Pharmacokinetics: Absorption & Distribution Flashcards
Define: Pharmacokinetics
The study of factors which determine the amount of chemical agents at their site of action at various times after their application (e.g. absorption, distribution)
i.e. what the body does to a drug
List 3 questions that are asked in pharmacokinetics
How much drug reaches the target organ?
Where in the body does the drug go?
How long does the drug stay in the body?
Describe the perfect drug
It reaches its biological target
Remains in the body long enough to achieve its therapeutic aim
Does not cause harm while in the body
What determines the absorption of a drug?
The chemical properties of a drug determines its absorption
Which factor is the most important physical property of a drug in pharmacokinetics?
Lipophilicity/hydrophilicity
Affects absorption, distribution, potency and elimination
What is logP a measure of?
How lipophilic/hydrophilic a drug is
- its ability to dissolve in ethanol/water
List 3 problems with a drug that is too lipophilic
It would:
Be insoluble in aqueous media (non-polar)
Bind too strongly to plasma proteins
Distribute into lipid bilayers
Name a problem with a drug that is too hydrophilic?
It will not be able to cross plasma membranes (too polar)
What is pH trapping?
When a molecule passes from one environment/compartment to another via the plasma membrane (e.g. urine to plasma) and can’t pass back through the other way
What happens to acidic molecules in pH trapping?
Molecules pass from urine to plasma
Formulated in its unionised form (DH)
Can pass through the membrane and dissociates into its ionised form (D-)
It is therefore trapped due to the H-H equation
What happens to basic molecules in pH trapping?
Molecules pass from plasma to urine
Unionised form of the molecule (D) passes through the membrane
Gets protonated once in the other compartment (acidic) = DH+
List 4 enteral routes of drug administration
Oral
Sublingual
Rectal
Inhalation
List 4 topical routes of drug administration
Skin
Cornea
Vagina
Nasal mucosa
List 3 parenteral routes of drug administration
Injection:
Subcutaneous
Intravenous
Intramuscular
Which factors decide the method of drug delivery to use?
Speed of delivery - IV fastest
Metabolism of compound - first pass effect for orally administered = decrease in concentration of drug
Targeting - where does the drug need to reach to have desired therapeutic effect?
List 4 factors which affect oral absorption (and therefore bioavailability)
GI motility
Splanchnic blood flow (abdominal organs)
Formulation of medicine
Physiochemical properties of drugs
Define: Bioavailability (F)
The fraction of administered dose that reaches the systemic circulation
List 2 factors which can cause incomplete bioavailability of orally administered drugs
Incomplete absorption (so drug lost in faeces) First pass metabolism (starts metabolising before it reaches the bloodstream)
What is the equation to calculate total body water?
Total body water = 0.6 x body weight
What makes up the total body’s water?
Extracellular = interstitial fluid & plasma
Intracellular
Define: Volume of distribution
The volume of fluid required to contain the total amount of drug in the body (D) at the same concentration as that present in the plasma (Cp)
What is the formula to calculate the volume of distribution (Vd)?
Vd(L) = total amount of drug in the body/blood concentration
–> Vd = D/Cp
What does a small Vd mean?
Drug retained in plasma
e. g. affinity to plasma proteins
0. 1 L/kg
What does a high Vd mean?
Large distribution of drug around the body
–> 115 L/kg
List 4 factors that affect tissue distribution
Physiochemical features of the drug
Pharmacological properties of the drug
Blood flow in the organ/tissue
Barriers of organ/tissue
Explain how physiochemical features of the drug affect tissue distribution
Size of the molecule - large = more difficult to cross membrane
pKa of drug - pH difference between plasma and tissue can cause accumulation (pH trapping)
Explain how the pharmacological properties of a drug affect tissue distribution
e.g. binding of molecule to plasma or tissue proteins may allow uptake into tissue so it is not available to be active at its therapeutic site
Explain how blood flow in the organ/tissue affects the tissue distribution of a drug
Decides the rate at which the drug is distributed to various organs
Therefore drugs are rapidly distributed to highly perfused tissues (e.g. brain, liver, kidney, heart)
Increased blood flow received = increased drug
How do barriers of the organ/tissue affect the tissue distribution of a drug?
2 major barriers = blood-brain barrier & placenta
Most drugs that penetrate the placenta and the blood-brain barrier are highly lipophilic
Some drugs bind to glucose transporters to get access to the brain
