Distribution (pharmacology)

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Distribution in pharmacology is a pharmacokinetic branch that describes the transfer of a drug that can be recovered from one location to another in the body.

Once the drug enters the systemic circulation by absorption or direct administration, it must be distributed to interstitial and intracellular fluids. Each organ or tissue can receive different doses of the drug and the drug may remain in various organs or tissues for various times. The distribution of drugs between tissues depends on the permeability of blood vessels, regional blood flow, cardiac output and tissue perfusion rates and the drug's ability to bind to tissue and plasma proteins and fat solubility. pH partitions play a major role too. These drugs are easily distributed in highly perfused organs such as liver, heart and kidneys. These are distributed in small amounts through less-absorbed tissues such as muscle, fat and peripheral organs. The drug can be transferred from plasma to tissue until equilibrium is formed (for unbound drugs in plasma).

The concept of compartmentalization of an organism should be considered when discussing the distribution of drugs. This concept is used in pharmacokinetic modeling.

Video Distribution (pharmacology)

Factors affecting distribution

There are many factors that affect the distribution of drugs throughout the organism, but Pascuzzo considers that the most important are the following: the physical volume of an organism, the rate of removal and the extent to which a drug is bound to proteins and/or plasma tissues.

Physical volume of an organism

This concept is related to multi-compartementalizotion. Any drug in an organism will act as a solute and the tissue of the organism will act as a solvent. Different specificities of different tissues will result in different concentrations of drugs in each group. Therefore, the chemical characteristics of a drug will determine the distribution within an organism. For example, drugs that dissolve in liposols will tend to accumulate in body fat and water-soluble drugs will tend to accumulate in extracellular fluids. The distribution volume (V _D ) of a drug is a property that quantifies its distribution level. This can be defined as the theoretical volume that must be occupied by the drug (if distributed uniformly), to provide the same concentration as currently in the blood plasma. This can be determined from the following formula: ${\ displaystyle Vd = {frac {Ab} {Cp}} \,}$ Where: $Â\; Â{\displaystyle Â\; Â\; Â\; Â\; Â\; Â\; Â\; Â\; ÂAÂ\; Â\; Â\; Â\; Â\; Â\; Â\; Â\; ÂbÂ\; Â\; Â\; Â\; Â\; Â}Â\; Â\; Â\; Â$ is the total number of drugs in the body and ${\ displaystyle Cp}$ is the plasma concentration of the drug.

Sebagai nilai untuk $            {\displaystyle         A        b      }        \{\backslash \; displaystyle\; Ab\}\;  ÂÂ$ setara dengan dosis obat yang telah diberikan rumus menunjukkan kepada kita bahwa ada hubungan berbanding terbalik antara ${\ displaystyle Vd}  ÂÂ$ dan ${\ displaystyle Cp}  ÂÂ$ . Yaitu, semakin besar ${\ displaystyle Cp}  ÂÂ$ adalah ${\ displaystyle Vd}  ÂÂ$ akan menjadi dan sebaliknya. Oleh karena itu mengikuti bahwa faktor-faktor yang meningkatkan ${\ displaystyle Cp}  ÂÂ$ akan menurunkan ${\ displaystyle Vd}  ÂÂ$ . Ini memberikan indikasi pentingnya pengetahuan yang berkaitan dengan konsentrasi plasma obat dan faktor-faktor yang memodifikasinya.

If this formula is applied to concepts related to bioavailability, we can calculate the amount of drug to be given to obtain the required drug concentration in the organism (' loading dose ):

${\ displaystyle Dc = {\ frac {Vd.Cp} {Da.B}}}  ÂÂ$

This concept is of clinical importance because it is sometimes necessary to attain a certain concentration of an optimally known drug in order to have the necessary effect on the organism (as it happens if the patient had to be scanned).

