2.2 Pharmacokinetics Flashcards
What is AD(M)E?
Summary of pharmacokinetics:
Absorption
Distribution
Metabolism (excretion)
Elimination
Water v lipid solubility
Water:
~ must be aqueous for absorption, distribution, interation with target, passagein circulation
Lipid:
~cross cell membranes by passive diffusion
~ distribute into fatty tissue
~ easy access to action sites in cells
~easily re-absorbed from kidney
What happens to drugs in plasma?
Drugs in plasma available for distribution to sites of action, passage to organs of excretion, metabolism
Passage of drugs into/from circulation
Cross the vascular endothelium via gaps between cells packed with matrix of proteins that act to retain molecules of high molecular weight
How do drugs pass across cell membranes?
Passive diffusion
Active/facilitated diffusion
~ pinocytosis
~ aqueous pores
Factors effecting drug movement
Molecular weight
Lipid solubility
Chemical nature
How does molecular weight alter absorption of a drug?
High molecular weight compounds will remain at the site of administration
How does lipid solubility alter absorption of a drug?
Lipid soluble drugs can readily cross cell membranes
How does chemical properties alter absorption of a drug?
Weak acid/base: partially ionised so unionised fraction readily cross cell membranes
Neutral drugs: readily cross cell membranes
Strong acid/base: 100% ionised - polar molecules do not readily cross cell membranes
What is pKA
pH + log (conc. protonated species / conc. non-protonated species)
What affects the rate of absorption?
- drug properties
- physiological properties
- drug formulation (e.g. coating)
How does pH affect drug absorption?
pH varies at different parts of the body so drug pH effects how well it absorbs:
In plasma:
~ weak base (unionised) readily absorbed
~ weak acid (ionised) less readily absorbed
In acid conditions:
~ weak base (ionised) less readily absorbed
~ weak acid (unionised) readily absorbed
How does the area of absorbing surface affect absorption?
surface area
compromised surfaces
How does local blood flow effect absorption?
vasoconstriction reduces rate of diffusion of a drug from injection site
What is bioavailability?
The fraction of administered dose that reaches the circulation in active form
(expressed as a % of total amount)
How can bioavailability be determined?
By measuring the amount of drug in the plasma overtime.
What is first pass metabolism?
When the drug is extensively metabolised before it reaches the systemic circulation
Explain Cmax and Tmax
Cmax (maximal plasma conc. of a drug) at Tmax (time achieved at)
What is volume of distribution?
A measure of volume of fluid required to contain the total amount of drug at plasma conc.
How is volume of distribution calculated?
Vd = Q/Cp
Q = Dose (total amount of drug in the body) mg/Kg
Cp = Plasma conc ng/ml
Why is Vd important?
predicts if a drug is likely to reach target site at effective concs
Determines loadinh dose necessary to achieve target plasma conc
Why might drugs accumulate in target tissues?
High lipid solubility (accumulates in fate)
Ion trapping (pH difference across barriers)
Binding to unrelated site from target
How are drugs eliminated?
Drug enters, reaches peak, plasma conc falls
Which drugs are eliminated more quickly?
water soluble
lipid soluble (reabsorbed)
