Pharmakokinetics Flashcards
With regard to exponential processes:
T/F
When considering a volatile anaesthetic ash-in curve, the rate of increase of the function decreases with time
True
With a volatile anaesthetic wash-in curve the FA/FI ratio (ratio of alveolar concentration/inspired concentration) is plotted against time. As time passes, the graph flattens as the alveolar and inspired concentrations equilibrate. Therefore the gradient of the graph reduces with time and consequently the rate of increase of the function decreases.
With regard to exponential processes:
T/F
Nitrogen washout during pre-oxygenation mist closely fits a linear process
False
With regard to exponential processes:
T/F
Bacterial growth is an example of an exponential tear-away function
True
Bacterial growth starts slowly and rapidly ‘takes off’ in an increasing exponential way - it is a ‘tear away’ function.
With regard to exponential processes:
T/F
When charging a capacitor, the graph of current versus time is similar to a volatile anaesthetic wash-in curve
False
When a capacitor charges, the charge versus time and the voltage versus time graphs resemble the wash-in curves. But, with respect to current, as charging proceeds less electrons are required to attempt to complete the charge and the current therefore falls. The current versus time graph therefore resembles a drug elimination curve.
In mathematics, with regard to exponential functions:
T/F
The term natural is used when the scaling uses base 2
False
The number e is the natural exponential because it arises naturally in mathematics and physical sciences, i.e. ‘real life’ situations. When the term natural is used, the base is e or 2.718.
In mathematics, with regard to exponential functions:
T/F
A natural exponential function can be transformed to give a straight line by usung any logarithmic transform
False
Natural exponential processes need natural logarithmic transforms to produce straight line graphs.
In mathematics, with regard to exponential functions:
T/F
Eulers number is 7.218
False
Euler’s number is 2.718
In mathematics, with regard to exponential functions:
T/F
They describe processes where a variable changes at a rate proportional to how long the process has been in operation
False
Natural exponential functions describe processes where the variable changes at a rate proportional to its own magnitude, not to time.
In mathematics, with regard to exponential functions:
T/F
A rectangular hyperbola is a special type of exponential function
False
Rectangular hyperbolae are conic sections and exponential functions model natural processes; look again at the graphs in the session and compare their features.
With regard to exponential processes:
T/F
They are useful when considering the mechanisms of physiological action potentials
True. Many of the processes surrounding the action potential relate to the difference in charges across the membrane and the capacitance of the cell; they are exponential.
Regarding the time constant, the rate constant and half-life:
T/F
The time constant, tau, is the time taken for the initial value to fall by e
False. The time constant is the time to fall to 1/e or 1/eth of the original value.
Regarding the time constant, the rate constant and half-life:
T/F
The half-life is never longer than the time constant
True. Since the half-life is the time to fall to 50% of the original value and time constant is the time to fall to 37% of the original value , the time constant must be greater.
Regarding the time constant, the rate constant and half-life:
T/F
The rate constant never has any units
False. The clue is in the phrase ‘rate constant’, the units must therefore be the units of rate i.e. per second (S-1).
Regarding the time constant, the rate constant and half-life:
T/F
The half-life is half the time constant
False. The half-life is 0.693 Tau i.e. roughly 2/3 of the time constant
Regarding the time constant, the rate constant and half-life:
T/F
It is necessary to know both the rate constant and the time constant to be able to plot an accurate graph of the function
False. You only need one of the constants to describe the graph, they are all mathematically related.
Regarding τ, k and t1/2:
T/F
τ is the time taken for the initial value to fall by e
False. τ is the time to fall to 1/e or 1/eth of the original value. Go back to page 20 for the three definitions.
Regarding τ, k and t1/2:
T/F
t1/2 is never longer than the time constant
True. Since t1/2 is the time taken to fall to 50% of the original value and τ is the time taken to fall to 37% of the original value, τ must be greater
Regarding τ, k and t1/2:
T/F
k never has any units
False. The clue is in the phrase ‘rate constant’, the units must be the units of rate i.e. per second (S-1).
