6/3/13

Drug Distribution

Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the interstitium (extracellular fluid) and/or the cells of the tissues. The delivery of a drug from the plasma to the interstitium primarily depends on blood flow, capillary permeability, the degree of binding of the drug to plasma and tissue proteins, and the relative hydrophobicity

A. Blood flow 

The rate of blood flow to the tissue capillaries varies widely as a result of the unequal distribution of cardiac output to the various organs. Blood flow to the brain, liver, and kidney is greater than that to the skeletal muscles; adipose tissue has a still lower rate of blood flow. This differential blood flow partly explains the short duration of hypnosis produced by a bolus IV injection of thiopental . 

The high blood flow, together with the superior lipid solubility of thiopental, permit it to rapidly move into the central nervous system (CNS) and produce anesthesia. Slower distribution to skeletal muscle and adipose tissue lowers the plasma concentration sufficiently so that the higher concentrations within the CNS decrease, and consciousness is regained. Although this phenomenon occurs with all drugs to some extent, redistribution accounts for the extremely short duration of action of thiopental and compounds of similar chemical and pharmacologic properties.


 B. Capillary permeability 

Capillary permeability is determined by capillary structure and by the chemical nature of the drug.

 1. Capillary structure: Capillary structure varies widely in terms of the fraction of the basement membrane that is exposed by slit junctions between endothelial cells. In the brain, the capillary structure is continuous, and there are no slit junctions.


(Figure Cross-section of liver and brain capillaries.)


 This contrasts with the liver and spleen, where a large part of the basement membrane is exposed due to large, discontinuous capillaries through which large plasma proteins can pass. a. Blood-brain barrier: To enter the brain, drugs must pass through the endothelial cells of the capillaries of the CNS or be actively transported. For example, a specific transporter for the large neutral amino acid transporter carries levodopa into the brain. By contrast, lipid-soluble drugs readily penetrate into the CNS because they can dissolve in the membrane of the endothelial cells. Ionized or polar drugs generally fail to enter the CNS because they are unable to pass through the endothelial cells of the CNS, which have no slit junctions. These tightly juxtaposed cells form tight junctions that constitute the so-called blood-brain barrier.

 2. Drug structure: The chemical nature of a drug strongly influences its ability to cross cell membranes. Hydrophobic drugs, which have a uniform distribution of electrons and no net charge, readily move across most biologic membranes. These drugs can dissolve in the lipid membranes and, therefore, permeate the entire cell's surface. The major factor influencing the hydrophobic drug's distribution is the blood flow to the area. By contrast, hydrophilic drugs, which have either a nonuniform distribution of electrons or a positive or negative charge, do not readily penetrate cell membranes, and therefore, must go through the slit junctions. 


C. Binding of drugs to plasma proteins 

Reversible binding to plasma proteins sequesters drugs in a nondiffusible form and slows their transfer out of the vascular compartment. Binding is relatively nonselective as to chemical structure and takes place at sites on the protein to which endogenous compounds, such as bilirubin, normally attach. Plasma albumin is the major drug-binding protein and may act as a drug reservoir; that is, as the concentration of the free drug decreases due to elimination by metabolism or excretion, the bound drug dissociates from the protein. This maintains the free-drug concentration as a constant fraction of the total drug in the plasma.

2 comments:

  1. Haloo pak^^

    Kami dari SENTANAPOKER ingin menawarkan pak^^

    Untuk saat ini kami menerima Deposit Melalui Pulsa ya pak.

    *untuk minimal deposit 10ribu
    *untuk minimal Withdraw 25ribu

    *untuk deposit pulsa kami menerima provider
    -XL
    -Telkomsel


    untuk bonus yang kami miliki kami memiliki
    *bonus cashback 0,5%
    *bunus refferal 20%
    *bonus gebiar bulanan (N-max,samsung Note 10+,Iphone xr 64G,camera go pro 7hero,Apple airpods 2 ,dan freechips)

    Daftar Langsung Di:

    SENTANAPOKER

    Kontak Kami;

    WA : +855 9647 76509
    Line : SentanaPoker
    Wechat : SentanaPokerLivechat Sentanapoker

    Proses deposit dan withdraw tercepat bisa anda rasakan jika bermain di Sentanapoker. So… ? tunggu apa lagi ? Mari bergabung dengan kami. Pelayanan CS yang ramah dan Proffesional dan pastinya sangat aman juga bisa anda dapatkan di Sentanapoker.

    ReplyDelete
  2. Dear friends online My name is Destiny Hudson And I live in the USA, Dominica I am here today to appreciate the good work of Dr Oyagu, for helping me curing my HSV 1&2 Disease, I contacted the virus from my Partner, i found out he was cheating on me, so i broke up with him, 2 month later i went to test myself in the hospital when i was seeing sore on my mouth and Private areas, i was diagnosed of HSV 1&2. i tried using the acyclovir medicine but it didn't help in curing it, i went on a search and found out Dr Oyagu curing people illness, and so i got his email and i was told how i can get his herbal cure, 3 days later i received his medicine after using it for 2 weeks i was tested again and was confirm negative, today i am totally free. If you are over there looking for solution email: oyaguherbalhome@gmail.com or contact him on whatsapp +2348101755322 or visit his website oyaguspellcaster.wixsite.com/oyaguherbalhometoday and share your own testimony. And He also has herbal cure for the Following DISEASES, eczema, urethra wart, chronic problems. Herpes, Cancer, Als, Hepatitis, Diabetes, HPV ,Infections, ulcer ETC

    ReplyDelete