What is pharmocokinetics?
What the body does to the drug
What the drug does to the body
Mechanism of actions of the drug
An method of calculating what the dose of the drug should be
How the drug is excreted from the body
Which of the following are included in pharmocokinetics?
Absorption
Distribution
Metabolism
Excretion
Mechanism of Action
Which of the following describes absorption in terms of pharmocokintetics?
How quickly and by what means the unchanged drug gets into the body
How and where the drug moves among fluids and tissues
Transformation of the drug into daughter compounds
Removal of a drug or metabolite from the body
What best describes the term distribution in relation to pharmocokinetics?
Transformation of a drug into daughter compounds
What description best describes the term metabolism in relation to pharmocokintetics?
Which description best describes the term excretion in relation to pharmocokinetics?
Why is pharmocokinetics important?
Safe use of medicines by doctors
Designing dosing regimes
Monitoring treatment compliance
Substance abuse monitoring
Medicine licensing requirements
Ensuring the medicine has the correct mechanism of action
What is the main reason that drugs are withdrawn from development?
Pharmocokinetics (undesirable effects on the body)
Commercial reasons
Lack of efficacy
Animal toxicity
In what circumstance do drugs not need to be absorbed into the body?
When they are injected straight into the blood
When they act on the stomach or intestines
When they act on where they are excreted
When they are only being used for clinical trials
When the dose of the drug needs to be really small
What is bio-availability?
The percentage of administered drug that enters the circulation
The proportion of cells within the body that the drug will affect
The proportion of cells within the body that the drug will enter
The percentage of administered drug that is absorbed in the stomach
The percentage of administered drug that is absorbed in the intestines
Which route of administration has the highest bio-availability?
Intravenous injection
Oral
Inhalation
Subcutaneous injection
Intramuscular injection
What is the bio-availability of a drug that is administered intravenously?
100%
99%
75%
90%
82%
Why aren't all drugs given by intravenous injection?
It's inconvenient
It requires a hospital setting
It's more expensive
It causes more side effects
The high bio-availability can cause toxicity when using some drugs
Why is the inhalation of a drug a good route of administration in conditions like asthma?
Because the drug goes straight to the site of action
Because it decreases the side effects
Because it is non-invasive
Because it prevents the drug being metabolized by the liver prior to reaching the tissues
What are some disadvantages of giving drugs orally?
They may metabolized by the liver before they reach the target tissue
The bio-availability is unlikely to be 100%
They cannot be absorbed in the stomach
It makes the drug harder to excrete
It leads to more side effects
What will increase the diffuse of drugs into the bloodstream?
Increased surface area to diffuse across
Increased concentration of the drug
Decreased surface area to diffuse across
Decreased concentration of the drug
Which type of absorption is most common?
Transcellular absorption
Paracellular absorption
What will be a problem if a drug is too lipophilic?
It will remain within the cell membrane instead of passing through it
It will not pass through the cell membrane
It will have more side effects
It is likely to have animal toxicity
What is permeability determined by?
How lipophilic the solute is
The size of the solute
Whether or not the solute is charged
The pH of the particle when it dissolves in the solution
The surface area available for diffusion to take place across
Where are acidic drugs most likely to be absorbed?
Stomach
Intestines
Liver
Where are basic drugs most likely to be absorbed?
Why are drugs often weak acids or weak bases?
It allows ion trapping
It allows them to be water soluble and lipophilic
It means they have a higher efficacy
It means they will have less side effects
It allows them to pass through cell membranes more easily
What state are acidic or basic drugs in when they pass through cell membranes?
Ionized
Unionized
Metabolized
Why are acidic drugs more likely to be absorbed in the stomach?
Because the stomach is acidic and they will be unionized so can move through the cell membrane
Because the stomach is basic and they will be unionized so can move through the cell membrane
Because the stomach is acidic and they will be ionized so can move through the cell membrane
Because the stomach is basic and they will ionized so can move through the cell membrane
What is ion trapping?
The prevention of ions leaving the bloodstream once they have been absorbed
The prevention of ions leaving the stomach or intestines because they are unable to be absorbed
The trapping of ions within the liver because they may be harmful to the body
What allows ion trapping to occur?
The pH of the stomach being ~1 and the bloodstream being ~7.4
The pH of the stomach being ~7.4 and the bloodstream being ~1
The stomach having a higher concentration of potassium than the bloodstream
The bloodstream having a higher concentration of potassium than the stomach
Which drugs are likely to be absorbed most quickly?
