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19 Cards in this Set
- Front
- Back
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Describe phase I reactions |
In phase I the drug is oxidized, reduced or hydrolysed to yield an -OH group |
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Which are the most important phase I enzymes? |
CYP450 enzymes, monoamine oxidase, alcohol dehydrogenase, etc |
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Describe phase II reactions |
In phase II the body attaches (conjugates) a chemical group to the -OH group on the drug which was created in phase I |
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Which are the most important phase II enzymes?
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Transferases, like UGT and NAT. |
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Name some chemical groups which are conjugated during phase II reactions |
Glucuronic acid, sulphuric acid, glycine, glutathione, acetyl, methyl |
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How have the properties of a drug changed after biotransformation? |
It's more water soluble, and in most cases less biologically active |
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What are the four possible outcomes of biotransformation of a drug? |
- The active parent drug is converted into an inactive metabolite (most common) - The inactive parent drug is converted into an active metabolite. This is what occurs when you give a prodrug - The active parent drug is converted into an active metabolite - The parent drug is converted into a toxic metabolite |
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What is the toxic metabolite of paracetamol called? |
NAPBQI |
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What is the antidote of paracetamol overdose? |
Acetylcysteine |
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Why do alcoholics tolerate smaller amounts of paracetamol? |
Their CYP2E1 enzyme is upregulated and they have less glutathione, which increases the accumulation of NAPBQI |
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Which phase II enzyme do neonates have less of? |
UGT |
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What is the most important consequence of neonates not having full UGT activity? |
They can't eliminate chloramphenicol, causing grey baby syndrome |
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What causes floppy infant syndrome? |
Neonates have decreased UGT and CYP450 activity, so they can't eliminate diazepam. Diazepam will cross the placental barrier, causing diazepam overdose in the neonate. |
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Why is ethanol consumption during pregnancy especially bad for the baby? |
Foetuses have decreased ADH activity and therefore reduced elimination of ethanol. |
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What are so-called slow acetylators? |
Slow acetylators have deficiency of NAT2, an acetylating phase II enzyme. |
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What is the pharmacological consequence of slow acetylators? |
They have decreased elimination of drugs which are eliminated by acetylation, especially isoniazid. |
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How are CYP450 enzymes induced? |
Drugs induce CYP enzymes by binding to receptors that increases gene transcription of the enzyme. |
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How are CYP450 enzymes inhibited? |
Inhibition of CYP450 enzymes is usually competitive. |
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How can we exploit CYP450 inhibition clinically, and can you mention some examples? |
By giving a CYP inhibitor together with a drug metabolized by CYP we can decrease the elimination of the second drug. For example giving ritonavir with other antiretrovirals, or ketoconazole with cyclosporine. |
