Pharmacoclogy & Drug Discovery

Toxicology is the scientific study of adverse effects that occur in living organisms due to chemicals. It involves observing and reporting symptoms, mechanisms, detection and treatments of toxic substances, in particular relation to the poisoning of humans. It includes environmental agents and chemical compounds found in nature, as well as pharmaceutical compounds that are synthesized for medical use by humans. These substances may produce toxic effects in living organisms including disturbance in growth patterns, discomfort, disease and death. LD50 is a common term used in toxicology, which refers to the dose of a substance that displays toxicity in that it kills 50% of a test population. In scientific research, rats or other surrogates are usually used to determine toxicity and the data are extrapolated to use by humans.

Clinical Pharmacology has been practiced for centuries through observing the effects of herbal remedies and early drugs on humans. The pharmacologic effect that a medication has on the body is known as pharmacodynamics. Pharmacokinetic and pharmacodynamics parameters become important because of the association between host drug concentrations, microorganism eradication, and resistance. Since long scientific advances allowed scientists to come together with the study of physiological effects with biological effects, Receptor theory for drug effects and its discovery with clinical pharmacology has stretched out to be a multidisciplinary field and has contributed to the findings of drug interaction, therapeutic effectiveness and safety. Drug interactions and pharmacological compatibilities include the study of pharmacokinetics that includes the absorption, distribution, metabolism, and elimination of drugs. The pharmacologic effect that a medication has on the body is known as pharmacodynamics. Pharmacokinetic and pharmacodynamics parameters become especially important because of the association between drug application, microorganism abolition, and resistance.
 

Psychopharmacology is the learning of the effects of medication on the psyche (psychology), observing changed behaviours and how molecular events are manifest in a measurable behavioural form. Neuropharmacology is the study of the effects of medication on central and peripheral nervous system performance. Neurogenesis and repair deal with other aspects on the indications for medications prescribed to address psychiatric and behavioural problems, that are associated with, including antipsychotic, anxiolytic and anticonvulsant medications, acquired brain injury and Neurocognitive effects associated with therapeutic drugs also include mood stabilizers and treatments prescribed for disorders of attention. The treatments may cause side effects such as induction of the metabolic syndrome, type-2 diabetes related to the medications prescribed for management of psychiatric and behavioural disorders and disturbances. Ethno psychopharmacology also deals with the biotransformation and metabolism of medications, as well as specific differential actions: i.e., CYP450 enzymatic inhibition and induction of metabolism of psychopharmacological and herbaceutical substrates. Neuropharmacology is the study of drugs and their targets that influence the functions of the nervous system (brain, spinal cord, and peripheral nerves) in health and disease.
 

Pharmacodynamics is the effect that drugs have on the body; while pharmacokinetics is the study of the way in which drugs move through the body during absorption, distribution, metabolism and excretion. Pharmacokinetics influences decisions over the route of administration. For drugs to produce their effects they must interact with the body. This can happen in many ways and depends on the properties of the drug. Pharmacokinetics influences decisions over the route of administration. The processes that occur after drug administration can be broken down into four distinct areas (known as ADME):

A  Absorption of the drug

D Distribution of the drug molecules

M Metabolism of the parent drug

E Excretion or elimination of the drug and its metabolites

Cardio pharmacodynamics of digitalis is most frequently used to increase the adequacy of the circulation in patients with CCF and to slow the ventricular rate in patients with atrial fibrillation or flutter NB. The main action of digitalis is its ability to increase myocardial contractility and its positive isotropic action resulting in increased cardiac output, decreased heart size, decreased venous pressure, decreased circulating blood volume, diuresis and relief of edema as digitalis frequently causes a dramatic reduction in the ventricular rate. It was originally believed that this was the main effect subsequently shown to be beneficial irrespective of the HR, its predominant effects being on contractility in addition to the cardiac effects, digitalis has a direct action on vascular smooth muscle, neural tissue. The later being responsible for indirect cardiac actions of the drug which frequently result in reflex autonomic & hormonal changes which affect the CVS.  The circulatory system is busy providing oxygen and nourishment to every cell of the body, let's not forget that the heart, which works hardest of all, needs nourishment.

Recent advances in DNA repair are DNA interstrand cross-links (ICLs) are lesions caused by a variety of endogenous metabolites, ecological exposures, and cancer chemotherapeutic agents that have two reactive groups. The general feature of these diverse lesions is that two nucleotides on opposite strands are joined covalently. Mutagenicity and carcinogenicity are clearly correlated. The somatic mutation theory of cancer holds that these agents cause cancer by causing the mutation of somatic cells. A unique feature of inter-strand cross-links repair is that both strands of DNA must be incised to completely remove the lesion. Drug dosing guidelines accomplished in sequential steps to prevent creating multiple double-strand breaks. Understanding the specificity of mutagens in bacteria has led to the direct implication of certain environmental mutagens in the cause of human cancers.

Reverse pharmacology and forward pharmacology are two approaches to drug discovery. Target based drug discovery is the process through which potential new medicines are identified. It involves a wide range of scientific disciplines, including biology, chemistry and pharmacology. Screening of chemical libraries and its pharmacology, methods to determine biological targeting by systematically perturbing and interrogating biological pathways with synthetically novel chemical tools, preclinical validation of target biology is beginning to illuminate a more cost effective and efficient paradigm for the development of novel drugs modulating novel targets.

Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxic kinetics (including toxic kinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. Human toxicology studies address the mechanisms/modes of toxicity that deals with the safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches. This also includes novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder.

Genetic toxicology helps discern the possibility of heritable mutations, developmental defects, cancer initiation, aging and other long-term adverse genetic effects. Genotoxicity describes the assets of chemical sellers that damage the genetic records inside cellular causing mutations, which may lead to most cancers. At the same time, genotoxicity is often stressed with mutagenicity; all mutagens are genotoxic, while no longer all genotoxic materials are mutagenic. The alteration could have direct or indirect consequences at the DNA: the induction of mutations, mistimed occasion activation, and direct DNA damage leading to mutations.

Ethnopharmacology is a study or comparison of the traditional medicine practiced by various ethnic groups and especially by indigenous peoples. The word ethnomedicine is sometimes used as a synonym for traditional medicine. Ethnomedical research is interdisciplinary; in its study of traditional medicines, it applies the methods of ethnobotany and medical anthropology. Often, the medicine traditions it studies are preserved only by oral tradition.

Scientific ethnomedical studies constitute either anthropological research or drug discovery research. Anthropological studies examine the cultural perception and context of a traditional medicine. The purpose of drug discovery research is to identify and develop a marketable pharmaceutical product. Various streams of ethnopharmacology include clinical ethnopharmacy and ethnopharmaceutics.