Acidic drugs
Basic drugs
Drugs that are neither acidic or basic
What makes up for the fact that basic drugs cannot be absorbed in the stomach?
The high surface area in the intestines
They have a higher efficacy than acidic drugs
They have a higher bio-availability than acidic drugs
Where will aspirin be absorbed?
What is the Lipinski rule?
A method of predicting the likelihood of a successful development of a drug
A method of predicting where a drug is most likely to be absorbed
A method of predicting the efficacy of a drug
A method of predicting the side effects of a drug
A method of calculating the appropriate dose of a drug
What are the Lipinski rules?
Molecular weight > 500
No more than 5 H-bond donors
No less than 10 H-bond acceptors
Log(partition coefficient) < 5
What is a partition coefficient?
How lipophilic a drugs is
How likely a drug is likely to be absorbed
How toxic a drug is
Another term for the bio-availability of a drug
Where will a drug move to most quickly?
A well-perfused muscle
A poorly-perfused area of adipose tissue
We assume the concentration of a drug is proportional to the concentration at the site of action. True or false?
Most drugs follow...
First order kinetics
Zero order kinetics
Second order kinetics
Which of the following describe first order kinetics?
The half life of the drug is constant
When the dose of the drug is increased the same fraction of the drug is removed
A constant volume of the drug is removed
The bigger the dose the longer it takes to remove it
Which is most desirable for clinically used drugs?
Which of the following are true about zero order drugs?
The half-life of the drug is constant
If you increase the drug dose the same fraction of drug is removed
The larger the dose of the drug the longer it will take to remove it
If there is only a small dose it will follow first order kinetics
If there is only a small dose of a drug it will follow second order kinetics
Alcohol is a zero order drug. True or false?
Why are zero order drugs dangerous?
Because there is saturation of the metabolic pathways
Because the drug has a lower efficacy
Because the drug will be more slowly removed
Because there will be more side effects
What is volume of distribution?
The volume of plasma that would be necessary to account for the total amount of drug in the patients body, if the drug was were present throughout the body at the same concentration as in the plasma
The concentration of the drug in the plasma, which is used to estimate the concentration of the drug at it's site of action
The volume of plasma required to dilute the drug to the necessary concentration to have the desired pharmacological effect on the body
What is the formula for volume of distribution (Vd)?
Vd = total amount of drug/concentration of drug in plasma
Vd = concentration of drug in plasma/total amount of drug
Vd = concentration of drug in bloodstream/total amount of drug
Vd = total amount of drug/concentration of drug at site of action
What is volume of distribution useful for?
Calculating the loading dose required for desired blood concentration
Estimating blood concentration in the treatment of overdose
Calculating the amount of time required between each dose of the drug
Estimating the percentage of the drug that is at the site of action
What is plasma clearance?
The volume of plasma cleared of the drug per unit of time
The percentage of drug cleared from the plasma per unit time
The percentage of plasma cleared of the drug per unit time
What is the equation for the plasma clearance of drugs?
Clearance = rate of elimination/concentration of drug in plasma
Clearance = concentration of drug in plasma/rate of elimination
Clearance = rate of elimination x concentration of drug in plasma
Which drugs will have a constant plasma clearance?
First order drugs
Zero order drugs
Second order drugs
How is bio-availability measured?
The fraction of drug in circulation compared to the dose
The volume of drug in circulation
The percentage of drug that is absorbed in the stomach
The percentage of drug that reaches the desired site of action
Which method of administration is used to calculate the bio-availability of a drug using a different method of administration?
What might cause poor bio-availability?
Poor absorption
Chemical reactions at the site of delivery
First pass metabolism
Chemical reaction at the site of action
The drug being acidic
What is first pass metabolism?
When the concentration of the drug is greatly reduced before it reaches the systemic circulation
When the concentration of the drug is greatly reduced before it reaches the pulmonary circulation
When the half-life of the drug is very short the very little drug reaches the site of action
Which route of administration will lead to the lowest concentration of drug in the circulation?
Intravenous
Subcutaneous
Intramuscular
What is multiple dosing designed to achieve?
A "steady state"
The least side effects
The highest bio-availability
The highest efficacy
There a no fluctuations in the concentration of drug once it has reached its "steady state" following multiple doses. True or false?
