Pharmokinetics Flashcards
What do drug effects depend on?
mechanism of action and effects of cellular protein and physiological properties
Physiochemical properties of a drug that effect diffusion through lipids
diffusion coefficient- how quickly it moves, lipid solubility- measured by partition coefficient, polarity
Being non-polar increases what rates?
Rate of absorption from gut, penetration into brain and other tissues, renal elimination
Types of drugs given intravenously
biological and small molecule drugs
What do intravenous drugs avoid?
Gut and portal system
Rate into plasma of oral or rectal drugs depends on what?
Contents of gut, gut motility, size of drug
Bioavailability of a drug
Fraction of ingested drug/ fraction in plasma- ie. how much drug actually ends up in plasma
Factors that affect absorption of a drug
Site/method of admin, molecular weight, lipid solubility, pH and ionisation
At what pH will weak acids be unionised?
Low pH
henderson Hasselbacks equation
pKa= pH+ log10(HA/A-)
What is pKa?
acid dissociation constant - pH at which 50% of the molecules are the dissociated form
Asprins pKa
3.5
pH of the gut
3
Plasmas pH
7.4
pH in Kidneys
8
What do you do if neurotoxicity from aspirin poisoning?
Increase pH by adding sodium bicarbonate- causing drug to be extracted from CNS into plasma where they get trapped
Percentage of fluid in extracellular fluid compartment?
Plasma-4.5%, interstitial- 65%, lymph-1-2%
Percentage of fluid intracellular fluid compartment
30-40%
Percentage of fluid that is transcellular
2.5%
Percentage of fluid in fat
20%
Structure of the blood brain barrier
Endothelial cells lining blood vessels in CNS form tight junctions
Factors that influence drug distribution
Binding to plasma proteins, partition into specific tissue
Why are Parkinson’s drugs complicated?
Dopamine drugs trigger CTZ as it has many DA receptors so have to administer other drugs that block CTZ DA receptors (i.e. large drug that won’t cross BBB)
2 biochemical reactions of drug metabolism
Catabolic and then synthetic/ anabolic to make conjugate
Examples of microsomal enzymes in liver for drug metabolism
Cytochrome p450, MAO, alcohol dehydrogenase
Aspirin metabolism
Phase 1- oxidation, hydroxylation, dealkylation, deamination, hydrolysis. Phase 2- conjugate
Different isoforms of p450 do what?
React with different drugs
What is pharmacokinetics?
Time course of drug concentration attained in the body during and after dosing
What is saturation kinetics?
Metabolism and excretion become overwhelmed so can’t go any faster
What does saturation kinetics result in?
Disproportionate increase in steady-state plasma concentration - clinical side effects
