drug-drug interactions Flashcards
Discuss factors which may predispose a patient to drug interactions. With medically important examples.
Dependent of genetic factors such: age, chronic disease( liver disease, renal failure, asthma, diabetes mellitus) , number of medications.
Food
Herbal medicines
Polypharmacy
e.g. with warfarin
- foods: greens, liver, fish oils, avocado
-herbal medicine: ginseng, green tea, tonka beans
Discuss the definition and classification of drug - drug interactions.
DRUG-DRUG INTERACTIONS: modification of a drugs effect prior or in concomitance with another drug, herb, food, drink.
- Pharmacokinetic
- Pharmaceutical interactions- interactions when drugs are mixed in the same solution.
- Pharmacodynamic- when the drug of one affects the action of the other
- direct: act on the same receptor
- indirect: act on different receptor
- synergist: warfarin and NSAID
- antagonist: NSAID and heart failure
Discuss the importance of therapeutic drug monitoring
Monitoring drug plasma levels of drugs which are toxic or have a narrow therapeutic index range.
TDM is most commonly used to monitor treatment with the
warfarin and paracetamol in overdose.
Pharmacokinetic interactions
Absorption
Absorption:
Usually affect the rate rather than the extent.
Important when the drug has a shortchanged half life- can be overcome by administering every 2-4 hours.
Pharmacokinetic interactions
Distribution
Distribution:
-Affects the amount of unbound drug. Uncommon- protected by metabolism and excretion.
Pharmacokinetic interactions
Metabolism
Interacts with cytochrome P450
Inhibitors:
Inducers:
-effects not seen for 2-3 weeks
broad spectrum antibiotics
Kills normal flora of the gut and leads to digoxin toxicity
Oral contraceptive
Ph changes
Alters the ionisation
e.g. antacids and proton pump inhibitors
Gut motility
Opiates- slows gastric emptying
Domperidone- fastens gastric emptying
gastric emptying is often the rate determining step
Unbound drug
Warfarin
alters bioaccumulation
Which are the two most important binding- proteins
Albumin and alpha1-glycoprotein
increases metabolism
st johns wort/rifampcin- cyclosporin
Phenytoin- warfarin and steroids
Slows down metabolism
metronidazole- warfarin and alcohol
Cimethidine- warfarin and diazepam
decreases elimination
Digoxin/ Lithium– increases toxic products released
ionisation
Proton pump inhibitors/ antacids- lower H+ and increase Ph
