Liver and drug metabolism Flashcards
1
Q
Drug disposition
A
Drug → absorption → distribution (blood) → metabolism (liver) → excretion (kidney)
2
Q
Oral bioavailability
A
- Same dose by two different routes - IV and oral
- Look at area under curve - oral / IV areas
3
Q
Factors affecting drug absorption
A
- Formulation - lipophilic = easier into tissue
- GI motility - rapid movement = lower chance of absorption
- Inflammation - inflammation = reduced
- pH - pH reduced = reduced absorption
- Food
- Bacteria
- Other drugs
4
Q
Routes of drug entry
A
- Mouth (swallowed), it is convenient and painless
- Buccal , sublingual (between gum and cheek, under tongue) not swallowing so avoiding gut and avoid first pass metabolism
- Injection - optimum treatment
- Rectum - absorption and distribution same as oral
- Lungs
- Eyes, ears, nostrils
- Skin
5
Q
Buccal
A
Between gum and cheek
6
Q
Sublingual
A
Under tongue
7
Q
Where does area between lower 1/3 o oesophagus and upper rectum drain to
A
Portal vein into liver
8
Q
Function of liver
A
- Detoxifies and degrades drugs
- Deactivates drugs by inactivating drugs by oxidation or producing inactive conjugate
9
Q
Phase 1 metabolism
A
- Introduce a polar group if doesn’t already have one - e.g. -OH or -COOH
- E.g. oxidation
- Smooth ER of liver in hepatocytes
- Cytochrome p450 catalyses metabolism of drugs, haem-like
- Drug binds to CYP
- Complex is reduced by an electron
- Molecular oxygen binds
- Another electron and two protons come in, forms water an oxidised drug-CYP complex
- Drug with oxygen atom is released and oxidised CYP is free for further use
10
Q
Oxidative reactions
A
- Aromatic hydroxylation - phenytoin, pheobarbital, propanolol
- N-oxidation - R-NH2 → RNHOH (chlorpheniramine)
- All driven by cytochrome-p450
11
Q
Why is phase ii metabolism needed?
A
If drug not able to be excreted after phase i
12
Q
Which enzymes catalyse conjugation reactions
A
Transferases
13
Q
How are conjugation reactions excreted?
A
Kidney or biliary system
14
Q
Conjugation reactions
A
- Lead to a covalent linkage between functional group on parent compound with glucuronic acid, sulfate, glutathione, amino acids or acetate
- Conjugates generally inactive
- Excreted by kidney or biliary system
- Catalysed by transferases
- Codeine undergoes glucuronidation to form codeine-6-glucuronide
15
Q
Enterohepatic recirculation
A
- Some conjugate cleaved by intestinal microflora
- High molecular weight conjugates excreted in bile
- Reabsorption to liver
