drug pollutant interaction and example of drug pollutant interaction

Drug-pollutant interaction is a complex phenomenon that occurs when exposure to environmental pollutants alters the mechanism of drugs in the body.

1. Presented By: Shubham Jat M.S Pharm/2023-25/RT/07 Dept. Of Regulatory Toxicology 1 st Year, NIPER, Hajipur DRUG POLLUTANT INTERACTION

2. TABLE OF CONTENT Introduction Source of pollutant Routes of exposure Mechanism of action Example of drug-pollutant interaction Prevention Reference 2

3. INTRODUCTION Every day, we are exposed to many environmental pollutants that can enter our body through different routes and cause adverse effects on our health. Epidemiological studies suggest that these pollutants are responsible for approximately nine million deaths per year. DRUG-POLLUTANT INTERACTION : Drug-pollutant interaction is a complex phenomenon that occurs when exposure to environmental pollutants alters the mechanism of drugs in the body. Pollutants can inhibit the body's ability to break down drugs, leading to higher levels of the drug in the bloodstream and potentially causing an overdose. Certain pollutants act as enzyme inducers, they increase the activity of enzymes responsible for the metabolism of drugs, causing rapid elimination of drugs in the body and reducing their therapeutic effect. Pollutants can compete with the drug for binding sites affecting the distribution of the drug throughout the body 3

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6. MECHANISM OF DRUG POLLUTANT INTERACTION

7. Interaction of smoke with antidepressants: Cigarettes contain certain chemicals that act as enzyme inducers. They induce the activity of enzymes resulting in the rapid breakdown of drugs and elimination of drugs from the body. In the majority of studies, the evidence suggests that smoking patients generally show lower serum levels of fluvoxamine, duloxetine, trazodone, and mirtazapine compared to nonsmokers. Tobacco smoke Release of polycyclic aromatic compound Stimulation of CYP1A2 enzymes Increase metabolism of tricyclic anti-depressants Reduced plasma levels Example of Drug-pollutant interaction: 8

8. Interaction of lead with Warfarin: Warfarin is metabolized primarily by hepatic mixed-function oxidases. Lead exposure can inhibit the activity of hepatic mixed-function oxidases. When lead interferes with the normal functioning of these enzymes, it slows down the metabolism of drugs like Warfarin. Lead exposure Inhibit the activity of hepatic mixed function oxidase enzyme This enzyme play role in metabolism of Warfarin Accumulation of Warfarin in the body Potentiate the anticoagulant effect of Warfarin Increased risk of bleeding 9

9. Organophosphate Pesticides and Anti-cholinesterase Medications: When Organophosphate pesticides Interact with anti-cholinesterase medications, they can produce synergistic effects on cholinergic transmission. Both substances inhibit AChE activity, leading to an accumulation of acetylcholine in the synaptic cleft. Exposure of pesticide Inhibition of acetylcholine esterase Accumulation of acetylcholine Overstimulation of cholinergic receptor Excessive of parasympathetic effect Symptoms of cholinergic toxicity 10

10. Arsenic and anti-diabetic drugs: Arsenic can also interfere with the effectiveness of some anti-diabetic drugs, such as Metformin. Studies have been suggested that arsenic exposure may reduce the therapeutic efficacy of metformin by altering its pharmacokinetics or by antagonizing its effects on glucose metabolism. Exposure of arsenic Inhibit the activation of AMPK Impaired AMPK signalling pathway Reduce glucose uptake and metabolism Decreased efficacy of metformin 11

11. Environmental chemicals as inhibitors of drug transporter activity: pesticides like organo-chlorines, organ phosphorus compounds, pyrethroids can inhibit the activity of specific drug transporters, particularly P-glycoprotein. Some pollutants directly bind to P- gp , inhibiting its function. Pesticides like endosulfan can block P- gp -mediated efflux of anticancer drugs like doxorubicin. Pesticide exposure Interaction with P-glycoprotein Disruption of P-glycoprotein confirmation Prevention of Doxorubicin binding Impaired efflux of doxorubicin Accumulation of doxorubicin within cell 12

12. Environmental chemicals as modulators of drug transporter expression: Environmental pollutants that act as agonists of aryl hydrocarbon receptor, such as 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) and polycyclic aromatic hydrocarbons, can alter the expression of drug transporters. Example of modulators: Polycyclic aromatic hydrocarbons and certain pesticides that induce oxidative stress and activate Nrf2 pathway. Exposure to PAHs Generation of reactive oxygen species Accumulation of ROS causes oxidative stress Oxidative stress trigger the activation of Nrf2 pathway Activated Nrf2 bind to anti-oxidant respond element in DNA It promote the transcription of genes encoding anti-oxidant enzymes Increased expression of anti-oxidant enzymes help to neutralize ROS 13

13. Prevention Environmental regulation Awareness Medication management Research and development Personal protective measure 14

14. REFERENCE Tumiatti , Vincenzo & Fimognari , Carmela & Milelli , Andrea & Manucra , Davide . (2017). Pollutants and Drugs: Interactions and Human Health. 10.1007/978-3-319-62731-1_12. Fardel O, Kolasa E, Le Vee M. Environmental chemicals as substrates, inhibitors or inducers of drug transporters: implication for toxicokinetics , toxicity and pharmacokinetics. Expert Opin Drug Metab Toxicology. 2012 Jan;8(1):29-46. doi: 10.1517/17425255.2012.637918. Epub 2011 Dec 19. PMID: 22176607. Oliveira P, Ribeiro J, Donato H, Madeira N. Smoking and antidepressants pharmacokinetics: a systematic review. Ann Gen Psychiatry. 2017 Mar 6;16:17. doi: 10.1186/s12991-017-0140-8. PMID: 28286537; PMCID: PMC5340025. Navas-Acien A, Silbergeld EK, Streeter RA, Clark JM, Burke TA, Guallar E. Arsenic exposure and type 2 diabetes: a systematic review of the experimental and epidemiological evidence. Environ Health Perspect . 2006 May;114(5):641-8. doi: 10.1289/ehp.8551. PMID: 16675414; PMCID: PMC1459913. 15

15. Thank you 16