Deletion rate

The rate of elimination of the drug will be determined by the proportion of drugs excluded from the circulation by each organ after the drug has been delivered to the organ by the circulating blood supply. This new concept builds on previous ideas and it depends on a number of different factors:

• Characteristics of the drug, including its pKa.
• Redistribution through a network of organisms: Some drugs are distributed rapidly in some tissues until they reach equilibrium with plasma concentrations. However, other networks with slower distribution rates will continue to absorb the drug from plasma for longer periods. This means that the drug concentration in the first tissue will be greater than the plasma concentration and the drug will move from the tissue back to the plasma. This phenomenon will continue until the drug has reached equilibrium across the organism. Therefore, the most sensitive tissues will experience two different drug concentrations: higher initial concentrations and subsequently lower concentrations as a consequence of tissue redistribution.
• Different concentrations between networks.
• Exchange Surface.
• Natural barriers exist. This is an obstacle to the diffusion of a drug similar to that encountered during its absorption. The most interesting are:
  • Capillary capillary permeability, which varies between tissues.
  • The blood-brain barrier: it lies between the blood plasma in the cerebral blood vessels and the extracellular space of the brain. The presence of this barrier makes it difficult for drugs to reach the brain.
  • Placental barrier: This prevents high concentrations of potentially toxic drugs to reach the fetus.

Plasma binding protein

Some drugs have the capacity to bind to certain types of proteins that are carried in the blood plasma. This is important because only the drugs present in the plasma in their free form can be transported to the tissues. Drugs bound to plasma proteins therefore act as drug reservoirs in the organism and this binding reduces the final concentration of the drug in the tissues. The binding of drugs and plasma proteins is seldom specific and usually labile and reversible. Binding generally involves ionic bonding, hydrogen bonding, Van der Waals forces and, more rarely, covalent bonds. This means that the bonds between drugs and proteins can be damaged and drugs can be replaced by other substances (or other drugs) and that, regardless of this, protein bonds are subject to saturation. Equilibrium also exists between the free drug in blood plasma and which is bound to proteins, which means that the proportion of drugs bound to the plasma proteins will be stable, independent of their total concentration in plasma.

In vitro studies performed under optimal conditions have shown that the balance between drug plasmatic concentration and tissue concentration has only changed significantly at plasma binding levels of more than 90%. Above this level, the drug is "sequestered", which lowers its presence in tissues by up to 50%. This is important when considering pharmacological interactions: the concentration of drug tissue with plasma protein binding levels of less than 90% will not increase significantly if the drug moves from its association with proteins by other substances. On the other hand, at a binding rate of more than 95% of small changes can lead to important modifications in drug tissue concentrations. This will, in turn, increase the risk of the drug having a toxic effect on the tissues.

Perhaps the most important plasma proteins are albumin because they are present in relatively high concentrations and they readily bind to other substances. Other important proteins include glycoprotein, lipoprotein and lower globulin levels.

It is therefore easy to see that the clinical conditions that alter plasma protein levels (eg, hypoalbuminemia caused by renal dysfunction) can affect the effects and toxicity of drugs that have a plasma binding rate above 90%.

Maps Distribution (pharmacology)

Redistribution

Medicines that are very soluble in fat given by intravenous or inhaled routes are initially distributed to organs with high blood flow. Then, fewer vascular but larger tissues (such as muscle and fat) take the drug - the plasma concentration falls and the drug is withdrawn from the site. If the drug action site is in one of the most perfused organs, redistribution leads to the cessation of drug action. The greater the solubility of the drug fat, the faster the redistribution. For example, thiopentone anesthesia is terminated within minutes due to redistribution. However, when the same drug is given repeatedly or continuously for a long time, low perfusion and high-capacity sites are progressively filled and the drug becomes longer acting.

This is a reversible process of a drug that moves from a highly perfused place to the systemic circulation, FMAS

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See also

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References

src: molpharm.aspetjournals.org

External links

• Distribution of Medicines

Source of the article : Wikipedia