Drug Interactions

Question 1

drug interaction

Answer 1

• one drug alters effect of another
  
  • not a side effect, an adverse reaction or a toxic effect
• incidence is proportional to number of drugs administered
• individual and species differences
• predictable or unpredictable

Question 2

possible consequences of drug interactions

Answer 2

• none
• altered therapeutic efficacy
• altered duration of action
• altered intensity of side effects
• novel effects

Question 3

categories of drug interactions

Answer 3

• incompatibilities
• pharmacokinetic interactions
• pharmacodynamic interactions

Question 4

drug incompatibilities

Answer 4

• physical
  
  • ​separation
• chemical
  
  • precipitation
  • chelation
  • binding

Question 5

consequences of incompatibilities

Answer 5

• damage from toxic compounds
• particulate emboli
• tissue irritation (pH changes)
• therapeutic failure

Question 6

sulcralfate

Answer 6

• coats stomach and binds to compounds
• binds to tetracycline, fluorquinolones, cimetidine, phenytoin, phenobarbital, griseofulvin

Question 7

pharmacokinetic interactions

Answer 7

• occurs when one drug alters another via change in:
  
  • absorption
  • distribution
  • metabolism
  • elimination
• most common type of drug interaction

Question 8

omeprazole and ketoconazole interactions

Answer 8

• omeprazole increases gastric pH and decreases absorption of ketoconazole by 50%
  
  • ketoconazole likes acidic pH

Question 9

effects of gastric pH change on absorption

Answer 9

• antacids (increased pH) will decrease absorption of weak acids and increase absorption of weak bases
• infections (decreased pH) will increase absorption of weak acids and decrease absorption of weak bases

Question 10

metoclopramide and digoxin

Answer 10

• metoclopramide increases gastric emptying (prokinetic) and decreases absorption of digoxin

Question 11

protein binding (distribution)

Answer 11

• some drugs are protein bound with varying affinities
• bound <–> unbound (active)
• competition arises when two highly protein bound drugs are simultaneously administered
  
  • erythromycin, doxycycline, NSAIDs, amphoteracin B, furosemides

Question 12

pharmacokinetic interaction: metabolism

Answer 12

• metabolism or biotransformation
• intestines -> portal circulation -> liver -> modified
  
  • oxidation, reduction, hydrolysis, inactivated
• most become water soluble
• tolerance: increase activity of microsomal enzymes to speed metabolism of drug
• inducers, inhibitors, metabolites

Question 13

inducers

Answer 13

• decrease duration/potency of others
• phenobarbital, rifampin

Question 14

inhibitors

Answer 14

• increase duration/potency of others (slow metabolism)
• cimetidine, chloramphenicol, ketoconazole

Question 15

drugs with active metabolites

Answer 15

• diazepam, ketamine, morphine

Question 16

pharmacokinetic interaction: elimination

Answer 16

• renal
  
  • competition for same renal tubular transport system
  • alter urinary pH (ion trapping)
  • alter renal BF
• biliary
  
  • enterohepatic recirculation
    
    • altered by abx
• respiratory

Question 17

drugs that compete for renal excretion

Answer 17

• acidic drugs
  
  • penicillins, cephalosporins, sulfonamides, furosemide, NSAIDs
• basic drugs
  
  • procainamide, dopamine, trimethoprim, opioids

Question 18

pharmacodynamic interaction

Answer 18

• act on same receptor (pharmacological)
• act on different receptors that regulate a common process (physiological)
• elicit effects that are not receptor-mediated but have final common pathway
• synergistic vs antagonistic

Question 19

synergistic pharmacodynamic drug interactions

Answer 19

• CNS depressants
• autonomic drugs
• ß-blockers and Ca²⁺ blockers (decrease HR)
• NSAIDs + steroids (ulcers)
• aminoglycosides + amphotericin B (kidneys)

Question 20

antagonistic pharmacodynamic drug interactions

Answer 20

• alcohol + caffeine
• anticoagulants + phytonadione
• furosemide + digoxin

Question 21

drug interactions and electrolyte changes

Answer 21

• diuretics w/ digitalis, antiarrhythmics, or muscle relaxants (decrease K)
  
  • hypokalemia: increased digitalis binding to Na/K ATPase (toxicity)
  • hyperkalemia: decreased digitalis binding to Na/K ATPase (decreased efficacy)

Question 22

digoxin drug interactions

Answer 22

• quinidine competes and decreases renal clearance
• diuretics: hypokalemia increases affinity to bind to Na/K ATPase
• hypercalcemia enhances digitalis-induced increased IC calcium
• hypomagnesemia (arrhythmia)
• decreased absorption when given with metoclopramide

Question 23

preventing drug interactions

Answer 23

• avoid polypharmacy
• assess and plan tx regimen
• compatibility assessment
• color code IV lines
• multilumen catheters
• in-line filters

Question 24

levetiracetam drug interactions

Answer 24

anti-convulsant

dose needs to be increased if given with P450 inducer like phenobarb

Question 25

phenobarbital drug interactions

Answer 25

• P450 inducer
• may need to increase dose of other drugs because increased clearance

Question 26

cimetidine drug interactions

Answer 26

• P450 inhibitor
• decreases metabolism of other drugs and can lead to toxicity (metronidazole)

Question 27

chloramphenicol drug interactions

Answer 27

• P450 inhibitor
• increases metabolism of other drugs, may lead to toxicity

Question 28

ketoconazole drug interactions

Answer 28

• P450 inhibitor
• decreases metabolism of other drugs, can lead to toxicity
  
  • can be used to an advantage to reduce dose of other drugs (cyclosporine)
• decreased absorption when administered with omeprazole

Question 29

diazepam drug interactions

Answer 29

• active metabolites
• preciptiation with ketamine

Question 30

potassium bromide drug interactions

Answer 30

affected by chloride intake (too much salt water)