Drug-Drug interactions Flashcards
5 Rs of prescribing
- Right patient
- Right drug
- Right route
- Right time
- Right dose
High risk patients of drug-drug interaction
- Increases exponentially with the number of medicaments
- Elderly
- Young
- Critically ill
- Patients undergoing complicated surgical procedures
- Diseases: liver, renal, diabetes, epilepsy, asthma
- Interactions which are minor in normal patients can be really severe in other patients
Drug-drug interaction definition
- Modification of a drug’s effect by prior or concomitant administration
Types of drug interactions
- Drug-drug
- Herbal-drug
- Food-drug
- Pharmacogenetic interactions
Characteristics of drugs likely to have a drug-drug interaction
- All these drugs are potent with a narrow therapeutic index: small change in blood levels can induce profound toxicity.
- Why it is necessary to have therapeutic drug monitoring
Mechanisms of drug-drug interaction: Absorption
- Formation of insoluble complexes
- Altered pH
- Altered bacterial flora
- Altered GI motility
How altered pH affected drug-drug interactions
- Absorption dependent on pH
- H2 antagonists, proton pump blockers (omeprazole) and antacid reduce H+ and increase the pH
How altered bacterial flora affected drug-drug interactions
- Usually found in the large bowel
- Broad spectrum antibiotics destroy normal gut flora
- May lead to failure of OCP or digoxin toxicity
How altered GI motility affected drug-drug interactions
- Complex
- Most of these interactions change absorption rate, not extent of absorption -> affects half life
- Some drugs bind to each other in GI tract: tetracycline and erythromycin complex with iron, calcium and magnesium
- Most oral medicines are absorbed in the small intestine
- Gastric emptying is rate limiting step.
Drugs that affect gastric emptying
- Delay emptying: anticholinergics, tricyclic, anti-depressants, opiates
- Increase gastric emptying and accelerate absorption of paracetamol: domeperidone, metoclopramide
Mechanisms of drug-drug interaction: Distribution
- Protein-protein placement
- Protein-binding displacement
How altered protein-binding displacement affected drug-drug interactions
- reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
- Results in increased bioavailability of displaced drug
- Type of interaction is common but patients are protected by increased metabolism and excretion
Examples of protein-binding displacement drugs
- Indomethacin and warfarin
- 95% of drugs have protein binding: amitripyline, furosemide, ibuprofen
- Lithium, as an antiepileptic has the same symptoms as the disease
Mechanisms of drug-drug interaction: Metabolism
- Occur when one drug induces or inhibits the metabolism of another
- Through Cytochrome P450
Examples of drugs that inhibit cytochrome system
- Clarithromycin
- Erythromycin
- Omeprazole
Examples of drugs that inhibit cytochrome inducers, increase metabolism
- Carbamazepine
- Phenytoin (w/warfarin, steroids, OCP)
- Rifampicin (ciclosporin, warfarin, OCP)
- Tobacco smoke
Elimination
- Most drugs excreted in urine or bile
- If patient gets dehydrated, they get renal damage due to nephrotoxicity of drug, stop drinking and this changes the GFR or tubular secretion
- Have to monitor bloods and fluid intake
- Loop diuretic increase tubular reabsorption e.g. furosemide
Examples of toxic agents eliminated by kidney
Digoxin and lithium are examples of toxic agents eliminated by kidney
Pharmacodynamic drug-drug interactions
- When 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
Synergistic or additive drugs
- Two drugs with the same pharmacological effect acting on the same receptor are given concurrently, effect can be additive or multiplicative
Indirect agonism
- Central nervous system depression: Benzodiazepines and tricyclics or alcohol
- Warfarin and NSAIDs (Indomethacin)
- Atenolol and verapamil
Antagonistic
- Direct antagonism: beta-blockers such as atenolol will block the actions of antagonists
- Indirect antagonism: NSAIDS raise blood pressure and antihypertensives lower BP
Examples of pharmacodynamic drug interactions
- Synergistic or additive
- Antagonistic
- Interactions due to changes in drug transport
- Interactions due to fldui and electrolyte disturbances
- Indirect pharmacodynamic interactions
Object drug
Drug whose activity is affected by such an interaction
Precipitant
- Agent which precipitates such an interaction
Examples of drug interactions which are not always detrimental
- Treatment of hypertension
- Treatment of Parkinsonism with carbidopa and levidopa. Carbidopa prevents the side effects of levodopa
How to deal with an interaction
- Is the interaction detrimental or desired?
- Is the interaction clinically important
- Will altering the dose timing solve the interaction?
- Will using an alternative solve the interaction
If altering the timing or no alternative solve the issues then adjust the drug dosage and monitor drug level (TDM) and physiological functions
