06 - Drug distribution & elimination Flashcards
Enterohepatic recirculation can extend the…
Half-life of a drug
Describe the stages of enterohepatic recirculation (6)…
- Drug given orally
- Moves through the gut
- Absorbed into blood
- Travels via hepatic portal vein
- Tramsfered tp gall bladder in bile
- Secreted back into intestine (back to step 2)
The ability of a drug to bind to blood plasma proteins affects…
Distribution
At equilibrium, the rate of clearance from the plasma (is greater than / less than / equal to) rate of clearence from the blood…
Equal to
To move from blood vessels into the tissues, drug can exit via…
Slit junctions (which are gaps between endothelial cells)
Drugs with a high molecular weight…
a) Do not bind to plasma proteins
b) Bind less readily to plasma proteins
c) Always bind to plasma proteins
d) Are highly bound to plasma proteins
d) Are highly bound to plasma proteins
If a drug is highly bound to plasma proteins, it tends to stay in the plasma, leading to poor…
Distribution
Only a ( bound / unbound) drug can partition into tissues/organs
Unbound
2 important plasma proteins…
- Alpha-1 acid glycoprotein (AAG)
* Albumin (Human serum albumin, HSA)
AAG binds mostly ( acidic / basic ) drugs…
Basic (and some neutral)
Higher levels of AAG are found in (2)…
Cancer and inflammatory diseases
If AAG levels are raised (such as by cancer), the dose may need to be ( increased / decreased )…
Increased
Albumin binds mostly ( acidic / basic ) drugs…
Acidic
Malnutrition and cirrhosis tend to ( increase / decrease ) HSA levels…
Decrease
If HSA levels are decreased (such as by cirrhosis), the dose may need to be ( increased / decreased )…
Decreased
Volume of distribution is a dilution factor which relates the amount of drug in the whole body to the amount…
Found in a sample of plasma
Vd =
total dose / plasma drug concentration
The liver is a major site of…
Metabolism
Prodrugs are drugs that must be…
Metabolised into their actrive form
Prodrugs can help reduce…
Side effects (as they can be targeted more specifically)
The mechanism of elimination depends on the…
Physiochemical properties of the drug and its metabolites
Elimination parameters are (3)…
- Clearence (CL)
- Elimation rate constant (K el)
- Half life (t 1/2)
Generally, drug levels are negligible after how many half lives?
6 half lives
Maintainence doses are usually administered after how many half lives?
4 half lives
The elimination constant is the…
Fraction of drug removed per unit time
t 1/2 =
ln2 / K el
ln2 =
0.693
Clearance =
Dose given / total exposure
Fenestrated
Perforated (such as endothelia with gaps)
Enterohepatic circulation
Cycling of drug between gut and liver
Partitioning
The movement of unbound drug from plasma into tissues