Regarding τ, k and t1/2:
T/F
t1/2 is half of τ
False. The t1/2 is 0.693 τ i.e. roughly 2/3 of τ.
Regarding τ, k and t1/2:
T/F
It is necessary to know both k and τ to be able to plot an accurate graph of the function
False. You only need one of the constants to describe the graph, they are all mathematically related.
With regard to exponential drug elimination:
T/F
37% of the process is complete in one τ
False. The process is 63% complete in one τ
With regard to exponential drug elimination:
T/F
A bigger k describes a steeper fall in concentration
True. A bigger k describes a bigger slope/height ratio for the graph i.e. a steeper fall
With regard to exponential drug elimination:
τ is equal to t1/2 x 0.693
T/F
False. It is the other way round. t1/2 = 0.693 x τ.
With regard to exponential drug elimination:
T/F
t1/2 is directly proportional to k
False. t1/2 is inversely proportional k.
With regard to exponential drug elimination:
T/F
After three x τ the process is 95% complete
True. After one τ a process is 63% complete.
After two τ 63% + 63% of the 37% which remains = 86.3% complete.
After three τ 86.3% + 63% of the 13.7% which remains = 94.9% complete.
With regard to exponential drug elimination:
T/F
Taking logarithms of the time axis transforms the graph into a straight line
False. To achieve a straight line, you take natural logarithms of the concentration axis, not the time axis.
With regard to exponential drug elimination:
T/F
τ is the reciprocal of the elimination k
True. τ and elimination k are inversely related; if you plot τ against k you get a rectangular hyperbola.
With regard to exponential drug elimination:
T/F
τ is the time taken for the variable to reach 1/e of its initial value
True. This is one of the three definitions given; the other two are to reach 37% of original value or the initial concentration’s tangential intersection with the time axis.
With regard to exponential drug elimination:
T/F
Three t1/2 is the time required for the variable to fall to 12.5% of its original value
True. In one t1/2 the variable falls to half. In two t1/2 the variable falls by 50% + 50% of 50% = 75%. In three t1/2 the variable falls by 75% + 50% of 25% = 87.5% which leaves only 12.5% of the original concentration.
With regard to exponential drug elimination:
T/F
The graph shows asymptotes on both axes
False. There is only a single asymptote which is to the Time axis.
Regarding drug clearance
T/F
It is the volume of plasma that is cleared of a drug per unit time
True. This is the definition.
Regarding drug clearance
T/F
Correct units include ml/kg/min and litre/min
True. The units of clearance are ‘volume per time’ or, if looking at clearance per kg body weight, then ‘volume per time per kg’.
Regarding drug clearance
T/F
It cannot be greater than liver blood flow
False. For drugs that have some extra-hepatic metabolism such as propofol, this can occur
Regarding drug clearance
T/F
It is closely related to t1/2
False. Cl is determined by both Vd and the shape of the elimination curve for the drug
Regarding drug clearance
T/F
It is the volume of distribution divided by the τ
True. This is one of definitions.
Regarding the volume of distribution
T/F
The initial Vd for propofol is large
True. The initial Vd of propofol is variously described by the different models, Schnider 4.27 L and Marsh 15.9 L.
Regarding the volume of distribution
T/F
The Vd of a drug can be greater than the volume of the body
True. Vd is a virtual concept, it can be much larger than body volume - see diagram on Marsh model.
Regarding the volume of distribution
T/F
Vd = Cl/elimination k
False. This is a way of showing how clearance links Vd and the exponential wash out curve
Regarding the volume of distribution
T/F
Correct units include kg/litre and litres
False. Units must be units of volume or in scientific papers, units of volume/kg of body mass - the first of these units is the ‘wrong way round’.
Regarding the volume of distribution
T/F
It can be calculated by using a drug infusion if the half-life and steady state drug concentration is known
True. You do not need to know t1/2 for this method and do need to know Cl.
