2. Pharmacokinetics Flashcards
Where does drug metabolism usually occur?
liver
What is the aim of drug metabolism? Describe in general the processes involved.
Enhances drug elimination.
Phase 1 - usually inactivates drug
- oxidation, reduction or hydrolysis to create/expose polar groups on drug
- cytochrome P450 (CYP) enzymes
Phase 2 - make it soluble
- drug conjugation with eg. glycine, glutatione, glucuronide
- conjugating enzymes
Suggest possible factors affecting CYP enzyme activity.
- genetics
- age
- gender
- enzyme inducing/inhibiting drugs
- smoking or alcohol consuption
- liver disease
Name examples of CYP inducers.
Carbamazepine
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulvin
Phenobarbitone
Sulphonylureas
Name examples of CYP inhibitors.
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole Alcohol (acute) Chloramphenicol Erythromycin Sulphonamides
Ciprofloxacin
Omeprazole
Metronidazole
What is the main route of drug elimination?
Kidney
Describe the 3 processes involved in drug elimination via the kidney.
- Glomerular filtration
- only unbound (free) drugs
- proportional to GFR - Active secretion - PCT
- via OATs and OCTs - Passive reabsorption - DCT and CDs
- water is reabsorbed along length of tubule, increasing drug conc. If lipophilic, is reabsorbed down conc. gradient.
- decreases rate of effective elimination
What is the main determinant of drug clearance rate?
GFR
Explain the difference between 1st order and 0 order kinetics.
1st order:
- rate of elimination is proportional to drug level, with constant fraction of drug eliminated in unit time
- T1/2 can be defined
- most drugs
0 order:
- rate of elimination is constant, independent of drug conc.
- some drugs (eg alcohol, phenytoin, aspirin, warfarin) and many drugs when at very high concs. as Rs/enzymes become saturated
- more likely to result in toxicity
How many t1/2 are required for a steady state to be reached during repeated drug administration?
3-5 t1/2
Why is a loading dose required when prescribing digoxin?
Large apparent Volume of Distribution (>200L) and thus long t1/2 (40hrs).
So need loading dose to achieve rapid therapeutic effect.
Do loading dose and maintenance doses need to be reduced in renal failure?
- Loading dose can remain the same (unless renal failure is very severe).
- Maintenance doses need reducing if renal failure leads to reduced clearance.
How is loading dose calculated?
Loading dose = Vd x [drug]target
= Vd x drug Cpss
