Pharmacokinetics Flashcards
Pharmacokinetics
Effect of drug on body
Why does ADME need to be calculated?
Ensure dose results in correct plasma concentration in all individuals
Absorption
Transfer of exogenous compounds from site of administrations o systemic circulation
What must a drug be able to do to be absorbed?
What molecules are the best for this?
Cross cell membranes = lipid soluble and unionised
Where to more drugs get absorbed
a) oral route - stomach
b) oral route - SI
b
What heavily control rate of absorption in the stomach?
Rate of gastric emptying
Why is the SI a more common site of absorption?
Large, highly vascularised SA
Enterocytes on epithelium contain metabolising enzymes and transporters
Advantages of oral admin
Cheap
No skill = patient can do it
Disadvantages of oral admin
Slower rate fo absorption
Dependent on pH
1st pass metabolism
4 factors affecting GI absorption
What do they all impact?
Rate of gastric emptying
pH (poor absorption of strong acids/bases)
Physcio-chemical interactions (tetracycline binds to Ca rich foods)
Particle size and formation
Bioavailability
Bioavailability?
Fraction of administered dose entering circulation
1st pass metabolism?
Metabolism in intestine and liver before reaching systemic circulation
How is absorption calculated from concentration time graph?
Area under the curve
Bioavailability (F) of IV vs any other route?
IV - F = 1
Any other F<1
No first pass metabolism in IV
Limitations of bioavailability?
Doesn’t consider individual variation e.g. gut motility
Cmax and Tmax?
Maximum concentration after admin
Time that Cmax occurs
Advantages of sublingual administration?
Fast response
Utilises drainage from mouth the sup vena cava so goes straight to intestine
Avoids its pass metabolism
Why is rectal/vaginal a possible route?
Bypasses first pass metabolism
Rich blood supply
Useful for someone how is vomiting/diarrhoea
Advantages of IV admin?
Bypass 1st pass metabolsim
Rapid response - straight into systemic
Disadvantages of IV?
Painful Needs a professional Adverse reactions expensive Infection
Advantages of intramuscular admin?
Local effect = good fro LA
Faster absorption than oral
3 ways a drug can pass through membrane (diffusion)?
Passive diffusion down concentration gradient
Diffusion through aqueous channel
Carriers
Many drugs are weak acids/bases.
What does this mean about ionisation state?
Unionised and ionised form dependent on pH
How is strength of acid calculated?
pKa
When pH=pKa how much of drug is ionised?
50%
At what pH is a weak acid and weak base unionised?
Weak acid unionised at low pH (acidic)
Weak base unionised at high pH (basic)
pH partitioning?
Acidic drugs accumulate in basic areas (where they are ionised so cannot pass through membranes)
Basic drugs accumulate in acidic areas
Aspirin is a weak acid
Is it mostly ionised or unsigned in the stomach?
Unionised
Distribution
Reversible transfer from systemic circulation to tissue
What is distribution dependent upon?
Ability to cross membrane, blood flow to tissues, extend of plasma binding proteins
When equilibrium between tissue and plasma is reached, plasma concentration decreases as elimination begins.
What occurs to tissue?
As plasma concentration decreases, drug diffuses back into plasma down the concentration gradient, this gets eliminated keeping the plasma concentration low so it keeps diffusing out = eliminated at same rate as plasma
What effects rate of distribution?
Membrane permeability
Vascularisation
What effects extent of distribution?
pKa of drug
Lipid solubility
Plasma binding protein
Tissue binding
What happens to drugs with high molecular weight or degree of plasma protein binding?
They are not distributed well because they cannot pass through the membrane
What does amount of plasma protein binding depend upon?
Concentration of free drug and concentration of plasma protein
Affinity for the free drug to the protein
What causes tissue binding?
Composition of drug e.g. lipid soluble drugs bind to fat
Cellular components e.g. tetracycline binds teeth and bone as they contain Ca2+
What distribution parameter shows distribution between plasma and tissue?
Vd = volume of distribution
How is Vd calculated?
Total amount of drug in body/concentration of drug in plasma
If the drug is confined to plasma Vd =
a) low
b) high
a
If drug is not lipid soluble so is distributed in extracellular compartments the Vd will be
a) higher than drug confined to plasma but lower than a well distributed drug
b) lower than drug in plasma but higher than a well distributed drug?
a
