Why We Swim Bonnie Tsui. Related Audiobooks Free with a 30 day trial from Scribd. Pamela Peeke, M. Factors affecting distribution of drug 1. Shubhrajit Mantry D. Pharm, B. Pharm, M. Pharm, Ph. Disposition is defined as the process that tend to lower the plasma concentration of drug. The two major drug disposition processes are as : 1. Distribution: Which involves reversible transfer of a drug between compartments.
Elimination: Which causes irreversible loss of drug from the body. Elimination is further divided into two processes: a Biotransformation metabolism b Excretion 3. Figure 1: The interrelationship between different process of drug disposition 4. Permeation of the drug present in the ECF through the membrane of tissue cells and into the intercellular fluid. Binding of drugs to tissue components. Almost all drugs having molecular weight less than to Daltons easily cross the capillary membrane to diffuse into the extracellular interstitial fluids.
However, penetration of drugs from the extracellular fluid into the cells is a function of molecular size, ionization constant and lipophilicity of the drug. Only small, water-soluble molecules and ions of size below 50 Daltons enter the cell through aqueous filled channels whereas those of larger size are restricted unless a specialized transport system exists for them.
The pH of the blood and the extravascular fluid also play a role in the ionization and diffusion of drugs into cells. A drug that remains unionized at these pH values can permeate the cells relatively more rapidly. Since the blood and the ECF pH normally remains constant at 7. All drugs that ionise at plasma pH i. Only unionized drugs which are generally lipophilicity, rapidly cross the cell membrane.
All drugs, ionised or unionised, with a molecular size less than Daltons, diffuse through the capillary endothelium and into the interstitial fluid. The brain capillaries consist of endothelial cells which are joined to one another by continuous tight intercellular junctions comprising is called as the blood-brain barrier.
Active transport of essential nutrients such as sugars and amino acid. Thus structurally similar foreign molecules can also penetrate the BBB by the same mechanism.
The capillary endothelium that lines the choroid plexus have open junctions or gaps and drugs can flow freely into the extracellular space between the capillary wall and the choroidal cells. However, the choroidal cells are joined to each other by tight junctions forming the blood- CSF barrier which has permeability characteristics similar to that of the BBB Clinical Significance As people age, the overall body water reduces.
Phase II reactions : Involves the coupling of the metabolite with glucuronic acid, acetyl groups, sulfates, amino acids, or glutathione. Inhibitors: amiodarone, cimetidine, diphenhydramine, fluoxetine, paroxetine, quinidine, ritonavir, terbinafine. Substrates: amitriptyline, carvedilol, codeine, donepezil, haloperidol, metoprolol, paroxetine, risperidone, tramadol. Substrates: alprazolam, amlodipine, atorvastatin, cyclosporine, diazepam, estradiol, simvastatin, sildenafil, verapamil, zolpidem.
Nursing, Allied Health, and Interprofessional Team Interventions The interprofessional team and healthcare professionals, including laboratory technologists, pharmacists, nurses, and clinicians, need to all work together to ensure the safety and efficacy of administered drugs. Review Questions Access free multiple choice questions on this topic. Comment on this article. Figure Pharmacy Calculations: Figure 3: The relationship between pharmacokinetics and pharmacodynamics.
References 1. An introduction to drug disposition: the basic principles of absorption, distribution, metabolism, and excretion. Toxicol Pathol. Feucht C, Patel DR. Principles of pharmacology. Pediatr Clin North Am. Currie GM. Pharmacology, Part 2: Introduction to Pharmacokinetics. J Nucl Med Technol. Dong X. Current Strategies for Brain Drug Delivery. Paediatric pharmacokinetics: key considerations. Br J Clin Pharmacol. Mansoor A, Mahabadi N. Volume of Distribution. Practical pharmacokinetics: what do you really need to know?
