Drug interactions Flashcards
Define the term “Drug interaction”
An interaction occurs when the effects of a drug are changed by another drug, food or any other substance
What are the three drug interactions
Drug-Drug
Drug-Food
Drug-Disease
what are the effects of drug interactions?
to render the drug inactive
to lessen the effect of the drug
to increase the effect of the drug, which in turn can lead to an ADR
which drugs are commonly prone to drug interactions?
drugs with a Narrow Therapeutic Index
BEWARE !!!!!
what is meant by “ Narrow Therapeutic Index (NTI)” ?
When the difference between the plasma concentrations of no effect and toxic effect is small
Often require monitoring of plasma levels
E.g.
Digoxin ,Theophylline, Lithium
Ciclosporin ,Tacrolimus ,Warfarin
What are the consequences of Drug interactions ?
Loss of therapeutic effect
Toxicity
Unexpected increase in pharmacological activity
Beneficial effects
e.g. additive and potentiation (intended) or anatagonism (unintended)
Chemical or physical interaction
e.g. IV incompatibility in fluid or syringe mixtures
which risk factors can precipitate Drug Interactions ?
Polypharmacy
Multiple prescribers
Genetics
Specific population (e.g. elderly, obese, critically ill patients)
Specific illnesses (e.g. hepatic/renal impairment)
Some high risk drugs (e.g. NTI – lithium, warfarin, digoxin)
What are the 2 mechanisms of drug interactions
Pharmacokinetics- Relates to the way drugs affect each other as they move through the body
Pharmacodynamics- The effects of a drug are changed by the presence of another drug at its site of action either directly (same receptor) or indirectly (different receptor)
What are the 3 types of Pharmacodynamic Drug interactions?
Additive - two or more medicines used in combination produce a total effect which isgreater than the sum of the individual effects of each drug
Synergistic - one drug increases the other’s effectiveness
Antagonistic- two or more medicines used in combination block or reduce the effect of one of the medicines
What are the 4 types of Pharmacokinetic drug interactions?
One drug alters the rate or extent of absorption, distribution, metabolism or elimination of another drug
how can drug interactions affect absorption of drugs ?
Drug interactions can either delay the onset of drug action or increase or decrease the amount of drug absorbed
Affected by:
Amount of drug
Altered pH
Altered bacterial flora
Altered GI tract motility
how can drug interactions affect distribution of drugs ?
Drugs in the bloodstream are often bound to plasma proteins; only unbound drugs can leave the blood and affect target organs
One drug can displace another from the protein
Low serum albumin can increase the availability of drugs and potentiate their effects
how can drug interactions affect metabolism of drugs ?
Drugs usually metabolised (inactivated) by the Liver:
Enzymes convert drug into an inactive substance
The rate of action of enzymes in the liver can be increased or decreased by some drugs
This means that drugs metabolised by the same enzyme will be affected:
enhanced effect if the enzyme is inhibited
decreased effect if the enzyme is induced
What is the CPY540 system and is role drug Metabolism?
A large family of enzymes - an individual one is called an isoenzyme
Liver is the main site of drug metabolism
Definitions:
Substrate: drug is metabolised by the enzyme system
Inducer: drug that will increase the synthesis of CYP450 enzymes
Inhibitor: drug that will decrease the synthesis of CYP450 enzymes
how can drug interactions effect elimination?
Drugs excreted through kidney by:
Glomerular filtration
Active tubular secretion
Competition occurs between drugs which share the same secretion mechanism in the tubule
E.g. Aspirin and methotrexate
E.g. Amiodarone and digoxin
