Drug-Drug Interactions Flashcards
A drug interaction is defined by…
The modification of a drugs effect by PRIOR or CONCOMITANT (naturally occurring) administration of another drug, herb, foodstuff drink
OR
A drug interaction has occurred when the pharmalogical effect of two or more drugs given together is not just a direct function of their individual effects
Types of things that can interact with drugs
Other drugs, Herbs, Food, Drink, Pharmacogenetic interactions, smoking, alcohol
Object Drug
The drug whose activity is effected by an interaction
Precipitant
The agent which precipitates such an interaction
Parkinson’s treated with carbidopa and levadopa
Carbidopa - dopa decarboxylase inhibitor which prevents the systemic side effects of levadopa
Warfarin
Blood thinner. (anticoagulant) Treats blood clots etc
SSRI
Selective Serotonin Reuptake inhibitors (anti-depressants)
Erythromycin
Treats various bacterial infections. eg chlamydia
Therapeutic drug monitoring is important because
A small change in blood levels can induce profound toxicity
SSRI, Lithium, Erythromycin etc
All are potent with a narrow therapeutic index
Foods etc that interact with Warfarin
Broccoli, Asparagus, Kale, spinach. Green teas etc avocado, fish oils
The more medications taken
the higher probability of drug-drug interactions
Susceptible patients include chronic conditions such as
Liver disease, Renal Impairment, Diabetes, epilepsy, asthma
Pharmacokinetics
Determining the bodies effect on the drug. Absorption, distribution, metabolism, elimination
Pharmacodynamics
Determining the drugs effects on the body
Pharmacokinetic interactions ADME
Absorption, distribution, metabolism, elimination of another drug
Mechanisms of absorption interactions
Formation of insoluble complexes, altered pH, altered bacterial flora, altered GIT motility
Absorption can be affected by ionisation which is dependent on…
pH
Change in Bacterial Flora
Bacterial flora are usually found in the large bowel. Broad spectrum antibiotics destroy normal gut flora
Rate limiting step of absorption
Gastric Emptying
Most oral medicines are absorbed in the…
Small intestine
Pharmacologically active drugs are…
unbound. The displacement of a drug (by another drug) from plasma protein results in increased bioavailability of the displaced drug.
If a drug is 99% bound displacement of only 1% will lead to
a doubling of free plasma levels
Drugs with protein binding >95%
Warfarin, Naproxen, Diazepam, Glyburide, Ibuprofen
Drug metabolism
Drug interactions involving metabolism occur when one drug induces or inhibits the metabolism of another
Metabolism occurs in the liver via the…
cytochrome p450 system
Inducers of the P450 system
Barbiturates, carbamazepine, phenytoin and tobacco smoke
Common example:
Phenytonin –> Warfarin, steroids
Rifampacin –> Warfarin
Rifampicin increases metabolism of…
Ciclosporin (by inducing CYP3A4)
St Johns Wort increases metabolism of
ciclosporin (by inducing CYP3A4)
Digoxin and Lithium
Toxic agents that are eliminated by the kidneys
Phamacodynamics interactions
Occur when the pharmacodynamics actions of a drug are changed due to the presence of another drug either acting directly on the same receptor or indirectly on different receptors
AGONIST/ANTAGONIST (direct and indirect)
Direct antagonism
Beta blockers (eg atenolol) will block the actions of agonists (eg salbutamol - bronchodilators)
Synergistic interactions (agonists)
When two drugs with the same pharmacological effect acting on the same receptor are given concurrently.
Indirect agonism
CNS depression, nexodiazapines, Warfarin
Indirect antagonism
NSAIDs and antihypertensive medication or NSAIDs and treatment for heart failure
