This document discusses drug-drug interactions, including their mechanisms and types. It notes that interactions can occur through pharmacokinetic or pharmacodynamic pathways. Pharmacokinetic interactions involve effects on absorption, distribution, metabolism or excretion of a drug. They are classified as interactions affecting gastrointestinal absorption, hepatic enzyme induction or inhibition, and protein binding effects. Pharmacodynamic interactions involve drug effects without changes in levels, and can be direct, involving similar drug actions, or indirect. The document provides many examples of interacting drug classes and specific drugs. It also discusses risk factors for interactions and outcomes. Food, alcohol and smoking are noted as other factors that can influence drug interactions.
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own.
Identify primary drug interaction concepts
Describe types and mechanisms of interactions
Identify drug interactions commonly encountered with antiretroviral drugs
Describe how to manage known interactions
This is a presentation regarding to Interaction between Prescription Drugs and nutraceuticals. Here you can able to find about information regarding to this topic and its health effects and precautions.
E-mail: Siddheshwarshinde@hotmail.com
Mr. Siddheshwar Bhagwanrao Shinde
College of Food Technology VNMKV Parbhani
Contribution of metabolites to the drug drug interactionRx Ravi Goyani
1. The contribution of drug metabolites to the drug drug interaction presented by RAVI GOYANI M.S(Pharm)pharmaceutics(NIPER).
2. Contents of the presentation: Introduction, Drug-drug interaction, regulatory perspectives of drug-drug interaction, potential pharmacokinetic interaction produced by metabolites, case study, evaluation of metabolites to drug interaction, conclusion , references.
3. Introduction of metabolites and its examples.
4.Types of metabolites and how its formation in to the body by phase 1&2 metabolism.
5.Types of drug drug interaction.
6.7. Short discussion about the pharmacokinetics drug interation which are essential for the preclinical pharmacokinetics drug interaction.
8. Regulatory perspective on the metabolites contribution to the drug drug interaction.
9. Criteria for the absence of a based drug interaction on the results of a clinical study.
10.11.12. Case study of the some drug metabolites(efavirenz, verapamil) participate in to the drug drug interaction by the known mechanism such as irreversible of CYP 450 enzymes bye protein adduct formation or intermediate complex formation.
13. Evaluation of metabolites drug interaction by following study.
1. Estimation of metabolites concentration
2. Metabolites and parent cytochrome P450 inhibition potency comparison
3. RMet strategy
14.15.16. Brief discussion about the evaluation and specific criteria for that evaluation parameters which are considering for the metabolites drug interaction.
17. Proposed algorithm for the evaluation of drug metabolites interaction.
18. Conclusion.
19. List of references.
Drug interaction - Potential antimicrobial drug interaction in a hospital set...Dr. Jibin Mathew
A drug interaction is a situation in which a substance affects the activity of a drug when both are administered together. This action can be synergistic or antagonistic or a new effect can be produced that neither produces on its own
A powerful presentation on the good and bad sides of drug interactions with examples. It may be used for academic purpose only. These days because of polypharmacy it has become necessary for all of us to be aware of possible drug interactions and how to avaoid them in order not to cause other detrimental conditions. All the major types of drug interactions are discussed here. It should be noted that reading other materials on drug interactions will also enhance your understanding of this intricate process.
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own.
Identify primary drug interaction concepts
Describe types and mechanisms of interactions
Identify drug interactions commonly encountered with antiretroviral drugs
Describe how to manage known interactions
This is a presentation regarding to Interaction between Prescription Drugs and nutraceuticals. Here you can able to find about information regarding to this topic and its health effects and precautions.
E-mail: Siddheshwarshinde@hotmail.com
Mr. Siddheshwar Bhagwanrao Shinde
College of Food Technology VNMKV Parbhani
Contribution of metabolites to the drug drug interactionRx Ravi Goyani
1. The contribution of drug metabolites to the drug drug interaction presented by RAVI GOYANI M.S(Pharm)pharmaceutics(NIPER).
2. Contents of the presentation: Introduction, Drug-drug interaction, regulatory perspectives of drug-drug interaction, potential pharmacokinetic interaction produced by metabolites, case study, evaluation of metabolites to drug interaction, conclusion , references.
