The scope of pharmacology has expanded greatly over the last decade to incorporate many new approaches such as:
- i. Computer-assisted drug design
- ii. Genetic screens
- iii. Protein engineering
- iv. Novel drug delivery Vehicles
Our society needs pharmacologists who understand the basis of modern therapeutics for careers within, academic, pharmaceutical, and governmental laboratories to study and develop tomorrow’s drugs.
Scope of Pharmacology
The effect of the body on the drug. To produce its characteristic effects, a drug must be present in appropriate concentrations at its sites of action. Thus, it is important to know the interrelationship of the absorption, distribution, binding, biotransformation, and excretion of a drug and its concentration at its locus of action.
i. Absorption: (oral or parenteral): A drug must be absorbed and achieve adequate concentration at its site of action to produce its biological effects. Thus, when a drug is applied to a body surface (e.g., G.L. tract, skin, etc.), its rate of absorption will determine the time for its maximal concentration in plasma and at the receptor to produce its peak effect.
II. Distribution: The blood, total body water, extracellular, lymphatic, and cerebrospinal fluids are involved in drug movement throughout the body. Depending upon its chemical and physical properties, the drug may be bound to plasma proteins or dissolved in body fat, delaying its progress to its sites of action or excretory mechanism.
III. Metabolism: This is how certain drugs are handled by the body in preparation for their and includes the fate of drugs-biotransformation (e.g, hydrolysis, conjugation, oxidation-reduction).
IV. Excretion: The kidney is the most important organ for drug excretion but the liver, lungs, and skin are also involved in drug elimination. Drugs excreted in feces are mostly derived from unabsorbed, orally ingested drugs or metabolites excreted in the bile and not reabsorbed by the intestine. The physical and chemical properties, especially the degree of ionization of the drug, are important in the rate of excretion.
V. Biological Factors Modifying Pharmacokinetic Aspects: Normal variations occur in population pharmacokinetic constants (absorption rates, elimination rates). Other factors include age, weight, obesity, edema, concurrent diseases, other drugs (various interactions including effects on protein binding or metabolic rate), diet, dose interval and route of administration, and genetic variations in elimination rate.
Drugs activity over the body The effect of the drug on the body. Pharmaco-dynamics is the study of the relationship between drug concentration and the biological effect (physiological or biochemical). For most drugs, it is necessary to know the site of action and mechanism of action at the le of the organ, functional system, or tissue. For example, the drug effect may be localized to the brain, the neuromuscular junction, the heart, the kidney, etc. Often the mechanism of action can be described in biochemical or molecular terms.
Most drugs exert effects on several organs or tissues and have unwanted as well as therapeutic effects. There is a dose-response relationship between wanted and unwanted (toxic) effects.
The chemical structures of drugs can provide information about the mechanism of action, pharmacokinetics, stability, and metabolic fate.
I. Structure-Activity Relationship: A modification of the chemical structure of a drug may accentuate or diminish its pharmacological effects, often providing clues as to the action. A picture of the biological reactive site (the receptor) can be developed in such studies. Also, drugs are metabolized by body systems, which may convert the parent drug to a more active or a less active form. The drug structure can be modified to enhance or diminish the rate of metabolic conversion.
II. Sites of Action: The organ or cellular target of drug action.
III. Drug Receptors: Macromolecules in cells or cell membranes with which drugs interact to exert their effects. Usually, the interacting forces are reversible ionic and Van der Waals bonds of relatively low energy, but sometimes covalent bonds are formed (e.g. organophosphate insecticides).
CLINICAL PHARMACOLOGY AND THERAPEUTICS
I. Indications and Therapeutic Uses: Emphasis is placed on the therapeutic use of drugs for the treatment of disease in clinical pharmacology, internal medicine, and therapeutics. There are specific clinical disorders or disease entities for which a given drug may be prescribed and the physician must weigh the potential benefit of drug use against the risks of adverse effects.
II. Contraindications and Factors (e.g., liver disease) May Modify Drug Action: Where detoxification of the drug by the liver is important. It is important to know that the presence of disease or organ pathology may influence the actions of a drug. Conditions such as age, pregnancy, concomitant administration of other drugs, and disease may alter the patient’s response to a given drug.
III. Posology: It is an archaic term describing dosage regimens. Consideration of dosage schedules is a part of pharmacokinetics.
IV. Bioavailability: The fraction of drug administered which is absorbed and reaches the systemic circulation following oral dosing. Preparations of the same drug by different manufacturers may have different bioavailability.
V. Prescription writing: The physician must write clear, error-free directions for the drug provider (pharmacist) and the patient. Physicians must guard against prescribing too many drugs, or preparations of little value.
Drugs of unproven clinical value should be avoided, as well as potentially toxic agents if drugs equally effective but less dangerous are available. Risk-benefit and cost-benefit should be considered. Drugs may be prescribed by generic name since often a less expensive drug product can be obtained in this way.
A particular manufacturer may be specified if the physician has reason to believe a better or more reliable preparation is available from that manufacturer.
VI. Drug Nomenclature: In addition to its formal chemical name, a new drug is usually assigned a code name by the pharmaceutical manufacturer. If the drug appears promising and the manufacturer wishes to place it on the market, a United States Adopted Name
(USAN) is selected by the USAN Council which is sponsored by:
- The American Medical Association.
- The American Pharmaceutical Association.
- The United States Pharmacopoeial Convention.
The aspect of Toxicology deals with the adverse effects of chemical agents. Toxicology is concerned not only with drugs used in therapy but also with the other chemicals that may be responsible for the household, environmental or industrial intoxication.
Addresses medicological aspects of the use of chemicals that are harmful to animals or man. Analytical chemistry and fundamental toxicological principles are hybridized to underlie this aspect of toxicology. Nonetheless, accidental poisoning with drugs is a health problem of major significance.
More than 1/4 of the fatalities and about 1/2 of all poisonings occur in children under 5 years of age. All common household articles that are poisonous should be made unavailable to children, and poisonous rodenticides and insecticides should not be placed in the home
Focuses on toxic events that are caused by or are uniquely associated with drugs or other chemicals
The study of drug effects at the population level is concerned with the variability of drug effects between individuals in a population and between populations. Eg: Responders and non-responders to LT antagonist therapy in case of asthma.
It is the treatment of systemic infection/malignancy with specific drugs that have selective toxicity for the infecting organism/ malignant cell with no/minimal effects on the host cells.