pharmacokinetics 1 Flashcards
define pharmacology
The origin, nature, chemistry, effects and uses of drugs
define toxicolgy
The study of the adverse effects of chemical, physical or biological agents
define pharmacodynamics
What the drug does to the body - interaction with the receptors
define pharmacokinetics
What the body does to the drug
list 5 important uses in understanding pharmacokinetics?
- How dose recommendations in inserts are arrived at
- to identify possible drug interactions
- To adjust strategies such as Therapeutic Dose Monitoring
- To safely administer drugs when urgency is required
- to predict the influence of disease on drugs
what are the 5 steps of pharmacokinetics? (LADME)
- (Liberation) - preparation of the drug
- Absorption - want most drugs to favour absorption, however minimising absorption is sometimes wanted
- Distribution - bringing the drug from plasma to the source, target organ/tissues
- Metabolism - how the body transforms drugs
- Excretion - how the drug is ultimately removed
what are the 7 routes of drug administration?
oral
sublingual
inhalation
topical
transdermal
intramuscular
intravenous
what are the advantages and disadvantages of oral administration?
advantages: convenient
disadvantages: first-pass effect, many variables and barriers
what are the advantages and disadvantages of sublingual administration?
advantages: no first-pass effect
disadvantages: inconvenient, small dose limit, taste
what are the advantages and disadvantages of inhalation administration?
advantages: fast, rapid delivery to blood
disadvantages: requires special properties of drug (e.g atomised, vapourised)
what are the advantages and disadvantages of topical administration?
advantages: convenient, localised
disadvantages: only local
what are the advantages and disadvantages of transdermal administration?
advantages: prolonged release
disadvantages: skin is a very effective barrier
what are the advantages and disadvantages of intramuscular administration?
advantages: rapid for aqueous, slow for oil
disadvantages: painful, requires trained personnel
what are the advantages and disadvantages of intravenous administration?
advantages: direct, total dose, rapid
disadvantages: requires professional, infection risk, rapid response
what is bioavailability of a drug?
what does a IV injection give compared to oral doses?
- fraction of an unchanged drug that reaches the systemic circulation
- IV injection gives 100% bioavailability (all reaches into the blood plasma)
- whereas oral doses has lesser bioavailability, not all of it reaches the blood plasma and is not metabolised
what happens if a drug is too charged?
if the drug is too charged, it is unable to get through barrier or is usually transported through a transmembrane protein
what are 4 ways to get small molecules across cell membranes?
- Diffusing directly through the lipid
– Lipid solubility highly important - Diffusing through aqueous pores
– More likely important for diffusion of gases - Transmembrane carrier protein*
– e.g. solute carriers - Pinocytosis
– Mostly macromolecules, not drugs
lipid diffusion:
- describe solubility of hydrophilic drugs
- describe the solubility of lipophilic drugs
- hydrophilic drugs are soluble in aqueous, polar media (blood plasma, cytosol + interstitial fluid) - require transport mechanisms
- lipophilic drugs are soluble in fats and non-polar solutions (interior of the lipid bilayer and fat) - can pass freely across
drug absorption and ionisation:
- what does the ionised:unionised ratio of drug depend on?
- what property do ionised drugs have?
- how does pH influence the degree of ionisation of a drug?
- many drugs are weak acids or bases and the ionised:unionised ratio depends on pH
- ionised drugs have low lipid solubility, drugs must be uncharged to cross the lipid membrane, to maximise the effect, it should be charged within the cell
- pH influences the degree of ionisation of a drug: if it is ionised, it cannot get across the membrane - therefore pH is a key indicator of how well a drug will be absorbed at different points of the gastrointestinal tract
- what 2 factors is the route of administration affected by?
- when are there not barriers to absorption?
- what are the 2 main drug properties which affect absorption?
- The route of administration is affected by both drug and by patient factors
- Unless the drug is injected directly to the systemic circulation, there are barriers to absorption
- The main drug properties that affect absorption are lipophilicity and ionisation (ionisation of drug is influenced by pH)
what are 6 factors which affect distribution?
- degree of drug ionisation
- lipid solubility
- pH of compartments, some compartments of the body vary in pH
- cardiac output and blood flow
- capillary permeability
- plasma protein binding
- define distribution?
- what properties do VRGs have? (vascular rich groups)
- distribution: the movement of that drugs from the plasma into other compartments
- VRG (such as kidneys, muscle, adipose) have a high blood supply so have a high level of perfusion and therefore receives drug dose rapidly
biphosphonates and bone (specific for osteoporosis):
- what do phosphonate groups have a high affinity for?
- how are phosphonate groups distributed?
- give two examples of phosphonate drugs and their dosage
- phosphonate groups of drug have a very high affinity for calcium
- quickly distributed to the skeleton from plasma
- oral alendronate
- daily/weekly
IV zoledronate
- yearly
protein binding:
- what 2 things must a drug be free to do?
- list 4 drugs which bind to plasma protein
- what can competition for binding sites cause?
- a drug must be free to distribute widely or bind to its receptor
- many drugs bind to plasma protein
- albumin
- alpha-1 acid glycoprotein
- lipoproteins
- globulins - competition for binding sites can cause big increases in free drug concentrations
describe the competition between warfarin and aspirin, where protein binding becomes a problem
- 98% of warfarin highly charged, and needs to bind to plasma proteins bound to albumin, so only 2% of warfarin is available to interact and have a pharmacological effect of thinning blood
- aspirin also has high affinity for the same binding site on albumin meaning there is competition if these two drugs are taken together
- this competition displaces warfarin causing it to increase free unbound warfarin (which has a therapeutic dose index)
how can side-effects of some drugs be minimised?
Side-effects of some drugs can be minimised by limiting their distribution via the route of administration
muscarinic ACh receptor agonists:
- give two examples of muscarinic ACh receptor agonists?
- what are their pharmacological properties?
- what are their clinical uses?
- pilocarpine and bethanechol
- they are both non-selective muscarinic agonists
- pilocarpine is used for: - the constriction of pupils (miosis)
- glaucoma (to decrease IOP)
- xerostomia (following head/neck radiotherapy)
bethanechol is used for bladder and gastrointestinal hypotonia
