“Dynamics Of Drug Metabolism” In Forensic Toxicology


 
WHAT DOES THE WORD DRUG MEAN?

Any substance modifying the physiological activities of the organism upon introduction is considered a drug. Drugs may be used in diagnosing, treating, or preventing disorders. They alter hormones and enzymes through their interaction. Drugs include both legal and illegal substances which have unique effects on the body.

Legal drugs : Caffeine and Nicotine acts as stimulants and increase alertness. Alcohol works as a depressant.

Illegal drugs : Cocaine and Methamphetamine are strong stimulants. Heroin is an extremely addictive narcotic.

DRUG METABOLISM- The pharmaceutical chemicals being changed by the body by certain processes to make their elimination easier is known as drug metabolism. Drugs when broken down produce metabolites. This takes place in the liver. The chemical structure of the drug is changed. This may activate or inactivate drugs and change how medicines work.

Significance Of Drug Metabolism In Forensic Toxicology:

  • Identification and qualification of drugs and metabolites.
  • Temporal Analysis of time elapsed since drug consumption.
  • Toxicity Assessment to evaluate fatal doses.                         
  • Expert Testimony by forensic experts.

ENZYMES AND PATHWAYS:

ENZYMES- Enzymes are highly specific biological molecules helping with metabolic and DNA replication activities. They attach themselves to specific substrates and catalyse and accelerate effective reactions within cells.

METABOLIC PATHWAY- A chain of interlinked chemical reactions occurring in a biological system that transforms an initial molecule into several intermediates to give one or more end products finally. Enzymes catalyse every stage of this process.

ENZYMESAND PATHWAYS INVOLVED IN DRUG METABOLISM:
Drug metabolism mostly takes place in the liver. The enzymes needed in drug metabolism are more concentrated in the liver. They assist in easy elimination of drugs.
Drug-metabolizing enzymes contain many enzymes such as cytochrome P450, cytochrome b5, and NADPH-cytochrome P450 reductase.

Drugs can be metabolised by the following processes:

  1. Oxidation      
  2. Reduction     
  3. Hydrolysis 
  4. Hydration 
  5. Conjugation  
  6. Condensation  
  7. Isomerization.

Metabolism occurs in 2 phases or pathways in the case of many drugs- Phase I (non-synthetic) and Phase II (synthetic) reactions. They : 

  • Increase the water solubility of the drug, 
  • Primarily occur in the liver, 
  • Elimination takes place in the form of urine.

 

FACTORS AFFECTING METABOLISM OF DRUGS:

Drug metabolism is influenced by several factors some of which are:

  • Genetic factors : Accounts for 20-95 % of patient variability in the rate of metabolism due to the rate of oxidation of different drugs.
  • Age : Young children have higher metabolic rates than adults. Maturation and development of the liver and kidneys help in drug removal.
  • Gender : Oestrogen and testosterone fluctuations in the body of males and females affect enzyme activity and drug metabolism.
  • Drug-drug interaction : Occurs when two or more drugs interact and increases its effectiveness and heightens its side effects.                     

METABOLITES AND DETECTION:

There are 4 stages of drug metabolism which are namely-

  1. Absorption
  2. Distribution
  3. Metabolism
  4. Excretion

Various metabolites are generated depending on the specificity of the drug and the pathways involved. Usually, a maximum amount of metabolites are produced in the 3rd stage - Metabolism.

A few analytical instruments which help in detecting these metabolites are-

  1. Mass Spectrometry (MS)
  2. Chromatography : High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC)
  3. Liquid Chromatography-Mass Spectrometry (LC-MS)
  4. GC-MS (Gas chromatography-mass spectrometry)
  5. Enzyme-Linked Immunosorbent Assay (ELISA)
  6. Tandem mass spectrometry (MS/MS)
  7. NMR (Nuclear magnetic resonance)

TOXICOLOGICAL IMPLICATION :


WHAT IS TOXICITY?

The term "toxicity" describes the level of damage or adverse effects substances cause to living beings including physiological and biochemical abnormalities depending on dosage & duration of exposure. Toxic substances can cause harm, and dysfunction in cells, tissues, organs, or the entire body.

Metabolite Formation : Some of the metabolites undergoing metabolism may be more toxic than the parent drug itself. Knowledge about the different metabolic pathways helps in the easy identification of the metabolites.

Activation and Inactivation : Toxic substances can be detoxified to less harmful metabolites and excreted while others can lead to the formation of highly toxic metabolites causing adverse effects.

Individual Variability : Different genes in people influence the way a drug metabolises in one's body. Variation noticed in response to toxicity levels in different organisms is important to prescribe personalized medicine.

Drug-drug interactions may lead to an increased level of toxicity in the body of an organism which may be harmful and cause adverse conditions.

An in-depth knowledge of drug metabolism in forensic investigations improves the accuracy and reliability of toxicological analysis offering vital evidence in court cases.

 

A few implications of drug metabolism in forensic investigations are:

Identifying Drugs : knowing about metabolic pathways helps in the identification of drug metabolites.

Changes occurring Postmortem can alter drug concentrations in the body.

The emergence of new designer drugs takes place every day, understanding drug metabolism helps to identify metabolites, helping in the detection of unknown substances in samples.


POSTMORTEM DRUG METABOLISM:

Studying drug metabolism postmortem can be challenging. The longer the PMI, the greater will be the cellular and biochemical reactions progression which can highly impact the results.