How strong is a covalent bond? Bernhardt R. Cytochromes P as versatile biocatalysts. J Biotechnol. Pharmacokinetic changes in critical illness. Crit Care Clin. J Pharm Pharm Sci. The effect of critical illness on drug distribution. Curr Pharm Biotechnol. Drug Metabolism in the Liver. Clin Liver Dis. Manikandan P, Nagini S. Curr Drug Targets. Clinical pharmacy practice in the care of Chronic Kidney Disease patients: a systematic review.
Int J Clin Pharm. J Multidiscip Healthc. Drug Distribution. In: StatPearls [Internet]. Blood-Brain Barrier is the brain capillaries that consist of endothelial cells that are joined to one another by continuous tight intercellular junctions. The presence of special cells called pericytes and astrocytes at the base of the endothelial membrane acts as a supporting tissue.
The specific areas like the trigger area and the hypothalamic eminence of the brain do not have BBB. A Solute passes the BBB by either of the following pathways:.
Active transport of essential nutrients like sugars and amino acids, hence the similar drugs can also pass the BBB by this mechanism. The different approaches that promote drugs to cross BBB are:. Use of permeation enhancers like dimethyl sulphoxide DMSO. Osmotic disruption of the BBB by infusion of mannitol into the internal carotid artery.
Use of a carrier system like dihydropyridine redox system for delivery of steroidal drugs to the brain. Blood-Cerebrospinal Fluid Barrier. The drug can flow freely into the extracellular space between the capillary endothelium wall and the choroid cells. The choroidal cells join to each other by tight junctions to form the blood CSF barrier that has the permeability and diffusion of the drug similar to BBB but, the degree of uptake may vary significantly.
The drug that enters the CSF slowly cannot achieve a high concentration as the bulk flow of CSF continuously removes the drug. CSF concentration may be higher than its cerebral concentration. Blood-Placental Barrier. The maternal mother and fetal blood vessels are separated by a fetal trophoblast basement membrane and the endothelium that together constitute the placental barrier.
The human placental barrier has a mean thickness of 25microns during early pregnancy and reduces to 2microns at full term but does not reduce its effectiveness.
The drugs having a molecular weight less than Daltons and moderate to high lipid solubility can cross the barrier rapidly by simple diffusion. It is not as effective as BBB. The nutrients essential for fetal growth are transported by carrier-mediated processes, and the immunoglobulins are transported by endocytosis.
Blood-Testis Barrier. This barrier is present at the Sertoli-Sertoli cell junction. It is the tight junction between the neighboring Sertoli cells that act as the blood-testis barrier. This barrier restricts the passage of drugs to spermatocytes and spermatids. Distribution is permeability rate-limited in the following cases:.
When the drug is ionic, or polar, or water-soluble, the highly selective physiological barrier restricts the diffusion of such drug to the inside of a cell. The distribution will be perfusion rate-limited in the following cases:.
When the drug is highly lipophilic. When the membrane is highly permeable. Distribution rate constant Kt and distribution half life are calculated as follows:. The greater the blood flow, the faster will be the distribution. Highly lipophilic drugs can cross the most selective barrier like BBB, E. The highly permeable capillary wall permits the passage of almost all drugs, except those bound to plasma protein.
Highly perfused tissues like the Lungs, Kidneys, Liver, Heart, Brain are rapidly equilibrated with the lipid-soluble drugs. But the brain is a highly perfused organ, so the drug is distributed fast and shows a rapid onset of action than poorly perfused adipose tissue.
Drugs can bind to the different components of tissue; they may be intracellular or extracellular. Drugs can bind to many of the blood components, which influences the distribution of the drugs. Plasma Protein Bindings. Human serum albumin: All types of drugs. Alpha Acid glycoprotein: Basic drugs. Lipoproteins: Basic, lipophilic drugs chlorpromazine.
Alpha 1-Globulin: Steroids like corticosterone, vitamin B Hemoglobin: Phenytoin, phenothiazines. The binding of the drug to the plasma protein is reversible. The order or extent of binding of drugs to various plasma proteins is:.
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