PED2001 Distribution Flashcards
What are the four main compartments of drug distribution in bodily fluids?
Intracellular, extracellular, transcellular, intravascular
What percentage of body weight does water comprise?
50% to 70%
What are the components of extracellular fluid and their approximate percentages of body weight?
- Blood plasma: about 4.5%
- Interstitial fluid: 16%
- Lymph: 1.2%
What percentage of body water does intracellular fluid constitute?
30-40%
What is transcellular fluid and its approximate percentage of body water?
Encompasses various specialized compartments and constitutes 2.5%
What forms do drugs exist in within aqueous compartments?
Free and bound forms
What influences the equilibrium of weak acids or bases in bodily fluids?
Fluid pH and drug pK
Who introduced the concept of the blood-brain barrier (BBB)?
Paul Ehrlich
What characterizes the structure of the blood-brain barrier?
Continuous endothelial cell layer with tight junctions, surrounded by pericytes
What is the primary limitation of the blood-brain barrier?
Many drugs with low lipid solubility cannot penetrate
What can disrupt the integrity of the blood-brain barrier?
Inflammation
What is the volume of distribution (Vd) mathematically represented as?
Vd = Q/Cp
What does apparent volume of distribution represent?
The volume that would contain the total body content of the drug at a concentration equal to that in the plasma
What is the approximate plasma volume per kilogram of body weight?
0.05 L/Kg
What are Class 1 and Class 2 drugs based on plasma albumin binding?
- Class 1: Dose < binding capacity of albumin
- Class 2: Dose > binding capacity of albumin
What is the total extracellular volume per kilogram of body weight?
0.2 L/Kg
What type of compounds have a volume of distribution close to extracellular volume?
Many polar compounds such as vecuronium, gentamycin, and carbenicillin
What is the volume of distribution for many drugs that readily cross cell membranes?
Approx. 0.55 L/Kg
What factors can increase the volume of distribution?
- Drug binding outside the plasma compartment
- Partitioning into body fat
What happens to drugs with a volume of distribution greater than total body volume during overdose?
Haemodialysis filters blood plasma, making it unhelpful in managing overdose with such agents
What can slow gastrointestinal absorption?
Drugs inhibiting gastric emptying like atropine or opiates
What is an example of drugs that can retard absorption through insoluble complexes?
Ca2+ and Fe2+ with tetracycline
What is a physiological effect on drug absorption mentioned in the text?
Adrenaline added to local anaesthetic injections causes vasoconstriction, slowing anaesthetic absorption
What are pro-drugs?
Inactive precursors metabolised to active metabolites
What is an example of a drug that is a pro-drug and its active metabolite?
Cyclophosphamide metabolises to active metabolites
What is the purpose of antibody-drug conjugates in cancer chemotherapy?
Improve selectivity of cytotoxic drugs
What is the size range of liposomes?
0.1-1 um in diameter
What are coated implantable devices used for?
Localized drug delivery from implants
What is the purpose of embedding sirolimus in drug-eluting stents?
Prevent re-stenosis
Fill in the blank: The volume of distribution for drugs like phenytoin and ethanol is close to _______.
Total body water volume
True or False: Drug interactions caused by altered absorption can be due to physiological effects.
True
What are some examples of drugs that act as displacing agents in plasma?
- Sulphonamides
- Choral hydrate
- Trichloroacetic acid