Some of the difficulties faced while studying drug metabolism in post-mortem Samples are :

Changes occurring postmortem : The environmental conditions where the corpse is present, and the PMI can create changes in drug metabolism. Some of them are :

1.     Autolysis : cellular breakdown releases inner enzymes from cells to speed up metabolism.

2.     Microbial action and decomposition of tissue : alter the drug concentration and distribution in samples.

3.     Temperature differences : harsh weather, heat and light intensity on the corpse give inaccurate results.

Drug-drug interactions : Interaction of already present medical drugs in the body with others can lead to difficulty in identification.

Challenges faced while handling analytical instruments -unwanted substances like enzymes and substances released in a body may interfere with analytical techniques.


CASE STUDIES:


A few Real-life incidents where knowing drug metabolism was deemed necessary forensically :

1.     Drug overdose cases-Michael Jackson the pop artist's death was caused due to acute propofol intoxication. His physician administered anaesthetic propofol, anti-anxiety benzodiazepines- lorazepam and midazolam which led to his death. (Read More : https://www.health.harvard.edu/blog/propofol-the-drug-that-killed-michael-jackson-201111073772)

 

2.     Driving under the influence cases (DUI)-Bhanu Kumar a 23-year-old man drove a new MUV which wasn't registered, under high influence of alcohol in 2013 and caused an accident that claimed the lives of his two friends Vishwanath (22), Santosh (20). This accident took place on NICE road near Electronics City in the morning hours.

 

3.     Medication-related drug case- Between 2019 and January 2020, a cough syrup and anti-allergy syrup made by Norris Medicines Ltd which were toxic took a toll on the lives of 141 children in India. The death was caused due to dilution of the formula of the cough syrup using diethylene glycol or ethylene glycol. (Read More : https://www.reuters.com/investigates/special-report/health-coughsyrup-india/)

 

4.     Athlete drug testing case-Ben Johnson a famous Canadian sprinter was disqualified at the Olympic games since he tested positive for stanozolol after winning the men's 100 metres in the Seoul Olympics 1988. Thus, at the Olympics or any other event athletes always get tested for drugs by collecting their urine samples. (Read More : https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61114-3/fulltext)

 

ADVANCEMENTS IN TECHNOLOGY:

    The field of drug metabolism in forensic toxicology has seen several advancements. These advancements in the field help in increasing the precision of the tests and instruments contributing to the efficiency of drug analysis. Some of the remarkable advancements are:

  • HRMS (High-resolution mass spectrometry)
  • Combining different analytical techniques such as GC-MS, and LC-MS.
  • Introduction of robotics and automation in sample preparation and loading reduces error. 
  • Data processing software in algorithms.
  • Imaging mass spectrometry.

 

CONCLUSION :

    Potential future developments will be seen in this field and several research are being done in this direction to understand drug metabolism.

    Studies and research will reveal the complex mechanisms by which disease–drug interactions are produced. Predicting drug metabolism more accurately and clarifying mechanisms responsible for adverse reactions will be made possible.

    Newer sensitive and accurate analytical instruments and technologies are being used to discover new metabolic reactions and pathways.

 

REFERENCES:

  1. https://healthpolicy-watch.news
  2. https://pubmed.ncbi.nlm.nih.gov
  3. https://www.news-medical.net/life-sciences/
  4. https://www.shutterstock.com/
  5. https://www.ncbi.nlm.nih.gov/
  6. https://link.springer.com/
  7. https://www.intechopen.com/
  8. https://journals.lww.com/
  9. https://www.sciencedirect.com/

Comments

Post a Comment

Popular posts from this blog

The Vital Role of Forensic Science in Modern Criminal Investigations

Image
               Depicted frequently in popular crime shows and novels, forensic science plays a crucial role in contemporary criminal investigations. This captivating discipline merges scientific precision with legal procedures to reveal the truth behind crimes. Let's explore the significance of forensic science and its contribution to the quest for justice. What is Forensic Science ?     Forensic science involves the application of scientific principles and techniques to solve crimes and support legal investigations. It encompasses a variety of disciplines, including biology, chemistry, physics, and digital technology, to analyze evidence collected from crime scenes. The goal is to provide objective, reliable, and scientifically validated information for court use. Key Techniques in Forensic Science:      DNA Analysis : DNA profiling is one of the most powerful tools in forensic science. By analyzing genetic materi...
Read more

Forensic Linguistics : Where Language meets Law

Image
Introduction      Forensic Linguistics is the study of how words, speech and writing can provide clues in investigation of criminal as well as civil cases. It is the analysis of given evidence such as anonymous letters, suicide notes or other things like emails to determine authorship, speaker or interpretation of legal documents. The admissibility of forensic linguistic evidence in court depends on the reliability, relevance and scientific validity. Only the qualified experts and evidence with proper chain of custody are preferred. Different countries have different legal standards.      Gibbons (2001) : Forensic linguistics is the study of language in legal contexts, examining written and spoken communication to assist law enforcement, courts, and legal practitioners.   Background :      The term ‘‘forensic linguistics’’ was coined by Jan Svartvik in 1968 after analyzing the Timothy Evans case. He identified the difference...
Read more

Indians in forensics: A brief walk through time

Image
  Since the time of the ancient Indians, forensics has been a topic of curiosity. Numerous academics have discussed the numerous facets of forensics and its applications, which are still relevant today. These academics achieved such fame that their names will live on in legal history. In comparison to experts in other countries, many forensic scientists in India are not as well recognized. The following list includes some of the forensics minds.   Sushruta:      Known as the ‘Father of Surgery’, He lived in India sometime between 1000 and 800 BC. Sushruta also had a helping hand in the field of forensics. In the book “Samudra Sashtra”, it is mentioned that poisons have a deleterious effect on human body, both internally and externally, deaths by plant poisons, animals’ poisons, and even manmade poisons with their symptoms before and after death were observed by him. Whorls, loops, and arch patterns are among the three main types of ridge patterns according...
Read more