3. Introduction of metabolites and its examples.
4.Types of metabolites and how its formation in to the body by phase 1&2 metabolism.
5.Types of drug drug interaction.
6.7. Short discussion about the pharmacokinetics drug interation which are essential for the preclinical pharmacokinetics drug interaction.
8. Regulatory perspective on the metabolites contribution to the drug drug interaction.
9. Criteria for the absence of a based drug interaction on the results of a clinical study.
10.11.12. Case study of the some drug metabolites(efavirenz, verapamil) participate in to the drug drug interaction by the known mechanism such as irreversible of CYP 450 enzymes bye protein adduct formation or intermediate complex formation.
13. Evaluation of metabolites drug interaction by following study.
1. Estimation of metabolites concentration
2. Metabolites and parent cytochrome P450 inhibition potency comparison
3. RMet strategy
14.15.16. Brief discussion about the evaluation and specific criteria for that evaluation parameters which are considering for the metabolites drug interaction.
17. Proposed algorithm for the evaluation of drug metabolites interaction.
18. Conclusion.
19. List of references.
Drug interaction - Potential antimicrobial drug interaction in a hospital set...Dr. Jibin Mathew
A drug interaction is a situation in which a substance affects the activity of a drug when both are administered together. This action can be synergistic or antagonistic or a new effect can be produced that neither produces on its own
A powerful presentation on the good and bad sides of drug interactions with examples. It may be used for academic purpose only. These days because of polypharmacy it has become necessary for all of us to be aware of possible drug interactions and how to avaoid them in order not to cause other detrimental conditions. All the major types of drug interactions are discussed here. It should be noted that reading other materials on drug interactions will also enhance your understanding of this intricate process.
discusses about the interaction of certain drugs with some food materials and explains in detail about the effect of food on absorption, distribution, metabolism and excretion. Also dicsussed about the pharmacodynamic and pharmacogenomic aspects
Drug interaction final edition -- animatedAhmed Omar
this is a lecture of " drug interactions " , shows:
-definitions
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-mechanisms
-high risk people
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-resources
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...........
hope u enjoy the lecture :)
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
Drug interaction is defined as the pharmacological activity of one drug is altered by the concomitant use of another drug or by the presence of some other substance
The Drug whose Activity is effected by such an Interaction is called as a “Object drug.”
The agent which precipitates such an interaction is referred as the “Precipitant”.
Definition of drug interaction ,types and factors contributing to drug interactions. Mechanisms of Drug Interaction. Absorption, Distribution, Metabolism and Excretion interactions with examples(ADME INTERACTIONS).Prevention of drug interaction.
BIO DRUG-DRUG & BIO DRUG–FOOD INTERACTION.pptxChhavi Singh
Introduction
Types of drug Interaction
Effects of drug Interaction
Factors contributing to drug interactions
Mechanism
Pharmaceutical Interactions
Pharmacokinetic Interactions
Pharmacodynamic Interaction
Consequences of drug interaction
Reducing the risk of drug interaction
Influence of Smoking and Alcohol
Bio drug – Food Interaction
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
2. INTRODUCTION
• An interaction occurs when the effects of one drug are changed
by another drug, food, drink or exposure to an environmental
chemical.
• A drug interaction occurs when two or more drugs interact in
such a way that the effectiveness or toxicity of one or more of
the drugs is altered.
• Interactions can be harmful, either by increasing the toxicity of a
drug or by reducing its efficacy. However, some drug
interactions can also be beneficial .
DRUG - DRUG INTERACTIONS
2
3. RISK FACTORS
• Genetic make up .
• Multiple prescribers .
• Multiple pharmacies .
• Specific population like e.g, females , elderly, obese, criticaly ill
patient , trasplant recipient .
• Specific illness E.g. Hepatic disease, Renal dysfunction .
• Narrow therapeutic index drugs as warfarin , digoxin ,
theophyllin .
DRUG - DRUG INTERACTIONS
3
4. OUTCOMES OF DRUG INTERACTIONS
1) Loss of therapeutic effect .
2) Toxicity .
3) Beneficial effects e.g additive & potentiation (intended) or
antagonism (unintended).
4) Chemical or physical interaction e.g I.V incompatibility in
fluid or syringes mixture .
