Top 10 dangerous Drug Interactions

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Top 10 dangerous drug interactions

• Dr. P.Naina Mohamed
• Pharmacologist

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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.

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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

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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

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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

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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

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Digoxin and Amiodarone

• Amiodarone
• Induce hypothyroidism
• Increase Serum digoxin levels
• Precipitation of digoxin toxicity

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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.

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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

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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

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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