Drug-Drug interactions Flashcards
A drug interaction =
the modification of a drugs effect by prior or concomitant administration of another Drug, Herb, Foodstuff, Drink
A drug interaction has occurred when
the pharmacological effect of two or more drugs given together is not just a direct function of their individual effects
types of drug interactions
- drug - drug interactions
- food - drug interactions
- herbal - drug interactions
- drink- drug interactions
- pharmacogenetic interactions
Object drug =
The Drug whose Activity is effected by drug interactions
Precipitant =
The agent which precipitates drug interaction
Factors which modify drug action also include
- food
- smoking
- alcohol
- herbs
Drugs Involved With Serious Interactions have
narrow therapeutic index. examples include; - Lithium - Digoxin - Warfarin - Erythromicin - Linezolid
narrow therapeutic index means
that a small change in bood levels can induce profound toxicity.
- therapeutic drug monitoring is required
Foods Interacting with Warfarin
vegetables
- Alfalfa
- Asparagus
- Broccoli
- Onions
Herbals
- Ginseng
- green tea
Miscellaneous
- avacado
- fish oils
- liver
The probability of a drug-drug interaction increases exponentially with
the number of medicaments.
- the elderly
- the young
- the critically ill (patients who have chronic conditions)
- patients undergoing complicated surgical procedures
drug - drug interactions may be severe in patients who have
- chronic conditions
- liver disease
- renal impairment
- diabetes mellitus
- epilepsy
- asthma
Pharmacodynamic interactions include
- Antagonistic Interactions
- Additive or synergistic interactions
- Interactions due to changes in drug transport
- Interactions due to fluid and electrolyte disturbances
- Indirect pharmacodynamic interactions
It is possible for one drug to alter the
- absorption
- distribution
- metabolism
- elimination
of another drug
we are able to predict
potential interactions but not who will have a clinically significant interaction
Absorption interactions include
- Formation of insoluble complexes
- Altered PH.
- Altered bacterial flora..
- Altered GIT motility.
most interactions of drugs in the GI tract change
absorption rate.
- Delayed absorption is important when a drug has a short half life or when we want high plasma levels rapidly
- Most interactions result in a delay in absorption and can be avoided if 2-4 hours are left between administration of the drugs
Cholestyramine resin used to bind cholesterol in the
GI tract also binds to a variety of drugs e.g. warfarin, digoxin
Absorption is affected by the degree of ionisation which is
dependent on pH.
- H2 antagonists, proton pump blockers and antacids reduce H+ and so increase the pH
Bacterial flora are usually found in the
large bowel.
- Broad spectrum antibiotics destroy normal gut flora
- May lead to failure of oral contraceptive or digoxin toxicity
Gastric emptying is the
rate limiting step.
- Many drugs which delay gastric emptying (anticholinergics, tricyclic anti-depressants, opiates)
- Some drugs increase gastric emptying and accelerate absorption of paracetamol, (domperidone, metoclopramide)
After absorption drugs are distributed to the site of action
Protein-binding displacement occurs when
here is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
- results in increased bioavailability of the displaced drug
Drugs with Protein Binding >95%
Phenytoin Valproic acid Warfarin Diazepam Ibuprofen
Drugs such as clarithromycin, erythromycin, cimetidine, ketoconazole, omeprazole, CCBs (diltiazem)
inhibit the cytochrome system.
Metabolism commonly occurs in
the liver via the cytochrome P450 system
potent inducers of cytochrome P450
Drugs such as barbiturates, carbamazepine, phenytoin, rifampacin and tobacco smoke
Rifampicin increase
metabolism of Ciclosporin by inducing CYP 3A4
St john’s wort increase
metabolism of ciclosporin by inducing CYP 3A4
Most drugs are excreted in
Urine or Bile.
- Changes in GFR or tubular secretion
Loop diuretics and lithium increase
tubular reabsorption
Pharmacodynamic Interactions can be
direct
indirect
antagonistic
synergistic/agonistic
Direct Antagonism include
beta-blockers such as atenolol will block the actions of agonists e.g. bronchodilators such as salbutamol
Synergistic Interactions is when
two drugs with the same pharma-cological effect acting on the same receptor are give concurrently
Indirect Antagonistic Pharmacodynamic Interactions
- NSAIDs and antihypertensive medication
- NSAIDs and treatment for heart failure
Pharmacodynamic Interactions Indirect Agonism
- Central Nervous System Depression
- Benzodiazepines and tricyclics or alcohol
- Warfarin and NSAIDs (Indomethacin)
- Atenolol and verapamil
If the altering dose timing or no alternative doesn’t solve the issue
Adjust drug dosage ± monitor drug level (TDM) and physiological functions
