Flashcards in Pharmacokinetics Deck (49):
Why doesn't eating a poisoned animal kill you?
Poison is highly ionised drug so cannot be absorbed into the bloodstream
Origin, nature, chemistry, effects and uses of drugs
Study of the adverse effects of chemical, physical or biological agents
What the drug does to the body
What the body does to the drug
List the 4(/5) stages of pharmacokinetics.
List the 7 different types of drug administration.
Sublingual (under the tongue)
Transdermal (directly onto the skin)
Give the advantages and disadvantages of oral drug administration.
First pass effect
Many variables & barriers
Give the advantages and disadvantages of sublingual drug administration.
No first pass effect
Small dose limit
Give the advantages and disadvantages of inhalation drug administration.
Fast, rapid delivery to blood
Requires special drug properties (e.g. atomised, vaporised)
Give the advantages and disadvantages of topical drug administration.
Give the advantages and disadvantages of transdermal drug administration.
Skin is a very effective barrier
Give the advantages and disadvantages of intramuscular drug administration.
Rapid for aqueous, slow for oil
Requires trained personnel
Give the advantages and disadvantages of intravenous drug administration.
What is the meaning of bioavailability?
The fraction of unchanged drug that reaches the systemic circulation
Which method of drug administration gives 100% bioavailability?
There are four ways in which small molecules cross cell membranes - name them.
Diffusion directly through phospholipid bilayer
Diffusion through aqueous pores
Transmembrane carrier proteins
Describe the solubility of hydrophilic drugs.
Soluble in aqueous, polar media
Describe the solubility of lipophilic drugs.
Soluble in fats & non polar solutions
What can you say about the lipid solubility of ionised drugs?
Low lipid solubility
Which range of pH do many drugs fit into?
Weak acids or weak bases
What are the main drug properties affecting absorption?
Name some factors that affect drug distribution.
Degree of ionisation
pH of compartments
Cardiac output & blood flow
Plasma protein binding
What does the compartment model state?
Some drugs occupy a single, well stirred compartment with a set volume, but some can occupy a peripheral compartment in addition
Why is having a high affinity for calcium an advantageous feature of the phosphonate group in bisphosphonates?
The drug can be quickly distributed to the skeleton
What factor can cause large increases in free drug concentrations
Competition for binding sites
Is it the bound drug or unbound drug concentration that has the pharmacological effect on the body?
Warfarin binds to albumin. As a percentage, how much of the drug is bound and how much is free to act?
In the presence however of aspirin, more like 2-4% of warfarin is left to act on the body. Why is this?
Aspirin has a high affinity for albumin
List the body fluid compartments and the relative percentages of drugs present in each.
Trans-cellular water: 2%
Plasma water: 5%
Interstitial water: 16%
Intracellular water: 35%
Where does drug metabolism generally occur?
What are the two phases of drug metabolism?
Phase 1: oxidation, reduction or hydrolysis creating reactive products used in phase 2...
Phase 2: synthetic, conjugative reactions generating hydrophilic, inactive compounds
What do monooxygenases do?
They are enzymes that add (a) hydroxyl group(s) to a compound/molecule.
Give an example of a group of enzymes that are members of the monooxygenase family.
Cytochrome P450 Enzymes
How do these monooxygenase enzymes act on paracetamol?
Cytochrome P450 enzymes metabolise a small proportion of the paracetamol drug into a toxic metabolite
What is the effect on warfarin if the concentration of enzyme metabolising it (CYP450) is increased?
The effectiveness of the warfarin drug decreases due to the fact that the drug is being metabolised
What is the drug simvastatin metabolised by and where does this occur?
The gut wall and the liver
What increases the expression of CYP450s?
What is meant by the first pass effect?
The concentration of a drug is greatly reduced before it reaches the systemic circulation
What does grapefruit juice do?
List onset, duration and metabolism/elimination for Vecuronium.
Liver - eliminated via urine & bile
List onset, duration and metabolism/elimination for Atracurium.
Spontaneous degradation in plasma
List onset, duration and metabolism/elimination for Mivacurium.
What is the 'aim' of drug metabolism?
To produce metabolites that can be excreted
Barring elimination from the lungs, which type of drugs are eliminated more readily: hydrophilic drugs or lipophilic drugs?
List some possible sources of excretion of drug metabolites.
What happens to plasma drug concentration during IV infusion?
Increases until rate of input equals rate of output - reaches a 'steady state'
What is meant by 'T max'?
The amount of time that a drug is present at maximum concentration in the plasma/in serum