Pharmacokinetics Flashcards
What are the 5 stages of a drugs journey through the body?
Absorption
Distribution
Metabolism
Excretion
Removal
List some routes of drug administration.
Inhalation, ingestion, dermal, intravenous, subcutaneous, intraperitoneal, intramuscular.
Why might different administration routes be more appropriate?
If you want a systemic or local effect.
Speed of action.
Time period within body.
Give some examples of local effect drugs.
Salbutamol (ventolin)
Antacids
Betnovate (betamethasone)
Give some examples of drugs with systemic effects.
Aspirin
Cannabis
Nicotine.
What is the difference between enteral and parenteral.
Parenteral = outside the GI tract (i.e. not orally administered)
Enteral = via GI tract.
What two ways to drug molecules move around the body?
Bulk flow transfer, i.e. in the blood stream.
Diffusional transfer = over short distances.
What key characteristic must drugs have?
Have to be able to transverse both hydrophilic and lipophilic environments.
They travel in aqueous compartments (e.g. bloodstram, lymph, etc.)
Must cross lipophilic barriers (e.g. cell membranes).
Name 4 ways drugs can cross lipid barriers?
- simple diffusion
- diffusion across aqeous pores.
- carrier mediated transport
- pinocytosis
Outline the route of aspirin and the barriers it must cross.
Ingested. Cross stomach lining to blood. Cross capillary wall to extracellular fluid. Cross from extracellular fluid into organs.
Which one of two characteristics will most drugs have? Why is this significant?
Weak acid or weak base.
Drugs exist in polar/non-polar (ionised/non-ionised) forms depending on pH.
How do aspirin and morphine differ at phyisological pH?
Morphine = basic. Proton acceptor.
Aspirin = acidic. Proton donor.
Give the Henderson-Hasselbalch equation for the dissaciation constand of weak acid and weak base.
How can the proportion of ionised:unionised molecules of a species be calculated?
What is ion trapping? Explain with aspirin as an example.
Localisation of a drug in certain body compartments. High ionisation of aspirin in the blood (pKa = 3.5) gives it difficulty crossing lipid membranes.
Why does IV Sodium Bicarbonate increase aspirin excretion.
Basic conditions –> increased aspirin ionisation –> reduced ability to pass back into blood after kidney ultrafiltration.
Give 4 factors that influence drug distribution.
Regional blood flow
Extracellular binding (Plasma-protein binding)
Capillary permeability (tissue alterations – renal, hepatic, brain/CNS, placental)
Localisation in tissues
What parts of the body receive the greatest regional blood flow?
Liver 27%
Heart 4%
Brain 14%
KIdneys 22%
Muscles 20% (when exercising)
What is the effect of plasma protein binding on drugs (e.g. 50-80% aspirin)? Why is this important?
It remains in the blood. Dose must be adjusted.
Why is it difficult for drugs to cross the BBB
tightly controlled substance transport. Tight continuous capillaries: difficult for ionised substances to pass through.
Why does adipose tissue pose a problem for lipid soluble drugs?
Despite low blood supply, lipophilic drugs contained within it.
What are the two major routes of drug excretion?
Kidney (urine)
Liver (bile in stool)
How are drug molecules too large for ultrafiltration moved into the kidney tubules?
Active secretion using transport proteins (lipophilic drugs can be reabsorbed)
How do hepatocytes move large metabolites into the bile?
active transport of the water soluble conjugates they create.
