Pharmacokinetics II Flashcards
What are the major body compartments
extracellular fluid, intracellular fluid, transcellular fluids, fat
Which type of drugs are effective
free drugs
What type of drugs does fat have an important impact on
lipophilic drugs
What is drug distribution based on
permeability and lipid solubility
What is meningitis
bacterial infection of the CNS
What is domperidone
antagonist of dopaminergic agonist receptors in chemoreceptor trigger zone
What regulates drug access to the CNS
blood brain barrier
Describe a junction in the CNS
endothelial cells line blood vessels and form tight junctions
What are tight junctions impermeable to
water soluble molecules
What can cross the BBB easily
lipid soluble molecules - ethanol and caffeine
What can happen to tight junctions during inflammation
become leaky
What can meningitis be treated with
iv penicillin
What other factors can influence drug distribution and elimination
binding to plasma proteins, partition into specific tissues
What does albumin bind to
mainly acidic drugs
What are the two main biochemical reactions for drug metabolism
catabolic reactions, synthetic (anabolic) reactions
What do catabolic reactions produce
more reactive compounds
What do anabolic reactions involve
conjugation
What do anabolic reactions produce
inactive product
Where does drug metabolism occur
liver
What affect can metabolism have on drug action
alter or prolong pharmacological drug action
What must drugs cross in order to be metabolised
plasma membrane
What speeds up drug metabolism
microsomal enzymes - cytochrome p450 in the liver
What are the stages of aspirin elimination
drug forms a derivative - then forms a conjugate
How can a drug form a derivative
oxidation, hydroxylation, dealkylation, deamination, hydrolysis
How does aspirin form its derivative
OCOCH3 group on aspirin is hydroxylated
What is the derivative of aspirin
salicylic acid
What hydroxylates aspirin into salicylic acid
p450 enzymes
What is the conjugate of aspirin
glucoronide
Name three important p450 enzymes
CYP1, CYP2, CYP3
What are CYP1, CYP2 and CYP3 involved in
drug and steroid metabolism
True or false - different iso-forms of p450 react with different drugs
true
Name some NSAIDs
ibuprofen, diclofenac, naproxen
What is paracetamol turned into
NAPQ1
What is a disadvantage of NAPQ1
extremely toxic
What is the effect of p450 inducers
increase drug metabolism
How do inducers increase drug metabolism
increase transcription of drugs
Name drug elimination routes
urine, faeces, milk, sweat, expired air
What are the three pathways of drug excretion
renal excretion, GI excretion, lung excretion
How does renal excretion of drugs occur
glomerular filtration, active tubular secretion
What does the primary organic cation transporter excrete
weak bases
What does the time course of clearance of drug concentrations follow
mono-exponential decay
What is saturation kinetics
disproportionate increase in steady state plasma concentration
Where do lipid soluble drugs accumulate
fat
Where are lipid insoluble drugs mainly confined to
plasma and interstitial fluids
What does the binding of drugs to plasma proteins reduce
free concentration of drug
