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10 Cards in this Set
- Front
- Back
Phase 1
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Catabolic reactions - oxidation, reduction and hydrolysis most common.
Aim to prepare drug for phase to by adding or forming a chemically reactive functional frouip (OH, NH2, OOH) Mostly occur in the liver. Oxidation is a major route which is catalysed by chtochrome p450 family of mixed oxidases. |
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Other enzymes
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Plasma esterases
monoamine oxidases decarboxylases |
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Most important isotypes in liver (cytochrome p450)?
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CYP1, 2 &3
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Most common cytochrome p450 reaction?
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monooxygenase reaction - insertion of one oxygen atom to a drug while the other is reduced to water
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Monooxygenase reaction requires?
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Cytochrome p450 haeme protein
O2 Cytochrome p450 reductase NADPH |
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Phase 2 aim?
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Enhancing water solubility (ionised or polar) to aid excretion through a series of conjugation reactions.
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Major conjugation reaction?
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Glucuronidation (morphine)
glycosidation sulfation (paracetemol) ->highly ionised methylation ->more polar acetylation ->more polar amino acid conjugation ->more polar glutathione conjugation |
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Monooxygenase oxidation reaction?
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O-dealkylation
Alpihatic hydroxylation Deamination N-dealkylation N-oxidation S-oxidation Aromatic hydroxylation |
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Enzyme inhibition +example
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Two drugs are metabolised by the same p450 enzyme they will inhibit eachothers metabolism therefore there is a risk of overdosing.
terfenadine & cimetidine (CYP3A4) |
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Enzyme induction
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Enzyme induces its own metabolism leading to tolerance.
(Phenobarbitone reduces effectiveness of digitoxin by enhancing its metabolism) |