The rate of drug absorption from the stomach is:
lower for fentanyl than diclofenac
True
The rate of drug absorption from the stomach is:
greater for weak acids than weak bases for drugs with a pKa of 6
True
The rate of drug absorption from the stomach is:
increased in the presence of metoclopromide
False
The rate of drug absorption from the stomach is:
always increased by omeprazole
False
The rate of drug absorption from the stomach is:
less important than absorption from the small intestine for most oral medication
True
When considering absorption of drugs from the GI tract:
fentanyl is better absorbed from the small intestine than the stomach
True
When considering absorption of drugs from the GI tract:
thiopental cannot be given through the GI tract route
False
When considering absorption of drugs from the GI tract:
atracurium cannot be given orally
True
When considering absorption of drugs from the GI tract:
neostigmine is better absorbed than physostigmine
False
When considering absorption of drugs from the GI tract:
ketoconazole absorption is increased in patients taking omeprazole
False
Which of the following drugs bind more to alpha-1 acid glycoprotein than to albumin?
diazepam
False
Which of the following drugs bind more to alpha-1 acid glycoprotein than to albumin?
fentanyl
True
Which of the following drugs bind more to alpha-1 acid glycoprotein than to albumin?
phenytoin
True
Which of the following drugs bind more to alpha-1 acid glycoprotein than to albumin?
ibuprofen
False
Which of the following drugs bind more to alpha-1 acid glycoprotein than to albumin?
lidocaine
True
Which of the following are true of plasma protein binding of therapeutic drugs?
Displacement of protein-bound drug by a second drug will necessarily cause toxic effects
False
Which of the following are true of plasma protein binding of therapeutic drugs?
Drugs with a low hepatic extraction ratio and high degree of protein binding are most affected by changes in protein binding
True
Which of the following are true of plasma protein binding of therapeutic drugs?
Drugs that show flow-dependent hepatic extraction are unaffected by changes in protein binding
True
Which of the following are true of plasma protein binding of therapeutic drugs?
The interaction between amiodarone and wafarin is entirely due to competition for plasma protein binding sites
False
Which of the following are true of plasma protein binding of therapeutic drugs?
The renal filtration of a drug is increased when plasma protein binding is decreased
True
Regarding the distribution of the drugs through the body:
the volume of dstribution at steady state for a drug is dependent only on its lipid solubility
False
Regarding the distribution of the drugs through the body:
in a one-compartment model, volume of distribution is directly proportional to drug clearance
True
Regarding the distribution of the drugs through the body:
drugs with greater than 95% protein binding have a realtively small volume of distribution
False
Regarding the distribution of the drugs through the body:
volume of distribution at a steady state is approximately equal to total body water for most drugs
False
Regarding the distribution of the drugs through the body:
Non-depolarising muscle relaxants have smaller volume of distribution than induction agents
True
Which of the following describe the distribution of propofol?
It has a volume of distribution of approximately 1.4L/Kg
False
Which of the following describe the distribution of propofol?
It is an acidic drug so binds albumin in plasma
True
Which of the following describe the distribution of propofol?
The volume of distribution is very large as it is essentially unionized at plasma pH
True
Which of the following describe the distribution of propofol?
the initial volume of distribution in adults is age-dependant
False
Which of the following describe the distribution of propofol?
The volume of distribution is high because propofol is highly protein bound
False
Which of the following are metabolites of atracurium?
cisatracurium
False
Which of the following are metabolites of atracurium?
desmethylatracurium
False
Which of the following are metabolites of atracurium?
laudanosine
True
Which of the following are metabolites of atracurium?
3,17-dihydroxy atracurium
False
Which of the following are metabolites of atracurium?
a monoquarternary alcohol derivative
True
Which of the following enzymes demonstrate important pharmacogenetic variation?
CYP2E1
False
Which of the following enzymes demonstrate important pharmacogenetic variation?
CYP2D6
True
Which of the following enzymes demonstrate important pharmacogenetic variation?
CYP3A5
False
Which of the following enzymes demonstrate important pharmacogenetic variation?
CYP2C9
Trua
Which of the following enzymes demonstrate important pharmacogenetic variation?
