week 19 p2

Question 1

What is excretion

Answer 1

• Process by which a drug/metabolite is eliminated from the body
  
  • Knowing this can is essential to optimise efficacy and mimise toxify

Question 2

2. Where can excretion take place

Answer 2

• Kidneys
• Milk
• Liver
Saliva

Question 3

What is the common elimation

Answer 3

process via urine
• Kidney
Defines as the volume of plasma containing the amount of substances that is removed from the body by kidneys

Question 4

4. What is the fundamental process of renal excretion

Answer 4

• Glomerular filtration
  
  • Active tubular secretion
  • Passive reabsorption

Question 5

6. What is first step for renal secretion- GL

Answer 5

• Filtration takes place in the glomerulus
  
  • About 1/4 of the blood flow from cardiac output circulates through the kidney à the greatest rate of blood flow for any organ.
  • blood plasma filters through the glomerulus into the nephron tubule.

Question 6

7. What is the reason that blood plasma filters through GL

Answer 6

• the large amount of blood flow through the glomerulus
  
  • the large pores (40 Angstrom [Å]) in the glomerular capillaries
  • the hydrostatic pressure of the blood

Question 7

8. What is filtrated in GF

Answer 7

Small molecules, including water, are readily filtered into the nephron tubule

Question 8

9. What will pass through GF

Answer 8

• Both lipid soluble and polar substances will pass through the glomerulus into the tubule filtrate.
  
  • About 99% of the water-like filtrate, small molecules, and lipid-soluble substances, are reabsorbed downstream in the nephron tubule.
  • The amount of urine eliminated is only about 1% of the amount of fluid filtrated through the glomeruli into the renal tubules.

Question 9

10. What cannot pass through GF

Answer 9

• Molecules with molecular weights greater than 60,000 (e.g., large proteins and blood cells)
  
  • cannot pass through the capillary pores and remain in the blood.
  • If urine contains albumin or blood cells, it indicates that the glomeruli have been damaged

Question 10

What influences the urinary excretion in GF

Answer 10

• Binding to plasma proteins
  
  • Polar substances usually do not bind with the plasma proteins. and thus can be filtered out of the blood into the tubule filtrate
  • and thus can be filtered out of the blood into the tubule filtrate

Question 11

What is the next step after GF

Answer 11

Reabsorption takes place mainly in the proximal convoluted tubule of the nephron.

Question 12

What occurs in the proximal convulsed tubule

Answer 12

• Nearly all of the water, glucose, potassium, and amino acids lost during glomerular filtration re-enter the blood from the renal tubules.
  
  • Occurs primarily by passive transfer based on a concentration gradient, moving from a high concentration in the proximal tubule to the lower concentration in the capillaries surrounding the tubule

Question 13

What factors can effects reabsorption in PCT

Answer 13

is the pH of the urine

Question 14

What does Ph of the urine plays a crucial part in PCT

Answer 14

• This is especially the case with weak electrolytes
  
  • If the urine is alkaline, weak acids are more ionized and excretion is increased
  • If the urine is acidic, weak acids (such as glucuronide and sulphate conjugates) are less ionized and undergo reabsorption and renal excretion is reduced.
  Since the urinary pH varies in humans, the urinary excretion rates of weak electrolytes also vary.

Question 15

16. Provide examples of pH drugs of PCT

Answer 15

• amphetamine (a basic drug) is ionized in acidic urine

phenobarbital (an acidic drug) is ionized in alkaline urine

Question 16

How can barbiturate poisoning (such as an overdose of phenobarbital) can be solved

Answer 16

changing the pH of the urine to facilitate excretion

Question 17

18. Why is reabsorption in PCT important

Answer 17

• The physical properties (molecular size and polarity) of a substance in the urinary filtrate greatly affect elimination by the kidney.
Ionised substances remain in the urine and leave the body (they cannot be reabsorbed)

Question 18

How can toxicity in pct for reabsorption occur

Answer 18

Lipid-soluble toxicants can be reabsorbed and re-enter the blood circulation, which lengthens their half-life in the body and potential for toxicity.

Question 19

20. After PCT function, what comes next

Answer 19

Secretion in the the proximal tubule and distal tubule

Question 20

21. What is the function of PTADT

Answer 20

• Secretion such as ions, hydrogen ions and some xenobiotics

* transport of certain molecules out of the blood and into the urine.

Question 21

22. How does secretion occur in PCADT

Answer 21

occurs by active transport mechanisms that are capable of differentiating compounds based on polarity

Question 22

23. What are the pathways/mechanism that exist in the secretion

Answer 22

Two systems exist:
• one that transports weak acids (such as many conjugated drugs and penicillins)
• the other that transports basic substances (such as histamine and choline)

Question 23

24. What is renal drug transporter

Answer 23

• primarily located in the renal proximal tubules

* play an important role in tubular secretion and reabsorption of drug molecules

Question 24

25. Example of renal drug transporter

Answer 24

• In the kidney, several transporters are involved in renal handling of organic cation (OC) and organic anion (OA) drugs.
  
  • OA can be transport drug mo9leculaes again gradient and reduce plasma concentration
  • OC facilities transport down the gradient as 80% of the drug delivered to the kidneys is presented to the carrier for elimination
  • drug–drug interactions (DDIs).

Question 25

What are three non renal excretion routes

Answer 25

• bile (and thereby with faeces)
	• sweat
	• exhaled air
	• saliva
breast milk

Question 26

27. What is faecal route of excretion

Answer 26

• that substance-specific portions of orally administered drugs are removed with faeces without entering the circulation. This is due to their incomplete absorption from the gastrointestinal tract

Question 27

What re the process where faceal excretion route occurs

Answer 27

• Excretion in bile, which then enters the intestine (“biliary excretion”)
Direct excretion into the lumen of the gastrointestinal tract (“intestinal excretion”)

Question 28

29. What is the process of biliary excretion

Answer 28

• Substances can be excreted by the liver into the bile, and then into the intestinal tract
• Substances are then eliminated from the body in the faeces, or it may be reabsorbed.
Since most of the substances excreted in the bile are water soluble, they are not likely to be reabsorbed

Question 29

30. What does it mean by enzyme sin intestinal floras in biliary excretion

Answer 29

• hydrolysing some glucuronide and sulphate conjugates
  
  • can release the less polar compounds that may then be reabsorbed.
  • This process of excretion into the intestinal tract via the bile and reabsorption and return to the liver by the portal circulation is known as the enterohepatic circulation.

Question 30

31. Why is biliary excretion important \

Answer 30

• Excretion of xenobiotics and metabolites
• Involves ac
• Specific transport systems appear to exist for certain types of substances, for example, organic bases, organic acids, and neutral substances
The most likely substances to be excreted via the bile have a large molecular weight (conjugates greater than 300)

Question 31

32. What is direct secretion route

Answer 31

• Some substances (e.g., weak bases that are poorly ionized in plasma)
  
  • can passively diffuse through the walls of the capillaries,
  • through the intestinal submucosa,
  • and into the intestinal lumen to be eliminated in faeces.

Question 32

What is the issue with directed excretion

Answer 32

a relatively slow process and therefore, it is an important elimination route only for those xenobiotics that have slow biotransformation, or slow urinary or biliary excretion.