Drug-Drug interactions Flashcards
Definition of drug interaction
Modification of a drugs effect by prior or concomitant administration of another drug, herb, foodstuff, drink
What can interact with drugs?
Drugs, Herbs, food, drink and pharmacogenetic
What is the object drugs?
Drug whose activity is effected
What is the precipitant?
Agents which effects a drugs interaction
What factors modify drug action?
Smoking, food, alcohol and herbs
What can drug interaction treat?
Hypertension and Parkinsonism with carbidopa and levadopa
What is the risk of a patient seeing multiple doctors?
Dangerous as the different doctors prescribe different drugs
Name drugs involved with serious interactions
- Lithium
- Digoxin
- Warfarin
- Theophylline
- Cylosporin
- Macrolides
Importance of therapeutic drug monitoring
Drugs involved in serious reactions have a narrow therapeutic index - therefore small change in blood levels can induce toxicity
Name foods that interact with Warfarin
Vegetables: broccoli, brussellese sprouts, cabbage, onion, spinach
Herbals: green tea, tonic beans, woodruff
Miscellaneous: avocado, fish oils, liver, soybeans
Name the susceptible patents
- Elderly
- Young
- Critically ill
- Patients undergoing complicated surgical procedures
Conditions that can make patients more susceptible
- Liver disease
- Renal disease
- Diabetes mellitus
- Epilepsy
- Asthma
Name the mechanisms of drug interactions
- Pharmacodynamic
- Pharmacokinetic - ADME
What is ADME of drug pharmacokinetics
One drug can alter a drugs: Absorption Distribution Metabolism Elimination
Describ pharmocodynamic drug interactions
- Antagonistic or additive/synergistic
- Due to to changes in drug transport
- Due to fluid ad electrolyte disturbances
How can a drug alter ADME?
There is marked inter-individual variation in these process - so predict potential interaction but not able to predict who will have interaction
Possible absorption interaction outcomes
- Formation of insoluble complexes
- Altered pH
- Altered bacterial flora
- Altered GIT motility
Describe interaction of drugs in the GI tract and how can it be avoided?
Result in change of absorption rate rather than the extent of absorption - this is bad if drug has short half life when high plasma levels rapidly
Delayed absorption can be avoided if 2-4hrs are left between administration
What drugs bind in the GI tract?
Tetracycine and erythromycin complex with Fe, Ca, Mg
Cholestyramin resin binds cholesterol and also drugs (warfarin, digoxin)
How does changes in pH affect absorption?
Alters degree of ionisation - H2 antagonists, proton pump blockers and antacids reduce H+ and so increase the pH
What drugs alter pH?
H2 antagonist, proton pump blockers and antacids
They reduce H+ so increase pH
Describe cause and effect of changes in GI bacterial flora
Broad spectrum antibiotics destroy normal gut flora and lead to failure of oral contraceptive or digoxin toxicity (nausea, vomiting)
What is the rate limiting step in GI motility?
Gastric emptying
What drugs delay gastric emptying?
Anticholinergics, tricyclic anti-depressants, opiates
What drugs increase gastric emptying?
Domperidone and metoclopramide
What is protein-binding displacement?
Occurs when there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
What is the effect of protein-binding displacement?
Increases bioavailability of the displaced drug as only unbound drug is pharmacologically active
Two important plasma proteins
Albumin and alpha1-glycoprotein
Problem and solution of protein-binding displacement
1% displacement doubles the free plasma levels but patients are protected by increase in metabolism and excretion
Examples of displacing drug
Indomethacin and warfarin
How do drugs alter drug metabolism
One drug can induces or inhibits the metabolism of another - commonly occurs in the liver via the cytochrome P450 system
What drugs inhibit the cytochrome P450 system in metabolism?
Macrolides, cimetidine, ketoconazole, omeprazole, CCBs (diltiazem)
What drug inhibits metabolism of warfarin and diazepam by the cytochrome P450 system?
Cimetidine
What drug inhibits metabolism of warfarin and alcohol by the cytochrome P450 system?
Metronidazole
What drug inhibits metabolism of warfarin and phenytoin by the cytochrome P450 system?
Omeprazole
What drugs induce cytochrome P450?
Barbiturates, carbamazepine, phenytoin, rifapacin and tobacco smoke
What does enzyme induction (i.e. cytochrome P450) depend on?
Age, disease, genetic and concurrent drug therapies
What drugs do phenytoin induce the metabolism of by cytochrome P450?
Warfarin, steroids and OC
What drugs do rifampacin induce the metabolism of by cytochrome P450?
Warfarin, OC
What drug does rifampacin increase the metabolism of by CYP 3A4?
Ciclosporin
What drug does St John’s Wort increase the metabolism of by CYP 3A4?
Ciclosporin
What are drugs excreted in?
Urine or bile
How do drugs effect elimination/excretion?
- Change GFR or tubular secretion
- Dogoxin and lithium are toxic agents eliminated by the kidney - problem could lead to their build up in blood
What drugs inhibit excretion?
CCBs - verapamil, diltiazem
What drugs increase tubular reabsorption in kidneys?
Loop diuretics and lithium
When do pharmacodynamic interactions occur?
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
What are the types of pharmacodynamic interaction?
Direct
Indirect
Antagonistic
Synergistic/Agonistic
Describe direct antagonism of Pharmacodynamic interactions
Beta-blockers (atenolol) block the actions of agonists i.e. bronchodilators such as salbutamol
Describe synergistic interactions of pharmacodynamic interactions
When two drugs with the same pharmacological effect acting on the same receptor are given together
Name drugs with indirect agonist effect and what the effect is
- Warfarin (anti-coagulant) and NSAIDs (indomethacin) - bleeding becomes increased
- Bendodiazepines (sedative) and tricyclics (anti-depressants) or alcohol - relax muscles and cause CNS depression
- Atenolol and verapamil
Drugs involved in indirect antagonistic interactions?
NSAIDS and antihypertensive medication or with treatment for heart failure
How do you deal with an interaction?
If altering dose timing or an alternative drug does not solve the issue ADJUST drug dosage and monitor drug level (TDM) and physiological functions
