Pharmacology Part 5

Question 1

How do most drugs leave the body?

Answer 1

In the urine as unchanged compounds or chemically transformed compounds rendered more polar by metabolism

Question 2

What other ways can drugs be excreted?

Answer 2

Bile
Sweat
Milk

Question 3

What is a xenobiotic?

Answer 3

a drug

Question 4

What does drug metabolism act to do?

Answer 4

Convert parent drugs into more polar metabolites that are not reabsorbed by the kindney

Convert into metabolites that are pharmacologically less active

Question 5

What may occasionally happen to metabolites in drug metabolism?

Answer 5

Be converted from inactive prodrugs to active compounds or gain activity

have unchanged activity

possess a different type, or spectrum of action (aspirin and its metabolite salicylic acid

Question 6

What is the main organ of drug metabolism

Answer 6

Liver

GI tract, lungs and plasma also have activity

Question 7

What are the two sequential phases of drug metabolism

Answer 7

Phase I
-makes drug more polar, adds chemically reactive group permitting conjugation

Phase II
Adds an endogenous compound increasing polarity

Question 8

What are the processes involved in phase I

Answer 8

Oxidation
Reduction
Hydrolysis

Question 9

What are the processes involved in phase II

Answer 9

Conjugation with glucuronyl, sulphate, methy, acetyl, glycol or gluthione

Question 10

Describe the phases of aspirin metabolism

Answer 10

Phase I (Catabolic) Drug to derivative (aspirin to salicylic acid)

Phase II
(anabolic) Derivative to conjugate (salicylic acid to glucuronide)

Question 11

What mediates oxidation reactions (Phase I) of drug metabolism of lipid soluble drugs?

Answer 11

Haem proteins located in the endoplasmic reticulum of liver hepatocytes (and elsewhere)

Question 12

What is the CYP family classified by?

Answer 12

on the basis of amino acid sequence similarities

Question 13

What do CYP family have in common in terms of function?

Answer 13

distinct, but frequently overlapping substrate specificities

Question 14

What are the main gene families in the human liver?

Answer 14

CYP1, CYP2 and CYP3

Question 15

Describe the monooxygenase P450 cycle?

Answer 15

Drug enters the cycle as substrate

Molecular oxygen provides two atoms

One atom of oxygen is added to the drug to yield the hydroxyl product- which leaves the cycle- the second combines with protons to form H2O

Question 16

What do phase II reactions produce and where do they occur?

Answer 16

Inactive products

In the liver

Question 17

What is glucoronidation?

Answer 17

common reaction involving the transfer of glucuronic acid to electron-rich atoms of the substrate (N, O, or S, forming amide, ester, or thiol bonds))

Question 18

Which endogenous substances undergo glucoronidation?

Answer 18

bilirubin, adrenal corticosteroids

Question 19

What is significant about clearance of phase I and phase II products

Answer 19

Almost always cleared from blood quicker than parent compound

Question 20

What are the three processes involved in renal excretion?

Answer 20

1. glomerular filtration
2. active tubular secretion
3. passive reabsorption by diffusion across the tubular epithelium

Question 21

For what drugs does glomerular filtration occur freely?

Answer 21

MW less than 20000, provided they are not bound to large plasma proteins

Question 22

What is unimportant in glomerular filtration

Answer 22

Drug charge

Question 23

What happens if drug binds appreciably to plasma protein?

Answer 23

GFR will be less than total plasma concentration

Question 24

What % of renal plasma flow is directed through the glomerulus vs the peritubular capillaries of the proximal tubule?

Answer 24

20%

Question 25

What two transporter systems are found in the proximal tubules?

Answer 25

Organic anion transporter

Organic cation transporter

Question 26

What is the role of OAT and OCT

Answer 26

Actively secrete drugs into the lumen of the nephron

Question 27

What does the AOT handle?

Answer 27

Acidic drugs, endogenous acids and the marker for renal plasma flow (PAH)

Question 28

What does the OCT handle?

Answer 28

Basic drugs

Question 29

What is the most effective mechanism of drug elimination by the kidney?

Answer 29

Tubular secretion

Question 30

What is special about tubular secretion of drugs?

Answer 30

Can concentrate drugs in tubular fluid agains electrochemical gradient

Question 31

What kind of process in tubular secretion?

Answer 31

Saturable- each carrier has a transport maximum for a particular drugs

Question 32

What occurs in tubular secretion that cannot in GF?

Answer 32

Can secrete drugs that are high protein bound

Question 33

What might some drugs sharing a transporter system cause?

Answer 33

compete with each other for secretion leading to interactions, e.g:

• Probenecid has been used to retard the excretion of penicillins
• Frusemide and thiazides may retard the excretion of uric acid and precipitate gout

Question 34

What percentage of water filtered at the glomerulus is reabsorbed?

Answer 34

99%

Question 35

What does concentration of urine favour?

Answer 35

Passive reabsorption of drugs across the distal tubule by diffusion

Question 36

What factors affect reabsorption rate?

Answer 36

> lipid solubility – drugs with high lipid solubility will be extensively reabsorbed and excreted slowly

> polarity – highly polar drugs will be excreted without reabsorption

> urinary flow rate – diuresis decreases reabsorption

> urinary pH – the degree of ionisation of weak acids and bases can strongly influence their reabsorption

Question 37

What does alkaline pH do to excretion?

Answer 37

Increases excretion of acids

Question 38

What does acidic pH do to excretion ?

Answer 38

Increases excretion of bases

Question 39

What is the clinical relevance on urinary alkalisation?

Answer 39

can be used to accelerate the excretion of aspirin (weak acid) in cases of overdosage