Drug Interactions

Drug Interactions

1. Drug to Drug

   • -Multiple drugs (OTC meds, caffeine, nicotine, alcohol)
   • Consequences
     • Indifference
       • Unaltered therapeutic effects
     • Potentiative
       • Intesnification of effects -Increased therapeutic and adverse effects -Ex: 2 bp medications increase therapautic effects, increase potential for adverse effects
     • Effect reduction
       • Reduced therapeutic and adverse effects
     • Unique response
       • Interaction creates response that was not expected
   • Chemical Interactions
     • -Mixing parenteral drugs (in same syringe or IV solution) can lead to incompatibility --> interfere with pharmacologic activity -Incompatibilities- formation of precipitate/change in color  -Most common in IV solution: Precipitate (do not administer!) -Never combine drugs in same container without establishing compatibility
   • Pharmacokinetic Interactions
     • Altered Absorption
       • -Elevated gastric pH -Laxatives -Depress peristalsis -Induce vomiting -Absorbent drugs -Reduce regional blood flow
     • Altered distribution
       • -Competition for protein binding -Alteration of extracellular pH
     • *Altered metabolism
       • -Most important and complex mechanism of drug interaction 
       • CYP450
         • Enzyme in liver that metabolizes drugs
         • Inducers
           • Increases metabolism of other drugs --> sub-therapeutic effects
         • Inhibitors
           • Inhibits (impairs) metabolism of other drugs --> prolonged effects, increased side effects
     • Altered renal excretion
       • Filtration, re-absorption, active secretion
   • Mechanisms
     • Pharmacodynamic
       • Same receptor
         • Almost always inhibitory (antagonist/agonist) Ex: Beta-blocker (blocks beta receptors) and beta-agonist (stimulates beta receptors): blocker would have more significant effects
         • Inhibitory
           • Drugs that act on the same receptor will always act in an inhibitory fashion towards each other 
       • Different receptor
         • May be Potentiative or Inhibitory
         • Inhibitory
           • Ex: HCTZ (diuretic agent) and spironolactone  -HCTZ wastes K+, spironolcatone saves K+ -Work on the mechanism of Aldosterone
         • Potentiative
           • Ex: morphine and diazepam  -Both act on the CNS -Working together, cause a greater depression of the CNS 
     • Combined toxicity
       • Drugs with overlapping toxicities (toxic to the same sites/organs) should not be used together
       • Similar side effects
         • -Two drugs given concurrently share same side effect --> combined effect will be more toxic  -Ex: Furosemide (lasix) + aminoglycoside --> Ototoxicity -Cause hearing disturbances and balance problems 
   • Clinical Significance
     • Low TI
       • -Interactions are especially important in drugs with low therapeutic index
     • Impact on outcome
       • Potential to significantly impact the outcome of theraphy
     • Altered responses
       • Responses may be increased on decreased
     • Risk proportional to number
       • -Risk for serious drug interaction is directly proportional to the number of drugs a patient is taking
   • Minimize Interactions
     • -Assessment: Drug history -Knowledge of drugs and interactions -Awareness of susceptible patients -Limit number of drugs -Alertness to unusual symptoms -Monitor for early signs of toxicity -Adjust drug doses when needed (metabolizing inducers/inhibitors are added/deleted) -Adjust timing of administration to minimize interference with absorption -Vigilant with low therapeutic index

2. Drug and Food

   • Absorption
     • Decreased
       • -Slows down absorption rate --> delayed onset of action -Interfere with extent of absorption (ex: tetracycline and Ca; drugs bind to food (Ca or other minerals) -> reduce absorption -> decreased therapeutic response 
     • Increased
       • Drugs may need food to increase extent of absorption 
     • Recommendations
       • -Usually drugs better absorbed on empty stomach; Ex: give drug 1 hour before meals or 2 hours after meal -With food: irritating to gastric mucosa, cause nausea with empty stomach 
   • Metabolism
     • -Ex: Grapefruit (juice, pulp, peel, dietary supplements) can interfere with enzymes that metabolize drugs  -List of drugs that should not be taken with grapefruit -Enzyme that impairs liver's ability to metabolize drug Ex: Tangelo (hybrid grapefruit) and Seville oranges Metabolism inhibited by Grapefruit juice: -Anti-seizure -Antidepressants -Tranquilizers -Anti-hypertensives -Anti-arrhythmics -HIV medications -Cholesterol lowering -Immunosuppresants -Analgesics -Erectile dysfunction medications
   • Detrimental effects
     • -May lead to drug toxicity, could be almost lethal  -Ex: MAOIs (depression) and tyramine-containing food (aged, processed) --> hypertensive crisis -Ex: Theophylline and caffein (jitters and heart effects) -Ex: Potassium-sparing diuretics and salt substitutes both increase K+ levels --> profound effects on heart
   • Counteract
     • -Coumadin (inhibits vitK), counteracted by green leafy vegetables (high levels of vitK)

3. Drugs and Dietary Supplements

   • FDA Definition
     • "Vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites" intended to supplement diet -Exempt from examination of FDA -Can be manufactured without proof of efficacy -FDA can remove dangerous supplements
   • Regulation of Herbal products
     • Dietary Supplement and Nonprescription Drug Consumer Protection Act (2007) -Labeling mandates to include contact information for consumers to report adverse effects -Manufacturer must report to FDA serious adverse

4. Drug-Herb

   • -Conventional drugs can interact with herbal preparations -Interactions with herbal medicines are just as likely as with prescription medicaitons -A lack of reliable information is available on drug-herb interactions -Ex: St. John's wort (used to treat depression) induces drug metabolizing enzymes and reduces levels of many drugs 
   • Black cohosh
     • Use: menopause DI: antihypertensives and insulin
   • St. John's Wort
     • Use: Depression DI: Many due to induction of P450 enzyemes and P-glycoproteins --> increase drug excretion --> decrease drug effect
   • Gingko
     • Use: PVD pain, improve memory? DI: supresses coagulation --> interacts with coagulants --> increases bleading
   • Garlic
     • Hyperlipidemia  DI: suppresses coagulation --> interacts with coagulants --> increases bleading  DI: Oral hypoglycemic agents --> increase hypoglycemia 
   • Special care
     • -Pts taking drug with low therapeutic index: anticoagulants, antiseizure, antidysrhythmias 

5. Other Influences

   • Gender variations
     • -Influences health-seeking behaviors and symptom manifestations
     • Alcohol
       • -Metabolized more slowly by women
     • Opioid analgesics
       • Certain ones are more effective in women
     • Adherence
       • May differ by gender due to side effects 
   • Ethnicity/Cultural
     • -Cultural plays role in how individuals respond to drug therapy -Aware of cultural dietary preferences
     • Incidence of disease
       • -AA highest rate of hypertension, death rate due to cancer -Compared to caucasians, hispanics 2x more likely to die from diabetes, increased obesity and hypertension
     • Beliefs
       • Cultural beliefs can influence compliance and use of alternative therapies
     • Pharmacogenetic variations
       • Result in altered differences based on ethnicity --> results in altered pharmacokinetic properties (ex: metabolism)
   • Socio-economic disparity
     • Degree to which individuals have the capacity to obtain, process and understand basic health info needed to make appropriate health decisions and services needed to prevent/treat illness
     • Low health literacy
       • Prevalent among: -Older adults -minority populations -low socioeconomic status -medical underserved difficulty finding providers, filling out forms, sharing medical history, managing health conditions, understanding medication directions

6. Responding by teaching

   • -Sensitive to client's need to seek alternative therapy -Discuss options -Complete a health history and check for drug interactions -Instruct to take as directed -Monitor for effectiveness