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Top 10 dangerous Drug Interactions

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AMDA and ASCP summarised top 10 danferous drug interactions involving Warfarin, ACE inhibitors, Digoxin or Theophylline with other drugs – PowerPoint PPT presentation

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Title: Top 10 dangerous Drug Interactions


1
Top 10 dangerous drug interactions
  • Dr. P.Naina Mohamed
  • Pharmacologist

2
Introduction
  • A group of experts convened by American Medical
    Directors Association (AMDA) in collaboration
    with American Society of Consultant Pharmacists
    (ASCP) summarised the following as top 10
    dangerous drug combinations
  • 1. Warfarin and NSAIDs
  • 2. Warfarin and Sulpha drugs
  • 3. Warfarin and Macrolides
  • 4. Warfarin and Quinolones
  • 5. Warfarin and Phenytoin
  • 6. ACE inhibitors and Potassium supplements
  • 7. ACE inhibitors and Spiranolactone
  • 8. Digoxin and Amiodarone
  • 9. Dogoxin and Verapamil
  • 10. Theophylline and Quinolones
  • The list was prepared on the basis of
  • The clinical significance and potential to cause
    harm
  • The frequency with which the interaction occurs,
    and
  • The frequency with which these drugs are
    prescribed in nursing homes.

3
Warfarin and NSAIDs
  • NSAIDs
  • Inhibit Cyclooxygenase 1 (COX 1) enzyme
  • Blockade of synthesis of Prostaglandin E (PGE)
  • Reduced mucous and bicarbonate secretions
  • Damage of Gastro intestinal mucosa
  • Gastro intestinal ulceration
  • GI Hemorrhage, perforation
  • Life-threatening bleeding (Acute) and Anemia
    (Chronic)
  • Warfarin increases the GI bleeding risk

4
Warfarin and NSAIDs
  • NSAIDs
  • Blockade of COX 1 of platelets
  • Reduced Thromboxane A2 (Tx A2) synthesis
  • Decreased Platelet aggregation
  • Increased risk of Bleeding
  • Warfarin aggravates the risk of hemorrhage

5
Warfarin and NSAIDs
  • Some NSAIDs
  • Inhibit cytochrome P450 isoenzyme
  • CYP2C9
  • Inhibition of the metabolism of Warfarin
  • Increased plasma concentration of Warfarin
  • Elevated risk of Bleeding

6
Warfarin and Sulpha drugs
  • Sulfamethoxazole
  • Inhibits cytochrome P450 isoenzyme CYP2C9
  • Decreased S-warfarin metabolism
  • Elevated plasma levels of Warfarin
  • Increased risk of Bleeding

7
Warfarin and Sulpha drugs
  • Sulpha drugs
  • Kill intestinal microflora
  • Decreased production of vitamin K by intestinal
    flora
  • Decreased ability of Coagulation
  • Warfarin increases the risk of Bleeding

8
Warfarin and Sulpha drugs
  • Sulpha Drugs (sulfaethoxazole/trimethoprim)
  • S-warfarin
  • Hypoprothrombinemic effect
  • Elevated risk of Hemorrhage

9
Warfarin and Macrolides
  • Macrolides (Erythromycin, clarithromycin and
    telithromycin)
  • Inhibit the cytochrome P450 isoenzyme CYP3A4
  • Inhibit the metabolism of less active R-warfarin
  • Minor increase in the levels of warfarin
  • Risk of Bleeding

10
Warfarin and Macrolides
  • Macrolides
  • Kill intestinal microflora
  • Decreased production of vitamin K by intestinal
    flora
  • Decreased ability of Coagulation
  • Warfarin increases the risk of Bleeding

11
Warfarin and Quinolones
  • Quinolones
  • Inhibit the cytochrome P450 isoenzyme CYP3A4
  • Inhibit the metabolism of less active R-warfarin
  • Minor increase in the levels of R- warfarin
  • Risk of Bleeding

12
Warfarin and Quinolones
  • Quinolones
  • Kill intestinal microflora
  • Decreased production of vitamin K by intestinal
    flora
  • Decreased ability of Coagulation
  • Warfarin increases the risk of Bleeding

13
Warfarin and Phenytoin
  • Phenytoin
  • Induce liver metabolism of warfarin genetically
  • May increase the effects of warfarin
  • Increased risk of Bleeding

14
ACE inhibitors and Potassium supplements
  • ACE Inhibitors
  • Decreased aldosterone production
  • Reduced potassium excretion
  • Hyperkalemia
  • Potassium supplements increase risk of
    Hyperkalemia further

15
ACE inhibitors and Spironolactone
  • ACE Inhibitors
  • Decreased aldosterone production
  • Reduced potassium excretion
  • Hyperkalemia
  • Potassium Sparing diuretics (Amiloride,
    Triamterene, spironolactone and Eplerenone)
    increase risk of Hyperkalemia further

16
Digoxin and Amiodarone
  • Amiodarone
  • P glycoprotein Inhbitor
  • Inhibits P-glycoprotein-mediated transcellular
    transport of digoxin
  • Inhibition of digoxin renal tubular secretion
  • Reduction of both the renal and non-renal
    excretion of digoxin
  • Elevated serum concentration of Digoxin
  • Risk of Digoxin Toxicity

17
Digoxin and Amiodarone
  • Amiodarone
  • Induce hypothyroidism
  • Increase Serum digoxin levels
  • Precipitation of digoxin toxicity

18
Digoxin and Amiodarone
  • Amiodarone
  • Prolong intestinal transit time
  • Enhanced absorption of Digoxin
  • Increased bioavailability of oral digoxin
  • Risk of Digoxin Toxicity
  • Amiodarone can also inhibit the metabolism of
    digitoxin by the liver, which would increase the
    serum levels of Digitoxin.

19
Dogoxin and Verapamil
  • Verapamil
  • P glycoprotein inhibitor
  • Inhibit P-glycoprotein-mediated transcellular
    transport of digoxin
  • Reduced renal and extra-renal (biliary) clearance
  • Rise in serum digoxin levels
  • Increased risk of Digoxin toxicity

20
Dogoxin and Verapamil
  • Verapamil
  • Enhance the digoxin-induced elevation of
    intracellular sodium
  • Increased risk of arrhythmias

21
Dogoxin and Verapamil
  • Digoxin Verapamil
  • Synergistic effect of slowing impulse conduction
    and muscle contractility
  • Bradycardia and possible heart block

22
Theophylline and Quinolones
  • Quinolones
  • Inhibit the cytochrome P450 isoenzyme CYP1A2
  • Inhibition of metabolism (N-demethylation) of
    theophylline
  • Slowing of Theophylline clearance
  • Elevated serum levels of Theophylline
  • Theophylline Toxicity

23
Theophylline and Quinolones
  • Theophylline Quinolones
  • Amplify the epileptogenic activity of the
    quinolones

24
References
  • Stockleys Drug Interactions, 9th Edition, Karen
    Baxter
  • http//www.amda.com/tools/clinical/m3/topten.cfm?p
    rintPage1
  • http//www.drugdanger.com/Elderly/4-12-14DrugInter
    actions.htm
  • http//www.thefreelibrary.com/StudyIdentifiesTop
    10LTCDrugInteractions.(NHNewsNotes).-a08071
    5636
  • http//mysccg.com/generalDocuments/Top20Ten20Dan
    gerous20Drug20Interactions20in20Long1.pdf
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