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Excretion Process in Pharmacokinetic Concept

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					Contents
What Is Pharmacokinetics? ........................................................................................................ 2
What Is Excretion ....................................................................................................................... 3
The Concept of Excretion ........................................................................................................... 3
   Renal Excretion....................................................................................................................... 4
      Glomerular Filtration .......................................................................................................... 4
      Active Tubular Secretion .................................................................................................... 4
      Passive Tubular Reabsorption ............................................................................................ 4
   Hepatic Excretion ................................................................................................................... 5
   Pulmonary Excretion .............................................................................................................. 5
      Lung Excretion .................................................................................................................... 5
      Other Routes of Drug Excretion ......................................................................................... 5
Effects of the Drugs to the Excretion ......................................................................................... 6
   Inhibition of tubular secretion ............................................................................................... 6
   Alteration of urine .................................................................................................................. 6
Factors excretion ....................................................................................................................... 7




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Pharmacokinetic Concept
What Is Pharmacokinetics?

Pharmacokinetics comes from Ancient Greek pharmakon "drug" and kinetikos "to do with
motion”. In simple words Pharmacokinetics can be defined as “What the body does to drug”
or it can be defined as:

“Pharmacokinetics is the study of how body reacts by absorbs, distributes, metabolizes, and
excretes drug”

It describes how a drug is absorbed into, distributed through, metabolized with in, and
excreted from the body. This branch of pharmacology also reflects the drug’s onset of
action, peak level, and duration of action.

Pharmacokinetics is often studied in conjunction with pharmacodynamics, and amount of
drug in the body will have the changing phenomenon that involve increase the amount of
drug in the body (absorption process), decrease the amount of drug in the body ( excression
process ), and no changing in amount of drug in the body ( distribution process )

Pharmacokinetics process involves Absorption, Distribution, Metabolism and Excretion or
can be simplified into ADME




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What Is Excretion

Excretion is the process of elimination by an organism of waste products that result from
metabolic processes. Animals have specific organs of excretion. In vertebrates, the kidney
filters blood, conserving water and producing urea and other waste products in the form of
urine. The urine is then passed through the ureters to the bladder and discharged through
the urethra. The skin and lungs, which eliminate carbon dioxide, are also excretory organs.



Drug that are excreted by the kidney typically have longer half-life, leading to a longer
duration of action (>60 minutes). Drug eliminated by the liver tend to have shorter half-life
and duration of action.


The Concept of Excretion

The Excretion of Drugs and Their Metabolites

Drug that we consume need to be excreted from our body as a waste product after it go
through absorption, distribution, and metabolism process and after it provide its
therapeutic effect to the body

Excretion is the amount of drug and drug metabolites excreted by any process per unit.
Three fundamental renal processes for renal drug excretion:

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Renal Excretion
Glomerular Filtration


After the drugs give it therapeutic effects to the part of the body, it will enter the kidney
through renal activities to undergo glomerular filtration. Free drugs which are drug that not
bound to albumin will flows through capillary ships into Bowman’s capsule as part of
glomerular filtration.

Lipid solubility and pH not influence the passage of drugs into Glomerular Filtration. It
depends on the size, charge and protein binding of a particular drug. Glomerular Filtration is
lower for highly protein bounded drugs.



Active Tubular Secretion


This process occurs in middle segment of the Proximal Convoluted Tubules in kidney. This is
very effective mechanism of renal drug excretion. Drug that was not undergoes into
Glomerular Filtration will leaves the glomeruli through efferent arteriole which divide to
form a capillary plexus surrounding the nephric lumen in the proximal tubule. Each
transport does not have high specificity and can transport many components. Risks of
competition between drugs for the carrier are high within each transport.



Passive Tubular Reabsorption


This mechanism depend on pH of urine in undergo excretion process. As drugs moves
toward the distal convoluted tubule, it will exceed the perivascular as its concentration
increases. Diffusion out of the nephric lumen back into the systemic circulation may occur if
there is any drug uncharged.
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Hepatic Excretion

This process occurs in bile which is a major route of excretion of few drugs and their
metabolites. Large polar compounds will secrete into bile actively and may be reabsorbed
from the intestine to undergo further cycles of biliary excretion that is called Enterohepatic
Recycling.

Significant proportion of drug in the body may be held in this enteric poll which may act to
increase drug’s half-life.



Pulmonary Excretion
Lung Excretion


Lungs also play an important part in excretion process of the drugs. It excretes the volatile
drugs from the body. This route is important mainly for general anesthetic drugs that exist
in gaseous or vapor forms.



Other Routes of Drug Excretion


Breast milk

Milk producing glands are surrounding by a network of capillaries and many substances
include drugs pass from maternal blood into the breast milk.

