Drug metabolism Flashcards

1
Q

What is first pass metabolism?

A

breakdown of drug before reaching systemic circulation
a medication undergoes metabolism at a specific location in the body. The first-pass effect decreases the active drug’s concentration upon reaching systemic circulation or its site of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What drugs have high first pass?

A

nitrates (but not isosorbide mononitrate)
opioid analgesics
beta-blockers
clomethiazole
chlorpromazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is a pro drug?

A

inactive precursors that are converted to active metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name some pro drugs

A

oral cyclophosphamide - doesn’t harm GI tract but active after liver metabolism

levodopa - crosses BBB using amino acid transport, converted to dopamine in brain

azathioprine - activated to mercaptopurine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How are most drugs eliminated?

A

by kidneys

water-soluble drugs easily eliminated
fat-soluble = difficult to remove in urine, must be converted to soluble product usually through liver metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe how there may be variations in liver metabolism

A

genetic differences in enzyme activity

environmental influences on activity - drugs that induce/inhibit enzymes, alcohol, smoking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give some examples of drugs that can reduce effect of COCP

A

carbamazepine
phenytoin
strong inducers of liver enzymes - enhanced enzyme activity breaks down oestrogen component of combined pill

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name some P450 inducers

A

phenytoin
carbamazepine
rifampicin
St John’s Wort
barbiturates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name some P450 inhibitors

A

antibiotics:
- macrolides (clarithromycin, erythromycin)
- quinolones (ciprofloxacin)

antifungals - fluconazole, itraconazole

SSRIs - fluvoxamine, fluoxetine, paroxetine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

If prodrug A is activated by an enzyme, and an inducer compound is given, what is the effect on the amount of drug A available?

A

increase amount of active drug A
more of prodrug A is metabolised into drug A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

If drug B is broken down by an enzyme and an inducer compound is given, what is the effect on the amount of drug B available?

A

less drug B
more drug B is broken down

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

If prodrug A is activated by an enzyme, and an inhibitor compound is given, what is the effect on the amount of drug A available?

A

less amount of active drug A
less prodrug A metabolised to drug A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

If drug B is broken down by an enzyme and an inhibitor compound is given, what is the effect on the amount of drug B available?

A

increased amount of drug B
less drug B is broken down

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What foods should be avoided while on isoniazid?

A

tyramine-rich foods (mature cheeses, salami, pickled herring, bovril, oxo, marmite)

histamine-rich foods (very mature cheese, scromboid fish eg. tuna, mackerel, salmon)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What drug does azathioprine have a serious interaction with?

A

allopurinol
Allopurinol and azathioprine should not be co-prescribed unless the combination cannot be avoided. Allopurinol interferes with the metabolism of azathioprine, increasing plasma levels of 6-mercaptopurine which may result in potentially fatal blood dyscrasias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Which blood test predicts toxicity in patients on azathioprine?

A

TPMT activity
enzyme that breaks down azathioprine
low activity = toxicity

17
Q

What drugs should you be careful prescribing in patients with liver disease?

A

have extensive 1st pass
pro-drugs
sedatives - benzos, opiates
affect electrolytes/kidneys
narrow therapeutic range + are metabolised in liver - warfarin, theophylline

18
Q

What should you do before prescribing in renal disease?

A

check medication history
assess volume status (JVP, ankle oedema)
determine level of renal insufficiency

19
Q

Problem drugs in renal disease

A

furosemide - bigger doses needed, potential toxicity worsened

NSAIDs - worsen renal failure

Metformin - lactic acidosis

Insulin - hypoglycaemia because kidneys not excreting injected insulin

Aminoglycosides - rapid rise in concentration with repeated dosing, monitoring needed

morphine

20
Q

With which drugs are elderly patients at increased risk of ADRs?

A

CNS drugs:
- greater response than expected from plasma concentration - increased sedation
- respiratory depression with opioids + sedatives

Orthostatic hypotension with many drugs due to poor baroceptor response