week 19 p2 Flashcards
What is excretion
- Process by which a drug/metabolite is eliminated from the body
- Knowing this can is essential to optimise efficacy and mimise toxify
- Where can excretion take place
• Kidneys
• Milk
• Liver
Saliva
What is the common elimation
process via urine
• Kidney
Defines as the volume of plasma containing the amount of substances that is removed from the body by kidneys
- What is the fundamental process of renal excretion
- Glomerular filtration
- Active tubular secretion
- Passive reabsorption
- What is first step for renal secretion- GL
- 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.
- What is the reason that blood plasma filters through GL
- 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
- What is filtrated in GF
Small molecules, including water, are readily filtered into the nephron tubule
- What will pass through GF
- 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.
- What cannot pass through GF
- 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
What influences the urinary excretion in GF
- 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
What is the next step after GF
Reabsorption takes place mainly in the proximal convoluted tubule of the nephron.
What occurs in the proximal convulsed tubule
- 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
What factors can effects reabsorption in PCT
is the pH of the urine
What does Ph of the urine plays a crucial part in PCT
- This is especially the case with weak electrolytes
- If the urine is alkaline, weak acids are more ionized and excretion is increased
Since the urinary pH varies in humans, the urinary excretion rates of weak electrolytes also vary.
- Provide examples of pH drugs of PCT
• amphetamine (a basic drug) is ionized in acidic urine
phenobarbital (an acidic drug) is ionized in alkaline urine
How can barbiturate poisoning (such as an overdose of phenobarbital) can be solved
changing the pH of the urine to facilitate excretion
- Why is reabsorption in PCT important
• 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)
How can toxicity in pct for reabsorption occur
Lipid-soluble toxicants can be reabsorbed and re-enter the blood circulation, which lengthens their half-life in the body and potential for toxicity.
- After PCT function, what comes next
Secretion in the the proximal tubule and distal tubule
- What is the function of PTADT
- Secretion such as ions, hydrogen ions and some xenobiotics
* transport of certain molecules out of the blood and into the urine.
- How does secretion occur in PCADT
occurs by active transport mechanisms that are capable of differentiating compounds based on polarity
- What are the pathways/mechanism that exist in the secretion
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)
- What is renal drug transporter
- primarily located in the renal proximal tubules
* play an important role in tubular secretion and reabsorption of drug molecules
- Example of renal drug transporter
- 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).
What are three non renal excretion routes
• bile (and thereby with faeces) • sweat • exhaled air • saliva breast milk
- What is faecal route of excretion
• 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
What re the process where faceal excretion route occurs
• Excretion in bile, which then enters the intestine (“biliary excretion”)
Direct excretion into the lumen of the gastrointestinal tract (“intestinal excretion”)
- What is the process of biliary excretion
• 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
- What does it mean by enzyme sin intestinal floras in biliary excretion
- 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.
- Why is biliary excretion important \
• 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)
- What is direct secretion route
- 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.
What is the issue with directed excretion
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.
