Drug Administration
Distribution of Drugs
The distribution of drugs from the site of absorption, through the bloodstream and to the target tissue depends upon
- The blood flow to the tissue is important in the rate of uptake of a drug. Tissues that receive a high degree of blood flow (eg, brain, kidney) have a fast rate of uptake whereas tissues with a low degree of blood flow accumulate drug more slowly
- Solubility of the drug in the tissue. Some tissues, eg, brain, have a high lipid content and dissolve a higher concentration of lipophilic
- Binding of the drug to macromolecules in the blood or tissue limits their distribution
- The ability to cross special barriers. Many drugs are poorly distributed to the brain and the testis because these tissues contain specialized capillaries (the smallest type of blood vessel). The endothelial cells that line these capillaries form a blood-brain barrier and a blood-testis barrier by preventing the movement of hydrophilic molecules out of the blood and into the tissue, and by actively pumping lipophilic molecules out of the endothelial cell and into the blood.Of special concern is the ability of drugs to distribute to breast milk in lactating women, and the ability of drugs to cross the placenta (the specialized tissue connecting a pregnant woman and her fetus) and affect the developing fetus.
Elimination of Drugs.
The rate of elimination is almost always related to termination of pharmacodynamic effect. Therefore, knowledge of plasma concentrations of a drug is important in describing the intensity and duration of a drug’s effect. There are two major routes of elimination:
- Excretion. The most common route for drug excretion is through the kidney and out of the body in the urine. To be excreted by the kidney, drugs need to be reasonably hydrophilic so that they will remain in the fluid that becomes the urine. Patients with impaired kidney function usually have a reduced ability to eliminate hydrophilic drugs. To avoid excessively high drug concentrations in these patients, you will need to reduce their dosages or give dosages less frequently. A few drugs enter the bile duct and are excreted in the feces
- Metabolism. The action of many drugs, especially lipophilic compounds, is terminated by enzymatic conversion, or metabolism, to biologically inactive derivatives. In most cases, the enzymatic conversion forms a more hydrophilic compound that can be more readily excreted in the urine. Most of the enzymes that catalyze drug-metabolizing reactions are located in the gastrointestinal tract and the liver. Some drugs inhibit drug-metabolizing enzymes and thus cause drug-drug interactions when co-administered with drugs that depend upon metabolism for elimination
Factors Related to Drug Distribution:
1. Lipid Solubility Greater the lipid solubility, more is the distribution and vice versa.
2. Molecular size Larger the size, less is the distribution. Smaller sized drugs are more extensively distributed.
3. Degree of Ionization Drugs exist as weak acids or weak bases when being distributed. Drugs are trapped when present in the ionized form, depending upon the pH of the medium. This fact can be used to make the drug concentrated in specific compartments.
4. Cellular binding Drugs may exist in free or bound form. Bound form of drugs exists as reservoirs. The free and bound forms co-exist in equilibrium. Cellular binding depends on the plasma binding proteins.
Tissue binding: Different drugs have different affinity for different cells. All cells do not bind the same drugs.
5. Duration of Action The duration of action of drugs is prolonged by the presence of bound form while the free form is released. This leads to a longer half life and duration of action of drug.
6. Therapeutic Effects: Bisphosphonate compounds bind with the bone matrix cells and strengthen them. They are used in the treatment of osteoporosis.