When using multiple dosing, when should the next dose of the drug be given to ensure a "steady state" is reached?
Before the concentration of the drug falls to zero
After the concentration of the drug has fallen to zero
After the first half life
After two half lives
What does the time taken for the drug to reach a "steady state" depend on?
The drugs half life
The drugs efficacy
The drugs bio-availability
How long does it typically take for the "steady state" to be achieved?
4-5 half lives
1 half life
1-2 half lives
A variable amount of half lives
Where can drug metabolism occur?
Site of administration
Site of action
Bloodstream
When does drug metabolism and excretion begin to occur?
Immediately
After one half life
It is impossible to tell
What is metabolism typically designed to do?
Make the drug easier to excrete
Reduce the side effects of the drug
Increase the amount of time the drug remains in the body
Prevent the drugs from being absorbed in the stomach
Give an example of a drug that is eliminated by the body without being metabolized?
Digoxin
Enalapril
Paracetamol
Alcohol
All drug metabolites are inactive. True or false?
How many phases are there to drug metabolism?
2
3
4
5
What happens during phase 1 of drug metabolism?
Introduction of chemically reactive groups
A increase in the water solubility of the drug for excretion
Removal of reactive groups from the drug
Ionization of the drug to prevent it from crossing cell memebranes
Where does phase 1 of drug metabolism usually take place?
In the liver
In the bloodstream
In the kidneys
At the site of action
What enzyme is usually involved in phase 1 of drug metabolism?
Cytochrome P450
Lipases
DNA polymerases
Amylase
What usually occurs during phase 2 of drug metabolism?
Conjugation of the drug with endogenous compounds
Addition of reactive groups to the molecule
Oxidation of the molecule
Hydrolysis of any hydrogen bonds within the molecule
Which drug is metabolised with phase 2 taking place before phase 1?
Which phase of paracetamol metabolism produces a toxic compound?
Phase 1
Phase 2
Why is paracetamol more likely to cause problems in alcoholics than in the general population?
Because alcoholics have more cytochrome P450 so phase 1 is more likely to occur
Because alcoholics have no cytochrome P450 so the toxic compound is readily produced
Because alcoholics lack thyamine which is a co-enzyme for the phase 2 part of paracetamol metabolism
Only unbound drugs can be excreted. True or false?
Which drugs are likely to be excreted more slowly?
Lipophilic drugs
Hydrophilic drugs
Why are lipophilic drugs likely to excreted more slowly?
Because they are likely to be reabsorbed
Because they cannot be filtered through the glomerulus
Because they are usually bigger
Because they are not secreted into the tubules
All drugs can be secreted into the renal tubules from the bloodstream. True or false?
What sort of process is tubular secretion in terms of drug elimination?
Active process requiring a carrier molecule
Passive process requiring an activated protein channel
Active process without a carrier molecule
Passive diffusion through the membrane
If renal clearance is slow, the plasma half-life of the drug will be...?
Longer
Shorter
Unchanged
Why can age affect drug metabolism and excretion?
Cytochrome P450 is less efficient in neonates
GFR is increased in elderly people
Increased percentage of fat in elderly people decreases excretion of lipophilic drugs
Cytochrome P450 is less efficient in elderly people
What disease is most likely to affect the pharmocokinetics of a drug?
Renal disease
Heart disease
Parkinson's disease
Learning difficulties
Which is the most common type of adverse drug reaction?
Type A
Type B
Which of the following describe type A drug reactions?
Reaction related to known drug mechanisms
Predictable
Unavoidable
Which of the following may cause type A drug reactions?
Wrong dose administered
Drug interactions
High therapeutic index of the drug
Immunological mechanisms
Which of the following describe a type 2 drug reaction?
Related to unknown mechanisms of the drug
Unexpected
Related to patient individuality
What is a drawback of the yellow form for monitoring adverse drug reactions?
It relies on doctors and patients self-reporting
It is only accessible to doctors
It only reports on one drug at a time
It does not monitor drugs throughout their whole lifetime
What is usually added to the yellow form when more information is required about a drug?
Black triangle
Green form
A priority index number
A warning about the drug from the BNF
What is a benefit of the green form?
It is used to record all significant events, not just adverse effects of a drug
It is easily accessible by all
It is compulsory to fill it in when an adverse reaction occurs
It is clearly visible in a copy of every BNF