CTP1A2
False
Which of the following drugs have an oral bioavailability of more than 75%?
Aspirin
False
Which of the following drugs have an oral bioavailability of more than 75%?
Paracetamol
True
Which of the following drugs have an oral bioavailability of more than 75%?
Oramorph
False
Which of the following drugs have an oral bioavailability of more than 75%?
diclofenac
False
Which of the following drugs have an oral bioavailability of more than 75%?
ibuprofen
True
Which of the following routes of elimination are the major route of the named drug?
lungs, sevoflurane
True
Which of the following routes of elimination are the major route of the named drug?
renal, benzylpenicillin
True
Which of the following routes of elimination are the major route of the named drug?
red cell esterases, esmolol
True
Which of the following routes of elimination are the major route of the named drug?
tissue esterases, remifentanil
True
Which of the following routes of elimination are the major route of the named drug?
non-enzymatic plasma degradation, mivacurium
False
In a one-compartment model for the kinetics of a drug:
The volume of distribution at steady state can be calculated using a single bolus dose of drug
True
In a one-compartment model for the kinetics of a drug:
if volume of distribution stays the same, clearance increases if the time constant increases
True
In a one-compartment model for the kinetics of a drug:
the context sensitive half life is proportional to the duration of an infusion
False
In a one-compartment model for the kinetics of a drug:
After giving an IV bolus dose, the rate of elimination at a particular time is dependent only on the clearance
False
In a one-compartment model for the kinetics of a drug:
the behaviour of the drug can be predicted as long as the clearance is known
False
If a drug given by continuous IV infusion behaves according to a 3 compartment model:
The volume of distribution at a steady state is the most important determinant of the variability of the context sensitive half time
False
If a drug given by continuous IV infusion behaves according to a 3 compartment model:
the second compartment has 3 rate constants associated with it
False
If a drug given by continuous IV infusion behaves according to a 3 compartment model:
it the plasma level has reached steady state, then clearance out of the body can be calculated from the infusion rate and concentration
True
If a drug given by continuous IV infusion behaves according to a 3 compartment model:
drug can be removed from the system from any of the 3 compartments
False
If a drug given by continuous IV infusion behaves according to a 3 compartment model:
the effect compartment equilibrates with the central compartment
True
When considering elimination of drug from the body:
the rate of elimination is equal to the clearance
False
When considering elimination of drug from the body:
if glomerular filtration rate doubles, then the amount of free drug excreted through urine also doubles
False
When considering elimination of drug from the body:
CYP450 enzymes are found only in hepatocytes
False
When considering elimination of drug from the body:
hepatic enzymes involved in xenobiotic metabolism are exclusively associated with the smooth endoplasmic reticulum
False
When considering elimination of drug from the body:
more than 99% of the drug will have been eliminated after 3 half lives
False
For a simple one-compartment model:
The half life is longer than the time contant
False
For a simple one-compartment model:
the rate constant for elimination is found from the slope of the graph that plots log(concentration) against time
True
For a simple one-compartment model:
the clearance is the ratio of the volume of distribution to the time constant
True
For a simple one-compartment model:
The volume of distribution multiplied by the rate constant for elimination divided by plasma concentration is equal to the clearance
False
For a simple one-compartment model:
The shape of the curve that describes the rise of drug concentration with time on starting a constant rate infusion is a negative exponential
True
In patients with hepatic failure and ascites
The volume of distribution for hydrophilic drugs is reduces
False
In patients with hepatic failure and ascites
the metabolism of all drugs is reduced
False
In patients with hepatic failure and ascites
The bioavailability of drugs with a moderate hepatic extraction ratio is increased
True
In patients with hepatic failure and ascites
The terminal elimination half-life for remifentanil is unaffected
True
In patients with hepatic failure and ascites
the dose of non-depolarising muscle relaxants required for intubation is increased
True
Which of the following will increase hepatic extraction of propofol?
dobutamine
True
Which of the following will increase hepatic extraction of propofol?
ciprofloxacin
False
Which of the following will increase hepatic extraction of propofol?
carbamezepine
False
Which of the following will increase hepatic extraction of propofol?
noradrenaline
False
Which of the following will increase hepatic extraction of propofol?
