Elementary drug metabolism Flashcards Preview

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Flashcards in Elementary drug metabolism Deck (53):
1

Name 4 processes that influence drug disposition?

  1. Absorption
  2. Distribution
  3. Metabolism
  4. Excretion

2

How do most drugs leave the body?

In the urine.

 

3

In what form are they excreted?

Either as unchanged (ie. highly charged) compounds

Chemically transformed compounds rendered more polar by metabolism

4

The bile?

Drugs can also be excreted by the bile

5

Drugs are xenobiotics act to?

Convert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney.

Converted drugs to metabolities that are usually pharmacological less active than parent compound

6

Drugs metabolities may also?

Be converted from inactive prodrugs to active compounds or gain activity.

Have unchanged activity

Possess a different action.

7

What is the main organ for drug metabolism?

What other organs also has an effect?

The liver

Additionally, the GI tract, lungs and plasma

8

Phase 1 of the drug metabolism?

  • Makes drug more polar, adds a chemically reactive group permitting conjugation.
  • Drug presented to the liver and enters hepatic cells.
  • Metabolism starts: oxidation, reducation & hydrolysis.
    • Provides the start point for phase 2
  • Catabolic- break down molecules

9

Phase 2 of drug metabolism?

  • Adds on endogeneous compound increasing polarity.
  • Metabolism: conjugation
  • Drugs is excreted by kidneys
  • Anabolic- synthesis of complex molecules

10

When can you skip phase 1?

If parent compound already has a handle (permitting conjugation)

11

When can phase 1 and 2 be skipped?

If parent compound is already polar

12

Where is haem protein located?

In the endoplasmic reticulum of liver hepatocyte

13

What does the haem proteins mediate?

Oxidation reaction of many lipid soluble drugs

14

Cytochrome P450 family?

Comprise a superfamily.

Different individuals have overlapping substrate specificites.

 

15

How to classify each individual in the cytochrome?

CYP3A4 

3- gene family

A- gene subfamily

4-individual gene

16

What are the main gene families in the human liver?

CYP1

CYP2

CYP3

17

The monooxygenase P450 cycle?

Drugs enter cycle as drug substrate.

Molecular oxygen provides two atoms of oxygen.

One atom of oxygen is added to the drug to yield the hydroxyl produce which leaves the cycle (as ROH)

The second atom of oxygen is combined with protons to form water. 

AS21

18

What is the cychrome P450 family used for?

To mediate the oxidation reaction (phase 1) of drug metabolism

In the liver

19

Drug metabolism pathway?

AS22

20

Phase 2 reactions?

Usually results in inactive products.

Largely occurs in the liver.

Involves conjugation of chemically reactive groups

21

Glucuronidation?

Involves the transfer of glucuranic acid to electron-rich atoms of the substrate.

Many endogenous substrances are subject to this.

 

A image thumb
22

Rate of renal excretion?

Differ greatly between drugs.

Products of phase 1/2 metabolism are excreted faster than the parent compound

23

What are the 3 basic processes involved in renal excretion?

  1. Glomerular filtration
  2. Active tubular secretion
  3. Passive reabsorption by diffusion across the tubular epithelium.

24

Diagram for the basic processes for renal excretion

AS23

25

If a drug is highly polar is it lipopholic of lipophilic

Less lipophilic 

More lipopholic

26

What weight does glomerular filtration occur freely?

Molecular weight of less than 20,000

Provided they are not bound to large plasma proteins.

27

Bound to plasma proteins?

If a drug molecule is bound it cannot enter the fitration via glomerular filtration.

 

28

The equation for the clearance by filtration

CL= GFR x fraction of drug unbound in plasma.

 

GFR: glomerular filtration rate

AS24

29

What is the normal GFR?

120ml/min

30

What percentage of renal plasam flow is filtered through the glomerulus?

20%

31

What is the remaining 80% go?

It is delivered to the peritubular capillaries of the proximal tubule.

32

What does the epithelial cells of the proximal tubule contain?

Contains 2, independent transporter systems that actively secretes drugs into the lumen of the nephron.

33

Name the two transport systems that the proximal tubules use?

  1. Organic anion transporter
  2. Organic cation transporter

 

34

Organic anion transporter?

Handles acidic drugs.

Endogenous acids and the marker for renal plasma flow.

35

Organic cation transporter

Handles basic drugs

36

What is more efficient?

Excretio by filtration or by tubular secretion?

Excretion by tubular secretion for drug elimination by the kidneys

37

The effect of the electrochemical gradient on tubular secretion?

Can concentrate drugs into the tubular fluid against the electrochemical gradient

 

38

Tubular secretion is a what process?

Saturable.

Each carrier has a transport maximum for a particular drug.

 

AS25

39

Why is tubular secretion importatnt for drugs that are highly protein-bound?

As they can secrete them which cannot be done by glomerlar filtration

Free drug concentration reduces secretion (as the drig dissociates from the protein therefore new equilibrium between bound and free drug).

Secretion can totally remove drug-bound by repeatedly producing new equilibrium

40

Name some drugs that are secreted by OAT?

Penicillin

Probasecid

Acetazolomide

Uric acid

Glucuronic acid

41

Name some drugs that are secreted by OCT?

Morphine

Neostigmine

Amilloide

42

Drugs that share the same transporter system?

Compete with each other for secretion leading to interactions

43

What percentage of water filtered at glomerulus is reabsorbed?

99%

44

What makes passive reabsoprtion favourable from drugs?

The concentration of the urine.

Passive reabsorption across the distal tubule by diffusion

45

Name the 4 factors that infleunce reabsoprtion?

  1. Lipid solubility
  2. Polarity
  3. Urinary flow rate
  4. Urinary pH

46

Lipid solubility?

Drugs with high lipid solubility will be extensively reabsorbed and excreted slowly.

47

Polarity?

Highly polar drugs will be excreted without reabsorption

48

Urinary flow rate?

Diuresis decrease absorption

49

Diuresis?

Excess production of urine

50

Urinary pH?

Degree of ionisation of weak acids and bases 

Can stronly influence their reabsorption

51

Alkaline pH?

Increase excretion of acids

 

52

Acidic pH?

Increase excretion of bases

53

Urinary alkalinisation?

Used to accelerate the excretion of aspirin in cases of overdosage

As it increases the movement of aspirin to the renal to be excreted