Drug Drug Interactions Flashcards
What is a drug interaction
The modification of a drugs effect by prior or concomitant administration of another Drug, Herb, Foodstuff, Drink
When does a drug interaction occur
When the pharmacological effect of two or more drugs given together is not just a direct function of their individual effects
What type of drug interactions can occur
Drug - drug interactions Herbal - drug interactions Food - drug interactions Drink - drug interactions Pharmacogenetic interactions
What is an object drug
The drug whose activity is effected by such an Interaction
What is a precipitant
The agent which precipitates such an interaction
What factors can also modify drug action
Smoking
Alcohol
When are drug interactions not detrimental
The treatment of hypertension
The treatment of Parkinsonism with carbidopa and levadopa
What is carbidopa
A dopa decarboxylase inhibitor and prevents the systemic side effects from levadopa
How many patients are affected by detrimental interactions in hospitals
2.2-30%
How many patients are affected by detrimental interactions in GP’s
9.2-70%
Name some drugs involved with serious interactions
Erythromicin Clarithromicin Warfarin Gentamicin SSRI Lithium Digoxin
What are some patient specific factors that can affect DDI’s
Advanced age
Genetic polymorphioms
Concomitant diseases
What are some drug specific factors that can affect DDI’s
Polypharmacy
Narrow therapeutic range
Dose
What are some other factors that can affect DDI’s
Multiple prescribing physcians
Self prescribing
What do drugs involved in serious interactions have in common
They are all potent with a narrow therapeutic index
So a small change in blood levels can induce profound toxicity
What can prevent drug toxicity
Therapeutic drug monitoring
What foods can interact with warfarin
Asparagus Broccoli Brussel sprouts Lettuce Onions Avocado Fish oils Green tea
What pateints are susceptible to DDI’s
Elderly
Young
Critically ill
Patients undergoing complicated surgical procedures
What increases the probability of DDI’s
Increases exponentially with the number of medicaments
What type of chronic conditions can make patients susceptible to DDI’s
Liver disease Renal impairment Diabetes mellitus Epilepsy Asthma
What are the mechanisms of drug interactions
Pharmaceutical
Pharmacokinetic
What pharmacokinetic interactions can a drug alter
Absorption
Distribution
Metabolism
Elimination
What kind of pharmacodynamic interactions are there
Antagonistic Interactions
Additive or synergistic interactions
Interactions due to changes in drug transport
Interactions due to fluid and electrolyte disturbances
Indirect pharmacodynamic interactions
Why can potential interactions be predicted
As there is marked inter-individual variation in the ADME processes
What cannot be predicted
Who will have a clinically significant interaction
What mechanisms can be used to disrupt absorption interactions
Formation of insoluble complexes
Altered pH
Altered bacterial flora
Altered GIT motility
What do most type of DDI’s involving absorption result in
Changes in absorption rate rather than the extent of absorption
When is delayed absorption important
When a drug has a short half life or when we want high plasma levels rapidly
What do most DDI’s involving absorption cause and how can it be avoided
A delay in absorption
Avoided if 2-4 hours are left between administration of the drugs
Where do some drugs bind to each other
GI tract
Give examples of drugs which bind to each other in the GI tract
1) Tetracycline and erythromicin complex with iron, calcium, magnesium
2) Cholestyramine resin used to bind cholesterol in GI tract binds to a variety of drugs (e.g. warfarin, digoxin)
What is dependent on pH in regards to drug absorption
The degree of ionisation which will affect absorption
What can increase pH
H2 antagonists, proton pump blockers and antacids which reduce H+
What is bacterial flora normally found in the GI tract
Large bowel
What can destroy normal gut flora
Broad spectrum antibiotics
What can the destruction of normal gut flora cause
May lead to failure of oral contraceptive or digoxin toxicity
Where are most oral medicines abdorbed
Small intestine
What is the rate limiting step in drug absorption
Gastric emptying
Name some drugs which delay gastric emptying
Anticholinergics
Tricyclic antidepressants
Opiates
Name some drugs which increase gastric emptying and accelerate the absorption
Domperidone
Metoclopramide
What drug can stop gastric emptying
Codine
What happens after drugs are absorbed
They are distributed to the site of action
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 the displacement of a drug from plasma protein result in
Increased bioavailability of the displaced drug
What form of drugs are pharmacologically active
Unbound
What can happen when 1% of 99% bound drug is displaced
Will lead to the doubling of free plasma levels
Which two proteins are important in distribution DDI’s
Albumin
Alpha 1-glycoprotein
How are patients protected from the common distribution DDI’s
By increased metabolism and excretion
Name some drugs which have over 95% protein binding
Clofibrate Diazepam Glyburide Ibuprofen Naproxen Oxazepam Thyroxine Warfarin
When do drug interactions involving metabolism occur
When one drug induces or inhibits the metabolism of another
Where does drug metabolism commonly occur
The liver via the cytochrome P450 system
Name some drugs that can inhibit the cytochrome system
Clarithromycin Erythromycin Cimetidine Ketoconazole Omeprazole CCBs
What in the cytochrome system do drugs inhibit
Inhibits the metabolism of a small group of drugs metabolised by the cytochrome P450 system
What can affect cimetidine
Warfarin
Diazepam
What can affect metronidazole
Warfarin
Alcohol
What can affect omeprazole
Phenytoin
Warfarin
Name some potent inducers of cytochrome P450
Barbiturates Carbamazepine Phenytoin Rifampacin Tobacco smoke
When can the effects of enzyme induction be seen
After 2-3 weeks
What are the effects of induction dependent on
Age
Disease
Genetics
Concurrent drug therapy
What can rifampicin and St John’s wort increase by inducing CYP3A4
Increase metabolism of ciclosporin
Where are most drugs excreted in
Urine
Bile
Name some toxic agents excreted by the kidney
Digoxin
Lithium
What can inhibit the excretion of verapamil/diltiazem and digoxin
CCBs
What do loop diuretics increase
Tubular reabsorption
What will effect drug excretion
Changes in GFR or tubular secretion
When do pharmacodynamic interactions occur
When the pharmacodynamic actions of a drug are changed due to presence of another drug either acting directly on the same receptor) or indirectly on different receptors
What type of pharmacodynamic interactions are there
Direct
Indirect
Antagonistic
Synergistic/Agonistic
Give an example of direct antagonism
Beta-blockers such as atenolol will block the actions of agonists (e.g. bronchodilators such as salbutamol)
Give an example of synergistic interactions
When two drugs with the same pharma-cological effect acting on the same receptor are give concurrently
What effect can pharmacodynamic interactions have
May be additive or multiplicative
Give an example of indirect agonism and the drugs that can cause it
Central Nervous System Depression Caused by: Benzodiazepines and tricyclics or alcohol Warfarin and NSAIDs (Indomethacin) Atenolol and verapamil
Give examples of indirect antagonistic pharmacodynamic interactions
NSAIDs and antihypertensive medication
NSAIDs and treatment for heart failure
