Drug Interactions Flashcards
What is a drug interaction?
Modification of a drugs effect by prior or concomitant administration of another drug
What are different things involved in drug interactions?
Drugs
Herbal
Food
Drinks
Pharmacogenetics
What is the object drug?
Drug which is effected by these interactions
What is the precipitant?
Agent which precipitants such a reaction
What are examples of drug interactions which are not always decremental?
Hypertension
Parkinson’s
What is epidermiology?
Branch of medicine that deals with incidence, distribution and possible control of disease
What is the incidence of significant interactions?
Relatively low at 1%
What are some examples of drug involved in serious reactions?
Lithium
Warfarin
Erythromycin
Linezolid
What are drugs involved in serious interactions often?
Potent with a narrow therapeutic index, meaning a small change in blood levels induce toxicity
What do lots of foods interact with?
Warfarin
What happens to the probability of a drug-drug interaction with more medicaments?
Increases exponentially
Who are some people more likely to suffer from a drug-drug interaction?
Elderly
Young
Critically ill
Patients undergoing complicated surgery procedures
Patients on many medications
What kinds of conditions make people susceptable to drug interactions?
Chronic
What are examples of chronic conditions that make people more susceptable to drug interactions?
Liver disease
Renal impairment
Diabetes mellitus
Epilepsy
Asthma
Who usually experience severe interactions?
Patients with chronic conditions
What is pharmacodynamics?
Study of how a drug affects an organism
What is pharmacokinetics?
Study of how the organism affects the drug
What can drug interactions be?
Additive or synergistic
Antagonistic
What can interactions be due to?
Changes in drug transport
Fluid and elctrolyte disturbances
Indirect pharmacodynamics interactions
What are the 4 stages of pharmacodynamics?
Absorption
Distribution
Metabolism
Elimination
What can a drug do to the pharmacokinetics of another drug?
Alter it
Why is it possible to predict potential interactions?
Due to marked inter-individual variations in pharmacodynamics process
What is it not possible to predict?
Patients who will have a clinically significant interaction
What do absorption interactions mechanisms include?
Formation of insoluble complexes
Altered pH
Altered bacterial flora
Altered GIT motility
What do most absorption interactions lead to?
Change in absorption rate and not the extend of absorption
When is delayed absorption likely to have a great impact?
When the drug has a short half life or when we want high plasma levels quickly
How can absorption interactions be avoided?
2-4 hours are left between administration of drugs
What do some drugs do in the GI tract?
Bind to each other
What are examples of drugs that bind to each other in the GI tract?
Tetracycline and erythromycin complex with iron, calcium and magnesium
Cholestryamine resin used to bind cholesterol in the GI tract also binds to other drugs like warfarin
What is absorption affected by (relates to acids/bases)?
Degree of ionisation which is dependant on pH
Why do drugs increase pH?
Reducing the [H+] ions
What are some drugs that increase pH?
H2 antagonists
Proton pump blockers
Antacids
What destroys normal gut flora?
Broad spectrum antibiotics
Where are most oral medicines absorbed?
Small intestine
What is the rate limiting step of most oral medicines?
Gastric emptying
What can some drugs do to gastric emptying?
Increase or decrease it and so impact absorption of other drugs
What is the drug interaction in distribution?
Protein-protein displacement
When does protein-protein displacement occur?
When there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
What does displacement of a drug from a plasma protein cause?
Increased bioavailability of that drug
What are the 2 most important plasma proteins?
Albumin
Alpha1-glycoprotein
What protect patients from distribution interactions?
Increased metabolism and excretion
What drugs cause distribution interactions?
Ones which are highly protein bound
What are examples of drugs which are highly protein bound?
Indomethacin
Warfarin
Ibuprofen
When do interactions involving metabolism occur?
When one drug induces or inhibits the metabolism of another
Where does metabolism of drugs commonly occur?
In the liver via the cytochrome P450 system
What are some drugs that can inhibit the cytochrome system?
Erythromycin
Cimetidine
What do drugs inhibiting the cytochrome system cause?
Inhibition of metabolism of drugs that use that cytochrome
What are drugs that can be affected by drugs inhibiting the cytochrome system?
Warfarin
Diazepam
What are some drugs that are potent inducers of cytochrome P450?
Barbiturates
Carbamazepine
How long does it take for the effects of enzyme induction to be seen?
2-3 weeks
What factors impact the effect of enzyme induction been seen?
Age
Disease
Genetics
Concurrent drug therapy
What are examples of drugs inducing the production of cytochrome P450 enzymes?
Rifampicin inducing CYP 3A4 increases metabolism of Ciclosporin
St John’s wort induces CYP 3A4 to increase metabolism of ciclosporin
Where are most drugs excreted?
In urine or bile
What do interactions in excretion involve changes in?
Glomerular filtration rate
Tubular secretion
What is glomerular filtration rate?
How much blood passes through the glomeruli each minute
What is the glomeruli?
Tiny filters in the kidney that filter waste from blood
What is an example of a drug that inhibits excretion?
Calcium channel blockers
When do pharmacodynamic interactions occur?
When the action of a drug is changed due to another drug acting directly on the same receptor or indirectly on a different receptor
What can pharmacodynamic interactions be?
Direct
Indirect
Antagonistic
Synergistic/Agonistic
What is an example of pharmacodynamic direct antagonsm?
Beta blockers blocking the site of agonists
What is an example of pharmacodynamic synergistic interactions?
Two drugs with the same pharmacological effect acting on the same receptor are given concurrently
What is an example of a pharmacokinetic indirect agonism?
CNS depression
Warfarin and NSAIDs
What is an example of pharmacodynamic indirect antagonist?
NSAIDs and antihypertensive medication
NSAIDs and treatment for heart failure
What is the process of clinically dealing with an interaction?
1) Determine if the interaction is clinically important
2) Will altering the dose timing solve the interaction
3) Will using an alternative solve the interaction
4) If no for all of above, adjust the dosage and monitor the drug level and physiological function
