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Pharmocolgy > P4: Drug Metabolism and Excretion > Flashcards

P4: Drug Metabolism and Excretion Flashcards

1
Q

Define drug clearance

A

The removal of a drug from the body by all metabolic and excretory processes

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2
Q

What are the two major mechanisms of drug clearance?

A
  • Renal clearance

- Hepatic clearance

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3
Q

What is renal clearance?

A

Elimination of the drug through the urine

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4
Q

What is hepatic clearance?

A

Metabolism of the drug in the liver

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5
Q

Name two drugs that are fully cleared by the kidney

A
  • Atenolol

- Gabapentin

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6
Q

For most drugs what clearance mechanism do they follow?

A

Combination of renal and hepatic clearances

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7
Q

How are volatile drugs such as inhalation anaesthetics or ethanol cleared?

A

Combination of renal, hepatic and lung clearance

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8
Q

Roughly how much plasma is filtered through the kidneys per day?

A

180L

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9
Q

What is the role of efflux transporters that are located on the wall of a PCT?

A

Removal of a wide range of molecules

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10
Q

Why is renal clearance of lipophilic drugs harder than other drugs?

A
  • Lipophilic molecules tend to bind to protein
  • As water is reabsorbed in the nephron the conc of the filtrate increases, filtrate to tissue fluid gradient is established, lipophilic drugs move down this and re-enter the plasma.
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11
Q

What is phase I metabolism?

A

Functionalisation – add or reveal reactive groups

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12
Q

What is phase II metabolism?

A

Conjugation – add groups that improve water solubility

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13
Q

List some phase I metabolism reactions

A
  • Oxidation
  • Reduction
  • Hydrolysis
  • Hydration
  • Dehalogenation
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14
Q

List some phase II metabolism reactions

A
  • Sulfation
  • Glucuronidation
  • Glutathione conjugation
  • Acetylation
  • Amino acid conjugation
  • Methylation
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15
Q

What are the 3 main enzyme families that are involved in Phase I metabolism reactions?

A
  • CYP1
  • CYP2
  • CYP3
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16
Q

Give an example of a drug that skips Phase I reactions

A

Temazepam

Diazepam undergoes Phase I to become Temazepam

17
Q

What is the difference between metabolism and detoxification?

A
  • Drug metabolism can produce toxic metabolites

- Detoxification does not produce these toxic metabolites

18
Q

Name some hepatic metabolism inhibitors

A
  • Grapefruit juice
  • Fluoxetine
  • Disulfiram
19
Q

Name some hepatic metabolism inducers

A
  • Barbiturates
  • St John’s wort
  • Tobacco
20
Q

Name some minor excretion routes

A
  • Bile - temoporfin (anti-cancer)
  • Lungs
  • Stomach and Intestine - nicotine excreted into gastric juices, water soluble drugs excreted into intestines
  • Saliva
  • Breast milk
  • Sweat
  • Semen
21
Q

Explain enterohepatic recirculation

A
  1. Drug absorbed and carried to liver
  2. Then converted to glucuronide conjugate, then secreted into bile
  3. Bile containing conjugate is secreted when food is eaten
  4. Conjugate is hydrolysed by beta - glucuronidase by GI flora
  5. Then it is reabsorbed
22
Q

Besides renal and hepatic clearance how else can clearance happen

A
  • Lungs - ethanol

- Faeces - carried in bile

23
Q

Quick note

A

Rate or clearance is proportional to drug conc and rate of clearance is important when choosing drugs, especially if patient has kidney of liver problems

24
Q

What is the equation for drug clearance

A 
rate = k x C^n
k = rate constant
n = order
25
Q

Describe a first order decay curve on a Conc/Time graph

A

Rate declines

Half life is constant

26
Q

Where are drugs reabsorbed in the nephron

A
  • PCT - active reuptake of drugs

- DCT - reabsorption of liphophilic drugs

27
Q

How does penicillin’s low pKa (2.7) affect its excretion

A

Actively secreted into tubular fluid

  • lower pKa = lower degree of penicillin ionisation
  • non-ionic penicillin is passively reabsorbed from urine
  • Increases penicillin half life
28
Q

What enzyme’s family members account for 75% of drug metabolising enzymes

A

Cytochrome P450

29
Q

What is the main reaction catalysed by drug metabolising enzymes

A

mono oxygenation

30
Q

Name some other major enzymes involved in drug metabolism

A
  • Flavin-containing monooxygenases (FMO)
  • Monoamine oxidases (MAO)
  • Alcohol Dehydrogenase
  • microsomal reductases
  • circulating esterases
31
Q

Give examples of phase 1 reactions

A

Alcohol oxidation -
Ethanol (+ alcohol dehydrogenase) –> Acetaldehyde (+ aldehyde dehydrogenase) –> Acetic Acid

S-oxidation -
Thioridazine (+ Cytochrome P450) –> Thioridazine 2-sulfoxide

32
Q

Why is it easy to maintain long half life drugs in a therapeutic window

A

Small fluctuations between doses

use loading dose to avoid lag time of onset

33
Q

Why is it hard to maintain short half life drugs in a therapeutic window

A

Large fluctuations between doses (rapid attainment of steady state)
E.g. morphine - respiratory depression at peaks and pain at troughs

Pharmocolgy (22 decks)

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