Drug Metabolism Flashcards

1
Q

Principle of drug metabolism

A

Converts lipid soluble and non-polar compounds to water soluble and polar compounds so that they can be excreted

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2
Q

Why so compounds have to be converted to water soluble and polar compounds?

A

Only water-soluble substances undergo excretion, whereas lipid soluble substances are reabsorbed from renal sites back into the blood

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3
Q

Important sites of metabolism

A
  • Liver

- Lining of gut

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4
Q

What are prodrugs?

A

Drugs that are activated following metabolism

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5
Q

Examples of prodrugs

A
  • Codiene

- Enalapril

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6
Q

Effects of metabolism

A
  • No pharmacological activity

- Production of toxic metabolites - direct toxicity, carcinogenesis, teratogenesis

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7
Q

What happens in the Phase 1 of drug metabolism?

A
  • Involves hydrolysis, oxidation or reduction
  • Increased polarity of compounds
  • Provides active sites for Phase 2
  • Cytochrome P450 metabolising enzymes
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8
Q

What happens in Phase 2 of metabolism?

A
  • Conjugation: increase water solubility
  • Inactivates drug
  • Molecule endogenous to body donates portion to foreign body
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9
Q

What does conjugation involve?

A

Attachment of:

  • Glucuronic acid
  • Glutathione
  • Sulphate
  • Acetate
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10
Q

Substrate for CYP1A2

A

Theophylline

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11
Q

Substrate for CYP2D6

A

Codeine, antidepressants

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12
Q

Substrate CYP3A4

A

Diazepam, methodone

-In liver

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13
Q

Factors affecting metabolism

A
  • Genetics
  • Hepatic blood flow
  • Liver disease
  • Age
  • Sex
  • Ethnicity
  • Pregnancy
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14
Q

What is enzyme induction?

A

The drug metabolising enzymes can be induced (activity increased) - decreases drug effect

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15
Q

What are common enzyme inducers?

A

-Alcohol and smoking
Drugs and herbals:
-St John’s Wort
-Rifampicin

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16
Q

What inhibits enzymes?

A

Some drugs, herbal medicines and foods will inhibit metabolising enzymes

17
Q

Explain influence of genetic diversity in metabolism of drugs

A

Proteins different - metabolising enzymes - therefore variation metabolism

Different response to drugs therefor therapeutic failure or ADR

18
Q

Explain genetic polymorphism

A

Drug metabolising enzymes different in people due to gene expression - gene mutations can alter enzymes also

19
Q

What does decreased activity of an enzyme cause?

A

Increased drug toxicity

20
Q

Subpopulations of metabolisers

A

Poor - PM
Intermediates - IM
Extensive -EM
Ultrarapid - um

21
Q

Who are more prone to polymorphisms?

A

Some ethnicities

22
Q

Drug metabolism in children

A
  • Enzyme deficient in the fetus
  • Renal deficient
  • 2yrs rapid metabolism
  • By puberty rate greater than adults
23
Q

Drug metabolism during pregnancy

A
  • Metab. enzymes induced in 2nd & 3rd trimester
  • Hormones affect metab.
  • Females adapted to cope with increased levels in liver
24
Q

Drug metabolism in the elderly

A

Plasma protein, body mass and liver weight decreased therefore altered metabolism.

25
Q

Drug metabolism in different ethnicities

A
  • Racial differences in genetic expression of cytochrome P-450 isoforms
  • Asian slower at drug metab. than causasians