DRUG - DRUG INTERACTIONS
4
8. ALTERED GIT ABSORPTION.
•Altered pH
•Altered bacterial flora
• formation of drug chelates or complexes
• drug induced mucosal damage
• altered GIT motility.
DRUG - DRUG INTERACTIONS
8
10. CYP450 ISOENZYMES
• Present in lipid layer of the endoplasmic reticulum of
hepatocytes .
• Major enzymes involved in metabolism and bioactivation .
• About 75% of reactions .
DRUG - DRUG INTERACTIONS
10
11. CYTOCHROME P450 (CYP450)
• Inducer
• Speeds up metabolism
• Decreases substrate level (lack of efficacy is concern)
• Gradual onset/offset
• Inhibitor
• Slows metabolism
• Increases substrate level (toxicity is concern)
• Quick onset/offset
DRUG - DRUG INTERACTIONS
11
14. PHARMACODYNEMIC INTERACTION
It means alteration of the dug action without change in its
serum concentration by pharmacokinetic factors.
These are of two types
1.direct pharmacodynamic interactions.
2.Indirect pharmacodynamic interactions
DRUG - DRUG INTERACTIONS
14
15. DIRECT PHARMACODYNAMIC INTERACTIONS:
In which drugs having similar or opposing pharmacological effects are
used concurrently.
The three consequences of direct interactions are
1.Antagonism.
2.Addition or summation.
3.Synergism or potentiation.
DRUG - DRUG INTERACTIONS
15
16. INDIRECT PHARMACODYNAMIC INTERACTION:
In which both the object and the precipitant drugs have unrelated
effects.but the latter in Some way alerts the effects of the former.
Example: salicylatesdecrease the ability of the platelets to aggregate
thus impairing the Homeostasis if warfarin indused bleeding occurs.
DRUG - DRUG INTERACTIONS
16
17. PHARMACEUTICAL INTERACTIONS
Also called as incompatibility.it is a physicochemical interaction that
occous when drugs are mixed in i.v . Infusions causing precipitation
or inactivation of active principles .
DRUG - DRUG INTERACTIONS
17
45. FOOD-DRUG INTERACTIONS…
• -Advise patients to take medication with a full glass of
water.
• -Do not take vitamin pills at the same time you take
medication (i.e, take medication 1 hour after taking
vitamins).
• -Not mix medication into hot drinks, because the heat
from the drink may destroy the effectiveness of the
drug.
• -Never take medication with alcoholic drinks.
DRUG - DRUG INTERACTIONS
45
46. INFLUENCE OF FOOD ON DRUG INTERACTION:
Food effects the rate and extent of absorption of drugs from the
GI tract.
Example: Many anti biotics should be given atleast 1hr before or 2hr
after meals to achieve Optimal absorption.
Diet also may influence urinary pH values.
Lime juice is most acidic
Milk products alter pH
DRUG - DRUG INTERACTIONS
46
47. DRUG INDUCED NUTRITIONAL EFICIENCIES
DRUG
ANTIEPILECTIC DRUGS
(phenytion ,
phenobarbitone, primidone,
valproic acid)
AFFECTED NUTRIENTS
POSSIBLE MECHANISM
EFFECT
Folate
Vitamin D
Vitamin E
Zinc
Decreased absorption
Enzyme induction
Excess utilization ?
Chelation
Selenium
Vitamin K
Peroxide damage
?
Megaloblastic anemia
Osteomalacia
Haemolysis
Anorexia , celebellar
dysfunction
Hepatotoxicity
Hemorrhage
ANTIFOLATE DRUGS
(e.g. methotrexate,
pyrimethamine,
trimethamine, trimethoprim)
Folate
Dihydrofolate reductase
inhibition
Megaloblastic anemia,
cytopenia
CEPHALOSPORINS
(Cefamendole,
cefoperazone, latamoxef)
Vitamin K
Decreased prothrombin
synthesis
Bleeding episodes
DRUG - DRUG INTERACTIONS
47
48. DRUG
AFFECTED
NUTRIENTS
POSSIBLE
MECHANISM
EFFECT
CORTICOSTEROIDS
Calcium
Decreased Ca, vitamin D
metabolism
Bone disorders
COUMARIN
ANTICOGULANTS
Vitamin K
?
