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Adverse Drug Reactions , Contraindications and Drug Interactions of OTC Analgesics

Adverse Drug Reactions , Contraindications and Drug Interactions of OTC Analgesics. P.Naina Mohamed Pharmacologist. Adverse Drug Reactions , Contraindications and Drug Interactions.

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Adverse Drug Reactions , Contraindications and Drug Interactions of OTC Analgesics

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  1. Adverse Drug Reactions, Contraindications and Drug Interactions of OTC Analgesics P.Naina Mohamed Pharmacologist

  2. Adverse Drug Reactions, Contraindications and Drug Interactions The basic knowledge of mechanisms underlying Adverse drug reactions, Contraindications and Drug interactions of OTC medicines provides the understanding of preventive measures. Adverse drug reaction (ADR): A response to a drug that is harmful or unpleasant and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function. Contraindication: A condition which makes a particular treatment (medicine) or procedure potentially inadvisable. Drug Interaction: A modification of the effect of a drug when administered with another drug, food, or herb.

  3. OTC Analgesics Non opioid or Non steroidal anti inflammatory drugs (NSAIDs) are available as OTC analgesics. They block the synthesis of inflammatory prostaglandins by inhibiting Cycloxygenase (COX) enzyme and relieve pain, fever and inflammation.

  4. OTC Analgesics Commonly used OTC Analgesics Non Opioid Analgesics 1. Paracetamol 2. Aspirin Non Steroidal Anti inflammatory Drugs (NSAIDs) 1. Ibuprofen 2. Diclofenac 3. Meloxicam 4. Indomethacin 5. Mefenemic Acid 6. Ketoprofen 7. Celecoxib

  5. Non Opioid Analgesics Paracetamol has only weak anti inflammatory property and it is indicated only for Pyrexia and Mild to moderate pain. Aspirin has very less anti inflammatory activity compared to other NSAIDs and it is indicated only for the inhibition of Platelet aggregation, mild to moderate pain and pyrexia.

  6. Paracetamol (Acetaminophen) ADRs Paracetamol produces rare adverse drug reactions such as… 1. Mild gastric discomfort (Nausea, Vomiting, Anorexia, Abdominal pain) 2. Hypersensitivity reactions (Rash, urticaria, Angioedema, Anaphylaxis, etc.) 3. Nephrotoxicity in toxic doses

  7. Paracetamol (Acetaminophen) Hepatotoxicity Paracetamol causes liver damage (Hepatotoxicity) in toxic doses. Paracetamol (Acetaminophen) overdose Saturation of sulfate and glucuronide conjugation metabolic pathways More paracetamol undergoes CYP2E1 metabolism Excessive production of N-Acetyl P- benzo quinone imine (NAPQI) Depletion of Glutathione (Natural antioxidant) Liver damage (Hepatotoxicity)

  8. Paracetamol (Acetaminophen) Paracetamol induced hepatotoxicity can be treated by administering N-Acetyl Cysteine which is a precursor of Glutathione. N-Acetyl Cysteine Precursor of Glutathione Increase the level of glutathione Glutathione detoxifies NAPQI to form cysteine and other metabolites Prevention of liver necrosis

  9. Paracetamol (Acetaminophen) Contraindications 1. Hypersensitivity to Paracetamol 2. Hepatic Impairment (Due to its Hepatoxic effects) Drug Interactions Paracetamol + Hyoscine butyl bromide (Buscopan) M3 receptor blockade by Buscopan Reduced gut motility Increased gastric emptying time Reduced absorption of Paracetamol

  10. Paracetamol (Acetaminophen) Drug Interactions Paracetamol + Metoclopramide D2 receptor blockade by Metoclopramide Increased gut motility Reduced gastric emptying time Increased absorption of Paracetamol

  11. Paracetamol (Acetaminophen) Paracetamol + Alcohol Alcohol induce the secretion of pro-inflammatory cytokines (TNF-alpha, IL6 and IL8), oxidative stress, lipid peroxidation, and acetaldehyde toxicity Inflammation, apoptosis and fibrosis of liver cells Increased risk of Hepatotoxicity

  12. Paracetamol (Acetaminophen) Paracetamol + Amyl nitrite, Sodium nitrite or Sodium thiosulphate Nitrates induce the oxidation of Fe2+ (Haeme) to form Fe3+ (Met-Haeme) Increased risk of methemoglobinemia Fe3+ ions cannot bind with oxygen Reduced oxygen carrying capacity Discolouration of skin, mouth or nail bed

  13. Paracetamol (Acetaminophen) Paracetamol + Leflunomide, Teriflunomide or Lomitapide Excessive levels of Liver enzymes like ALT & AST Increased risk of Hepatotoxicity

  14. Paracetamol (Acetaminophen) Paracetamol + Prilocaine Prilocaine metabolises to form O-Toluidine O-Toluidine induce the oxidation of Fe2+ to form Fe3+ Increased risk of Methemoglobinemia Reduced oxygen carrying capacity Discolouration of Skin, Mouth or Nail bed

  15. ASPIRIN ADRs 1. Risk of bleeding 2. Aspirin induced Asthma 3. GI bleeding 4. Primary Respiratory Alkalosis

  16. ASPIRIN Risk of Bleeding Aspirin blocks COX 1 more than COX 2 and has the increased risk of bleeding compared to other NSAIDs. Aspirin Blockade of COX 1 of platelets Reduced Thromboxane A2 (TXA 2) synthesis Decreased Platelet aggregation Increased risk of Bleeding

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