Perspiration, Saliva and Tears

Drugs may be excreted passively via these secretions if the drugs are lipid soluble. Non lipid
soluble drugs do not undergo this secretion process.
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Effects If Drug Excretion Not Occur

Main mechanism by which drug can affect the rate of renal excretion of another is by



      Inhibit tubular secretion
      and the alteration of urine and or urine pH




Inhibition of tubular secretion
Probenecid developed and inhibits penicillin secretion. It makes the action become long.
Apart from that, it also inhibits another drug and also includes ziduvusile. There are also
drugs have an indicated probenecid such as effect and enhance action of substances that
rely on tubular secretion for their elimination. For example, diuretics act for within the
tubular lumen, drugs inhibit their secretion into tubular fluid like NSAID, which reduce their
effect.



Alteration of urine
Diuretics have the ability to increase urinary secretion of other drug, but this seldom
clinically. In conversely, loop diuretics and thiazide diuretics indirectly increase the proximal
tubular reabsorption of lithium (the similar way to handle as Na+). Moreover, it can cause
lithium toxicity in patients treated with lithium carbonate for mood disorders. The effects of
urinary pH on excretion of weak acid and bases is put to use treatment of poisoning with
salicylate but not to be used as interactions.


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Factors excretion

The factor that effect the rates of drugs excretes is depends on the size, charges and
protein bindings of specific drugs. The rate of drugs filtrates will low if the drugs are highly
protein-bounded drugs. For examples warfarin, it approximately 98% bound to albumin
because its concentration in the filtrate will be less than the total plasma concentration. So,
the process is slower.



The excretion process are depends on the competition between carrier and polarity of the
drugs itself. If the drugs are high polarity, it will slower down reabsorption process at active
tubular and the process of excretion will be slower. Basically, competition between drugs
for the carrier can occurs within each transport system. For examples, in premature infants
the certain drugs may retain because of incomplete developed of their tubular mechanism.



This mechanism also depends on the pH of the urine because its concentration will increase
and exceeds that of perivascular space when the drugs move towards the distal convoluted
tubules. Both acidic and basic drugs are secreted into the lumen via its specific ‘acid’ and
‘base’ pumps. For examples, the drugs that excrete via acid pump are penicillin and
probenecid. While the drugs that secrete via base pump are ranitidine and prolacamide. The
excretion of acidic drugs will be slower at acidic medium where the pH<7.Also the basic
drugs will be slower at the base medium, pH>7.



Depends on renal function the renal function will be decrease in development if age more
elderly. It is a normal aging process. Also when a person has a chronic renal failure, it will
affect the excretion process of drugs. The excretion of most drugs almost none exist.
Another factor is when people have cardiac failure; kidneys also will be decrease the renal
excretion of unchanged drugs and drugs metabolites as blood flow to kidneys is low.



The factor in liver excretion is depends on the polar compound of drugs because the major
product of excretion of few drugs and metabolites is bile. The more polar is the drugs, the
more higher its molecular weight. So, the higher the molecular weight of drugs will produce
more actively will secrete into bile. Although it is secreted into bile then reabsorb again at
small intestine but it will interrupted by agent drugs in the intestine for examples charcoal
and chaestyramine.
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The factors of the rates of loss are depends on the volatility of drugs and rate of
respiration or expired air. Some drugs such as ethyl alcohol and paraldehyde are highly
soluble in blood and excreted in small or limited amount by lungs. Because of their vitality,
these compounds are easy to volatile and detected because the individual exhale the
gaseous into atmosphere. The rate of respiration also increasing the rates of excretion for
examples if take deep breathing and exercise, it could raises the cardiac output and
subsequently will increase in pulmonary blood flow that lead to promotes excretion.




The excretion process at breast depends on the maternal plasma drug concentration and
the amount of milk ingest by the baby or infant. The breast milk is acidic (pH 6.6); therefore
basic drugs with low plasma protein binding and high lipid solubility such as narcotics drugs
for examples morphine and codeine will achieve higher concentration in breast milk. Also,
the drugs excretion in milk is higher if the transfer of drugs from mother to infant is in large
volume. But the drugs in milk are excreting in small amounts and it also can lead sedation to
infants if the mother is taking narcotics drugs.



The excretion of drugs at saliva and through sweat is depends on diffusion of lipids-
soluble drugs through the epithelial cell of glands. The excretion of drugs will be easier if
the compounds are lipid soluble although it only represents minor proportion of total
excretion.




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References


Lecture Note by Pn Noraziah Bt Ali

Mc Graw Hill, Lange, Bertram Katzung, Susan B. Master, Anthony J. Travel, “Basic
Pharmacology And Clinical Pharmacology”, 11th Edition

Rang and Dale’s 6th Edition, H.P. Rang, M.M Dale, J.M. Ritter, R.J. Flower “Rang and Dale’s
6th Edition”

http://en.wikipedia.org/wiki/Pharmacokinetics




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Description: all you need to know about excretion process regarding to Pharmacokinetic process