Principles Of Toxicology I & II Past Paper PDF

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF TOXICOLOGY I&II 11&25 NOV 2024 WO N G C H U N K E U N G 1 EXAMPLE OF DRUG SYNERGISM Aspirin and caffeine Good example of synergism With combination – giving greater efficacy and pain relief for patie...

PHARMACOLOGY AND TOXICOLOGY PRINCIPLES OF TOXICOLOGY I&II 11&25 NOV 2024 WO N G C H U N K E U N G 1 EXAMPLE OF DRUG SYNERGISM Aspirin and caffeine Good example of synergism With combination – giving greater efficacy and pain relief for patients with pain Without combination – Efficacy and pain relief not as high https://images.freshop.com/00310158109501/8078a2998a50df17d0df8d9fc55641d9_large.png 16 DRUG-FOOD INTERACTION The reaction between drug and food or beverage When food affects medications in the body – Food may affect the medicine in its proper working – May also affect the medicinal side effects Becoming better or worse Causing new side effects https://pharmafactz.com/wp-content/uploads/2016/02/important-food-drug-interaction.jpg On the other hand, the drug may change the way that the body uses food 18 COCA-COLA AND NSAID A significant increase in plasma concentration of ibuprofen when taken with Coca-Cola Showing an increased extent of absorption of ibuprofen Daily dosage and frequency of https://caogam.vn/sites/default/files/styles/anh_detail/public/2021-08/thuoc- nsaid_0.jpg?itok=8c90OOCo NSAID’s like ibuprofen should be well observed when Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines used for administered with Coca-Cola relieving pain, reducing inflammation, and bringing down a high temperature of the body 19 GREEN VEGETABLES AND WARFARIN ↑ vita K -> Hotty Spinach is rich in vitamin K Vitamin K is important for the production of clotting factors that help prevent bleeding On the other hand, anticoagulants such as warfarin effects by inhibiting vitamin K Warfarin is clinically used for decreasing the tendency for thrombosis An increased intake of spinach thus may https://img.cndoct.com/upload/202112/17/202112171735256977.png prevent the warfarin from working 20 MILK AND TETRACYCLINES calcium->bioavailability -> antibiotics Milk, being the main component of dairy products, is rich in calcium Calcium can interact with certain antibiotics such as tetracyclines Tetracyclines may bind with calcium and forming insoluble substances The bioavailability of tetracyclines can be influenced Bioavailability refers to the extent a drug becomes completely available to its intended https://pngimg.com/uploads/milk/milk_PNG12726.png biological destination(s) 21 MATURED CHEESE AND PHENELZINE Mature cheese is the cheese product undergone with e umature/aged -> yum ripening process for a specific amount of time managed with temperature and humidity Aging cheese is important for changing the cheese's flavor and texture. As cheese ages, it loses moisture and concentrating its flavors Matured cheese contains the amino acid tyramine Tyramine interactions with phenelzine that is used for treating depressive disorders Eating mature cheese while taking phenelzine can raise the blood pressure to dangerous levels, causing life- threatening side effects Complications may included cardiac arrhythmias, https://www.pngmart.com/image/260742 cardiac failure, pulmonary edema, and death 22 GRAPEFRUIT AND STATINS Avoid eating grapefruit or drinking grapefruit juice while taking cholesterol lowering agents Such as statins: e.g. atorvastatin, lovastatin Grapefruit contain furanocoumarin chemicals causing an increase in statins potency Raising the level of the drug in bloodstream Increase the risk of side effects, such as leg pain and muscular weakness https://www.goodrx.com/classes/statins/why-cant-i-have-grapefruit- with-my-statin 23  MECHANISMS OF DRUG TOXICITY Major drug toxicities commonly grouped into five categories on the basis of their underlying mechanism: On-target Hypersensitivity and immunological Off-target Biological activation Idiosyncratic 25 CLASSIFICATIONS IN THE CONTEXTS OF DRUG TOXICITY Type Example On-target Statins (chlorosterols Hypersensitivity and immunological Penicillins Off-target Terfenadine Biological activation Acetaminophen Idiosyncratic Halothane https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707670/ 26 MITOCHONDRIAL TOXICITY Inhibition