pharmacokinetics 1

Question 1

define pharmacology

Answer 1

The origin, nature, chemistry, effects and uses of drugs

Question 2

define toxicolgy

Answer 2

The study of the adverse effects of chemical, physical or biological agents

Question 3

define pharmacodynamics

Answer 3

What the drug does to the body - interaction with the receptors

Question 4

define pharmacokinetics

Answer 4

What the body does to the drug

Question 5

list 5 important uses in understanding pharmacokinetics?

Answer 5

• 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

Question 6

what are the 5 steps of pharmacokinetics? (LADME)

Answer 6

1. (Liberation) - preparation of the drug
2. Absorption - want most drugs to favour absorption, however minimising absorption is sometimes wanted
3. Distribution - bringing the drug from plasma to the source, target organ/tissues
4. Metabolism - how the body transforms drugs
5. Excretion - how the drug is ultimately removed

Question 7

what are the 7 routes of drug administration?

Answer 7

oral
sublingual
inhalation
topical
transdermal
intramuscular
intravenous

Question 8

what are the advantages and disadvantages of oral administration?

Answer 8

advantages: convenient

disadvantages: first-pass effect, many variables and barriers

Question 9

what are the advantages and disadvantages of sublingual administration?

Answer 9

advantages: no first-pass effect

disadvantages: inconvenient, small dose limit, taste

Question 10

what are the advantages and disadvantages of inhalation administration?

Answer 10

advantages: fast, rapid delivery to blood

disadvantages: requires special properties of drug (e.g atomised, vapourised)

Question 11

what are the advantages and disadvantages of topical administration?

Answer 11

advantages: convenient, localised

disadvantages: only local

Question 12

what are the advantages and disadvantages of transdermal administration?

Answer 12

advantages: prolonged release

disadvantages: skin is a very effective barrier

Question 13

what are the advantages and disadvantages of intramuscular administration?

Answer 13

advantages: rapid for aqueous, slow for oil

disadvantages: painful, requires trained personnel

Question 14

what are the advantages and disadvantages of intravenous administration?

Answer 14

advantages: direct, total dose, rapid

disadvantages: requires professional, infection risk, rapid response

Question 15

what is bioavailability of a drug?

what does a IV injection give compared to oral doses?

Answer 15

1. fraction of an unchanged drug that reaches the systemic circulation
2. 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

Question 16

what happens if a drug is too charged?

Answer 16

if the drug is too charged, it is unable to get through barrier or is usually transported through a transmembrane protein

Question 17

what are 4 ways to get small molecules across cell membranes?

Answer 17

1. Diffusing directly through the lipid
   – Lipid solubility highly important
2. Diffusing through aqueous pores
   – More likely important for diffusion of gases
3. Transmembrane carrier protein*
   – e.g. solute carriers
4. Pinocytosis
   – Mostly macromolecules, not drugs

Question 18

lipid diffusion:

1. describe solubility of hydrophilic drugs
2. describe the solubility of lipophilic drugs

Answer 18

1. • hydrophilic drugs are soluble in aqueous, polar media (blood plasma, cytosol + interstitial fluid) - require transport mechanisms
2. lipophilic drugs are soluble in fats and non-polar solutions (interior of the lipid bilayer and fat) - can pass freely across

Question 19

drug absorption and ionisation:

1. what does the ionised:unionised ratio of drug depend on?
2. what property do ionised drugs have?
3. how does pH influence the degree of ionisation of a drug?

Answer 19

1. many drugs are weak acids or bases and the ionised:unionised ratio depends on pH
2. 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
3. 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

Question 20

1. what 2 factors is the route of administration affected by?
2. when are there not barriers to absorption?
3. what are the 2 main drug properties which affect absorption?

Answer 20

1. • The route of administration is affected by both drug and by patient factors
2. Unless the drug is injected directly to the systemic circulation, there are barriers to absorption
3. The main drug properties that affect absorption are lipophilicity and ionisation (ionisation of drug is influenced by pH)

Question 21

what are 6 factors which affect distribution?

Answer 21

• 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

Question 22

1. define distribution?
2. what properties do VRGs have? (vascular rich groups)

Answer 22

1. distribution: the movement of that drugs from the plasma into other compartments
2. VRG (such as kidneys, muscle, adipose) have a high blood supply so have a high level of perfusion and therefore receives drug dose rapidly

Question 23

biphosphonates and bone (specific for osteoporosis):

1. what do phosphonate groups have a high affinity for?
2. how are phosphonate groups distributed?
3. give two examples of phosphonate drugs and their dosage

Answer 23

1. phosphonate groups of drug have a very high affinity for calcium
2. quickly distributed to the skeleton from plasma
3. oral alendronate
   • daily/weekly

IV zoledronate
- yearly

Question 24

protein binding:

1. what 2 things must a drug be free to do?
2. list 4 drugs which bind to plasma protein
3. what can competition for binding sites cause?

Answer 24

1. a drug must be free to distribute widely or bind to its receptor
2. many drugs bind to plasma protein
   - albumin
   - alpha-1 acid glycoprotein
   - lipoproteins
   - globulins
3. competition for binding sites can cause big increases in free drug concentrations

Question 25

describe the competition between warfarin and aspirin, where protein binding becomes a problem

Answer 25

• 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)

Question 26

how can side-effects of some drugs be minimised?

Answer 26

Side-effects of some drugs can be minimised by limiting their distribution via the route of administration

Question 27

muscarinic ACh receptor agonists:

1. give two examples of muscarinic ACh receptor agonists?
2. what are their pharmacological properties?
3. what are their clinical uses?

Answer 27

1. pilocarpine and bethanechol
2. they are both non-selective muscarinic agonists
3. 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