Chronic alcohol intake
False
A mammilary 3 compartment model used to model effect-site targeting of drug concentration
elimination occurs from the effect sire
False
A mammilary 3 compartment model used to model effect-site targeting of drug concentration
the volume of the effect site is not included in the volume of distribution at steady state
True
A mammilary 3 compartment model used to model effect-site targeting of drug concentration
there are two inter-compartmental clearances included in the model
True
A mammilary 3 compartment model used to model effect-site targeting of drug concentration
the t1/2keo describes the rate of equilibration between plasma and effect compartments
True
A mammilary 3 compartment model used to model effect-site targeting of drug concentration
clearance from the system can be found from steady state infusion rate and plasma concentration
True
When measuring bioavailability:
drug behaviour must be fitted to a known model in order to calculate bioavailability
False
When measuring bioavailability:
bioavailability refers only to oral compared with IV administration
False
When measuring bioavailability:
oral bioavailability can be found by dividing clearance of the drug when given orally by the clearance found when given IV
False
When measuring bioavailability:
The same dose of drug must be given orally and IV to find oral bioavailability
True
When measuring bioavailability:
interindividual variability must be expected
True
Which of the listed drugs have a volume of distribution at steady state grater then total body water?
cisatracurium
False
Which of the listed drugs have a volume of distribution at steady state grater then total body water?
neostigmine
False
Which of the listed drugs have a volume of distribution at steady state grater then total body water?
Atropine
True
Which of the listed drugs have a volume of distribution at steady state grater then total body water?
noradrenaline
False
Which of the listed drugs have a volume of distribution at steady state grater then total body water?
sevoflurane
True
Which of the following drugs readily cross the placenta?
S-bupivicaine
True
Which of the following drugs readily cross the placenta?
diazepam
True
Which of the following drugs readily cross the placenta?
fentanyl
True
Which of the following drugs readily cross the placenta?
succinylcholine
False
Which of the following drugs readily cross the placenta?
isoflurane
True
The following are true regarding Volume of Distribution (Vd):
It is the amount of drug that distributes following administration
False. It is the volume that a drug distributes into following administration.
The following are true regarding Volume of Distribution (Vd):
Can be greater than total body water
True. TBW = 42L whilst Vd can be up to 1000L.
The following are true regarding Volume of Distribution (Vd):
Is measured in kg/L
False. It is measured in L/Kg.
The following are true regarding Volume of Distribution (Vd):
Is a constant for a given drug
True
The following are true regarding Volume of Distribution (Vd):
The following are true regarding Volume of Distribution (Vd):
False. Vd = Clearance x Time Constant.
Context sensitive half-time:
Is a decrement time
True. Decrement time = the time taken of the plasma level for a drug to fall to a specified value (Context-Sensitive Half-Time is 50%).
Context sensitive half-time:
Shares a constant relationship with elimination half-life
False. There is no such relation.
Context sensitive half-time:
Varies with duration of drug infusion
True. This is the ‘context’.
Context sensitive half-time:
Is reliably used to describe time for recovery
False. It is the time for the plasma levels to fall to 50% of the value when the infusion is stopped.
Context sensitive half-time:
Reflects the combined effects of absorption and distribution
False. It reflects the combined effects of distribution and metabolism.
The following influence Volume of Distribution (Vd):
Regional blood flow
True
The following influence Volume of Distribution (Vd):
Lipid solubility
True
The following influence Volume of Distribution (Vd):
Degree of tissue protein binding
True
The following influence Volume of Distribution (Vd):
Degree of plasma protein binding
True
The following influence Volume of Distribution (Vd):
Degree of ionisation
True
Infusion kinetics:
It takes 5 half-times to reach steady state concentration
False. It takes 5 Half-lives to reach steady state concentration.
Infusion kinetics:
Steady state volume of distribution is dependent on lipid solubility and molecular weight
False. Steady state volume of distribution is dependent on lipid solubility and clearance.
