Drug Metabolism and Renal Excretion Flashcards

1
Q

How do most drugs leave the body?

A

in urine as unchanged or chemically transformed compounds - occasionally excreted in bile

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2
Q

What does metabolism of drugs act to do?

A

convert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney.
Convert drugs to metabolites that are usually less pharmacologically active than the parent

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3
Q

What can occasionally happen in drug metabolism?

A

may convert from inactive drugs to active compounds or cause a gain in activity
may have unchanged activity
may possess at different action

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4
Q

What is a drug that may gain activity?

A

codeine may be converted to morphine

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5
Q

What is a drug that may have unchanged activity?

A

diazepam - nordiazepam

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6
Q

What is the main organ of drug metabolism?

A

liver

GI tract, lungs and plasma may also contribute

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7
Q

What is the first phase of drug metabolism?

A

Oxidation, reduction hydrolysis

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8
Q

What is the function of the first phase of metabolism?

A

makes the drug more polar and adds a chemically reactive group which allows conjugation

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9
Q

What is the second phase of drug metabolism?

A

conjugation

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10
Q

What is added during conjugation?

A
glucoronyl
sulphate
methyl
acetyl
glycyl
or glutathione
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11
Q

What are the cytochrome P450 monoxygenases?

A

haem proteins located in the endoplasmic reticulum of liver hepatocytes mediating oxidation reactions

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12
Q

What are the main CYP450 enzymes in the liver?

A

CYP1,2,3

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13
Q

Where do the oxygens go in the monooxygenase cycle?

A

one yields ROH, the hydroxyl product

one yields H2O

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14
Q

What is glucuronidation?

A

a common reaction involving the transfer of glucuronic acid to electron rich atoms of the substrate

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15
Q

What is the enzyme involved in glucuronidation?

A

UDP-glucuronyl transferase

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16
Q

What sort of endogenous substances are subject to glucuronidation?

A

bilirubin

adrenal corticosteroids

17
Q

What are the active processes involved with renal excretion?

A

glomerular filtration
active tubular secretion
passive reabsorption by diffusion

18
Q

What kind of drugs can be filtered at the glomerulus?

A

any free drug with a MW less than 20000

19
Q

What is the equation for clearance by filtration?

A

CL = GFR x fraction of unbound drug (fu)

where GFR is typically 120ml min-1

20
Q

What are the two transporter systems in the proximal tubule?

A

organic anion transporter

organic cation transporter

21
Q

What does the anion transporter handle?

A

acidic drugs, endogenous acids and the marker for renal plasma flow

22
Q

What does the cation transporter handle?

A

basic drugs

23
Q

What is the most effective mechanism for drug elimination?

A

excretion by tubular secretion

24
Q

Why is tubular secretion graph a curve?

A

Because the transporters have a limit

25
Q

What happens as free drug is excreted?

A

more drug is freed by the protein into the plasma for excretion

26
Q

What drugs might the organic anion transporter excrete?

A

penicillins
probenecid
frusemide

27
Q

What drugs might the organic cation transporter excrete?

A

morphine
neostigmine
amiloride

28
Q

What may happen with use of frusemide and thiazides?

A

may precipitate gout as uric acid is not so easily excreted

29
Q

What may occur with probenicid?

A

may retard excretion of penicillins

30
Q

What are some factors influencing reabsorption of the drug?

A

lipid solubility
polarity
urinary flow rate
urinary pH

31
Q

What is significant about lipid solubility?

A

highly lipid soluble drugs will be extensively reabsorbed

32
Q

What is significant about polarity?

A

polar drugs will be excreted

33
Q

What is significant about urinary flow rate?

A

diuresis decreases reabsorption

34
Q

What is significant about urinary pH?

A

degree of ionisation of weak acids and bases can influence reabsorption

35
Q

What does an alkaline pH do?

A

increase excretion of acids

36
Q

What does an acidic pH do?

A

increases excretion of bases

37
Q

What can urinary alkalinisation be used to accelerate?

A

excretion of aspirin in cases of overdose