Excretion Flashcards
How is elimination from the body fluid achieved by?
Metabolizing drugs into hydrophilic forms or by simply excreting hydrophilic drugs in their original form
What 7 ways are drug excreted?
Bile, breath, sweat, tears, salvia, breast milk and urine
What is the most common form of excretion?
Through the kidneys
What is the rate of excretion determined by?
Glomerular filtration
Tubular secretion
Passive diffusion
How is penicillin cleared from the body?
Almost completely on a single transit through the kidneys
What is the main function of the kidney and what is the process called?
Filter blood and produce urine and the process is called glomerular filtration
What does the afferent artery do?
Brings blood to the glomerulus for filtration
What does the efferent artery do?
Takes the filtered blood away from the glomerulus
What happens as the blood flows through the glomerular capillaries?
10-20% of the fluid in the bloodstream is passed out in the Bowmans space
What happens to the other 90%?
Must be filtered on the other pass through the kidneys
How is filtrate formed?
When blood pressure forces the fluid from the blood in the glomerulus into the lumen of the Bowmans capsule
What do cells lining the glomerular capillaries have? What does this allow the drug to do?
Have pores between them allowing most drugs to pass through them
How are low molecular drugs eliminated?
Through glomerular filtration
If a drug bind to to plasma albumin what is filtered?
Only free drug
What 3 major regions of the nephron does the drug pass through?
- proximal tubule
- loop of henle
- distal tubule
Where do all 3 excretion processes happen?
In the nephron
How does metabolite pass out through the urine?
Filtered into the nephron > flows through the nephron > into the collecting ducts > out in the urine
What does filtrate contain?
Things we want rot excrete (waste products, inactive metabolites) and things we want to reabsorb back into the bloodstream (glucose, amino acids)
What happens to 80% of the drug? How does it carry and where does it go?
Stays in the bloodstream carries in the efferent arteriole to the peritubular capillaries around the proximal tubule
How can one drugs to be transported from the blood for excretion?
They are actively transported from the blood directly into the tubules for excretion
There are 2 carrier systems in the tubular cells. What are these for?
One for acids and one for bases
What is tubular secretion?
Unidirectional
What is tubular secretion? What does it need?
An active process, needs energy to carry drugs against a favorable chemical gradient
How does tubular secretion removes bound and free drug?
By creating a concentration gradient - drug released from protein > passes into the capillary tubule
How does tubular reabsorption happen?
Through passive diffusion
What happens in tubular reabsorption?
Reabsorbing Drugs (nutrients) into the bloodstream from the tubule
What will happen to lipid soluble drugs?
Passively diffuse into the capillaries surrounding the tubule
What will happen if drugs aren’t lipid soluble?
Stay in the tubule, pass into the collecting ducts and out in the urine
What happens to water soluble metabolites?
Can’t get out of the tubules, all excreted
Glomerular filtration
Blood to tubule
Tubular selection
blood to tubule
Tubular reabsorption
Tubule to blood
What are the 3 factors that affect renal drug excretion?
1.ph
2.age
3.disease
What are weak acids more likely to be in alkaline urine?
Excreted and vice versa
Why can renal excretion be decreased with age?
Renal mass and renal perfusion reduce with increasing age, decreased blood flow through the kidneys and fewer functional nephrons
What types of disease can decrease renal function?
Renal disease, reduced renal mass, shock, decreased blood flow
What occurs in the proximal tubule?
Competition occurs between drugs that share transport mechanisms
How can drugs be made active again?
If they have been metabolized can enter the GI tract in the bile, where the metabolic process can be reversed making the drug active again
How can drugs that have been metabolized in the liver be excreted?
They can via the bile duct into the gut and excreted in the faeces
Enterohepatic recycling
Enterohepatic recycling, also known as enterohepatic circulation, refers to the process where certain substances, including drugs, bile acids, and other metabolites, are reabsorbed into the bloodstream from the intestines after being excreted into the bile by the liver. This recycling process prolongs the presence of these substances in the body, often extending their duration of action.
When does biliary excretion become important?
When renal function is poor
What type of molecules are removed by biliary excretion?
Large, ionized molecules
How are the phase 2 metabolites transferred from hepatocytes to the bile?
What can these be?
By non specific carrier systems and these can be inhibited in a manner similar to that seen in the renal tubule
What type of molecules compete with each other?
Negatively charged drugs/metabolites compete with other negatively charged drugs/metabolites while positively charged drugs/metabolites compete with other positively charged drugs/metabolites
What is the result of enterohepatic recycling?
The result of enterohepatic cycling is a ‘reservoir’ of recirculating drug that can amount to about 20% of total drug in the body, prolonging drug action
When drugs are delivered to the small intestine by the biliary system what may happen?
May be excreted in the faeces or may undergo enterohepatic recycling
What does enterohepatic circulation vary between?
Between individuals
Half life
Time taken for the concentration of the drug to decrease by 50%
Zero order kinetics
When all the enzymes are occupied and the system is saturated, then the rate of metabolism is limited. At this point, a small increase in dose can lead to a large increase in drug concentrations.
Steady state
Steady state- is reached when the rate of absorption equals the rate of elimination.
Why is half life important?
Half-life is important in determining how long it takes for drug concentrations to reach a steady state in the plasma.
How many drug half lives does it take for the drug ton achieve steady state in plasma concentrations?
About 5 times
Want is steady state used to evaluate?
The pharmacological effect conduct therapeutic monitoring
What is half life important in determining?
Time interval between drug doses and time taken to reach a steady state
First order kinetics
First-order kinetics refers to the most common pattern of drug elimination, where the rate of elimination of a drug is directly proportional to the drug concentration in the bloodstream. This means that the higher the concentration of the drug, the faster it is eliminated from the body, and as the drug concentration decreases, the elimination rate also decreases.
Why is zero order kinetics unpredictable?
Because the enzymes can become saturated
