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(Drug-Drug Interaction)

(Drug-Drug Interaction). Pharmacodynamics interactions Antagonistic e ffect Additive e ffect Synergistic effect. Antagonistic effect. A-Interactions Based on Opposing Action(Antagonism ): Examples: 1 ) Beta2 agonists + Beta-blocker e.g : Salbutamol + Propranolol

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(Drug-Drug Interaction)

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  1. (Drug-Drug Interaction) Pharmacodynamics interactions • Antagonistic effect • Additive effect • Synergistic effect

  2. Antagonistic effect

  3. A-Interactions Based on Opposing Action(Antagonism): Examples: 1) Beta2 agonists + Beta-blocker e.g : Salbutamol + Propranolol 2)Anticoagulant + Vitamin K Vitamin k is responsible for activation (gamma carboxylation) of vitamin k dependent clotting factors.

  4. 3) Hypoglycemics + Corticosteroids As corticosteroidsincrease plasma glucose level by -Gluconeogenesis (is a metabolic pathway  that results in the generation of glucose from certain non-carbohydrate carbon substrates) - increase insulin resistance (is when cells in your muscles, body fat and liver start ignoring the signal that the hormone insulin is trying to send out—which is to grab glucose out of the bloodstream and put it into our cells ). - impair glucose tolerance (is an umbrella term for metabolic conditions which result in higher than normal blood glucose level).

  5. 4)NSAIDs decrease antihypertensive effect of β blockers except sulindac

  6. Additive effect

  7. B. Interactions Based on Additive Effects Additive effect (1+1=2) Examples Methotrexate+ Co-trimoxazole (Trimethoprim)→ Megaloblastic anemia due to folic acid inhibition.

  8. Megaloblastic Anemia • Inhibition of DNA synthesis • Cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage BUT RNA and cytoplasmic elements are synthesized at a constant rate despite the cells' impaired DNA synthesis • This leads to continued cell growth without division leading to megaloblasts (unusually large cells)

  9. Synergistic effect

  10. C-Interactions Based on synergetic effects Synergistic effect (1+1>2) Examples: A- Anticoagulants + Aspirin→ severe bleeding Anticoagulants as warfarin which inhibit epoxide reductase → inhibit coagulation Aspirin : inhibit Thromboxane A2 → inhibit platelets aggregation → inhibit Blood Clotting )

  11. INR [international normalized ratio] -It is the ratio between patient prothrombin time (PT)/ normal PT. -It can be used as an indicator for warfarin effect. -INR normal value (0.9-1.3) -INR should be : (2:3) in Atrial fibrillation (AF) - Rheumatic heart disease (RHD) patients. (3:4) in Deep vein thrombosis (DVT) -Stroke patients.

  12. B- Aminoglycosides + Penicillin

  13. C- Sulfonamide + Trimethoprim (co-trimoxazole)

  14. Cases

  15. Case 1 Mrs.PG is a 65 years old woman, nonsmoker with no family history of Diabetes. she was on Warfarin (60 mg daily) for recurrent Deep Venous Thrombosis(DVT). She was admitted to the hospital with hypertension (B.P 190\100) and the physician prescribed HCTZ (50mg daily) for her BP. She told the Dr. that she is also taking ibuprofen for headache and Miconazole for fungal infection. After several months Mrs. PG complained from Orthostatic hypotension (drowsiness) & pain in her joints in the morning & skin rash. After that the physician added Captopril to her HCTZ therapy & asked her to make some laboratory tests including K, Na & uric acid levels , GFR, SCr. Fortunately, her BP became well controlled & but she is complaining from a little dry cough.

  16. 1)What is the cause of the following adverse drug reactions &mention their types? • Orthostatic hypotension • Hypokalemia • Hyponatremia • Hyperurecemia Thiazide ( type A ) • Skin rash Thiazide ( type B ) • Dry cough Captopril ( type B )

  17. 2)How could the Dr have better served Mrs. PG? we can decrease thiazide dose to 25 mg instead of 50 mg to decrease type A ADR. caused by thiazide. 3) what are the changes suspected to occur in GFR,SCR? GFR decreases and SCR increases 4) write a drug interaction report.

  18. These are brief answers, detailed mechanism should be provided in the exam

  19. Case 2 Mrs. N is a 54 year-old female who is suffering from severe rheumatoid arthritis for which she was prescribed Methotrexate 70mg/ kg/ week. she also takes ketoprofen as analgesic, and Lithium was added lately for the management of her bipolar disorder. She is suffering from UTI for which she takes Co-trimoxazole. Q:Mention the possible drug interactions??

  20. These are brief answers, detailed mechanism should be provided in the exam

  21. THANK YOU

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