Drug Discovery & Toxicology

Drug chemistry is a branch of pharmacy that overlaps with the disciplines of chemistry that involves drug design, chemical synthesis, drug formulation, drug testing, and development. Compounds used as medicines are usually organic or organometallic compounds. Today’s pharmaceutical industry evolved largely from the chemical industries. Modern advancements in biological sciences related to the structure and function of DNA as well as precise methods for manipulating DNA and making proteins has led to a more balanced partnership for drug discovery between chemistry and biology. The field of drug chemistry focuses on four key points to arrive at a compound of pharmaceutical importance, they are drug synthesis, interpretation of the chosen target to a defined pharmacodynamics and pharmacokinetics mechanism of drug action, drug screening to analyze blood, urine, hair, saliva or tissue samples to detect the presence residual chemicals and contaminants left behind in the body as a result of drug use, toxicity assessments and adverse drug reaction studies.           

The drug toxicology studies play a very important role in the drug development process that evaluates the safety of potential drug candidates. Toxicity assessments are done using relevant animal models and validated procedures. Once a new drug entity is synthesized it is subjected to various in vitro and in vivo toxicity tests. The ultimate aim of it is to translate the animal model responses into predictable toxic responses in humans. 

A clinical trial is an examination program led with patients to evaluate a new treatment or medication. The motivation behind clinical preliminaries is to discover better strategies for treating, screening and diagnosing distinctive ailments. Clinical trials are responsible for the wide application of the latest scientific and technological advances to patient care. Each clinical trial has criteria describing the participants. Children, adults, healthy volunteers, patients and people of a diverse group of ethnic and racial foundations are urged to participate in clinical trials. Clinical preliminaries are partitioned into 4 stages, called clinical trial phases. The first two phase trials assess the drug for its lethality or the side effects it causes and later phase trials aim to test a new drug for its efficiency than the existing medications. Each new phase of a clinical preliminary expands data from past stages. A dose-ranging study is a part of phase II clinical trial where different doses of a drug molecule are tested to establish which dose is effective with least or no lethality. The dose-response relationships in clinical trials are necessary for determining the safe quantity of drugs. Thus the vast data accumulated by clinical trials form the basis for public policy and drug approval process. Once the drug enters the market it is subjected to post-market drug safety surveillance to assess further problems.

Drug delivery is a process that includes approaches and techniques for transporting a pharmaceutical compound in the body is ordered to safely achieve its desired therapeutic effect. In order to minimize drug degradation, prevention of harmful side effects, increasing drug bioavailability and the amount of the drug accumulated in the precise zone of requirement various drug delivery and targeting systems are currently under development. Well-designed drug carriers that carry drug molecules are being innovated and utilized for site-specific drug delivery. Some of them include liposomes, micelles, dendrimers, liquid crystals, nanocapsules, and nanospheres. The mode of drug delivery is responsible for the drug’s success or failure as the choice of a drug is often influenced by the way the medicine is administered. The pulsatile release is a newly developed method of drug delivery as it mimics the glands that produce hormones in a controlled way. It is achieved by using drug-carrying polymers that respond to specific stimuli hence this system is called the stimuli-responsive system.

The pharmacogenomics comprises of genomic information being used to study an individual’s responses to drugs based on their genetic profile. When a gene variant is responsible for a particular drug response in a patient then based on genetics it is possible to derive clinical decisions by adjusting the dosage or choosing an alternative drug. Researchers study gene variants affecting an individual's drug response in a similar process as of assessing variants associated with diseases and disorders. Recent approaches include multigene analysis or whole-genome Single Nucleotide Polymorphism (SNP) profiles which are used in designing and developing drugs. By the application of human genomic data a new technique called precision medicine is being established, which is based on using an individual's genetic data to make a best therapeutic choice by facilitating predictions about whether a particular person will be beneficial by a particular medicine or suffer by serious side effects. Drugs are tested on a large population of people and the average response is reported. Personalized medicine acknowledges that no two patients are similar with respect to reaction towards medication.

Radioactive drugs or radiopharmaceuticals are drugs containing a radioactive component which are administered to humans for the purpose of diagnosis or treatment of a disease. These radioactive drugs are available in commercial nuclear pharmacies or can be synthesized in hospital-based nuclear pharmacies. In nuclear medicine industries, devices such as cyclotron and radionuclide generators are used to manufacture nuclear drugs with reduced risk condition. Radiopharmaceuticals play a vital role in curing diseases such as cancer, thyroid conditions, and polycythemia vera. Extensive research is going to make nuclear medicines safer by limiting the health risks of radiation sickness and inappropriate dosing.

Neuropharmacology is the investigation of how medication influence cellular process in the nervous system and the neural mechanisms through which they impact on behavior. It is divided into two parts behavioral neuropharmacology and molecular neuropharmacology, the former focuses on the study of how drugs affect human behavior which includes the study of how drug dependence and drug addiction affects the human brain and later focuses on the study of neurons and their neurochemical interactions to develop drugs having beneficial effects on neurological health. Antidepressants, antianxiety, anticonvulsant and antipsychotic drugs are the most widely prescribed neuroactive medications.