Infusion kinetics:
Loading Dose = Vd x Desired Plasma Concentration
True
Infusion kinetics:
Maintenance Dose = Steady State Vd x Clearance
False. Maintenance Dose = Steady State Concentration x Clearance.
Infusion kinetics:
Clearance = Input (mg/min) x Plasma Concentration (mg/ml)
False. In infusion kinetics at steady state Input = Elimination
Input (mg/min) is therefore equal to Clearance (ml/min) x Plasma Concentration (mg/min)
Therefore:
Clearance = Input (mg/min) / Plasma Concentration (mg/ml)
The following statements are true of Cytochrome P450 enzyme isoforms:
CYP2E1 is involved in metabolism of paracetamol
True
The following statements are true of Cytochrome P450 enzyme isoforms:
CYP3A4 is involved in metabolism of phenytoin
False. CYP3A4 is important in the metabolism of both midazolam and alfentanil.
The following statements are true of Cytochrome P450 enzyme isoforms:
Are only found in the liver
False. CYP2E1 is found in the kidneys.
The following statements are true of Cytochrome P450 enzyme isoforms:
Account for most phase 2 reactions
False. Account for most phase 1 reactions.
The following statements are true of Cytochrome P450 enzyme isoforms:
CYP2E1 is involved in the metabolism of chloride containing volatile agents
False. CYP2E1 is involved in the metabolism of fluoride containing volatile agents.
The following are enzyme inducers:
Rifampicin
True
The following are enzyme inducers:
Metronidazole
False it is an enzyme inhibitor
The following are enzyme inducers:
Acute alcohol use
False. Acute alcohol use inhibits whilst chronic use induces.
The following are enzyme inducers:
Carbemazepine
True
The following are enzyme inducers:
Chloramphenicol
False. It is an enzyme inhibitor.
Phase 2 reactions include:
Oxidation
False. This is a Phase I reaction.
Phase 2 reactions include:
Acetylation
True
Phase 2 reactions include:
Sulphation
True
Phase 2 reactions include:
Hydrolysis
False. This is a Phase I reaction.
Phase 2 reactions include:
Glucuronidation
True
Elimination:
Can only be by either distribution or metabolism
False. Can also be by excretion.
Elimination:
In 1st order kinetics, half-life is constant
True
Elimination:
In 1st order kinetics, a constant amount of drug is eliminated per unit time
False. A constant proportion is eliminated per unit time.
Elimination:
Zero order kinetics is a linear process
False. Zero order kinetics is also known as non-linear kinetics.
Elimination:
In zero order kinetics, half-life increases with dose administered
True
Hepatic clearance:
A drug with a high extraction ratio is not affected by protein binding
True. It is not affected by enzyme level either.
Hepatic clearance:
Lignocaine is an example of an enzyme limited drug
False. Lignocaine has a high extraction ratio (>0.7) and is therefore flow / perfusion limited (as opposed to enzyme / capacity limited).
Hepatic clearance:
High extraction ratio implies significant 1st pass metabolism
True. Most of the drug is extracted on the first pass through the liver, hence why changes in hepatic blood flow can drastically affect clearance.
Hepatic clearance:
Enzyme induction / inhibition can profoundly affect the clearance of drugs with a low extraction ratio
True. Drugs with a low extraction ratio are enzyme / capacity limited drugs.
Hepatic clearance:
Warfarin is an example of an enzyme limited drug
True. As are phenytoin, theophylline and most benzodiazepines and barbituates.
Bioavailability:
Of drugs administered via the IV route can be as high as 90%
False. IV drug administration provides 100% bioavailability.
Bioavailability:
Is the fraction of administered drug that reaches systemic circulaiton
True
Bioavailability:
Glycopyrrolate has >80% bioavailability
False. Glycopyrrolates bioavailability is < 5%.
Bioavailability:
Is influenced by genetics
True. There are phenotypic variations in bioavailability.
Bioavailability:
Is influenced by circadian rhythm
True
