Principles of Drug Action Practicum of Health Science Technology

General Properties of Drugs Drugs do not confer any new functions on a tissue or organ in the body, they only modify existing functions Drugs in general exert multiple actions rather than a single effect Drug action results from a physiochemical interaction between the drug and a functionally important molecule in the body

Mechanisms of Drug Action To produce its optimal effect, a drug must reach appropriate concentrations at its site of action

Pharmacokinetics The study of the concentration of a drug during the process of absorption, distribution, biotransformation, and excretion.

Pharmacokinetic Activities Absorption Distribution Biovailibility Excretion

Absorption The process involving the movement of drug molecules from the site of entry into the body to the circulation The rate of absorption depends on the route of administration

Routes of Drug Administration Enteral – oral Parenteral – injection - Subcutaneous - Intramuscular - Intravenous - Intrathecal - Epidural

Routes of Drug Administration Pulmonary – inhalation; nebulilzers Topical – skin and mucous membranes - Skin - transdermal - Eyes - Ears - Nasal mucosa

Bioavailability The percentage of active drug substance absorbed and available to target tissues, following administration

Distribution The transport of a drug in body fluids from the bloodstream to various tissues of the body and ultimately to its site of action

Drug Reservoirs Allow a drug to accumulate by binding to specific tissues in the body Sustains the pharmacologic effect of the drug at its point of action Involve two general types of drug pooling: - Plasma Protein Binding - Tissue Binding

Plasma Protein Binding On entry into the circulatory system drugs may become attached to proteins, mainly albumin contained in the blood Protein binding decreases the amount of free drug in circulation, which limits the amount of drug that travels to the site of action

Tissue Binding Fat tissue – Lipid soluble drugs have a high affinity for adipose tissue, which is where these drugs are stored Relatively low blood flow in fat tissue makes it a stable reservoir Bone – Some drugs have an unusual affinity for bone;

Barriers to Drug Distribution Specialized structures made up of biologic membranes can serve as barriers to the passage of drugs at certain sites in the body - Blood Brain Barrier - Placental Barrier

Blood - Brain Barrier Special anatomic arrangement that allows distribution of only lipid – soluble drugs into the brain and cerebrospinal fluid; Compounds that are strongly ionized and poorly soluble in fat cannot enter the brain

Placental Barrier The membrane layers that separate the blood vessels of the mother and the fetus Does not completely protect the fetus The barrier is permeable to lipid soluble and insoluble drugs Many drugs intended to produce a therapeutic response in the mother also my affect the developing baby

Biotransformation or Metabolism Chemical inactivation of a drug by converting it into a more water-soluble compound, or metabolite, that can be excreted from the body Liver is the primary site of metabolism of drugs

Excretion The process where drugs and pharmacologically active or inactive metabolites are eliminated from the body; - Kidneys - Intestine - Lungs - Sweat and salivary glands - Mammary glands

Kidneys Most important route of drug elimination The availability of a drug for kidney filtration depends on its concentration in unbound form in the plasma Lipid soluble drugs are not excreted by the kidneys Water-soluble drugs are excreted by the kidneys

Intestines Some of the medications are eliminated through the intestines through biliary excretion After metabolism by the liver, the metabolite is secreted into the bile, passed into the duodenum and is eliminated with the feces

Lungs Most drugs removed by the pulmonary route are intact, and not metabolites Agents such as gases and volatile liquids that are administered through the respiratory system usually are eliminated by the same route.

Sweat and Salivary Glands Relatively unimportant because excretion of a drug through this route requires diffusion of lipid-soluble drugs through the epithelial cells of the glands. May result in dermatitis or other skin reactions.

Mammary Glands Many drugs or their metabolites cross the epithelium of the mammary glands and are excreted in breast milk Breast milk is acidic, and therefore basic compounds such as narcotics achieve high concentrations in this fluid Major concern is transference of drugs from mother to child