Proportion of medicine that is the active drug
How do we calculate amount of drug in body
Amount = dose x F x S
What is volume of distribution (Vd) and how is it calculated?
The volume in which a drug is dissolved in the body Vd = dose / initial [plasma] (at t=0)
If a drug has a high Vd , it means it has accumulated in different organs around the body (called high binding/distribution)
Vd tells us the extent to which a drug stays in the blood or enters organs
takes into account the body weight so multiply the value by total body weight if value is given per kg (sometimes question will give you the unit in L/kg)
Desribe drug elimination
Balance between hepatic metabolism and renal excretion Some drugs are excreted unchanged
it is most commonly a first order process
What is clearance
Measure of drug removal
The vol of plasma clear of a drug in unit time Units = ml/min or L/h
Clearance = renal clearance (eGFR) + hepatic clearance
First order kinetics
Rate of elimination is proportion to [drug]
Ct = C0e-kt
Ct = conc at t=t
C0 = conc at t=0
k = rate constant
What is t½ ?
Time taken for [drug] to half
t½ = ln2 / k
How do you calculate the rate constant?
K is the fraction eliminated per unit time
e.g if k = 0.1 /day then there is 10% of the drug eliminated per day
k is usually given per hour (h-1)
k= clearance/ Vd
What is a loading dose ?
An initial high dose used to achieve a rapid rise to Css
how to calculate loading dose
loading dose = (desired [plasma] x Vd ) / F
select desired [plasma] by picking a value halfway through the range of suggested values
What is the steady state ?
Administration rate = elimination rate
What kind of a process are IV infusion and elimination ?
Drug administered at a constant rate (zero order process used therefore)
elimination is a first-order process (this means if we half the infusion rate, the [plasma] will also half
What is Css ?
conc at which steady state is established (rate in = rate out )
How do you calculate the infusion rate for a maintenance dose
Once Css is achieved then input=output
maintenance dose = amount re moved
infusion rate = clearance x Css
Oral dosing
Prolonged rising and falling phase
shape of curve greatly influenced by formulation
the slower the absorption, the lower the peak conc as elimination will occur at the same time as absorption
How many half lives does it take to achieve steady state ?
5
What is the equation to calculate the oral regimen
𝜏 (tau) is the dosage intervals
double the dose - double the plasma conc
dose - number of doses per day
Describe how dosage regimens are decided
Therapeutic windows and half life - if large maximal dose strategy ; if small, target level strategy ( IV infusion may be needed to maintain drug in TW)
How to calculate maintenance dose (oral regimen)
what types of drugs is this equation suitable for?
Used for drugs with long half lifes and daily dosing
maintenance dose - amount eliminated in 24 hours
How does tau change for renally impaired patients
Tau doubles to avoid toxicity
What does tau mean?
Dose per day
if daily dose then tau = 1
A patient requires a loading dose for digoxin. The following are relevant parameters for the pharmacokinetics of digoxin:
Volume of distribution = 450 L ; Desired plasma concentration = 0.8 - 2 micrograms/L Bioavailability (F) = 0.7
What is the most appropriate loading regimen for digoxin?
Loading dose = (Vd x conc)/F
loading dose = (450 x 1.4)/0.7 = 900 micrograms
but pills are made in 1mg dosages
so the most appropriate regimen in 1mg given In divided doses
A 60 year old man was receiving 250 micrograms of oral digoxin per day and his plasma concentration was measured as 3.5 microgramsg/L. You are also provided with the following information:
MeasurementValueDesired plasma concentration0.8 - 2 micrograms/LBioavailability (F)0.7
What is the plasma clearance (expressed as litres per hour) of digoxin for this patient?
Dose = (CL x Css)/F
dose per day = 250 micrograms
Css = 3.5 micrograms/L (plasma conc when taking maintenance dose)
F=0.7
250= (CL x 3.5)/0.7
CL=50 L per day
CL = 50/24 L per hour = 2.08 L/hr
For digoxin tablets F=0.7 Desired plasma concentration = 0.8 - 2 micrograms per litre
Patient B (75 kg) has been taking oral digoxin at 187.5 µg per day and his plasma concentration is 3.5 µg/L.
a) Using the Cl for digoxin for this patient (1.56 L/h), and assuming his Vd = 7.3L/kg, what is the elimination constant (k) for digoxin?
b) What is the half-life for digoxin for this patient?
c) How long should digoxin be stopped in patient B for his plasma concentration to return to safe, therapeutic levels?
A) Vd is given in L so Vd= 7.3 x 75 = 547.5L
k = clearance/Vd
k =1.56/547.5= 2.85 x 10-3 h-1
B) t½ = ln2/k = ln2/0.00285 = 243.2 hours = 10.1 days
c) use the exponential equation here as oral dosing is a first order process
Ct = C0e-kt
Ct = 2 micrograms/L (highest safe therapeutic level)
C0 = 3.5 micrograms/L (plasma conc before stopping regimen)
k = 0.00285
2= 3.5e-0.00285t
ln2 = ln 3.5e-0.00285
ln2 = ln3.5 + (-0.00285t)
t= (ln2-ln3.5)/-0.00285 = 196 hours
Patient C (70kg) had a severe asthmatic attack and requires intravenous aminophylline. Given the desired plasma concentration of aminophylline is 10-20mg/L, the S factor for aminophylline is 0.8 and Cltheophylline = 0.65 mL/min/kg.
A)Suggest a therapeutic infusion rate for aminophylline.
B) after giving him this infusion, his Css is 30 mg/L. Calculate his actual CL
C) his aminophylline concentration was measured as 30mg/L ; how should you revise the infusion rate
A)CL is in the wrong units = 0.65 x70 x 60 x10-3 L/h = 2.73 L/h
Infusion rate = CL x Css(this will be taken as the desired [plasma]) / S
infusion rate = (15x0.65)/0.8 = 51.2 mg/h
B) infusion rate= 51.2 mg/h
Css = 30mg/L and S = 0.8
51.2=(30xCL)/0.8
CL = 1.36 L/h
C) [plasma] directly proportional to dose given ; if infusion rate is halved , [plasma] will also halve and return to being in the therapeutic window (15mg/L)
The half life of digoxin is 40 hours
calculate the rate constant of elimination
Common examples of drugs given as infusions
Aminophylline (for asthma)
Antibacterial agents (often for severe infections)
Anticancer agents
General anaesthetics
Some anti-arrhythmics
What does a 1% solution mean
1g per 100ml
or 100mg per 10ml
or 10mg per ml
What does a 0.1% solution mean
100mg per 100 ml
10mg per 10 ml
1mg per ml
1:1000
Adrenaline is given a ratio
1: 1000
1: 10000
1: 200000
convert the ratios to mg/ml or micrograms/ml
1: 1,000 = 1 mg/ml
1: 10,000 = 100 micrograms/ml
1: 200,000 = 5 micrograms/ml