Hemorrhage
DIURETICS
Zn , Ca, K, Mg
Urinary loss depression
Weakness , electrolyte
imbalance
DRUG
AFFECTED
NUTRIENTS
POSSIBLE
MECHANISM
EFFECT
ISONIAZED (INH)
Pyridoxine
Complex formation
Peripheral neuropathy,
Convulsions, psychatric
manifestation
DRUG - DRUG INTERACTIONS
48
49. DRUG
AFFECTED
NUTRIENTS
POSSIBLE
MECHANISM
EFFECT
PARA – AMINO
SALICYCLIC (PAS)
Vitamin B12
decreased absorption
Megaloblastic anaemia
POTASSIUM CHLORIDE
Vitamin B12
decreased ileal Ph
Decreased absorption
RIFAMPCIN
Vitamin D
Enzyme induction
Osteomalacia
SALICYLATES
Vitamin C, Folate
Increased excretion,
decreased uptake
Anemia ,infection
DRUG - DRUG INTERACTIONS
49
for example, an additive effect is seen when diuretics and beta-blockers are combined to treat hypertension
Antacids and binding agents such as cholestyramine may impair absorption of other drugs from the gastrointestinal tract by forming complexes with them.For example, antacids reduce the absorption of quinolones such as ciprofloxacin. Otherdrugs, such as metoclopramide or opiates, may affect gut transit time. This generally influences the rate, rather than the extent, of drug absorption. Most absorption interactions are not clinically significant and can be managed by separating the administration of the drugsDrug displacement interactions occur when two drugs compete for the same protein binding site and one or both is displaced. This results in an increase in the concentration of free (active) drug, but is usually compensated for by an increase in excretion.These interactions usually involve highly protein bound drugs such as phenytoin, warfarin and tolbutamide. However, the effects of displacement interactions are usually minor and transient.Many drugs are metabolised in the liver, mainly by the cytochrome P450 enzyme system. Induction of enzymes by one drug can increase the rate of metabolism of another, resulting in a reduced effect. Conversely, enzyme inhibitors may result in accumulation and increased toxicity of other drugsFinally, drugs that alter renal excretion can affect plasma levels of other drugs. For example, methotrexate and non-steroidalanti-inflammatory drugs compete for renal excretion. Concomitant use of these agents may result inraised methotrexate levels and an increased risk of toxicity, although this combination may be used successfully under specialist supervision. The importance of this type of interaction depends on the extentto which a drug and/or its metabolites are renally excreted.The mechanism of an interaction can also have an effect on its time course.Enzyme inducers stimulate the production of new metabolising enzymes and it often takes between one and three weeks before their effects are at a maximum. In contrast, enzyme inhibitors usually have an effect on hepatic metabolism within 24 hours.
Antacids and binding agents such as cholestyramine may impair absorption of other drugs from the gastrointestinal tract by forming complexes with them.For example, antacids reduce the absorption of quinolones such as ciprofloxacin. Otherdrugs, such as metoclopramide or opiates, may affect gut transit time. This generally influences the rate, rather than the extent, of drug absorption. Most absorption interactions are not clinically significant and can be managed by separating the administration of the drugsDrug displacement interactions occur when two drugs compete for the same protein binding site and one or both is displaced. This results in an increase in the concentration of free (active) drug, but is usually compensated for by an increase in excretion.These interactions usually involve highly protein bound drugs such as phenytoin, warfarin and tolbutamide. However, the effects of displacement interactions are usually minor and transient.Many drugs are metabolised in the liver, mainly by the cytochrome P450 enzyme system. Induction of enzymes by one drug can increase the rate of metabolism of another, resulting in a reduced effect. Conversely, enzyme inhibitors may result in accumulation and increased toxicity of other drugsFinally, drugs that alter renal excretion can affect plasma levels of other drugs. For example, methotrexate and non-steroidalanti-inflammatory drugs compete for renal excretion. Concomitant use of these agents may result inraised methotrexate levels and an increased risk of toxicity, although this combination may be used successfully under specialist supervision. The importance of this type of interaction depends on the extentto which a drug and/or its metabolites are renally excreted.The mechanism of an interaction can also have an effect on its time course.Enzyme inducers stimulate the production of new metabolising enzymes and it often takes between one and three weeks before their effects are at a maximum. In contrast, enzyme inhibitors usually have an effect on hepatic metabolism within 24 hours.