Traditional medicine or ethnomedicine refers to the knowledge, skills, and practices based on the speculations, convictions, and experiences indigenous to different cultures used in the maintenance of health and to prevent, diagnose, improve or treatment of physical and mental illness. Herbal treatments are the most popular form of traditional medicine and about 70 to 80 percent of the regions have been using it across the world as a form of primary health care. The traditional medicinal knowledge is thought to be within everyone’s reach and does not require training to practice it. In the present day context contribution made by traditional medicine to modern medicine is enormous. Many well-established drugs such as leptospermone came from phytomedicine research and identification of bioactive molecules of the therapeutic significance of plants used traditionally by tribals and villagers. 

Probiotics are live microorganisms or microbial mixtures administered to improve the patient's microbial balance thus curing the disease. On the other hand, prebiotics is certain substances which on administration stimulate the growth of beneficial bacteria which eventually leads to curing of the disease. These are usually non-digestible carbohydrates found in fibrous foods. The mixture of probiotics and prebiotics is called synbiotics. Such medicines have wide applications in the treatment of various gastrointestinal disorders, irritable bowel syndrome, urinary tract infections, etc. The effectiveness and less health risk make probiotic drugs a promising drug for the future by replacing conventional medicines for certain diseases.

In recent years nanotechnology has found its significant interest in a wide range of applications in the pharmaceutical industry. Nanomaterials have been used in in-vivo preclinical and clinical trials.  The choice of a particular technique depends on a variety of factors such as administration route, dose, drug physicochemical properties, drug target, and target cells or tissues. Many diverse nano-sized structures have been investigated for drug formulation and delivery. The nano-sized crystalline drug, drug-polymer and drug-antibody conjugates, dendrimers, liposomes, lipid emulsions, and solid drug-polymer nanoparticle dispersions are some drug carriers containing nanomaterial.

In the current scenario, the most commonly used types of cancer treatment are chemotherapy, radiotherapy, tumor surgery, and hormonal therapy. Small molecule inhibitors are being extensively studied for precise target treatment. Their extremely small size allows them to diffuse through the plasma membrane and interact with the cytoplasmic domain of cell-surface receptors and intracellular signaling molecules that eventually blocks cancer cell proliferation. The application of genomic data in the field of oncology has given an insight into genetic modifications and epigenetic modifications such as chromatin-modification and DNA Methylation. Use of bioinformatics and proteomics has further speeded up the drug discovery process in cancer.

Drug resistance or antimicrobial resistance is a phenomenon where microorganisms such as bacteria, fungi, viruses, and parasites change and develop resistance towards treatment by antimicrobial drugs rendering it ineffective hence infection persists in the body increasing the risk. Drug resistance occurs naturally over time by frequent misuse or overuse of antimicrobial drugs via genetic changes. Advancements in molecular and biochemical techniques have given an insight into antibiotic resistance genes and mechanisms such as mutation and gene transfer through which bacteria develop resistance. Antibiotic resistance is a major menace in modern-day therapeutics. Inorder to reduce the drug-induced resistance in bacteria many antibiotic replacement therapies are put to use, such as phage therapy, use of bacteriocin, predatory bacteria and by competitive exclusion.

Drug tolerance is a phenomenon of adaptation for frequent exposure to a drug that results in a diminution of one or more of the drug's effects over time. The drug tolerance is classified into 3 types, which are acute tolerance (short-term, tolerance caused by repeated exposure to a drug for short period of time), chronic tolerance (long-term tolerance that develops when an individual’s body adapts to constant exposure to a drug over weeks or months) and behavioral tolerance (Due to overuse of certain psychoactive drugs). The drug tolerance development is reversible and it depends upon both physiology and psychology of individuals. 

Clinical Toxicology involves the study of the toxicity of substances that are related to therapeutics or healthcare. It contains the interaction of various disciplines such as pharmacology, environmental toxicology, biochemistry, computational toxicology, etc. The particular field focuses on treatment techniques of patients who have been poisoned with a drug or other substance either accidentally or intentionally. The application of this is also used in forensic sciences. Toxicology studies mainly rely on xenobiotics which are substances foreign to the particular biological system such as drugs, environmental toxins, food additives, etc. Hence identification, mechanism and studying its metabolism give information on various ways to treat fatality.

Pharmaceutical biotechnology is the reconciliation of pharmacy with various scientific orders that include biochemistry, microbiology, genetics, organic chemistry, and chemical engineering. It utilizes living systems or products from the biological system to make or alter valuable biological substances with therapeutic value. Modern application of biotechnology in pharmacy involves hereditary building, protoplast fusion; monoclonal antibody systems and powerful new devices intended to create effective bioprocess technology and products for the growth of pharmaceutical industries.