Pharmacokinetics and pharmacodynamics Flashcards
Give a definition of pharmacodynamics
the study of a drug’s molecular, biochemical, and physiologic effects or actions
What does drug absorption usually involve?
Diffusion of drugs
Carriers and channels
Pinocytosis (for large molecules)
Which mechanism transports insulin across the blood/brain barrier?
Pinocytosis
What determines how long a drug is in the body?
Diffusion of the drug through lipids. The larger the molecule, the longer it takes to move through the lipid membrane
What is the diffusion coefficient equation?
1/sqrt (molecular weight)
What 5 factors affect drug absorption?
Method of administration
Molecular weight
Lipid solubility
pH and ionisation
Carrier transport
What is the quickest drug administration route?
Intravenous
Which drug administration route is done for rapid access to the CNS?
Intrathecal (puncture into the spinal fluid)
Which drug administration route is through the skin
Percutaneous, e.g nicotine patches
Which drug administration route avoids first pass metabolism?
Sublingual
How are drugs distributed around the body?
Cardiovascular system
Non-polar molecules dissolving freely in lipids
How does increasing blood pH affect weak acids in the body?
Increases excretion through urine.
Weak acids move from the CNS to plasma
When tight junctions lining the blood brain barrier become leaky, how can the damage be treated?
IV penicillin
Albumin is highly charged so mainly distributes what sorts of drug?
Acidic drugs.
How is volume of distribution calculated?
Dose/Cp
High Vd means the drug makes its way into lots of compartments
What part of renal excretion are weak acids and bases excreted?
Active tubular secretion
What do phase 1 catabolic reacitons do?
Produce a more reactive compound
What do phase 2 synthetic reactions do?
Produce an inactive compound
What sort of graph does a drug time course give?
mono-exponential decay, determined by metabolism and excretion
Give a definition of pharmacokinetics
the study of drug absorption, distribution, metabolism, and excretion
What are genetic variants of organic cation transporter (OCT1) associated with?
Different metformin responses in healthy humans
What can drug occupancy at equilibrium be used to determine?
Affinity
How is drug occupancy measured?
Radioligand binding curves
Give some advantages and disadvantages of using 3H as a radioligand marker
Labelled product
indistinguishable from native compound
Good stability
12.5 year half life
Expensive
Difficult labelling
Give some advantages and disadvantages of using 125I as a radioligand marker
Can be incorporated at high specific activities if there is an aromatic hydroxyl group
Readily degraded
Short half life
How should radioligands so that they stay biologically active?
Pure
Labelling must have high specific activity
Store in free-radical scavenger
stored at low temperature
avoid light
Store with antioxidants
Why did sulfathiazole kill 300 people?
Had sedative phenobarbital
Multiple control deficiencies in the plant
Why did thalidomide cause severe birth defects?
The stereoisomer of the drug caused these
What does general toxicology address?
Clinical pathology (find which organs are affected)
Haematology
Kidney and liver function
Coagulation
How is dose selection for humans usually found?
Doses being refined on animals
