Drug Administration and pharmacokinetics 1

Question 1

What are the common abbreviations for drug frequency

Answer 1

Once daily = o.d.
Twice daily = b.d.
Thrice daily = t.d.s.
Four times daily = q.d.s
As required = p.r.n

Question 2

What are the common abbreviation for routes of drug administration

Answer 2

Orally = po
Intramuscularly = im
Intravenously = iv
Subcutaneously = sc
Nebuliser = neb

Question 3

What are the advantages and disadvantages of administering drugs via the intravenous route?

Answer 3

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

Question 4

Compare the bioavailability of a drug that is administered orally vs i.v.

Answer 4

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

Question 5

Describe the advantages and disadvantages of intramuscular drug administration

Answer 5

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

Question 6

Desribe the advantages and disadvantages of subcutaneous drug administration

Answer 6

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

Question 7

What is the main disadvantage of oral administration

Answer 7

Variable bioavailability - different patients absorb different amounts of the drug

Question 8

What can affect absorption of a drug

Answer 8

Way of administration - oral or parenterally (i.v. , i.m. , s.c.)
Presence of food

Question 9

What does ‘first pass’ metabolism mean?

Answer 9

Drugs that are broken down by the liver as soon as they reach it, so only a fraction of the drug reaches circulation

Question 10

What are zero-order and first-order processes?

Answer 10

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

Question 11

How to calculate bioavailability

Answer 11

Denoted by F
It is the fraction of the drug absorbed
F= Area under oral log curve/ area under iv curve

Question 12

What affects bioavailability

Answer 12

Surface area of drug

method of administration

Formulation of drug

Question 13

How do we calculate the dose given using bioavailability

Answer 13

Dose given = amount needed / F

Question 14

What is salt factor?

Answer 14

Proportion of medicine that is the active drug

Question 15

How do we calculate amount of drug in body

Answer 15

Amount = dose x F x S

Question 16

What is volume of distribution (Vd) and how is it calculated?

Answer 16

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)

Question 17

Desribe drug elimination

Answer 17

Balance between hepatic metabolism and renal excretion Some drugs are excreted unchanged

it is most commonly a first order process

Question 18

What is clearance

Answer 18

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

Question 19

First order kinetics

Answer 19

Rate of elimination is proportion to [drug]

C_t = C₀e^-kt

C_t = conc at t=t

C₀ = conc at t=0

k = rate constant

Question 20

What is t_½ ?

Answer 20

Time taken for [drug] to half

t_½ = ln2 / k

Question 21

How do you calculate the rate constant?

Answer 21

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/ V_d

Question 22

What is a loading dose ?

Answer 22

An initial high dose used to achieve a rapid rise to C_ss

Question 23

how to calculate loading dose

Answer 23

loading dose = (desired [plasma] x V_d ) / F

select desired [plasma] by picking a value halfway through the range of suggested values

Question 24

What is the steady state ?

Answer 24

Administration rate = elimination rate

Question 25

What kind of a process are IV infusion and elimination ?

Answer 25

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

Question 26

What is C_ss ?

Answer 26

conc at which steady state is established (rate in = rate out )

Question 27

How do you calculate the infusion rate for a maintenance dose

Answer 27

Once C_ss is achieved then input=output

maintenance dose = amount re moved

infusion rate = clearance x C_ss

Question 28

Oral dosing

Answer 28

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

Question 29

How many half lives does it take to achieve steady state ?

Answer 29

5

Question 30

What is the equation to calculate the oral regimen

Answer 30

𝜏 (tau) is the dosage intervals

double the dose - double the plasma conc

dose - number of doses per day

Question 31

Describe how dosage regimens are decided

Answer 31

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)

Question 32

How to calculate maintenance dose (oral regimen)

what types of drugs is this equation suitable for?

Answer 32

Used for drugs with long half lifes and daily dosing

maintenance dose - amount eliminated in 24 hours

Question 33

How does tau change for renally impaired patients

Answer 33

Tau doubles to avoid toxicity

Question 34

What does tau mean?

Answer 34

Dose per day

if daily dose then tau = 1

Question 35

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?

Answer 35

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

Question 36

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?

Answer 36

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

Question 37

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?

Answer 37

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) t_½ = 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

C_t = C₀e^-kt

C_t = 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

Question 38

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 Cl_theophylline = 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

Answer 38

A)CL is in the wrong units = 0.65 x70 x 60 x10-3 L/h = 2.73 L/h

Infusion rate = CL x C_ss(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)

Question 39

The half life of digoxin is 40 hours

calculate the rate constant of elimination

Answer 39

Question 40

Common examples of drugs given as infusions

Answer 40

Aminophylline (for asthma)

Antibacterial agents (often for severe infections)

Anticancer agents

General anaesthetics

Some anti-arrhythmics

Question 41

What does a 1% solution mean

Answer 41

1g per 100ml

or 100mg per 10ml

or 10mg per ml

Question 42

What does a 0.1% solution mean

Answer 42

100mg per 100 ml

10mg per 10 ml

1mg per ml

1:1000

Question 43

Adrenaline is given a ratio

1: 1000
1: 10000
1: 200000

convert the ratios to mg/ml or micrograms/ml

Answer 43

1: 1,000 = 1 mg/ml
1: 10,000 = 100 micrograms/ml
1: 200,000 = 5 micrograms/ml