Drug Elimination - Pharmacokinetics

The drug is excreted in the form of pure or have been transformed.

Excreted renally

This is the most important sugar excretion of water-soluble drugs, has a molecular weight of less than 300.

The process of elimination

Passive glomerular filtration: free drug form, not attached to plasma proteins.

Last active tubular secretion: due to quality ransfer transport (carrier) so there is competition for elimination. For example, prolonged thiazide use, due to elimination of thiazide, the body reduces uric acid, prone to gout (thiazide and a.uric same tubular carrier).

The process of active secretion occurs mainly in the proximal tubule, there are two different transport systems, a system for the anion (carboxylic acids such as penicillin, thiazide, glucuro substances - and sulfo- case), and a for the cation (the organic base such as morphine, thiamin).

Passive diffusion through the tubules: a part of th Pass drugs except in the initial urine is re-absorbed into the bloodstream. It is lipid soluble drugs, not ionized in urine pH (pH = 5 -6) as phenobarbital, salicylates. The main base is not reabsorbed.

This process occurs in the proximal tubule and distal tubule by both terraced levels generated during re-absorption of sodium and water and other inorganic ions. The process of passive reabsorption here depends on the pH of urine. When the base of the urine, the weak acid (barbituric acid) will be eliminated faster because ionized much should reuptake fell. Conversely, when the urine more acid, the base (amphetamine) will be eliminated more. This is used in the treatment of poisoning.

The clinical significance

Reduce drug elimination to save: penicillin and probenecid have in common renal tubular transport systems. Kidneys probenecid (cheaper, less effective treatments) and retained penicillin (more expensive, have a therapeutic effect).

Increases excretion to treat poisoning: base urine, increasing the ionization of phenobarbital, increased excretion of phenobarbital when contaminated (see "passive diffusion").

In cases of renal impairment, the dose should be reduced using

Biliary excretion

Once metabolized by the liver, and metabolites excreted in bile will to pleasure p out. Much more after being metabolized in the intestine will be reabsorbed into the blood for excretion through the kidneys.

Some of the metabolites of drugs glycuronid molecular weight above 300 after biliary excretion into the intestine can be hydrolyzed by  glycuronidase then be reabsorbed liver intravenous bear left into circulation Full called intestinal drug cycle - liver.

These drugs accumulate in the body, making lasting effect (morphine, tetracycline, digitalis cardiac ...).

Excreted through the lungs

The volatiles such as wine, oil (Eucalyptol, menthol)

These gases: nitrogen protoxyd, halothane

Excreted in milk

The strong solute in lipid (barbiturates, nonsteroidal anti-inflammatory, tetracycline, alkaloids), with a molecular weight below 200 usually easily excreted in milk.

Because milk slightly acid pH than plasma so the base is weak drug concentration may have slightly higher in milk and plasma drug is weak acid concentration is lower.

Excreted via other routes

The drug can also be excreted in sweat, tears through, through keratinocytes (feathers, hair, nails), salivary glands. The number of insignificant little significance in terms of treatment. Can often cause unwanted effects (causing increased production diphenyl hydantoin benefits being excreted in saliva). Or used to detect toxins (legally valid y): detection of arsenic in Napoleon's hair after 150 years!

Pharmacokinetic parameters of metabolism and excretion

The purpose of the transformation is to make the drug inactivation, water-soluble and excreted. Therefore,

metabolism is the process of excretion. There are two pharmacokinetic parameters are the bar

waste (CL) and the half-life (t1 / 2) were to evaluate the metabolism and excretion.

Clearance (clearance CL)

define

Clearance (CL) denotes the ability of one organ (liver, kidney) in the body completely eliminated a drug (or a substance) from the blood plasma circulating through the agency.

Clearance expressed in mL / min, the number of mL plasma drug is eliminated completely in 1 minute when the last time the agency. Or as per kg body weight: mL / min / kg.

CL = (V / Cp) (mL / min)

V: speed through the elimination of the drug agency (mg / min) Cp: plasma concentrations (mg / L).

Clearance is also a virtual value, theoretical because the circulation of blood through the organ is constantly repeated. In fact, the drug is considered to be purified from plasma after a period of 7 x t1 / 2.

Two government agencies Participation excretion from the body is the liver (amount of drug metabolized and excreted in the bile pure) and kidney, therefore, be regarded as the entire CL CL CL liver + kidney.

meaning

Drugs big CL drug is excreted rapidly, so the half-life (t 1/2) will be short.

CL used to calculate the dose can only be dragged t stable drug levels in plasma. This concentration is achieved when excretion rate by the rate of absorption.

Know CL to adjust the dose in cases of liver failure, kidney failure.

The half (half- LIFE- t1 / 2)

define

The half-life t1 / 2 was distinguished as two types:

- T1 / 2 α or t1 / 2 absorption is the time required for half the amount of drug absorbed is used in circulation. if therapy is administered intramuscularly, the t 1/2  negligible.

- T1 / 2 β or t1 / 2 elimination is the time required for the drug concentration in plasma decreased to 1/2.

In practice treatment, or use t1 / 2 õ and usually written as t1 / 2 or t / 2.

meaning

From this formula we see t1 / 2 is inversely related to clearance. When CL vary with the cause physiological or pathological would t1 / 2thay change, the effect of treatment affected. Need dose adjustment or distance between doses (see section "Changes of pharmacokinetics").

In practice treatment, often considered 5 l ần time t1 / 2 (5 times equidistant medication), the drug concentration in the blood reach steady state (CSS), and after a threshold of about 7 times t 1 drug / 2 is regarded as the drug has been completely eliminated from the body.

For each drug, the half-life is the same for all doses. Because it can be inferred about medication:

When t1 / 2 <6: if less toxic drugs, the prolonged high doses to be effective concentration of drug in plasma. If you are unable to get higher doses (such as heparin, insulin), the continuous intravenous infusion or produce slow-release form of the drug.

When t1 / 2 from 6 to 24: Using the correct dose with distance with t 1/2. When t1 / 2> 24: 1 single dose once a day.