Drug to Drug interaction Flashcards
modification of a drugs effect by prior or concomitant administration of another drug
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
drug interaction
Factors which modify drug action -
drugs, food, smoking, alcohol, and herbs
Those drugs most commonly involved with serious interactions and which give rise to serious toxicity are those ……
with a narrow therapeutic index
small change in blood levels = TOXIC! require TDM Lithium Digoxin OCP Warfarin Gentamicin Cyclosporin Fluconazole Erythromycin Clarithromycin Ketoconazole
Susceptible patients
elderly young critically ill those going for complicated surgery those with chronic condition (DM, asthma, epilepsy)
The outcome of direct interaction between 2 drugs e.g. through IV
precipitation
pharmaceutical
drug transport
fluid and electrolyte disturbance
indirect pharmacodynamics interactions
Pharmacodynamic interactions
It is possible to predict potential interactions but possible to predict who will have a ……
clinically significant interaction
Drug interactions affect absorption rate rather than the ….. of absorption. When the drug has short 1/2 life or when we want high [plasma], ….absorption is important
extent
delayed
Most interactions result in a delay in absorption and can be avoided if 2-4 hours are left between administration of the drugs
The Drug whose Activity is effected by such an Interaction is called the..
Object drug
The agent which precipitates such an interaction is referred to as the …
Precipitant
Foods interacting with warfarin
veg, herbals, miscellaneous
absorption interactions
formation of insoluble complexes
altered pH
altered bacterial flora
altered GIT motility
The interaction of drugs result in changes in ……. rather than the ….. of absorption
absorption rate
extent
Some drugs bind to each other in the GI tract, what are they?
tetracycline and erythromicin complex with iron, calcium, magnesium
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
Most oral medicines are absorbed in the
small intestine
Gastric emptying in the rate limiting step
Drugs which delay gastric emptying
(anticholinergics, tricyclic anti-depressants, opiates
Absorption
Some drugs increase gastric emptying and accelerate absorption of paracetamol
Domperidone, Metoclopramide
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
Distribution
The displacement of a drug from plasma protein results in increased bioavailability of the displaced drug
Another type: Protein-protein displacement
Only unbound drug = pharmacologically active
The two most important proteins are:
Albumin
1-glycoprotein
This type of interaction is common but patients are protected by increased metabolism and excretion
Drugs with Protein Binding >95%
warfarin
Indomethacin
ketoconazole
Thyroxine
Diazepam
Ibuprofen
Drug interactions involving metabolism occur when one drug induces or inhibits the metabolism of another.Metabolism commonly occurs in the liver via the cytochrome P450 system.
Which drugs inhibit the cytochrome system?
clarithromycin, erythromycin, cimetidine(inhibits warfarin,diazepam), ketoconazole, omeprazole(phenytoin, warfarin), CCBs
metronidazole (warfarin, alcohol)
Drug Metabolism
Potent inducers of cytochrome P450
,phenytoin(warfarin, steroids, OC), rifampicin (warfarin, OC), tobacco smoke, barbiturates, carbamazepine
The effects of enzyme induction are not seen for 2-3 weeks
The effects of induction depend on age, disease, genetics and concurrent drug therapy
….. increase metabolism of Ciclosporin by inducing…..
Rifampicin and St John’s Wort
CYP 3A4
Most drugs are excreted in …. or …..
Urine
Bile
……….. are toxic agents that are eliminated by the kidney
Digoxin and Lithium
…… inhibit ….. of
Verapamil/diltiazem and digoxin
CCBs
excretion
Loop diuretics increase …..
tubular reabsorption
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.
Pharmacodynamics interactions
Different types of pharmacodynamics interactions
Direct
Indirect
Antagonistic
Synergistic /Agonistic
beta-blockers such as atenolol will block the actions of agonists e.g. bronchodilators such as salbutamol
Direct Antagonism
When two drugs with the same pharma-cological effect acting on the same receptor are give concurrently
Synergistic Interactions
The effect may be additive or multiplicative
Central Nervous System Depression
Benzodiazepines and tricyclics or alcohol
Warfarin and NSAIDs (Indomethacin)
Atenolol and verapamil
NSAIDs (Increase BP) and antihypertensive (decrease BP) medication
NSAIDs and treatment for heart failure
Pharmacodynamic Interactions Indirect Agonism
Monitor drug level
TDM