of Protein Complexes Five protein complexes (Complexes I, II, III, IV and V) are located within the inner mitochondrial membrane and involved in ATP production Certain drugs, such as some antidiabetic and cancer drugs, etc are able to inhibit the protein complex Impair the mitochondrial ATP synthesis https://sitn.hms.harvard.edu/art/2018/mothers-mitochondria/ https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex- Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 35 MITOCHONDRIAL TOXICITY Inhibition of Mitochondrial Membrane Transporters Inhibition of transporters - such as the adenine nucleotide translocator The proteins that exchange mitochondrial ATP for cytosolic ADP https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg Cause substrate depletion and https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf reduced ATP production 36 MITOCHONDRIAL TOXICITY Inhibition of Krebs Cycle Enzymes and Fatty Acid Metabolism Inhibition of enzymes involved in the Krebs cycle (e.g., fluoroacetate) or Inhibition of enzymes involved in the fatty acid β-oxidation (e.g., tetracyclins) https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf Cause substrate depletion and reduced ATP production 37 MITOCHONDRIAL TOXICITY Inhibition of mitochondrial DNA (mtDNA) replication and mtDNA-encoded protein synthesis Some drugs (e.g., nucleoside reverse transcriptase inhibitors) able to – inhibit mtDNA replication or mtDNA-encoded protein https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- synthesis Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 38 MITOCHONDRIAL TOXICITY Oxidative Stress An imbalance of free radicals and antioxidants in the body can leads to cell damage For example, depletion of reactive oxygen species (e.g., acetaminophen) Lead to activation of cell death https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg signaling and apoptosis (a series https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf of molecular steps in a cell lead to its death) 39  MITOCHONDRIAL TOXICITY Mitochondrial Permeability Transition Pore Some drugs (such as some anticancer drugs) may induce irreversible opening of the pore Leading to influx of water and osmotic swelling Resulting in drug induced https://ohiostate.pressbooks.pub/app/uploads/sites/36/2017/07/Mitochondrion-structure-1536x783.jpg mitochondrial toxicity https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex- Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 40  TARGETS OF OXIDATIVE STRESS Lipid membranes Damage to cellular membranes DNA Modification of DNA bases Damage to deoxyribose sugar Proteins Damage to specific amino acid residues Changes in structure Degradation and fragmentation resulting in loss of enzyme activity https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 43  CELL CYCLE MEDIATED TOXICITY There are 4 main sequential phases of the cell cycle: G1 Phase (first growth phase) S Phase (synthesis phase) G2 Phase (second growth phase) M Phase (mitosis phase) https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 51  APOPTOSIS Mitochondrial Mediated (Intrinsic Pathway): Mitochondria play a key role in apoptosis In response to cell stress, mitochondria initiate or enhance cell death signalling An induction of mitochondrial outer membrane permeabilisation – Allowing water and other molecules to enter the mitochondria – Swelling and rupture of the membranes and release of mitochondrial pro-apoptotic factors – The pro-apoptotic factors being released and cross the outer membrane – Induce apoptosis by caspase activation and DNA fragmentation https://www.evotec.com/uploads/download-files/Downloadable_Publications/Cyprotex-Guides/Cyprotex-Mechanisms-of-Drug-Induced-Toxicity-Guide.pdf 61 ORGAN AND TISSUE TOXICITY https://image1.slideserve.com/2159450/drug-toxicity-in-various-organ-systems-l.jpg 67  WHAT DRUGS ARE RENAL TOXIC? Antimicrobials such as: Aminoglycosides Antifungals (such as amphotericin B) Beta-lactams (such as cephalosporins, penicillins) Quinolones (such as ciprofloxacin) Rifampin (such as Rifadin) Vancomycin (such as Vancocin) Can lead to drug-induced acute renal failure 77  SYMPTOMS OF NEUROTOXICITY Dysfunction relating to the nervous system such as: Confusion Poor concentration Memory loss Personality changes Loss of sensation Muscle weakness 82